KEGG DISEASE is a collection of disease entries, each containing a list of human disease genes and/or pathogens. The details of how molecular networks are perturbed by such perturbants are represented as network variation maps in the KEGG NETWORK database. KEGG DISEASE used to contain environmental factors, but they are now included only in KEGG NETWORK when molecular level information is available. Each disease entry is identified by the H number and may contain the link to network variation maps (see, for example, the disease entry of spinal muscular atrophy H00455). Therapeutic drugs are shown in the Drug field; those indicated in the FDA drug labels appear in the English version and those indicated in the Japanese drug labels appear in the Japanese version.

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

Network variation maps in the KEGG NETWORK database are a realization of the concept shown in the figure above. They indicate how perturbants, including human gene variants, viral and other pathogenic proteins and environmental factors, affect reference molecular networks (colored in green) and are associated with various diseases.

• KEGG network variation maps

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.

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