diseasegene

A disease gene is a gene whose alteration is involved in the development or progression of a disease. The term can refer to genes whose rare variants are causative for Mendelian disorders, as well as genes whose common or rare variants modify the risk or severity of complex diseases. Disease genes may affect health through changes in the amount, structure, or regulation of the encoded protein.

Causative disease genes are often linked to specific inherited conditions. For example, pathogenic variants in CFTR cause cystic fibrosis, mutations in BRCA1 or BRCA2 raise the risk of hereditary breast and ovarian cancer, and expansions in the HTT gene cause Huntington disease. In many diseases, a single gene is primarily responsible (high penetrance), while others involve multiple genes and environmental factors.

In complex diseases, disease genes usually contribute as susceptibility or risk factors. Variants in genes such as APOE or LDLR can influence risk or onset age for conditions like Alzheimer’s disease or familial hypercholesterolemia, often with lower penetrance and larger population effects.

Somatic mutations in disease genes can drive acquired diseases such as cancer. Alterations in oncogenes and tumor suppressor genes accumulate in cells, promoting uncontrolled growth and malignancy.

Identification and interpretation of disease genes rely on genetic linkage, population association studies, and sequencing approaches (genome, exome). Functional studies, clinical genetics, and guidelines help classify variants as pathogenic, likely pathogenic, or of uncertain significance.

Clinical applications include genetic testing for diagnosis, carrier screening, risk assessment, and informing treatment strategies or gene-targeted therapies. Key databases that curate disease-gene relationships include OMIM, ClinVar, and HGMD.