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Database: UniProt/SWISS-PROT UniProt/TrEMBL
Entry: CP21A_HUMAN Q08AG9_HUMAN Q16874_HUMAN
LinkDB: CP21A_HUMAN Q08AG9_HUMAN Q16874_HUMAN
Original site: CP21A_HUMAN Q08AG9_HUMAN Q16874_HUMAN 
tr:Q16874_HUMAN : No such data.

ID   CP21A_HUMAN             Reviewed;         495 AA.
AC   P08686; A2BHY6; P04033; Q01204; Q08AG8; Q16749; Q16806; Q16874; Q5ST44;
AC   Q96NU8;
DT   01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
DT   24-JAN-2024, sequence version 2.
DT   24-JAN-2024, entry version 241.
DE   RecName: Full=Steroid 21-hydroxylase {ECO:0000303|PubMed:25855791};
DE            EC=1.14.14.16 {ECO:0000269|PubMed:16984992, ECO:0000269|PubMed:22014889, ECO:0000269|PubMed:25855791, ECO:0000269|PubMed:27721825};
DE   AltName: Full=21-OHase;
DE   AltName: Full=Cytochrome P-450c21;
DE   AltName: Full=Cytochrome P450 21;
DE   AltName: Full=Cytochrome P450 XXI;
DE   AltName: Full=Cytochrome P450-C21;
DE   AltName: Full=Cytochrome P450-C21B;
GN   Name=CYP21A2; Synonyms=CYP21, CYP21B;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE CYP21A2*1A), AND VARIANTS LEU-6
RP   DEL; LYS-103 AND ASN-494.
RX   PubMed=3486422; DOI=10.1073/pnas.83.9.2841;
RA   Higashi Y., Yoshioka H., Yamane M., Gotoh O., Fujii-Kuriyama Y.;
RT   "Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly
RT   arranged in human chromosome: a pseudogene and a genuine gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 83:2841-2845(1986).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ALLELE CYP21A2*1B) (ISOFORM 1),
RP   AND VARIANTS LEU-6 DEL AND ASN-494.
RX   PubMed=3487786; DOI=10.1073/pnas.83.14.5111;
RA   White P.C., New M.I., Dupont B.;
RT   "Structure of human steroid 21-hydroxylase genes.";
RL   Proc. Natl. Acad. Sci. U.S.A. 83:5111-5115(1986).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT AH3 THR-269, VARIANTS LYS-103
RP   AND ASN-494, AND INVOLVEMENT IN AH3.
RX   PubMed=3038528; DOI=10.1002/j.1460-2075.1987.tb02414.x;
RA   Rodrigues N.R., Dunham I., Yu C.Y., Carroll M.C., Porter R.R.,
RA   Campbell R.D.;
RT   "Molecular characterization of the HLA-linked steroid 21-hydroxylase B gene
RT   from an individual with congenital adrenal hyperplasia.";
RL   EMBO J. 6:1653-1661(1987).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT AH3 LEU-282.
RX   PubMed=3267225; DOI=10.1172/jci113562;
RA   Globerman H., Amor M., Parker K.L., New M.I., White P.C.;
RT   "Nonsense mutation causing steroid 21-hydroxylase deficiency.";
RL   J. Clin. Invest. 82:139-144(1988).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS AH3 HIS-340 AND SER-454.
RC   TISSUE=Peripheral blood;
RX   PubMed=1406709; DOI=10.1210/mend.6.8.1406709;
RA   Helmberg A., Tusie-Luna M.-T., Tabarelli M., Kofler R., White P.C.;
RT   "R339H and P453S: CYP21 mutations associated with nonclassic steroid 21-
RT   hydroxylase deficiency that are not apparent gene conversions.";
RL   Mol. Endocrinol. 6:1318-1322(1992).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-6 DEL; LYS-103 AND
RP   ASN-494.
RX   PubMed=19505723; DOI=10.1016/j.molimm.2009.04.033;
RA   Blasko B., Banlaki Z., Gyapay G., Pozsonyi E., Sasvari-Szekely M.,
RA   Rajczy K., Fust G., Szilagyi A.;
RT   "Linkage analysis of the C4A/C4B copy number variation and polymorphisms of
RT   the adjacent steroid 21-hydroxylase gene in a healthy population.";
RL   Mol. Immunol. 46:2623-2629(2009).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=23241443; DOI=10.1093/gbe/evs121;
RA   Banlaki Z., Szabo J.A., Szilagyi A., Patocs A., Prohaszka Z., Fust G.,
RA   Doleschall M.;
RT   "Intraspecific evolution of human RCCX copy number variation traced by
RT   haplotypes of the CYP21A2 gene.";
RL   Genome Biol. Evol. 5:98-112(2013).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=24312389; DOI=10.1371/journal.pone.0081977;
RA   Szabo J.A., Szilagyi A., Doleschall Z., Patocs A., Farkas H., Prohaszka Z.,
RA   Racz K., Fuest G., Doleschall M.;
RT   "Both positive and negative selection pressures contribute to the
RT   polymorphism pattern of the duplicated human CYP21A2 gene.";
RL   PLoS ONE 8:e81977-e81977(2013).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=28401898; DOI=10.1038/ejhg.2017.38;
RA   Doleschall M., Luczay A., Koncz K., Hadzsiev K., Erhardt E., Szilagyi A.,
RA   Doleschall Z., Nemeth K., Toeroek D., Prohaszka Z., Gereben B., Fekete G.,
RA   Glaz E., Igaz P., Korbonits M., Toth M., Racz K., Patocs A.;
RT   "A unique haplotype of RCCX copy number variation: from the clinics of
RT   congenital adrenal hyperplasia to evolutionary genetics.";
RL   Eur. J. Hum. Genet. 25:702-710(2017).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE CYP21A2*6) (ISOFORMS 1 AND
RP   2).
RC   TISSUE=Adrenal gland;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [11]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14656967; DOI=10.1101/gr.1736803;
RA   Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D.,
RA   Hood L.;
RT   "Analysis of the gene-dense major histocompatibility complex class III
RT   region and its comparison to mouse.";
RL   Genome Res. 13:2621-2636(2003).
RN   [12]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [13]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [14]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LYS-103.
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [15]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 110-186, AND VARIANT AH3 ASN-173.
RX   PubMed=8485582; DOI=10.1038/ng0393-260;
RA   Collier S., Tassabehji M., Sinnott P., Strachan T.;
RT   "A de novo pathological point mutation at the 21-hydroxylase locus:
RT   implications for gene conversion in the human genome.";
RL   Nat. Genet. 3:260-265(1993).
RN   [16]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 150-183, AND VARIANT AH3 ASN-173.
RX   PubMed=3871526; DOI=10.1073/pnas.82.2.521;
RA   Carroll M.C., Campbell R.D., Porter R.R.;
RT   "Mapping of steroid 21-hydroxylase genes adjacent to complement component
RT   C4 genes in HLA, the major histocompatibility complex in man.";
RL   Proc. Natl. Acad. Sci. U.S.A. 82:521-525(1985).
RN   [17]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 150-183, AND VARIANT AH3 ASN-173.
RX   PubMed=3257825; DOI=10.1073/pnas.85.5.1600;
RA   Amor M., Parker K.L., Globerman H., New M.I., White P.C.;
RT   "Mutation in the CYP21B gene (Ile-172-->Asn) causes steroid 21-hydroxylase
RT   deficiency.";
RL   Proc. Natl. Acad. Sci. U.S.A. 85:1600-1604(1988).
RN   [18]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 266-495 (ISOFORM 1), VARIANT AH3 LEU-282, AND
RP   VARIANT ASN-494.
RX   PubMed=3497399; DOI=10.1073/pnas.84.16.5858;
RA   Matteson K.J., Phillips J.A. III, Miller W.L., Chung B.C., Orlando P.J.,
RA   Frisch H., Ferrandez A., Burr I.M.;
RT   "P450XXI (steroid 21-hydroxylase) gene deletions are not found in family
RT   studies of congenital adrenal hyperplasia.";
RL   Proc. Natl. Acad. Sci. U.S.A. 84:5858-5862(1987).
RN   [19]
RP   FUNCTION.
RX   PubMed=10602386; DOI=10.1038/sj.gt.3301018;
RA   Tajima T., Okada T., Ma X.M., Ramsey W., Bornstein S., Aguilera G.;
RT   "Restoration of adrenal steroidogenesis by adenovirus-mediated transfer of
RT   human cytochromeP450 21-hydroxylase into the adrenal gland of21-
RT   hydroxylase-deficient mice.";
RL   Gene Ther. 6:1898-1903(1999).
RN   [20] {ECO:0007744|PDB:4Y8W}
RP   X-RAY CRYSTALLOGRAPHY (2.64 ANGSTROMS) OF 30-495 IN COMPLEX WITH HEME AND
RP   PROGESTERONE, FUNCTION, COFACTOR, CATALYTIC ACTIVITY, AND
RP   BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=25855791; DOI=10.1074/jbc.m115.646307;
RA   Pallan P.S., Wang C., Lei L., Yoshimoto F.K., Auchus R.J., Waterman M.R.,
RA   Guengerich F.P., Egli M.;
RT   "Human Cytochrome P450 21A2, the major steroid 21-hydroxylase: structure of
RT   the enzyme-progesterone substrate complex and rate-limiting c-h bond
RT   cleavage.";
RL   J. Biol. Chem. 290:13128-13143(2015).
RN   [21]
RP   CHARACTERIZATION OF VARIANT AH3 LEU-282, AND MUTAGENESIS OF SER-269;
RP   VAL-282 AND CYS-429.
RX   PubMed=1864962; DOI=10.1172/jci115334;
RA   Wu D.-A., Chung B.-C.;
RT   "Mutations of P450c21 (steroid 21-hydroxylase) at Cys428, Val281, and
RT   Ser268 result in complete, partial, or no loss of enzymatic activity,
RT   respectively.";
RL   J. Clin. Invest. 88:519-523(1991).
RN   [22]
RP   POLYMORPHISM.
RX   PubMed=8081391; DOI=10.1002/humu.1380030408;
RA   White P.C., Tusie-Luna M.-T., New M.I., Speiser P.W.;
RT   "Mutations in steroid 21-hydroxylase (CYP21).";
RL   Hum. Mutat. 3:373-378(1994).
RN   [23]
RP   VARIANTS AH3 LEU-212 AND LEU-282.
RX   PubMed=3260007; DOI=10.1056/nejm198807073190104;
RA   Speiser P.W., New M.I., White P.C.;
RT   "Molecular genetic analysis of nonclassic steroid 21-hydroxylase deficiency
RT   associated with HLA-B14,DR1.";
RL   N. Engl. J. Med. 319:19-23(1988).
RN   [24]
RP   VARIANTS AH3 ASN-173 AND TRP-357.
RX   PubMed=2303461; DOI=10.1016/s0021-9258(19)39804-7;
RA   Chiou S.-H., Hu M.-C., Chung B.-C.;
RT   "A missense mutation at Ile172-->Asn or Arg356-->Trp causes steroid 21-
RT   hydroxylase deficiency.";
RL   J. Biol. Chem. 265:3549-3552(1990).
RN   [25]
RP   VARIANT AH3 ASN-173.
RX   PubMed=1937474; DOI=10.1007/bf00201731;
RA   Partanen J., Campbell R.D.;
RT   "Substitution of Ile-172 to Asn in the steroid 21-hydroxylase B (P450c21B)
RT   gene in a Finnish patient with the simple virilizing form of congenital
RT   adrenal hyperplasia.";
RL   Hum. Genet. 87:716-720(1991).
RN   [26]
RP   VARIANT AH3 LEU-31, AND VARIANT THR-269.
RX   PubMed=2072928; DOI=10.1210/mend-5-5-685;
RA   Tusie-Luna M.T., Speiser P.W., Dumic M., New M.I., White P.C.;
RT   "A mutation (Pro-30 to Leu) in CYP21 represents a potential nonclassic
RT   steroid 21-hydroxylase deficiency allele.";
RL   Mol. Endocrinol. 5:685-692(1991).
RN   [27]
RP   VARIANTS AH3 LEU-31; ASN-173; ASN-237; GLU-238; LYS-240; LEU-282 AND
RP   TRP-357.
RX   PubMed=1644925; DOI=10.1172/jci115897;
RA   Speiser P.W., Dupont J., Zhu D., Serrat J., Buegeleisen M.,
RA   Tusie-Luna M.-T., Lesser M., New M.I., White P.C.;
RT   "Disease expression and molecular genotype in congenital adrenal
RT   hyperplasia due to 21-hydroxylase deficiency.";
RL   J. Clin. Invest. 90:584-595(1992).
RN   [28]
RP   VARIANT AH3 SER-454.
RX   PubMed=1406699; DOI=10.1210/mend.6.8.1406699;
RA   Owerbach D., Sherman L., Ballard A.L., Azziz R.;
RT   "Pro-453 to Ser mutation in CYP21 is associated with nonclassic steroid 21-
RT   hydroxylase deficiency.";
RL   Mol. Endocrinol. 6:1211-1215(1992).
RN   [29]
RP   VARIANTS AH3 LEU-106; SER-292 AND SER-454.
RX   PubMed=1496017; DOI=10.1073/pnas.89.15.7232;
RA   Wedell A., Ritzen E.M., Haglund-Stengler B., Luthman H.;
RT   "Steroid 21-hydroxylase deficiency: three additional mutated alleles and
RT   establishment of phenotype-genotype relationships of common mutations.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:7232-7236(1992).
RN   [30]
RP   VARIANT AH3 PRO-484.
RX   PubMed=8478006; DOI=10.1007/bf00218263;
RA   Wedell A., Luthman H.;
RT   "Steroid 21-hydroxylase (P450c21): a new allele and spread of mutations
RT   through the pseudogene.";
RL   Hum. Genet. 91:236-240(1993).
RN   [31]
RP   VARIANTS AH3 ASN-173; ASN-237; LEU-282 AND PRO-484.
RX   PubMed=7749410; DOI=10.1002/humu.1380050205;
RA   Barbat B., Bogyo A., Raux-Demay M.-C., Kuttenn F., Boue J., Simon-Bouy B.,
RA   Serre J.-L., Boue A., Mornet E.;
RT   "Screening of CYP21 gene mutations in 129 French patients affected by
RT   steroid 21-hydroxylase deficiency.";
RL   Hum. Mutat. 5:126-130(1995).
RN   [32]
RP   VARIANT AH3 ASP-381.
RX   PubMed=9067760;
RX   DOI=10.1002/(sici)1098-1004(1997)9:2<181::aid-humu12>3.0.co;2-z;
RA   Kirby-Keyser L., Porter C.C., Donohoue P.A.;
RT   "E380D: a novel point mutation of CYP21 in an HLA-homozygous patient with
RT   salt-losing congenital adrenal hyperplasia due to 21-hydroxylase
RT   deficiency.";
RL   Hum. Mutat. 9:181-182(1997).
RN   [33]
RP   VARIANTS AH3 PRO-357 AND GLN-357.
RX   PubMed=9187661; DOI=10.1007/s004390050436;
RA   Lajic S., Levo A., Nikoshkov A., Lundberg Y., Partanen J., Wedell A.;
RT   "A cluster of missense mutations at Arg356 of human steroid 21-hydroxylase
RT   may impair redox partner interaction.";
RL   Hum. Genet. 99:704-709(1997).
RN   [34]
RP   VARIANTS AH3 LEU-106 AND SER-454.
RX   PubMed=8989258; DOI=10.1210/jcem.82.1.3678;
RA   Nikoshkov A., Lajic S., Holst M., Wedell A., Luthman H.;
RT   "Synergistic effect of partially inactivating mutations in steroid 21-
RT   hydroxylase deficiency.";
RL   J. Clin. Endocrinol. Metab. 82:194-199(1997).
RN   [35]
RP   VARIANTS ARG-99; LYS-103; GLU-184 AND ASN-494.
RX   PubMed=9580109; DOI=10.1007/s004390050672;
RA   Ordonez-Sanchez M.L., Ramirez-Jimenez S., Lopez-Gutierrez A.U., Riba L.,
RA   Gamboa-Cardiel S., Cerrillo-Hinojosa M., Altamirano-Bustamante N.,
RA   Calzada-Leon R., Robles-Valdes C., Mendoza-Morfin F., Tusie-Luna M.T.;
RT   "Molecular genetic analysis of patients carrying steroid 21-hydroxylase
RT   deficiency in the Mexican population: identification of possible new
RT   mutations and high prevalence of apparent germ-line mutations.";
RL   Hum. Genet. 102:170-177(1998).
RN   [36]
RP   VARIANTS AH3 GLU-197 DEL; SER-292 AND PRO-484.
RX   PubMed=9497336; DOI=10.1074/jbc.273.11.6163;
RA   Nikoshkov A., Lajic S., Vlamis-Gardikas A., Tranebjaerg L., Holst M.,
RA   Wedell A., Luthman H.;
RT   "Naturally occurring mutants of human steroid 21-hydroxylase (P450c21)
RT   pinpoint residues important for enzyme activity and stability.";
RL   J. Biol. Chem. 273:6163-6165(1998).
RN   [37]
RP   VARIANT AH3 GLN-31, CHARACTERIZATION OF VARIANT AH3 GLN-31, SUBCELLULAR
RP   LOCATION, TOPOLOGY, AND DOMAIN.
RX   PubMed=10198222; DOI=10.1006/bbrc.1999.0482;
RA   Lajic S., Nikoshkov A., Holst M., Wedell A.;
RT   "Effects of missense mutations and deletions on membrane anchoring and
RT   enzyme function of human steroid 21-hydroxylase (P450c21).";
RL   Biochem. Biophys. Res. Commun. 257:384-390(1999).
RN   [38]
RP   VARIANTS AH3 LEU-31; VAL-91; ASN-173; ALA-179; LEU-282; CYS-292; HIS-355;
RP   TRP-357 AND SER-454.
RX   PubMed=10364682; DOI=10.1159/000022866;
RA   Lobato M.N., Ordonez-Sanchez M.L., Tusie-Luna M.T., Meseguer A.;
RT   "Mutation analysis in patients with congenital adrenal hyperplasia in the
RT   Spanish population: identification of putative novel steroid 21-hydroxylase
RT   deficiency alleles associated with the classic form of the disease.";
RL   Hum. Hered. 49:169-175(1999).
RN   [39]
RP   VARIANTS AH3 TYR-170; LEU-282 AND GLN-357.
RX   PubMed=10094562;
RX   DOI=10.1002/(sici)1098-1004(1999)13:2<172::aid-humu17>3.0.co;2-n;
RA   Witchel S.F., Smith R., Suda-Hartman M.;
RT   "Identification of CYP21 mutations, one novel, by single strand
RT   conformational polymorphism (SSCP) analysis.";
RL   Hum. Mutat. 13:172-172(1999).
RN   [40]
RP   VARIANTS AH3 LEU-31; GLU-65; ASN-173; ASN-237; LEU-282; SER-292; TRP-357
RP   AND VAL-363.
RX   PubMed=10408778;
RX   DOI=10.1002/(sici)1098-1004(1999)13:6<482::aid-humu8>3.0.co;2-0;
RA   Ohlsson G., Mueller J., Skakkebaek N.E., Schwartz M.;
RT   "Steroid 21-hydroxylase deficiency: mutational spectrum in Denmark, three
RT   novel mutations, and in vitro expression analysis.";
RL   Hum. Mutat. 13:482-486(1999).
RN   [41]
RP   VARIANTS AH3 LEU-31; ASN-173; ASN-237; GLU-238; LYS-240; LEU-282 AND
RP   TRP-357.
RX   PubMed=10408786;
RX   DOI=10.1002/(sici)1098-1004(1999)13:6<505::aid-humu16>3.0.co;2-0;
RA   Kapelari K., Ghanaati Z., Wollmann H., Ventz M., Ranke M.B., Kofler R.,
RA   Peters H.;
RT   "A rapid screening for steroid 21-hydroxylase mutations in patients with
RT   congenital adrenal hyperplasia.";
RL   Hum. Mutat. 13:505-505(1999).
RN   [42]
RP   VARIANTS AH3 LEU-282; TRP-357 AND SER-425.
RX   PubMed=10443693; DOI=10.1210/jcem.84.8.5937;
RA   Billerbeck A.E.C., Bachega T.A.S.S., Frazatto E.T., Nishi M.Y.,
RA   Goldberg A.C., Marin M.L.C., Madureira G., Monte O., Arnhold I.J.P.,
RA   Mendonca B.B.;
RT   "A novel missense mutation, GLY424SER, in Brazilian patients with 21-
RT   hydroxylase deficiency.";
RL   J. Clin. Endocrinol. Metab. 84:2870-2872(1999).
RN   [43]
RP   VARIANTS AH3 LEU-31; ASN-173; LEU-282 AND TRP-357, AND VARIANT THR-269.
RX   PubMed=10496074; DOI=10.1007/s100380050167;
RA   Asanuma A., Ohura T., Ogawa E., Sato S., Igarashi Y., Matsubara Y.,
RA   Iinuma K.;
RT   "Molecular analysis of Japanese patients with steroid 21-hydroxylase
RT   deficiency.";
RL   J. Hum. Genet. 44:312-317(1999).
RN   [44]
RP   VARIANTS AH3 ASN-173 AND TRP-357.
RX   PubMed=10051010;
RA   Lako M., Ramsden S., Campbell R.D., Strachan T.;
RT   "Mutation screening in British 21-hydroxylase deficiency families and
RT   development of novel microsatellite based approaches to prenatal
RT   diagnosis.";
RL   J. Med. Genet. 36:119-124(1999).
RN   [45]
RP   VARIANTS AH3 LEU-282 AND SER-454, AND VARIANT THR-269.
RX   PubMed=10391209; DOI=10.1038/10290;
RA   Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA   Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA   Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA   Lander E.S.;
RT   "Characterization of single-nucleotide polymorphisms in coding regions of
RT   human genes.";
RL   Nat. Genet. 22:231-238(1999).
RN   [46]
RP   ERRATUM OF PUBMED:10391209.
RA   Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA   Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA   Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA   Lander E.S.;
RL   Nat. Genet. 23:373-373(1999).
RN   [47]
RP   VARIANTS AH3 LEU-31; ASN-173; LEU-282; GLY-282; PHE-301; CYS-355; TRP-357
RP   AND SER-454.
RX   PubMed=10720040; DOI=10.1210/jcem.85.3.6441;
RA   Krone N., Braun A., Roscher A.A., Knorr D., Schwarz H.P.;
RT   "Predicting phenotype in steroid 21-hydroxylase deficiency? Comprehensive
RT   genotyping in 155 unrelated, well defined patients from southern Germany.";
RL   J. Clin. Endocrinol. Metab. 85:1059-1065(2000).
RN   [48]
RP   VARIANTS AH3 LEU-31; ASN-173; PRO-262; TRP-357 AND PRO-484.
RX   PubMed=11598371; DOI=10.1159/000049992;
RA   Loke K.Y., Lee Y.S., Lee W.W.R., Poh L.K.S.;
RT   "Molecular analysis of CYP-21 mutations for congenital adrenal hyperplasia
RT   in Singapore.";
RL   Horm. Res. 55:179-184(2001).
RN   [49]
RP   VARIANTS AH3 LEU-31; ASN-173; LEU-282; MET-318; TRP-357; CYS-436 AND
RP   SER-454.
RX   PubMed=11232002; DOI=10.1210/jcem.86.1.7131;
RA   Deneux C., Tardy V., Dib A., Mornet E., Billaud L., Charron D., Morel Y.,
RA   Kuttenn F.;
RT   "Phenotype-genotype correlation in 56 women with nonclassical congenital
RT   adrenal hyperplasia due to 21-hydroxylase deficiency.";
RL   J. Clin. Endocrinol. Metab. 86:207-213(2001).
RN   [50]
RP   VARIANTS AH3 LEU-31; ASN-173; LEU-282; SER-292; TRP-357; SER-425; HIS-427;
RP   SER-454 AND PRO-484, AND CHARACTERIZATION OF VARIANT AH3 HIS-427.
RX   PubMed=11600539; DOI=10.1210/jcem.86.10.7898;
RA   Baumgartner-Parzer S.M., Schulze E., Waldhaeusl W., Pauschenwein S.,
RA   Rondot S., Nowotny P., Meyer K., Frisch H., Waldhauser F., Vierhapper H.;
RT   "Mutational spectrum of the steroid 21-hydroxylase gene in Austria:
RT   identification of a novel missense mutation.";
RL   J. Clin. Endocrinol. Metab. 86:4771-4775(2001).
RN   [51]
RP   VARIANT AH3 TRP-364.
RX   PubMed=11746135; DOI=10.1002/pd.167;
RA   Levo A., Partanen J.;
RT   "Novel mutations in the human CYP21 gene.";
RL   Prenat. Diagn. 21:885-889(2001).
RN   [52]
RP   VARIANTS AH3 LEU-31; ASN-173; LEU-282; LEU-284; TRP-357 AND SER-454.
RX   PubMed=12222711; DOI=10.1080/080352502760148595;
RA   Ezquieta B., Cueva E., Varela J., Oliver A., Fernandez J., Jariego C.;
RT   "Non-classical 21-hydroxylase deficiency in children: association of
RT   adrenocorticotropic hormone-stimulated 17-hydroxyprogesterone with the risk
RT   of compound heterozygosity with severe mutations.";
RL   Acta Paediatr. 91:892-898(2002).
RN   [53]
RP   VARIANTS HYPERANDROGENISM MET-305; SER-376 AND SER-454, AND
RP   CHARACTERIZATION OF VARIANTS HYPERANDROGENISM MET-305; SER-376 AND SER-454.
RX   PubMed=12050257; DOI=10.1210/jcem.87.6.8525;
RA   Lajic S., Clauin S., Robins T., Vexiau P., Blanche H.,
RA   Bellanne-Chantelot C., Wedell A.;
RT   "Novel mutations in CYP21 detected in individuals with hyperandrogenism.";
RL   J. Clin. Endocrinol. Metab. 87:2824-2829(2002).
RN   [54]
RP   VARIANTS AH3 CYS-409 AND SER-425.
RX   PubMed=12213891; DOI=10.1210/jc.2001-011939;
RA   Billerbeck A.E.C., Mendonca B.B., Pinto E.M., Madureira G., Arnhold I.J.P.,
RA   Bachega T.A.S.S.;
RT   "Three novel mutations in CYP21 gene in Brazilian patients with the
RT   classical form of 21-hydroxylase deficiency due to a founder effect.";
RL   J. Clin. Endocrinol. Metab. 87:4314-4317(2002).
RN   [55]
RP   VARIANTS AH3 THR-16; LEU-31; ASN-173; LEU-282 AND SER-454.
RX   PubMed=12887291; DOI=10.1530/eje.0.1490137;
RA   Dolzan V., Stopar-Obreza M., Zerjav-Tansek M., Breskvar K., Krzisnik C.,
RA   Battelino T.;
RT   "Mutational spectrum of congenital adrenal hyperplasia in Slovenian
RT   patients: a novel Ala15Thr mutation and Pro30Leu within a larger gene
RT   conversion associated with a severe form of the disease.";
RL   Eur. J. Endocrinol. 149:137-144(2003).
RN   [56]
RP   VARIANTS AH3 LEU-31; LEU-63; ASN-173; LEU-282; PRO-342; TRP-357; SER-454
RP   AND PRO-484.
RX   PubMed=12788866; DOI=10.1210/jc.2002-021433;
RA   Pinto G., Tardy V., Trivin C., Thalassinos C., Lortat-Jacob S.,
RA   Nihoul-Fekete C., Morel Y., Brauner R.;
RT   "Follow-up of 68 children with congenital adrenal hyperplasia due to 21-
RT   hydroxylase deficiency: relevance of genotype for management.";
RL   J. Clin. Endocrinol. Metab. 88:2624-2633(2003).
RN   [57]
RP   VARIANTS AH3 ASN-173; LEU-282; ARG-292; TYR-302; TRP-357 AND GLN-484.
RX   PubMed=12915679; DOI=10.1210/jc.2002-021681;
RA   Stikkelbroeck N.M., Hoefsloot L.H., de Wijs I.J., Otten B.J., Hermus A.R.,
RA   Sistermans E.A.;
RT   "CYP21 gene mutation analysis in 198 patients with 21-hydroxylase
RT   deficiency in The Netherlands: six novel mutations and a specific cluster
RT   of four mutations.";
RL   J. Clin. Endocrinol. Metab. 88:3852-3859(2003).
RN   [58]
RP   VARIANTS AH3 ASN-173; TRP-357 AND TRP-484.
RX   PubMed=14715874; DOI=10.1210/jc.2003-031056;
RA   Kharrat M., Tardy V., M'Rad R., Maazoul F., Jemaa L.B., Refai M., Morel Y.,
RA   Chaabouni H.;
RT   "Molecular genetic analysis of Tunisian patients with a classic form of 21-
RT   hydroxylase deficiency: identification of four novel mutations and high
RT   prevalence of Q318X mutation.";
RL   J. Clin. Endocrinol. Metab. 89:368-374(2004).
RN   [59]
RP   VARIANT AH3 HIS-125.
RX   PubMed=14676460; DOI=10.1159/000075587;
RA   Usui T., Nishisho K., Kaji M., Ikuno N., Yorifuji T., Yasuda T., Kuzuya H.,
RA   Shimatsu A.;
RT   "Three novel mutations in Japanese patients with 21-hydroxylase
RT   deficiency.";
RL   Horm. Res. 61:126-132(2004).
RN   [60]
RP   VARIANTS AH3 THR-16; LEU-31; LEU-282 AND SER-483, AND CHARACTERIZATION OF
RP   VARIANTS AH3 THR-16 AND SER-483.
RX   PubMed=15126570; DOI=10.1210/jc.2003-031630;
RA   Barbaro M., Lajic S., Baldazzi L., Balsamo A., Pirazzoli P., Cicognani A.,
RA   Wedell A., Cacciari E.;
RT   "Functional analysis of two recurrent amino acid substitutions in the CYP21
RT   gene from Italian patients with congenital adrenal hyperplasia.";
RL   J. Clin. Endocrinol. Metab. 89:2402-2407(2004).
RN   [61]
RP   VARIANTS AH3 LEU-31; ASN-173; ASN-237; GLU-238; LYS-240; LEU-282; SER-292;
RP   GLN-357; TRP-357; TYR-366; SER-454; LEU-480 AND PRO-484.
RX   PubMed=15110320; DOI=10.1016/j.ymgme.2004.02.006;
RA   Zeng X., Witchel S.F., Dobrowolski S.F., Moulder P.V., Jarvik J.W.,
RA   Telmer C.A.;
RT   "Detection and assignment of CYP21 mutations using peptide mass signature
RT   genotyping.";
RL   Mol. Genet. Metab. 82:38-47(2004).
RN   [62]
RP   VARIANTS AH3 LEU-31; ASN-173 AND TRP-357.
RX   PubMed=16046588; DOI=10.1210/jc.2005-0379;
RA   Grigorescu Sido A., Weber M.M., Grigorescu Sido P., Clausmeyer S.,
RA   Heinrich U., Schulze E.;
RT   "21-Hydroxylase and 11beta-hydroxylase mutations in Romanian patients with
RT   classic congenital adrenal hyperplasia.";
RL   J. Clin. Endocrinol. Metab. 90:5769-5773(2005).
RN   [63]
RP   VARIANTS AH3 ARG-170; ARG-179; ARG-303 AND CYS-427, CHARACTERIZATION OF
RP   VARIANTS AH3 ARG-170; ARG-179; ARG-303; CYS-427 AND HIS-427, FUNCTION, AND
RP   CATALYTIC ACTIVITY.
RX   PubMed=16984992; DOI=10.1210/jc.2006-0777;
RA   Grischuk Y., Rubtsov P., Riepe F.G., Groetzinger J., Beljelarskaia S.,
RA   Prassolov V., Kalintchenko N., Semitcheva T., Peterkova V., Tiulpakov A.,
RA   Sippell W.G., Krone N.;
RT   "Four novel missense mutations in the CYP21A2 gene detected in Russian
RT   patients suffering from the classical form of congenital adrenal
RT   hyperplasia: identification, functional characterization, and structural
RT   analysis.";
RL   J. Clin. Endocrinol. Metab. 91:4976-4980(2006).
RN   [64]
RP   VARIANTS AH3 LEU-31; LEU-63; ASN-173; TRP-357 AND SER-454, AND
RP   CHARACTERIZATION OF VARIANTS AH3 LEU-63 AND SER-454.
RX   PubMed=18319307; DOI=10.1210/jc.2007-2701;
RA   Menassa R., Tardy V., Despert F., Bouvattier-Morel C., Brossier J.P.,
RA   Cartigny M., Morel Y.;
RT   "p.H62L, a rare mutation of the CYP21 gene identified in two forms of 21-
RT   hydroxylase deficiency.";
RL   J. Clin. Endocrinol. Metab. 93:1901-1908(2008).
RN   [65]
RP   VARIANTS AH3 ARG-57; LEU-63; ARG-108; PRO-143; ASN-173; TRP-357; CYS-409
RP   AND SER-454, AND CHARACTERIZATION OF VARIANTS AH3 ARG-57; LEU-63; ARG-108;
RP   PRO-143; CYS-409 AND SER-454.
RX   PubMed=18381579; DOI=10.1210/jc.2007-2594;
RA   Soardi F.C., Barbaro M., Lau I.F., Lemos-Marini S.H., Baptista M.T.,
RA   Guerra-Junior G., Wedell A., Lajic S., de Mello M.P.;
RT   "Inhibition of CYP21A2 enzyme activity caused by novel missense mutations
RT   identified in Brazilian and Scandinavian patients.";
RL   J. Clin. Endocrinol. Metab. 93:2416-2420(2008).
RN   [66]
RP   VARIANTS AH3 GLN-122 AND SER-454, AND CHARACTERIZATION OF VARIANT AH3
RP   GLN-122.
RX   PubMed=18445671; DOI=10.1210/jc.2007-2646;
RA   Riepe F.G., Hiort O., Grotzinger J., Sippell W.G., Krone N.,
RA   Holterhus P.M.;
RT   "Functional and structural consequences of a novel point mutation in the
RT   CYP21A2 gene causing congenital adrenal hyperplasia: potential relevance of
RT   helix C for P450 oxidoreductase-21-hydroxylase interaction.";
RL   J. Clin. Endocrinol. Metab. 93:2891-2895(2008).
RN   [67]
RP   VARIANTS AH3 THR-78; PRO-168; ASN-173; THR-231; LYS-234; LEU-282; SER-292;
RP   ASP-293; LYS-321; PRO-342; HIS-355; TRP-357; TRP-370; CYS-409; SER-425;
RP   HIS-427 AND SER-454, AND CHARACTERIZATION OF VARIANTS AH3 PRO-168; ASN-173;
RP   LEU-282; ASP-293; LYS-321; TRP-370 AND SER-425.
RX   PubMed=20080860; DOI=10.1210/jc.2009-1202;
RA   Tardy V., Menassa R., Sulmont V., Lienhardt-Roussie A., Lecointre C.,
RA   Brauner R., David M., Morel Y.;
RT   "Phenotype-genotype correlations of 13 rare CYP21A2 mutations detected in
RT   46 patients affected with 21-hydroxylase deficiency and in one carrier.";
RL   J. Clin. Endocrinol. Metab. 95:1288-1300(2010).
RN   [68]
RP   VARIANT AH3 PHE-199.
RX   PubMed=21169732; DOI=10.3275/7417;
RA   Niceta M., Bono M., Fabiano C., Pojero F., Niceta F., Sammarco P.,
RA   Corsello G., Garofalo P.;
RT   "A large view of CYP21 locus among Sicilians and other populations:
RT   identification of a novel CYP21A2 variant in Sicily.";
RL   J. Endocrinol. Invest. 34:847-854(2011).
RN   [69]
RP   VARIANTS AH3 HIS-192 AND ASN-283, CHARACTERIZATION OF VARIANTS AH3 HIS-192
RP   AND ASN-283, FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP   PROPERTIES.
RX   PubMed=22014889; DOI=10.1016/j.metabol.2011.08.008;
RA   Concolino P., Mello E., Patrosso M.C., Penco S., Zuppi C., Capoluongo E.;
RT   "p.H282N and p.Y191H: 2 novel CYP21A2 mutations in Italian congenital
RT   adrenal hyperplasia patients.";
RL   Metabolism 61:519-524(2012).
RN   [70]
RP   VARIANTS AH3 MET-13; PHE-114; 390-GLN--ALA-392 DEL AND PRO-451, VARIANTS
RP   CYS-17; GLY-203; LEU-268 AND MET-451, CHARACTERIZATION OF VARIANTS AH3
RP   MET-13; PHE-114; 390-GLN--ALA-392 DEL; PRO-451 AND SER-483,
RP   CHARACTERIZATION OF VARIANTS CYS-17; GLY-203; LEU-268 AND MET-451,
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=27721825; DOI=10.1155/2016/4209670;
RA   de Paula Michelatto D., Karlsson L., Lusa A.L., Silva C.D., Oestberg L.J.,
RA   Persson B., Guerra-Junior G., de Lemos-Marini S.H., Barbaro M.,
RA   de Mello M.P., Lajic S.;
RT   "Functional and structural consequences of nine CYP21A2 mutations ranging
RT   from very mild to severe effects.";
RL   Int. J. Endocrinol. 2016:4209670-4209670(2016).
RN   [71]
RP   VARIANT AH3 TRP-342.
RX   PubMed=29328376; DOI=10.3892/mmr.2018.8391;
RA   Liu J., Zhang X., Zhang H., Fang L., Xu J., Guan Q., Xu C.;
RT   "Identification of a novel compound heterozygous mutation of the CYP21A2
RT   gene causing 21-hydroxylase deficiency in a Chinese pedigree.";
RL   Mol. Med. Report. 17:4265-4272(2018).
CC   -!- FUNCTION: A cytochrome P450 monooxygenase that plays a major role in
CC       adrenal steroidogenesis. Catalyzes the hydroxylation at C-21 of
CC       progesterone and 17alpha-hydroxyprogesterone to respectively form 11-
CC       deoxycorticosterone and 11-deoxycortisol, intermediate metabolites in
CC       the biosynthetic pathway of mineralocorticoids and glucocorticoids
CC       (PubMed:25855791, PubMed:10602386, PubMed:16984992, PubMed:22014889,
CC       PubMed:27721825). Mechanistically, uses molecular oxygen inserting one
CC       oxygen atom into a substrate, and reducing the second into a water
CC       molecule, with two electrons provided by NADPH via cytochrome P450
CC       reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:25855791).
CC       {ECO:0000269|PubMed:10602386, ECO:0000269|PubMed:16984992,
CC       ECO:0000269|PubMed:22014889, ECO:0000269|PubMed:25855791,
CC       ECO:0000269|PubMed:27721825}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=O2 + progesterone + reduced [NADPH--hemoprotein reductase] =
CC         21-hydroxyprogesterone + H(+) + H2O + oxidized [NADPH--hemoprotein
CC         reductase]; Xref=Rhea:RHEA:50304, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC         COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:16973, ChEBI:CHEBI:17026, ChEBI:CHEBI:57618,
CC         ChEBI:CHEBI:58210; EC=1.14.14.16;
CC         Evidence={ECO:0000269|PubMed:16984992, ECO:0000269|PubMed:22014889,
CC         ECO:0000269|PubMed:25855791, ECO:0000269|PubMed:27721825};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50305;
CC         Evidence={ECO:0000305|PubMed:16984992, ECO:0000305|PubMed:22014889,
CC         ECO:0000305|PubMed:25855791, ECO:0000305|PubMed:27721825};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=17alpha-hydroxyprogesterone + O2 + reduced [NADPH--hemoprotein
CC         reductase] = 11-deoxycortisol + H(+) + H2O + oxidized [NADPH--
CC         hemoprotein reductase]; Xref=Rhea:RHEA:50308, Rhea:RHEA-COMP:11964,
CC         Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17252, ChEBI:CHEBI:28324,
CC         ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.16;
CC         Evidence={ECO:0000269|PubMed:16984992, ECO:0000269|PubMed:22014889,
CC         ECO:0000269|PubMed:25855791, ECO:0000269|PubMed:27721825};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50309;
CC         Evidence={ECO:0000305|PubMed:16984992, ECO:0000305|PubMed:22014889,
CC         ECO:0000305|PubMed:25855791, ECO:0000305|PubMed:27721825};
CC   -!- COFACTOR:
CC       Name=heme b; Xref=ChEBI:CHEBI:60344;
CC         Evidence={ECO:0000269|PubMed:25855791};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1.59 uM for 17alpha-hydroxyprogesterone
CC         {ECO:0000269|PubMed:22014889};
CC         KM=12.5 uM for 17alpha-hydroxyprogesterone (at 37 degrees Celsius)
CC         {ECO:0000269|PubMed:27721825};
CC         KM=1.5 uM for 17alpha-hydroxyprogesterone
CC         {ECO:0000269|PubMed:25855791};
CC         KM=1.05 uM for progesterone {ECO:0000269|PubMed:22014889};
CC         KM=0.21 uM for progesterone {ECO:0000269|PubMed:25855791};
CC         Vmax=5.8 nmol/min/mg enzyme {ECO:0000269|PubMed:22014889};
CC         Vmax=0.5 nmol/min/mg enzyme (at 37 degrees Celsius)
CC         {ECO:0000269|PubMed:27721825};
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC       membrane protein {ECO:0000269|PubMed:10198222}. Microsome membrane
CC       {ECO:0000269|PubMed:10198222}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:10198222}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P08686-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P08686-2; Sequence=VSP_062040;
CC   -!- DOMAIN: The leucine-rich hydrophobic amino acid N-terminal region
CC       probably helps to anchor the protein to the microsomal membrane.
CC       {ECO:0000269|PubMed:10198222}.
CC   -!- POLYMORPHISM: Several non deleterious alleles have been described
CC       including CYP21A2*1A, CYP21A2*1B, CYP21A2*2, CYP21A2*3, CYP21A2*4,
CC       CYP21A2*5 and CYP21A2*6. Deleterious alleles are mostly generated by
CC       recombinations between CYP21A2 and the pseudogene CYP21A1P through gene
CC       conversion. This process consists of recombination events that either
CC       delete CYP21A2 or transfer deleterious mutations from CYP21A1P to
CC       CYP21A2. {ECO:0000303|PubMed:8081391}.
CC   -!- DISEASE: Adrenal hyperplasia 3 (AH3) [MIM:201910]: A form of congenital
CC       adrenal hyperplasia, a common recessive disease due to defective
CC       synthesis of cortisol. Congenital adrenal hyperplasia is characterized
CC       by androgen excess leading to ambiguous genitalia in affected females,
CC       rapid somatic growth during childhood in both sexes with premature
CC       closure of the epiphyses and short adult stature. Four clinical types:
CC       'salt wasting' (SW, the most severe type), 'simple virilizing' (SV,
CC       less severely affected patients), with normal aldosterone biosynthesis,
CC       'non-classic form' or late-onset (NC or LOAH) and 'cryptic'
CC       (asymptomatic). {ECO:0000269|PubMed:10051010,
CC       ECO:0000269|PubMed:10094562, ECO:0000269|PubMed:10198222,
CC       ECO:0000269|PubMed:10364682, ECO:0000269|PubMed:10391209,
CC       ECO:0000269|PubMed:10408778, ECO:0000269|PubMed:10408786,
CC       ECO:0000269|PubMed:10443693, ECO:0000269|PubMed:10496074,
CC       ECO:0000269|PubMed:10720040, ECO:0000269|PubMed:11232002,
CC       ECO:0000269|PubMed:11598371, ECO:0000269|PubMed:11600539,
CC       ECO:0000269|PubMed:11746135, ECO:0000269|PubMed:12213891,
CC       ECO:0000269|PubMed:12222711, ECO:0000269|PubMed:12788866,
CC       ECO:0000269|PubMed:12887291, ECO:0000269|PubMed:12915679,
CC       ECO:0000269|PubMed:1406699, ECO:0000269|PubMed:1406709,
CC       ECO:0000269|PubMed:14676460, ECO:0000269|PubMed:14715874,
CC       ECO:0000269|PubMed:1496017, ECO:0000269|PubMed:15110320,
CC       ECO:0000269|PubMed:15126570, ECO:0000269|PubMed:16046588,
CC       ECO:0000269|PubMed:1644925, ECO:0000269|PubMed:16984992,
CC       ECO:0000269|PubMed:18319307, ECO:0000269|PubMed:18381579,
CC       ECO:0000269|PubMed:18445671, ECO:0000269|PubMed:1864962,
CC       ECO:0000269|PubMed:1937474, ECO:0000269|PubMed:20080860,
CC       ECO:0000269|PubMed:2072928, ECO:0000269|PubMed:21169732,
CC       ECO:0000269|PubMed:22014889, ECO:0000269|PubMed:2303461,
CC       ECO:0000269|PubMed:27721825, ECO:0000269|PubMed:29328376,
CC       ECO:0000269|PubMed:3038528, ECO:0000269|PubMed:3257825,
CC       ECO:0000269|PubMed:3260007, ECO:0000269|PubMed:3267225,
CC       ECO:0000269|PubMed:3497399, ECO:0000269|PubMed:3871526,
CC       ECO:0000269|PubMed:7749410, ECO:0000269|PubMed:8478006,
CC       ECO:0000269|PubMed:8485582, ECO:0000269|PubMed:8989258,
CC       ECO:0000269|PubMed:9067760, ECO:0000269|PubMed:9187661,
CC       ECO:0000269|PubMed:9497336}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; M12792; AAB59440.1; -; Genomic_DNA.
DR   EMBL; M13936; AAA59695.1; -; Genomic_DNA.
DR   EMBL; M26856; AAA52064.1; -; Genomic_DNA.
DR   EMBL; X58906; CAA41709.1; -; Genomic_DNA.
DR   EMBL; GQ222278; ACT35404.1; -; Genomic_DNA.
DR   EMBL; GQ222283; ACT35409.1; -; Genomic_DNA.
DR   EMBL; GQ222286; ACT35412.1; -; Genomic_DNA.
DR   EMBL; GQ222289; ACT35415.1; -; Genomic_DNA.
DR   EMBL; GQ222296; ACT35422.1; -; Genomic_DNA.
DR   EMBL; GQ222301; ACT35427.1; -; Genomic_DNA.
DR   EMBL; GQ222319; ACT35445.1; -; Genomic_DNA.
DR   EMBL; GQ222295; ACT35421.1; -; Genomic_DNA.
DR   EMBL; GQ222312; ACT35438.1; -; Genomic_DNA.
DR   EMBL; GQ222297; ACT35423.1; -; Genomic_DNA.
DR   EMBL; GQ222320; ACT35446.1; -; Genomic_DNA.
DR   EMBL; GQ222321; ACT35447.1; -; Genomic_DNA.
DR   EMBL; GQ222327; ACT35453.1; -; Genomic_DNA.
DR   EMBL; GQ222323; ACT35449.1; -; Genomic_DNA.
DR   EMBL; GQ222334; ACT35460.1; -; Genomic_DNA.
DR   EMBL; GQ222340; ACT35466.1; -; Genomic_DNA.
DR   EMBL; JN034391; AFK10114.1; -; Genomic_DNA.
DR   EMBL; JN034393; AFK10116.1; -; Genomic_DNA.
DR   EMBL; JN034394; AFK10117.1; -; Genomic_DNA.
DR   EMBL; JN034395; AFK10118.1; -; Genomic_DNA.
DR   EMBL; JN034396; AFK10119.1; -; Genomic_DNA.
DR   EMBL; JN034397; AFK10120.1; -; Genomic_DNA.
DR   EMBL; JN034398; AFK10121.1; -; Genomic_DNA.
DR   EMBL; JN034401; AFK10124.1; -; Genomic_DNA.
DR   EMBL; JN034403; AFK10126.1; -; Genomic_DNA.
DR   EMBL; JN034402; AFK10125.1; -; Genomic_DNA.
DR   EMBL; JN034410; AFK10133.1; -; Genomic_DNA.
DR   EMBL; JN034411; AFK10134.1; -; Genomic_DNA.
DR   EMBL; KC493622; AHA59281.1; -; Genomic_DNA.
DR   EMBL; KU302773; APT40592.1; -; Genomic_DNA.
DR   EMBL; KU302772; APT40591.1; -; Genomic_DNA.
DR   EMBL; AK054616; BAB70774.1; -; mRNA.
DR   EMBL; AK314651; BAG37212.1; -; mRNA.
DR   EMBL; AF019413; AAB67982.1; -; Genomic_DNA.
DR   EMBL; AL049547; CAB89301.1; -; Genomic_DNA.
DR   EMBL; AL645922; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL662828; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL662849; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL844853; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL929593; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BX679671; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CR753845; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CR936924; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471081; EAX03570.1; -; Genomic_DNA.
DR   EMBL; CH471081; EAX03571.1; -; Genomic_DNA.
DR   EMBL; BC125182; AAI25183.1; -; mRNA.
DR   EMBL; K02771; AAA59706.1; -; Genomic_DNA.
DR   EMBL; M19711; AAA83248.1; -; Genomic_DNA.
DR   EMBL; M17252; AAA59985.1; -; mRNA.
DR   CCDS; CCDS47406.1; -. [P08686-2]
DR   PIR; A25446; O4HUC2.
DR   RefSeq; NP_000491.4; NM_000500.7.
DR   RefSeq; NP_001122062.3; NM_001128590.3.
DR   PDB; 4Y8W; X-ray; 2.64 A; A/B/C=30-495.
DR   PDB; 5VBU; X-ray; 3.31 A; A/B/C=30-495.
DR   PDBsum; 4Y8W; -.
DR   PDBsum; 5VBU; -.
DR   AlphaFoldDB; P08686; -.
DR   SMR; P08686; -.
DR   BioGRID; 107961; 20.
DR   IntAct; P08686; 2.
DR   STRING; 9606.ENSP00000496625; -.
DR   BindingDB; P08686; -.
DR   ChEMBL; CHEMBL2759; -.
DR   DrugBank; DB01026; Ketoconazole.
DR   DrugBank; DB05667; Levoketoconazole.
DR   DrugCentral; P08686; -.
DR   SwissLipids; SLP:000001618; -.
DR   iPTMnet; P08686; -.
DR   PhosphoSitePlus; P08686; -.
DR   BioMuta; CYP21A2; -.
DR   DMDM; 117275; -.
DR   MassIVE; P08686; -.
DR   PaxDb; 9606-ENSP00000408860; -.
DR   PeptideAtlas; P08686; -.
DR   ProteomicsDB; 52155; -. [P08686-1]
DR   ProteomicsDB; 63894; -.
DR   Antibodypedia; 53182; 387 antibodies from 28 providers.
DR   DNASU; 1589; -.
DR   Ensembl; ENST00000383321.4; ENSP00000372811.4; ENSG00000206338.9.
DR   Ensembl; ENST00000434026.2; ENSP00000392321.2; ENSG00000232414.6.
DR   Ensembl; ENST00000435122.3; ENSP00000415043.2; ENSG00000231852.9.
DR   Ensembl; ENST00000436607.6; ENSP00000403721.2; ENSG00000235134.7. [P08686-1]
DR   Ensembl; ENST00000448314.6; ENSP00000398594.2; ENSG00000198457.13. [P08686-1]
DR   Ensembl; ENST00000452386.2; ENSP00000403230.2; ENSG00000233151.6.
DR   GeneID; 1589; -.
DR   KEGG; hsa:1589; -.
DR   MANE-Select; ENST00000644719.2; ENSP00000496625.1; NM_000500.9; NP_000491.4.
DR   UCSC; uc003nzf.3; human. [P08686-1]
DR   AGR; HGNC:2600; -.
DR   CTD; 1589; -.
DR   DisGeNET; 1589; -.
DR   GeneCards; CYP21A2; -.
DR   GeneReviews; CYP21A2; -.
DR   HGNC; HGNC:2600; CYP21A2.
DR   HPA; ENSG00000231852; Tissue enriched (adrenal).
DR   MalaCards; CYP21A2; -.
DR   MIM; 201910; phenotype.
DR   MIM; 613815; gene.
DR   neXtProt; NX_P08686; -.
DR   Orphanet; 315306; Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, salt wasting form.
DR   Orphanet; 315311; Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, simple virilizing form.
DR   Orphanet; 95698; NON RARE IN EUROPE: Non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
DR   PharmGKB; PA27096; -.
DR   VEuPathDB; HostDB:ENSG00000231852; -.
DR   eggNOG; KOG0156; Eukaryota.
DR   GeneTree; ENSGT00940000158338; -.
DR   HOGENOM; CLU_001570_22_0_1; -.
DR   InParanoid; P08686; -.
DR   OMA; PWKADIK; -.
DR   OrthoDB; 2900138at2759; -.
DR   PhylomeDB; P08686; -.
DR   TreeFam; TF105095; -.
DR   BioCyc; MetaCyc:HS09769-MONOMER; -.
DR   BRENDA; 1.14.14.16; 2681.
DR   PathwayCommons; P08686; -.
DR   Reactome; R-HSA-193993; Mineralocorticoid biosynthesis.
DR   Reactome; R-HSA-194002; Glucocorticoid biosynthesis.
DR   Reactome; R-HSA-211976; Endogenous sterols.
DR   Reactome; R-HSA-5579021; Defective CYP21A2 causes AH3.
DR   SignaLink; P08686; -.
DR   SIGNOR; P08686; -.
DR   BioGRID-ORCS; 1589; 13 hits in 1141 CRISPR screens.
DR   ChiTaRS; CYP21A2; human.
DR   GeneWiki; 21-Hydroxylase; -.
DR   GenomeRNAi; 1589; -.
DR   Pharos; P08686; Tchem.
DR   PRO; PR:P08686; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; P08686; Protein.
DR   Bgee; ENSG00000231852; Expressed in right adrenal gland and 92 other cell types or tissues.
DR   ExpressionAtlas; P08686; baseline and differential.
DR   Genevisible; P08686; HS.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0103069; F:17-hydroxyprogesterone 21-hydroxylase activity; IDA:UniProtKB.
DR   GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0106309; F:progesterone 21-hydroxylase activity; IDA:UniProtKB.
DR   GO; GO:0004509; F:steroid 21-monooxygenase activity; IBA:GO_Central.
DR   GO; GO:0005496; F:steroid binding; IEA:UniProtKB-KW.
DR   GO; GO:0008395; F:steroid hydroxylase activity; IMP:UniProtKB.
DR   GO; GO:0006704; P:glucocorticoid biosynthetic process; IBA:GO_Central.
DR   GO; GO:0006705; P:mineralocorticoid biosynthetic process; TAS:Reactome.
DR   GO; GO:0006694; P:steroid biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0008202; P:steroid metabolic process; IMP:UniProtKB.
DR   GO; GO:0016125; P:sterol metabolic process; TAS:Reactome.
DR   CDD; cd20674; CYP21; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002401; Cyt_P450_E_grp-I.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   PANTHER; PTHR24289; STEROID 17-ALPHA-HYDROXYLASE/17,20 LYASE; 1.
DR   PANTHER; PTHR24289:SF13; STEROID 17-ALPHA-HYDROXYLASE/17,20 LYASE; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Congenital adrenal hyperplasia;
KW   Disease variant; Endoplasmic reticulum; Heme; Iron; Lipid metabolism;
KW   Lipid-binding; Membrane; Metal-binding; Microsome; Monooxygenase;
KW   Oxidoreductase; Reference proteome; Steroid-binding; Steroidogenesis.
FT   CHAIN           1..495
FT                   /note="Steroid 21-hydroxylase"
FT                   /id="PRO_0000051976"
FT   BINDING         92
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /evidence="ECO:0000269|PubMed:25855791,
FT                   ECO:0007744|PDB:4Y8W"
FT   BINDING         121
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /evidence="ECO:0000269|PubMed:25855791,
FT                   ECO:0007744|PDB:4Y8W"
FT   BINDING         234
FT                   /ligand="17alpha-hydroxyprogesterone"
FT                   /ligand_id="ChEBI:CHEBI:17252"
FT                   /evidence="ECO:0000250|UniProtKB:P00191"
FT   BINDING         234
FT                   /ligand="progesterone"
FT                   /ligand_id="ChEBI:CHEBI:17026"
FT                   /evidence="ECO:0000269|PubMed:25855791,
FT                   ECO:0007744|PDB:4Y8W"
FT   BINDING         366
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /evidence="ECO:0000269|PubMed:25855791,
FT                   ECO:0007744|PDB:4Y8W"
FT   BINDING         427
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /evidence="ECO:0000269|PubMed:25855791,
FT                   ECO:0007744|PDB:4Y8W"
FT   BINDING         429
FT                   /ligand="heme b"
FT                   /ligand_id="ChEBI:CHEBI:60344"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000269|PubMed:25855791,
FT                   ECO:0007744|PDB:4Y8W"
FT   VAR_SEQ         69..98
FT                   /note="Missing (in isoform 2)"
FT                   /id="VSP_062040"
FT   VARIANT         6
FT                   /note="Missing"
FT                   /evidence="ECO:0000269|PubMed:19505723,
FT                   ECO:0000269|PubMed:3486422, ECO:0000269|PubMed:3487786"
FT                   /id="VAR_088451"
FT   VARIANT         13
FT                   /note="L -> M (in AH3; uncertain significance; non-classic
FT                   form; no effect on steroid 21-monooxygenase activity)"
FT                   /evidence="ECO:0000269|PubMed:27721825"
FT                   /id="VAR_077582"
FT   VARIANT         16
FT                   /note="A -> T (in AH3; uncertain significance; salt wasting
FT                   form; no significant difference in steroid 21-monooxygenase
FT                   activity; dbSNP:rs63749090)"
FT                   /evidence="ECO:0000269|PubMed:12887291,
FT                   ECO:0000269|PubMed:15126570"
FT                   /id="VAR_026059"
FT   VARIANT         17
FT                   /note="R -> C (decreased steroid 21-monooxygenase activity;
FT                   dbSNP:rs757608533)"
FT                   /evidence="ECO:0000269|PubMed:27721825"
FT                   /id="VAR_077583"
FT   VARIANT         31
FT                   /note="P -> L (in AH3; non-classic form; 50% steroid 21-
FT                   monooxygenase activity; dbSNP:rs9378251)"
FT                   /evidence="ECO:0000269|PubMed:10364682,
FT                   ECO:0000269|PubMed:10408778, ECO:0000269|PubMed:10408786,
FT                   ECO:0000269|PubMed:10496074, ECO:0000269|PubMed:10720040,
FT                   ECO:0000269|PubMed:11232002, ECO:0000269|PubMed:11598371,
FT                   ECO:0000269|PubMed:11600539, ECO:0000269|PubMed:12222711,
FT                   ECO:0000269|PubMed:12788866, ECO:0000269|PubMed:12887291,
FT                   ECO:0000269|PubMed:15110320, ECO:0000269|PubMed:15126570,
FT                   ECO:0000269|PubMed:16046588, ECO:0000269|PubMed:1644925,
FT                   ECO:0000269|PubMed:18319307, ECO:0000269|PubMed:2072928"
FT                   /id="VAR_001281"
FT   VARIANT         31
FT                   /note="P -> Q (in AH3; does not affect membrane binding;
FT                   enzyme function abolished)"
FT                   /evidence="ECO:0000269|PubMed:10198222"
FT                   /id="VAR_026060"
FT   VARIANT         57
FT                   /note="G -> R (in AH3; loss of activity;
FT                   dbSNP:rs1413433421)"
FT                   /evidence="ECO:0000269|PubMed:18381579"
FT                   /id="VAR_065668"
FT   VARIANT         63
FT                   /note="H -> L (in AH3; non-classic form; simple virilizing
FT                   form when associated with a second mild mutation such as S-
FT                   453 or L-30; activity is significantly reduced in
FT                   association with S-453; dbSNP:rs9378252)"
FT                   /evidence="ECO:0000269|PubMed:12788866,
FT                   ECO:0000269|PubMed:18319307, ECO:0000269|PubMed:18381579"
FT                   /id="VAR_018364"
FT   VARIANT         65
FT                   /note="G -> E (in AH3; no activity)"
FT                   /evidence="ECO:0000269|PubMed:10408778"
FT                   /id="VAR_007923"
FT   VARIANT         78
FT                   /note="I -> T (in AH3; simple virilizing form;
FT                   dbSNP:rs1333278223)"
FT                   /evidence="ECO:0000269|PubMed:20080860"
FT                   /id="VAR_065669"
FT   VARIANT         91
FT                   /note="G -> V (in AH3)"
FT                   /evidence="ECO:0000269|PubMed:10364682"
FT                   /id="VAR_026061"
FT   VARIANT         99
FT                   /note="K -> R (in dbSNP:rs1268071078)"
FT                   /evidence="ECO:0000269|PubMed:9580109"
FT                   /id="VAR_001282"
FT   VARIANT         103
FT                   /note="R -> K (in dbSNP:rs6474)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:19505723, ECO:0000269|PubMed:3038528,
FT                   ECO:0000269|PubMed:3486422, ECO:0000269|PubMed:9580109"
FT                   /id="VAR_001283"
FT   VARIANT         106
FT                   /note="P -> L (in AH3; dbSNP:rs550051210)"
FT                   /evidence="ECO:0000269|PubMed:1496017,
FT                   ECO:0000269|PubMed:8989258"
FT                   /id="VAR_001284"
FT   VARIANT         108
FT                   /note="L -> R (in AH3; loss of activity;
FT                   dbSNP:rs957886272)"
FT                   /evidence="ECO:0000269|PubMed:18381579"
FT                   /id="VAR_065670"
FT   VARIANT         114
FT                   /note="S -> F (in AH3; non-classic form; loss of steroid
FT                   21-monooxygenase activity; dbSNP:rs1296268275)"
FT                   /evidence="ECO:0000269|PubMed:27721825"
FT                   /id="VAR_077584"
FT   VARIANT         122
FT                   /note="K -> Q (in AH3; non-classic form; reduced activity;
FT                   decreased affinity for 17-hydroxyprogesterone and
FT                   progesterone; dbSNP:rs547552654)"
FT                   /evidence="ECO:0000269|PubMed:18445671"
FT                   /id="VAR_065671"
FT   VARIANT         125
FT                   /note="R -> H (in AH3; dbSNP:rs72552750)"
FT                   /evidence="ECO:0000269|PubMed:14676460"
FT                   /id="VAR_026062"
FT   VARIANT         143
FT                   /note="L -> P (in AH3; loss of activity;
FT                   dbSNP:rs755020999)"
FT                   /evidence="ECO:0000269|PubMed:18381579"
FT                   /id="VAR_065672"
FT   VARIANT         168
FT                   /note="L -> P (in AH3; salt wasting form; loss of
FT                   activity)"
FT                   /evidence="ECO:0000269|PubMed:20080860"
FT                   /id="VAR_065673"
FT   VARIANT         170
FT                   /note="C -> R (in AH3; loss of hydroxylase activity toward
FT                   17-hydroxyprogesterone and progesterone)"
FT                   /evidence="ECO:0000269|PubMed:16984992"
FT                   /id="VAR_075372"
FT   VARIANT         170
FT                   /note="C -> Y (in AH3)"
FT                   /evidence="ECO:0000269|PubMed:10094562"
FT                   /id="VAR_001285"
FT   VARIANT         173
FT                   /note="I -> N (in AH3; simple virilizing form; 1-4%
FT                   activity; dbSNP:rs6475)"
FT                   /evidence="ECO:0000269|PubMed:10051010,
FT                   ECO:0000269|PubMed:10364682, ECO:0000269|PubMed:10408778,
FT                   ECO:0000269|PubMed:10408786, ECO:0000269|PubMed:10496074,
FT                   ECO:0000269|PubMed:10720040, ECO:0000269|PubMed:11232002,
FT                   ECO:0000269|PubMed:11598371, ECO:0000269|PubMed:11600539,
FT                   ECO:0000269|PubMed:12222711, ECO:0000269|PubMed:12788866,
FT                   ECO:0000269|PubMed:12887291, ECO:0000269|PubMed:12915679,
FT                   ECO:0000269|PubMed:14715874, ECO:0000269|PubMed:15110320,
FT                   ECO:0000269|PubMed:16046588, ECO:0000269|PubMed:1644925,
FT                   ECO:0000269|PubMed:18319307, ECO:0000269|PubMed:18381579,
FT                   ECO:0000269|PubMed:1937474, ECO:0000269|PubMed:20080860,
FT                   ECO:0000269|PubMed:2303461, ECO:0000269|PubMed:3257825,
FT                   ECO:0000269|PubMed:3871526, ECO:0000269|PubMed:7749410,
FT                   ECO:0000269|PubMed:8485582"
FT                   /id="VAR_001286"
FT   VARIANT         179
FT                   /note="G -> A (in AH3; dbSNP:rs72552751)"
FT                   /evidence="ECO:0000269|PubMed:10364682"
FT                   /id="VAR_026063"
FT   VARIANT         179
FT                   /note="G -> R (in AH3; loss of enzymatic activity toward
FT                   17-hydroxyprogesterone and progesterone;
FT                   dbSNP:rs772317717)"
FT                   /evidence="ECO:0000269|PubMed:16984992"
FT                   /id="VAR_075373"
FT   VARIANT         184
FT                   /note="D -> E (in allele CYP21A2*4; dbSNP:rs397515531)"
FT                   /evidence="ECO:0000269|PubMed:9580109"
FT                   /id="VAR_001287"
FT   VARIANT         192
FT                   /note="Y -> H (in AH3; exhibits low enzymatic activity
FT                   toward 17-hydroxyprogesterone and progesterone)"
FT                   /evidence="ECO:0000269|PubMed:22014889"
FT                   /id="VAR_075374"
FT   VARIANT         197
FT                   /note="Missing (in AH3; moderate)"
FT                   /evidence="ECO:0000269|PubMed:9497336"
FT                   /id="VAR_008688"
FT   VARIANT         199
FT                   /note="L -> F (in AH3; dbSNP:rs143240527)"
FT                   /evidence="ECO:0000269|PubMed:21169732"
FT                   /id="VAR_075375"
FT   VARIANT         203
FT                   /note="S -> G (decreased steroid 21-monooxygenase activity;
FT                   dbSNP:rs372964292)"
FT                   /evidence="ECO:0000269|PubMed:27721825"
FT                   /id="VAR_077585"
FT   VARIANT         212
FT                   /note="V -> L (in AH3; uncertain significance; non-classic
FT                   form)"
FT                   /evidence="ECO:0000269|PubMed:3260007"
FT                   /id="VAR_026064"
FT   VARIANT         231
FT                   /note="I -> T (in AH3)"
FT                   /evidence="ECO:0000269|PubMed:20080860"
FT                   /id="VAR_065674"
FT   VARIANT         234
FT                   /note="R -> K (in AH3)"
FT                   /evidence="ECO:0000269|PubMed:20080860"
FT                   /id="VAR_065675"
FT   VARIANT         237
FT                   /note="I -> N (in AH3; salt wasting form;
FT                   dbSNP:rs111647200)"
FT                   /evidence="ECO:0000269|PubMed:10408778,
FT                   ECO:0000269|PubMed:10408786, ECO:0000269|PubMed:15110320,
FT                   ECO:0000269|PubMed:1644925, ECO:0000269|PubMed:7749410"
FT                   /id="VAR_001288"
FT   VARIANT         238
FT                   /note="V -> E (in AH3; salt wasting form;
FT                   dbSNP:rs12530380)"
FT                   /evidence="ECO:0000269|PubMed:10408786,
FT                   ECO:0000269|PubMed:15110320, ECO:0000269|PubMed:1644925"
FT                   /id="VAR_001289"
FT   VARIANT         240
FT                   /note="M -> K (in AH3; salt wasting form; dbSNP:rs6476)"
FT                   /evidence="ECO:0000269|PubMed:10408786,
FT                   ECO:0000269|PubMed:15110320, ECO:0000269|PubMed:1644925"
FT                   /id="VAR_001290"
FT   VARIANT         262
FT                   /note="L -> P (in AH3; dbSNP:rs750337015)"
FT                   /evidence="ECO:0000269|PubMed:11598371"
FT                   /id="VAR_026065"
FT   VARIANT         268
FT                   /note="P -> L (decreased steroid 21-monooxygenase activity;
FT                   dbSNP:rs61732108 and dbSNP:rs142028935)"
FT                   /evidence="ECO:0000269|PubMed:27721825"
FT                   /id="VAR_077586"
FT   VARIANT         269
FT                   /note="S -> T (in allele CYP21A2*5; dbSNP:rs6472)"
FT                   /evidence="ECO:0000269|PubMed:10391209,
FT                   ECO:0000269|PubMed:10496074, ECO:0000269|PubMed:2072928,
FT                   ECO:0000269|PubMed:3038528"
FT                   /id="VAR_001291"
FT   VARIANT         282
FT                   /note="V -> G (in AH3; salt wasting form)"
FT                   /evidence="ECO:0000269|PubMed:10720040"
FT                   /id="VAR_026066"
FT   VARIANT         282
FT                   /note="V -> L (in AH3; non-classic form; 50% activity; most
FT                   common variant; normal KM but 20% reduced Vmax;
FT                   dbSNP:rs6471)"
FT                   /evidence="ECO:0000269|PubMed:10094562,
FT                   ECO:0000269|PubMed:10364682, ECO:0000269|PubMed:10391209,
FT                   ECO:0000269|PubMed:10408778, ECO:0000269|PubMed:10408786,
FT                   ECO:0000269|PubMed:10443693, ECO:0000269|PubMed:10496074,
FT                   ECO:0000269|PubMed:10720040, ECO:0000269|PubMed:11232002,
FT                   ECO:0000269|PubMed:11600539, ECO:0000269|PubMed:12222711,
FT                   ECO:0000269|PubMed:12788866, ECO:0000269|PubMed:12887291,
FT                   ECO:0000269|PubMed:12915679, ECO:0000269|PubMed:15110320,
FT                   ECO:0000269|PubMed:15126570, ECO:0000269|PubMed:1644925,
FT                   ECO:0000269|PubMed:1864962, ECO:0000269|PubMed:20080860,
FT                   ECO:0000269|PubMed:3260007, ECO:0000269|PubMed:3267225,
FT                   ECO:0000269|PubMed:3497399, ECO:0000269|PubMed:7749410"
FT                   /id="VAR_001292"
FT   VARIANT         283
FT                   /note="H -> N (in AH3; exhibits low enzymatic activity
FT                   toward 17-hydroxyprogesterone and progesterone)"
FT                   /evidence="ECO:0000269|PubMed:22014889"
FT                   /id="VAR_075376"
FT   VARIANT         284
FT                   /note="M -> L (in AH3)"
FT                   /evidence="ECO:0000269|PubMed:12222711"
FT                   /id="VAR_026067"
FT   VARIANT         292
FT                   /note="G -> C (in AH3)"
FT                   /evidence="ECO:0000269|PubMed:10364682"
FT                   /id="VAR_026068"
FT   VARIANT         292
FT                   /note="G -> R (in AH3; dbSNP:rs201552310)"
FT                   /evidence="ECO:0000269|PubMed:12915679"
FT                   /id="VAR_018365"
FT   VARIANT         292
FT                   /note="G -> S (in AH3; salt wasting form; less then 1%
FT                   activity; dbSNP:rs201552310)"
FT                   /evidence="ECO:0000269|PubMed:10408778,
FT                   ECO:0000269|PubMed:11600539, ECO:0000269|PubMed:1496017,
FT                   ECO:0000269|PubMed:15110320, ECO:0000269|PubMed:20080860,
FT                   ECO:0000269|PubMed:9497336"
FT                   /id="VAR_001293"
FT   VARIANT         293
FT                   /note="G -> D (in AH3; salt wasting form; less then 1%
FT                   activity)"
FT                   /evidence="ECO:0000269|PubMed:20080860"
FT                   /id="VAR_065676"
FT   VARIANT         301
FT                   /note="L -> F (in AH3; salt wasting form;
FT                   dbSNP:rs765001985)"
FT                   /evidence="ECO:0000269|PubMed:10720040"
FT                   /id="VAR_026069"
FT   VARIANT         302
FT                   /note="S -> Y (in AH3)"
FT                   /evidence="ECO:0000269|PubMed:12915679"
FT                   /id="VAR_018366"
FT   VARIANT         303
FT                   /note="W -> R (in AH3; loss of enzymatic activity toward
FT                   17-hydroxyprogesterone and progesterone)"
FT                   /evidence="ECO:0000269|PubMed:16984992"
FT                   /id="VAR_075377"
FT   VARIANT         305
FT                   /note="V -> M (in hyperandrogenism; due to 21-hydroxylase
FT                   deficiency; non-classic type; residual activity of 46% for
FT                   conversion of 17-hydroxyprogesterone and 26% for conversion
FT                   of progesterone compared with the normal enzyme;
FT                   dbSNP:rs151344505)"
FT                   /evidence="ECO:0000269|PubMed:12050257"
FT                   /id="VAR_026070"
FT   VARIANT         318
FT                   /note="L -> M (in AH3)"
FT                   /evidence="ECO:0000269|PubMed:11232002"
FT                   /id="VAR_026071"
FT   VARIANT         321
FT                   /note="E -> K (in AH3; simple virilizing form; 4%
FT                   activity)"
FT                   /evidence="ECO:0000269|PubMed:20080860"
FT                   /id="VAR_065677"
FT   VARIANT         340
FT                   /note="R -> H (in AH3; non-classic form; 50% activity;
FT                   dbSNP:rs72552754)"
FT                   /evidence="ECO:0000269|PubMed:1406709"
FT                   /id="VAR_001294"
FT   VARIANT         342
FT                   /note="R -> P (in AH3; simple virilizing form;
FT                   dbSNP:rs747079101)"
FT                   /evidence="ECO:0000269|PubMed:12788866,
FT                   ECO:0000269|PubMed:20080860"
FT                   /id="VAR_018367"
FT   VARIANT         342
FT                   /note="R -> W (in AH3; non-classic form; mild;
FT                   dbSNP:rs72552755)"
FT                   /evidence="ECO:0000269|PubMed:29328376"
FT                   /id="VAR_001295"
FT   VARIANT         355
FT                   /note="R -> C (in AH3; salt wasting form;
FT                   dbSNP:rs772900496)"
FT                   /evidence="ECO:0000269|PubMed:10720040"
FT                   /id="VAR_026072"
FT   VARIANT         355
FT                   /note="R -> H (in AH3; salt wasting form;
FT                   dbSNP:rs760216630)"
FT                   /evidence="ECO:0000269|PubMed:10364682,
FT                   ECO:0000269|PubMed:20080860"
FT                   /id="VAR_026073"
FT   VARIANT         357
FT                   /note="R -> P (in AH3; salt wasting form; 0.15% activity)"
FT                   /evidence="ECO:0000269|PubMed:9187661"
FT                   /id="VAR_001296"
FT   VARIANT         357
FT                   /note="R -> Q (in AH3; simple virilizing form; mild; 0.65%
FT                   activity; dbSNP:rs574370139)"
FT                   /evidence="ECO:0000269|PubMed:10094562,
FT                   ECO:0000269|PubMed:15110320, ECO:0000269|PubMed:9187661"
FT                   /id="VAR_001297"
FT   VARIANT         357
FT                   /note="R -> W (in AH3; salt wasting form; dbSNP:rs7769409)"
FT                   /evidence="ECO:0000269|PubMed:10051010,
FT                   ECO:0000269|PubMed:10364682, ECO:0000269|PubMed:10408778,
FT                   ECO:0000269|PubMed:10408786, ECO:0000269|PubMed:10443693,
FT                   ECO:0000269|PubMed:10496074, ECO:0000269|PubMed:10720040,
FT                   ECO:0000269|PubMed:11232002, ECO:0000269|PubMed:11598371,
FT                   ECO:0000269|PubMed:11600539, ECO:0000269|PubMed:12222711,
FT                   ECO:0000269|PubMed:12788866, ECO:0000269|PubMed:12915679,
FT                   ECO:0000269|PubMed:14715874, ECO:0000269|PubMed:15110320,
FT                   ECO:0000269|PubMed:16046588, ECO:0000269|PubMed:1644925,
FT                   ECO:0000269|PubMed:18319307, ECO:0000269|PubMed:18381579,
FT                   ECO:0000269|PubMed:20080860, ECO:0000269|PubMed:2303461"
FT                   /id="VAR_001298"
FT   VARIANT         363
FT                   /note="A -> V (in AH3; no activity)"
FT                   /evidence="ECO:0000269|PubMed:10408778"
FT                   /id="VAR_007924"
FT   VARIANT         364
FT                   /note="L -> W (in AH3)"
FT                   /evidence="ECO:0000269|PubMed:11746135"
FT                   /id="VAR_026074"
FT   VARIANT         366
FT                   /note="H -> Y (in AH3; dbSNP:rs1330554738)"
FT                   /evidence="ECO:0000269|PubMed:15110320"
FT                   /id="VAR_026075"
FT   VARIANT         370
FT                   /note="R -> W (in AH3; dbSNP:rs781074931)"
FT                   /evidence="ECO:0000269|PubMed:20080860"
FT                   /id="VAR_065678"
FT   VARIANT         376
FT                   /note="G -> S (in hyperandrogenism; due to 21-hydroxylase
FT                   deficiency; almost completely abolished enzyme activity;
FT                   dbSNP:rs151344506)"
FT                   /evidence="ECO:0000269|PubMed:12050257"
FT                   /id="VAR_026076"
FT   VARIANT         381
FT                   /note="E -> D (in AH3; salt wasting form;
FT                   dbSNP:rs72552756)"
FT                   /evidence="ECO:0000269|PubMed:9067760"
FT                   /id="VAR_001299"
FT   VARIANT         390..392
FT                   /note="Missing (in AH3; salt wasting form; loss of steroid
FT                   21-monooxygenase activity)"
FT                   /evidence="ECO:0000269|PubMed:27721825"
FT                   /id="VAR_077587"
FT   VARIANT         409
FT                   /note="R -> C (in AH3; very low residual activity;
FT                   dbSNP:rs72552757)"
FT                   /evidence="ECO:0000269|PubMed:12213891,
FT                   ECO:0000269|PubMed:18381579, ECO:0000269|PubMed:20080860"
FT                   /id="VAR_026077"
FT   VARIANT         425
FT                   /note="G -> S (in AH3; very low activity;
FT                   dbSNP:rs72552758)"
FT                   /evidence="ECO:0000269|PubMed:10443693,
FT                   ECO:0000269|PubMed:11600539, ECO:0000269|PubMed:12213891,
FT                   ECO:0000269|PubMed:20080860"
FT                   /id="VAR_026078"
FT   VARIANT         427
FT                   /note="R -> C (in AH3; loss of enzymatic activity toward
FT                   17-hydroxyprogesterone and progesterone;
FT                   dbSNP:rs1370167869)"
FT                   /evidence="ECO:0000269|PubMed:16984992"
FT                   /id="VAR_075378"
FT   VARIANT         427
FT                   /note="R -> H (in AH3; loss of enzymatic activity toward
FT                   17-hydroxyprogesterone; dbSNP:rs151344504)"
FT                   /evidence="ECO:0000269|PubMed:11600539,
FT                   ECO:0000269|PubMed:16984992, ECO:0000269|PubMed:20080860"
FT                   /id="VAR_026079"
FT   VARIANT         436
FT                   /note="R -> C (in AH3; dbSNP:rs767333157)"
FT                   /evidence="ECO:0000269|PubMed:11232002"
FT                   /id="VAR_026080"
FT   VARIANT         451
FT                   /note="T -> M (decreased steroid 21-monooxygenase activity;
FT                   dbSNP:rs1319651744)"
FT                   /evidence="ECO:0000269|PubMed:27721825"
FT                   /id="VAR_077588"
FT   VARIANT         451
FT                   /note="T -> P (in AH3; salt wasting form; loss of steroid
FT                   21-monooxygenase activity)"
FT                   /evidence="ECO:0000269|PubMed:27721825"
FT                   /id="VAR_077589"
FT   VARIANT         454
FT                   /note="P -> S (in AH3; non-classic form; simple virilizing
FT                   form when associated with L-62; 50% of activity; almost
FT                   completely abolished enzyme activity when associated with
FT                   S-375; dbSNP:rs6445)"
FT                   /evidence="ECO:0000269|PubMed:10364682,
FT                   ECO:0000269|PubMed:10391209, ECO:0000269|PubMed:10720040,
FT                   ECO:0000269|PubMed:11232002, ECO:0000269|PubMed:11600539,
FT                   ECO:0000269|PubMed:12050257, ECO:0000269|PubMed:12222711,
FT                   ECO:0000269|PubMed:12788866, ECO:0000269|PubMed:12887291,
FT                   ECO:0000269|PubMed:1406699, ECO:0000269|PubMed:1406709,
FT                   ECO:0000269|PubMed:1496017, ECO:0000269|PubMed:15110320,
FT                   ECO:0000269|PubMed:18319307, ECO:0000269|PubMed:18381579,
FT                   ECO:0000269|PubMed:18445671, ECO:0000269|PubMed:20080860,
FT                   ECO:0000269|PubMed:8989258"
FT                   /id="VAR_001300"
FT   VARIANT         480
FT                   /note="R -> L (in AH3; dbSNP:rs184649564)"
FT                   /evidence="ECO:0000269|PubMed:15110320"
FT                   /id="VAR_026081"
FT   VARIANT         483
FT                   /note="P -> S (in AH3; reduced enzyme activity to 70% of
FT                   normal; dbSNP:rs776989258)"
FT                   /evidence="ECO:0000269|PubMed:15126570,
FT                   ECO:0000269|PubMed:27721825"
FT                   /id="VAR_026082"
FT   VARIANT         484
FT                   /note="R -> P (in AH3; moderate; 1-2% of activity;
FT                   dbSNP:rs200005406)"
FT                   /evidence="ECO:0000269|PubMed:11598371,
FT                   ECO:0000269|PubMed:11600539, ECO:0000269|PubMed:12788866,
FT                   ECO:0000269|PubMed:15110320, ECO:0000269|PubMed:7749410,
FT                   ECO:0000269|PubMed:8478006, ECO:0000269|PubMed:9497336"
FT                   /id="VAR_001301"
FT   VARIANT         484
FT                   /note="R -> Q (in AH3; dbSNP:rs200005406)"
FT                   /evidence="ECO:0000269|PubMed:12915679"
FT                   /id="VAR_018368"
FT   VARIANT         484
FT                   /note="R -> W (in AH3; salt wasting form;
FT                   dbSNP:rs759736443)"
FT                   /evidence="ECO:0000269|PubMed:14715874"
FT                   /id="VAR_026083"
FT   VARIANT         494
FT                   /note="S -> N (in dbSNP:rs6473)"
FT                   /evidence="ECO:0000269|PubMed:19505723,
FT                   ECO:0000269|PubMed:3038528, ECO:0000269|PubMed:3486422,
FT                   ECO:0000269|PubMed:3487786, ECO:0000269|PubMed:3497399,
FT                   ECO:0000269|PubMed:9580109"
FT                   /id="VAR_001302"
FT   MUTAGEN         269
FT                   /note="S->C,M,T: No effect on progesterone 21-hydroxylase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:1864962"
FT   MUTAGEN         282
FT                   /note="V->I: Decreased 21-hydroxylase activity. Normal KM
FT                   but 50% reduced Vmax."
FT                   /evidence="ECO:0000269|PubMed:1864962"
FT   MUTAGEN         282
FT                   /note="V->T: Decreased 21-hydroxylase activity. Normal KM
FT                   but 10% reduced Vmax."
FT                   /evidence="ECO:0000269|PubMed:1864962"
FT   MUTAGEN         429
FT                   /note="C->M,S,T: Loss of progesterone 21-hydroxylase
FT                   activity and loss of P450 absorption."
FT                   /evidence="ECO:0000269|PubMed:1864962"
FT   CONFLICT        156
FT                   /note="G -> D (in Ref. 10; BAB70774)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        243
FT                   /note="R -> G (in Ref. 10; BAB70774)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        278
FT                   /note="L -> Q (in Ref. 10; BAB70774)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        305
FT                   /note="V -> A (in Ref. 10; BAB70774)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        312
FT                   /note="P -> L (in Ref. 18; AAA59985)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        347
FT                   /note="N -> I (in Ref. 18; AAA59985)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        427
FT                   /note="R -> P (in Ref. 1; AAB59440)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        438
FT                   /note="E -> D (in Ref. 1; AAB59440)"
FT                   /evidence="ECO:0000305"
FT   HELIX           39..41
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           45..51
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           53..56
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   STRAND          58..64
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   STRAND          67..72
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           75..82
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   TURN            83..85
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           86..89
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           96..100
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           115..129
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   TURN            130..135
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           136..151
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           161..178
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           180..183
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   TURN            184..186
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           188..202
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           205..212
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           214..217
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           224..246
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           257..262
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           279..310
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           312..325
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   TURN            337..339
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           344..356
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   STRAND          370..374
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   STRAND          377..379
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   STRAND          384..387
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           389..393
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   TURN            396..398
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   STRAND          399..401
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           407..410
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   HELIX           432..447
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   STRAND          450..458
FT                   /evidence="ECO:0007829|PDB:4Y8W"
FT   STRAND          479..483
FT                   /evidence="ECO:0007829|PDB:4Y8W"
SQ   SEQUENCE   495 AA;  56001 MW;  CE5C4EE9D3A0851C CRC64;
     MLLLGLLLLL PLLAGARLLW NWWKLRSLHL PPLAPGFLHL LQPDLPIYLL GLTQKFGPIY
     RLHLGLQDVV VLNSKRTIEE AMVKKWADFA GRPEPLTYKL VSRNYPDLSL GDYSLLWKAH
     KKLTRSALLL GIRDSMEPVV EQLTQEFCER MRAQPGTPVA IEEEFSLLTC SIICYLTFGD
     KIKDDNLMPA YYKCIQEVLK TWSHWSIQIV DVIPFLRFFP NPGLRRLKQA IEKRDHIVEM
     QLRQHKESLV AGQWRDMMDY MLQGVAQPSM EEGSGQLLEG HVHMAAVDLL IGGTETTANT
     LSWAVVFLLH HPEIQQRLQE ELDHELGPGA SSSRVPYKDR ARLPLLNATI AEVLRLRPVV
     PLALPHRTTR PSSISGYDIP EGTVIIPNLQ GAHLDETVWE RPHEFWPDRF LEPGKNSRAL
     AFGCGARVCL GEPLARLELF VVLTRLLQAF TLLPSGDALP SLQPLPHCSV ILKMQPFQVR
     LQPRGMGAHS PGQSQ
//
ID   Q08AG9_HUMAN            Unreviewed;       495 AA.
AC   Q08AG9;
DT   31-OCT-2006, integrated into UniProtKB/TrEMBL.
DT   31-OCT-2006, sequence version 1.
DT   24-JAN-2024, entry version 103.
DE   SubName: Full=Cytochrome P450, family 21, subfamily A, polypeptide 2 {ECO:0000313|EMBL:AAI25182.1};
GN   Name=CYP21A2 {ECO:0000313|EMBL:AAI25182.1};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606 {ECO:0000313|EMBL:AAI25182.1};
RN   [1] {ECO:0000313|EMBL:AAI25182.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RA   Gerhard D.S., Wagner L., Feingold E.A., Shenmen C.M., Grouse L.H.,
RA   Schuler G., Klein S.L., Old S., Rasooly R., Good P., Guyer M., Peck A.M.,
RA   Derge J.G., Lipman D., Collins F.S., Jang W., Sherry S., Feolo M.,
RA   Misquitta L., Lee E., Rotmistrovsky K., Greenhut S.F., Schaefer C.F.,
RA   Buetow K., Bonner T.I., Haussler D., Kent J., Kiekhaus M., Furey T.,
RA   Brent M., Prange C., Schreiber K., Shapiro N., Bhat N.K., Hopkins R.F.,
RA   Hsie F., Driscoll T., Soares M.B., Casavant T.L., Scheetz T.E.,
RA   Brown-stein M.J., Usdin T.B., Toshiyuki S., Carninci P., Piao Y.,
RA   Dudekula D.B., Ko M.S., Kawakami K., Suzuki Y., Sugano S., Gruber C.E.,
RA   Smith M.R., Simmons B., Moore T., Waterman R., Johnson S.L., Ruan Y.,
RA   Wei C.L., Mathavan S., Gunaratne P.H., Wu J., Garcia A.M., Hulyk S.W.,
RA   Fuh E., Yuan Y., Sneed A., Kowis C., Hodgson A., Muzny D.M., McPherson J.,
RA   Gibbs R.A., Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S.,
RA   Sanchez A., Whiting M., Madari A., Young A.C., Wetherby K.D., Granite S.J.,
RA   Kwong P.N., Brinkley C.P., Pearson R.L., Bouffard G.G., Blakesly R.W.,
RA   Green E.D., Dickson M.C., Rodriguez A.C., Grimwood J., Schmutz J.,
RA   Myers R.M., Butterfield Y.S., Griffith M., Griffith O.L., Krzywinski M.I.,
RA   Liao N., Morin R., Morrin R., Palmquist D., Petrescu A.S., Skalska U.,
RA   Smailus D.E., Stott J.M., Schnerch A., Schein J.E., Jones S.J., Holt R.A.,
RA   Baross A., Marra M.A., Clifton S., Makowski K.A., Bosak S., Malek J.;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family.
CC       {ECO:0000256|ARBA:ARBA00010617, ECO:0000256|RuleBase:RU000461}.
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DR   EMBL; BC125181; AAI25182.1; -; mRNA.
DR   RefSeq; NP_000491.4; NM_000500.7.
DR   RefSeq; NP_001122062.3; NM_001128590.3.
DR   AlphaFoldDB; Q08AG9; -.
DR   SMR; Q08AG9; -.
DR   IntAct; Q08AG9; 17.
DR   PeptideAtlas; Q08AG9; -.
DR   DNASU; 1589; -.
DR   GeneID; 1589; -.
DR   KEGG; hsa:1589; -.
DR   CTD; 1589; -.
DR   PharmGKB; PA27096; -.
DR   OrthoDB; 2900138at2759; -.
DR   BioGRID-ORCS; 1589; 13 hits in 1141 CRISPR screens.
DR   ChiTaRS; CYP21A2; human.
DR   GenomeRNAi; 1589; -.
DR   Genevisible; Q08AG9; HS.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR   CDD; cd20674; CYP21; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002401; Cyt_P450_E_grp-I.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   PANTHER; PTHR24289; STEROID 17-ALPHA-HYDROXYLASE/17,20 LYASE; 1.
DR   PANTHER; PTHR24289:SF13; STEROID 17-ALPHA-HYDROXYLASE/17,20 LYASE; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   2: Evidence at transcript level;
KW   Endoplasmic reticulum {ECO:0000256|ARBA:ARBA00022824};
KW   Heme {ECO:0000256|ARBA:ARBA00022617, ECO:0000256|RuleBase:RU000461};
KW   Iron {ECO:0000256|ARBA:ARBA00023004, ECO:0000256|RuleBase:RU000461};
KW   Lipid metabolism {ECO:0000256|ARBA:ARBA00023098};
KW   Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW   ECO:0000256|RuleBase:RU000461}; Microsome {ECO:0000256|ARBA:ARBA00022848};
KW   Monooxygenase {ECO:0000256|RuleBase:RU000461};
KW   Oxidoreductase {ECO:0000256|RuleBase:RU000461};
KW   Signal {ECO:0000256|SAM:SignalP}.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000256|SAM:SignalP"
FT   CHAIN           17..495
FT                   /evidence="ECO:0000256|SAM:SignalP"
FT                   /id="PRO_5004166638"
SQ   SEQUENCE   495 AA;  55973 MW;  F98A00BE05EE372E CRC64;
     MLLLGLLLLL PLLAGARLLW NWWKLQSLHL PPLAPGFLHL LQPDLPIYLL GLTQKFGPIY
     RLHLGLQDVV VLNSKRTIEE AMVKKWADFA GRPEPLTYKL VSRNYPDLSL GDYSLLWKAH
     KKLTRSALLL GIRDSMEPVV EQLTQEFCER MRAQPGTPVA IEEEFSLLTC SIICYLTFGD
     KIKDDNLMPA YYKCIQEVLK TWSHWSIQIV DVIPFLRFFP NPGLRRLKQA IEKRDHIVEM
     QLRQHKESLV AGQWRDMMDY MLQGVAQPSM EEGSGQLLEG HVHMAAVDLL IGGTETTANT
     LSWAVVFLLH HPEIQQRLQE ELDHELGPGA SSSRVPYKDR ARLPLLNATI AEVLRLRPVV
     PLALPHRTTR PSSISGYDIP EGTVIIPNLQ GAHLDETVWE RPHEFWPDRF LEPGKNSRAL
     AFGCGARVCL GEPLARLELF VVLTRLLQAF TLLPSGDALP SLQPLPHCSV ILKMQPFQVR
     LQPRGMGAHS PGQSQ
//
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