KEGG DISEASE: Spinocerebellar ataxia (SCA)

DISEASE: Spinocerebellar ataxia (SCA)

Entry

H00063                      Disease

Name

Spinocerebellar ataxia (SCA)

Subgroup

Machado-Joseph disease [DS:H01478]

Supergrp

Spinocerebellar degeneration [DS:H01616]

Description

The autosomal dominant spinocerebellar ataxias (SCAs) are a group of progressive neurodegenerative diseases characterised by loss of balance and motor coordination due to the primary dysfunction of the cerebellum. Compelling evidence points to major aetiological roles for transcriptional dysregulation, protein aggregation and clearance, autophagy, the ubiquitin-proteasome system, alterations of calcium homeostasis, mitochondria defects, toxic RNA gain-of-function mechanisms and eventual cell death with apoptotic features of neurons during SCA disease progression.

Category

Neurodegenerative disease

Brite

Human diseases [BR:br08402]
Nervous system diseases
  Neurodegenerative diseases
   H00063  Spinocerebellar ataxia (SCA)
Human diseases in ICD-11 classification [BR:br08403]
08 Diseases of the nervous system
  Movement disorders
   8A03  Ataxic disorders
    H00063  Spinocerebellar ataxia (SCA)

Pathway

hsa05017

Spinocerebellar ataxia

Related
pathway

hsa05022

Pathways of neurodegeneration - multiple diseases

Network

nt06410  Calcium signaling
nt06411  Potassium transport
nt06413  Autophagy
nt06415  PI3K signaling
nt06440  Transcription
nt06462  Spinocerebellar ataxia

Gene

(SCA1) ATXN1 (CAG repeat expansion) [HSA:6310] [KO:K23616]
(SCA2) ATXN2 (CAG repeat expansion) [HSA:6311] [KO:K23625]
(SCA3) ATXN3 (CAG repeat expansion) [HSA:4287] [KO:K11863]
(SCA5) SPTBN2 [HSA:6712] [KO:K23932]
(SCA6) CACNA1A (CAG repeat expansion) [HSA:773] [KO:K04344]
(SCA7) ATXN7 (CAG repeat expansion) [HSA:6314] [KO:K11318]
(SCA8) ATXN8OS (CTG/CAG repeat expansion) [HSA:6315] [KO:K23933]
(SCA10) ATXN10 (ATTCT repeat expansion) [HSA:25814] [KO:K19323]
(SCA11) TTBK2 [HSA:146057] [KO:K08815]
(SCA12) PPP2R2B (CAG repeat expansion) [HSA:5521] [KO:K04354]
(SCA13) KCNC3 [HSA:3748] [KO:K04889]
(SCA14) PRKCG [HSA:5582] [KO:K19663]
(SCA15) ITPR1 (deletion) [HSA:3708] [KO:K04958]
(SCA17) TBP (CAG repeat expansion) [HSA:6908] [KO:K03120]
(SCA19/22) KCND3 [HSA:3752] [KO:K04893]
(SCA21) TMEM240 [HSA:339453] [KO:K24870]
(SCA23) PDYN [HSA:5173] [KO:K15840]
(SCA26) EEF2 [HSA:1938] [KO:K03234]
(SCA27) FGF14 [HSA:2259] [KO:K23920]
(SCA28) AFG3L2 [HSA:10939] [KO:K08956]
(SCA31) BEAN1 [HSA:146227] [KO:K19324]
(SCA34) ELOVL4 [HSA:6785] [KO:K10249]
(SCA35) TGM6 [HSA:343641] [KO:K05624]
(SCA36) NOP56 [HSA:10528] [KO:K14564]
(SCA37) DAB1 [HSA:1600] [KO:K20054]
(SCA38) ELOVL5 [HSA:60481] [KO:K10244]
(SCA40) CCDC88C [HSA:440193] [KO:K25811]
(SCA41) TRPC3 [HSA:7222] [KO:K04966]
(SCA42) CACNA1G [HSA:8913] [KO:K04854]
(SCA43) MME [HSA:4311] [KO:K01389]
(SCA44) GRM1 [HSA:2911] [KO:K04603]
(SCA45) FAT2 [HSA:2196] [KO:K16506]
(SCA46) PLD3 [HSA:23646] [KO:K16860]
(SCA47) PUM1 [HSA:9698] [KO:K17943]

Comment

Disease class: polyglutamine disease
Affected region: cerebellum, dentate nucleus, brain stem (SCA1); cerebellum, brain stem, frontotemporal lobes (frontal lobe and temporal lobe) (SCA2); cerebellum, basal ganglia, brain stem, spinal cord (SCA3); cerebellum (SCA5); cerebellum, dentate nucleus, inferior olive (SCA6); cerebellum, inferior olive, dentate nucleus, pontine nuclei (also the retina) (SCA7); cerebral cortex, cerebellum (SCA12); cerebellum, inferior olive (SCA17)
Microscopic lesion: neuronal inclusions (SCA1, SCA2, SCA3, SCA7, SCA17); cytoplasmic inclusions (SCA6)

Other DBs

ICD-11:

8A03.16

ICD-10:

G31.9

MeSH:

D020754

Reference

PMID:14585172

Authors

Rudnicki DD, Margolis RL.

Title

Repeat expansion and autosomal dominant neurodegenerative disorders: consensus and controversy.

Journal

Expert Rev Mol Med 5:1-24 (2003)
DOI:10.1017/S1462399403006598

Reference

PMID:19890685

Authors

Matilla-Duenas A, Sanchez I, Corral-Juan M, Davalos A, Alvarez R, Latorre P

Title

Cellular and molecular pathways triggering neurodegeneration in the spinocerebellar ataxias.

Journal

Cerebellum 9:148-66 (2010)
DOI:10.1007/s12311-009-0144-2

Reference

PMID:30284037

Authors

Sullivan R, Yau WY, O'Connor E, Houlden H

Title

Spinocerebellar ataxia: an update.

Journal

J Neurol 266:533-544 (2019)
DOI:10.1007/s00415-018-9076-4

Reference

PMID:17620880

Authors

Soong BW, Paulson HL

Title

Spinocerebellar ataxias: an update.

Journal

Curr Opin Neurol 20:438-46 (2007)
DOI:10.1097/WCO.0b013e3281fbd3dd

Reference

PMID:12869811

Authors

Albin RL

Title

Dominant ataxias and Friedreich ataxia: an update.

Journal

Curr Opin Neurol 16:507-14 (2003)
DOI:10.1097/01.wco.0000084230.82329.d5

Reference

PMID:10525976 (SCA1, SCA2, SCA3)

Authors

Burk K, Fetter M, Abele M, Laccone F, Brice A, Dichgans J, Klockgether T

Title

Autosomal dominant cerebellar ataxia type I: oculomotor abnormalities in families with SCA1, SCA2, and SCA3.

Journal

J Neurol 246:789-97 (1999)
DOI:10.1007/s004150050456

Reference

PMID:17390258 (SCA3)

Authors

Paulson HL

Title

Dominantly inherited ataxias: lessons learned from Machado-Joseph disease/spinocerebellar ataxia type 3.

Journal

Semin Neurol 27:133-42 (2007)
DOI:10.1055/s-2007-971172

Reference

PMID:18317266 (SCA3)

Authors

Rub U, Brunt ER, Deller T

Title

New insights into the pathoanatomy of spinocerebellar ataxia type 3 (Machado-Joseph disease).

Journal

Curr Opin Neurol 21:111-6 (2008)
DOI:10.1097/WCO.0b013e3282f7673d

Reference

PMID:16927298 (SCA5)

Authors

Bauer P, Schols L, Riess O

Title

Spectrin mutations in spinocerebellar ataxia (SCA).

Journal

Bioessays 28:785-7 (2006)
DOI:10.1002/bies.20443

Reference

PMID:17590087 (SCA15)

Authors

van de Leemput J, Chandran J, Knight MA, Holtzclaw LA, Scholz S, Cookson MR, Houlden H, Gwinn-Hardy K, Fung HC, Lin X, Hernandez D, Simon-Sanchez J, Wood NW, Giunti P, Rafferty I, Hardy J, Storey E, Gardner RJ, Forrest SM, Fisher EM, Russell JT, Cai H, Singleton AB

Title

Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 in humans.

Journal

PLoS Genet 3:e108 (2007)
DOI:10.1371/journal.pgen.0030108

Reference

PMID:23280838 (SCA19)

Authors

Duarri A, Jezierska J, Fokkens M, Meijer M, Schelhaas HJ, den Dunnen WF, van Dijk F, Verschuuren-Bemelmans C, Hageman G, van de Vlies P, Kusters B, van de Warrenburg BP, Kremer B, Wijmenga C, Sinke RJ, Swertz MA, Kampinga HH, Boddeke E, Verbeek DS

Title

Mutations in potassium channel kcnd3 cause spinocerebellar ataxia type 19.

Journal

Ann Neurol 72:870-80 (2012)
DOI:10.1002/ana.23700

Reference

PMID:25070513 (SCA21)

Authors

Delplanque J, Devos D, Huin V, Genet A, Sand O, Moreau C, Goizet C, Charles P, Anheim M, Monin ML, Buee L, Destee A, Grolez G, Delmaire C, Dujardin K, Dellacherie D, Brice A, Stevanin G, Strubi-Vuillaume I, Durr A, Sablonniere B

Title

TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and severe cognitive impairment.

Journal

Brain 137:2657-63 (2014)
DOI:10.1093/brain/awu202

Reference

PMID:21035104 (SCA23)

Authors

Bakalkin G, Watanabe H, Jezierska J, Depoorter C, Verschuuren-Bemelmans C, Bazov I, Artemenko KA, Yakovleva T, Dooijes D, Van de Warrenburg BP, Zubarev RA, Kremer B, Knapp PE, Hauser KF, Wijmenga C, Nyberg F, Sinke RJ, Verbeek DS

Title

Prodynorphin mutations cause the neurodegenerative disorder spinocerebellar ataxia type 23.

Journal

Am J Hum Genet 87:593-603 (2010)
DOI:10.1016/j.ajhg.2010.10.001

Reference

PMID:23001565 (SCA26)

Authors

Hekman KE, Yu GY, Brown CD, Zhu H, Du X, Gervin K, Undlien DE, Peterson A, Stevanin G, Clark HB, Pulst SM, Bird TD, White KP, Gomez CM

Title

A conserved eEF2 coding variant in SCA26 leads to loss of translational fidelity and increased susceptibility to proteostatic insult.

Journal

Hum Mol Genet 21:5472-83 (2012)
DOI:10.1093/hmg/dds392

Reference

PMID:24566826 (SCA34)

Authors

Cadieux-Dion M, Turcotte-Gauthier M, Noreau A, Martin C, Meloche C, Gravel M, Drouin CA, Rouleau GA, Nguyen DK, Cossette P

Title

Expanding the clinical phenotype associated with ELOVL4 mutation: study of a large French-Canadian family with autosomal dominant spinocerebellar ataxia and erythrokeratodermia.

Journal

JAMA Neurol 71:470-5 (2014)
DOI:10.1001/jamaneurol.2013.6337

Reference

PMID:25253745 (SCA35)

Authors

Guo YC, Lin JJ, Liao YC, Tsai PC, Lee YC, Soong BW

Title

Spinocerebellar ataxia 35: novel mutations in TGM6 with clinical and genetic characterization.

Journal

Neurology 83:1554-61 (2014)
DOI:10.1212/WNL.0000000000000909

Reference

PMID:21683323 (SCA36)

Authors

Kobayashi H, Abe K, Matsuura T, Ikeda Y, Hitomi T, Akechi Y, Habu T, Liu W, Okuda H, Koizumi A

Title

Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied by motor neuron involvement.

Journal

Am J Hum Genet 89:121-30 (2011)
DOI:10.1016/j.ajhg.2011.05.015

Reference

PMID:25065913 (SCA38)

Authors

Di Gregorio E, Borroni B, Giorgio E, Lacerenza D, Ferrero M, Lo Buono N, Ragusa N, Mancini C, Gaussen M, Calcia A, Mitro N, Hoxha E, Mura I, Coviello DA, Moon YA, Tesson C, Vaula G, Couarch P, Orsi L, Duregon E, Papotti MG, Deleuze JF, Imbert J, Costanzi C, Padovani A, Giunti P, Maillet-Vioud M, Durr A, Brice A, Tempia F, Funaro A, Boccone L, Caruso D, Stevanin G, Brusco A

Title

ELOVL5 mutations cause spinocerebellar ataxia 38.

Journal

Am J Hum Genet 95:209-17 (2014)
DOI:10.1016/j.ajhg.2014.07.001

Reference

PMID:25062847 (SCA40)

Authors

Tsoi H, Yu AC, Chen ZS, Ng NK, Chan AY, Yuen LY, Abrigo JM, Tsang SY, Tsui SK, Tong TM, Lo IF, Lam ST, Mok VC, Wong LK, Ngo JC, Lau KF, Chan TF, Chan HY

Title

A novel missense mutation in CCDC88C activates the JNK pathway and causes a dominant form of spinocerebellar ataxia.

Journal

J Med Genet 51:590-5 (2014)
DOI:10.1136/jmedgenet-2014-102333

Reference

PMID:21321808 (SCA41)

Authors

Becker EB, Fogel BL, Rajakulendran S, Dulneva A, Hanna MG, Perlman SL, Geschwind DH, Davies KE

Title

Candidate screening of the TRPC3 gene in cerebellar ataxia.

Journal

Cerebellum 10:296-9 (2011)
DOI:10.1007/s12311-011-0253-6

Reference

PMID:11927664 (SCA42)

Authors

Chemin J, Monteil A, Perez-Reyes E, Bourinet E, Nargeot J, Lory P

Title

Specific contribution of human T-type calcium channel isotypes (alpha(1G), alpha(1H) and alpha(1I)) to neuronal excitability.

Journal

J Physiol 540:3-14 (2002)
DOI:10.1113/jphysiol.2001.013269

Reference

PMID:27583304 (SCA43)

Authors

Depondt C, Donatello S, Rai M, Wang FC, Manto M, Simonis N, Pandolfo M

Title

MME mutation in dominant spinocerebellar ataxia with neuropathy (SCA43).

Journal

Neurol Genet 2:e94 (2016)
DOI:10.1212/NXG.0000000000000094

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Pathway (1)   
   KEGG PATHWAY (1)   
Network (22)   
   KEGG NETWORK (22)   
Disease (34)   
   OMIM (34)   
Gene (68)   
   KEGG ORTHOLOGY (34)   
   KEGG GENES (34)   
Literature (22)   
   PubMed (22)   
All databases (147)   

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