In KEGG, diseases are viewed as perturbed states of the molecular network system. Genetic and environmental factors of diseases, as well as drugs, are considered as perturbants to this system. Different types of diseases, including single-gene (monogenic) diseases, multifactorial diseases, and infectious diseases, are all treated in a unified manner by accumulating such perturbants and their interactions.

Our knowledge on perturbed molecular networks has been captured and represented as disease pathway maps in the KEGG PATHWAY database (see, for example, the disease pathway map of chronic myeloid leukemia hsa05220). Although disease genes (genetic perturbants) are marked in red in these maps, details of perturbations, such as mutation and fusion, are not given. Such details are now accumulated in the KEGG NETWORK database.

KEGG DISEASE is a collection of disease entries focusing only on the perturbants, for the details of molecular networks are unknown for most diseases. Each entry is identified by the H number and contains a list of known genetic factors (disease genes), environmental factors, pathogens and therapeutic drugs (see, for example, the disease entry of chronic myeloid leukemia H00004). Disease entries are classified in the following BRITE hierarchy files.

• Human diseases in ICD-11 classification
• Pathway-based classification of diseases
• Genome-based classification of infectious diseases

The KEGG DISEASE entry only indicates membership information, i.e., association of genes and molecules to diseases, but may reflect the underlying molecular network. For single-gene diseases, perturbed pathway maps are not drawn, but causative genes are mapped to normal pathway maps through disease entries (see, for example, the disease entry of congenital disorders of glycosylation type I H00118 and the normal pathway map of N-glycan biosynthesis hsa00510).

The Human Diseases category of the KEGG PATHWAY database is a collection of disease pathway maps.

• KEGG Pathway Maps: Human Diseases

It contains multifactorial diseases such as cancers, immune system diseases, neurodegenerative diseases, cardiovascular diseases, and metabolic diseases where known disease genes are marked in red. It also contains infectious diseases where interacting molecular networks of both pathogens and humans are depicted.

Network variation maps in the KEGG NETWORK database indicate how perturbed molecular networks caused by gene variants, viruses and other factors are associated with selected classes of diseases.

• KEGG network variation maps

The KEGG Mapper Search tool with "hsa" mode contains a feature to search against disease genes accumulated in KEGG DISEASE entries, together with related KEGG pathway maps. The user may upload a set of human genes or KOs to check if any diseases may be associated with the dataset.

• KEGG Mapper - Search

Pathway/Brite mapping of disease genes and drug targets

Disease genes accumulated in the KEGG DISEASE database and drug targets stored in the KEGG DRUG database are often represented in the KEGG PATHWAY and BRITE databases as well. The pathway maps and BRITE hierarchy files with mapping of disease genes and drug targets are identified by the five-letter organism code "hsadd" and the extension code "_dd", respectively.

For example, hsadd04620 represents disease/drug mapped toll-like receptor signaling pathway with the coloring convention as follows:

• When the gene is associated with a disease, it is marked in pink.
• When the gene (product) is a drug target, it is marked in light blue.
• When the gene is both a disease gene and a drug target, its coloring is split into pink and light blue.

The disease/drug mapped version is precomputed in the daily KEGG database update procedure, and each map or BRITE hierarchy can be selected from the organisms selection menu. For the disease/drug pathway maps the following list may also be used.

• Disease genes and drug targets in KEGG pathways

The following international standards are utilized in KEGG.

• ICD-11 International classification of diseases
• ICD-10 International classification of diseases
• ICD-O International classification of diseases for oncology