Inflammatory bowel disease: genes and variants

Genes linked to Inflammatory bowel disease

• IL10RA: Interleukin-10 receptor subunit alpha

  It is required for cells to respond to the anti-inflammatory cytokine IL-10 and activate downstream STAT3 signaling. Biallelic loss-of-function variants cause severe infantile or very-early-onset inflammatory bowel disease, often with perianal disease and systemic inflammation.

  7 disease-causing and 157 uncertain variants in IL10RA are linked to Inflammatory bowel disease.

• NOD2: Nucleotide-binding oligomerization domain-containing protein 2

  It detects bacterial muramyl dipeptide in the cytosol and activates antimicrobial and inflammatory responses. Common loss-of-function variants strongly increase Crohn-disease susceptibility, whereas distinct gain-of-function variants cause Blau syndrome.

  0 disease-causing and 17 uncertain variants in NOD2 are linked to Inflammatory bowel disease.

• IL10: Interleukin-10

  It suppresses excessive inflammatory cytokine production and restrains antigen-presenting cells and effector lymphocytes, protecting tissues from immune-mediated damage. Loss of IL-10 signaling causes severe early-onset intestinal inflammation and inflammatory bowel disease.

  0 disease-causing and 44 uncertain variants in IL10 are linked to Inflammatory bowel disease.

• IL23R: Interleukin-23 receptor

  It enables lymphocytes to respond to IL-23 and maintain Th17-type inflammatory programs. Common variants can strongly modify inflammatory bowel disease risk, and therapeutic interruption of IL-23 signaling is effective in several immune-mediated disorders.

  0 disease-causing and 0 uncertain variants in IL23R are linked to Inflammatory bowel disease.

• BACH2: Transcription regulator protein BACH2

  It controls transcriptional programs that balance lymphocyte differentiation, immune tolerance, and effector-cell development. Haploinsufficiency can cause immunodeficiency with autoimmunity, and common variation influences susceptibility to several autoimmune diseases.

  0 disease-causing and 0 uncertain variants in BACH2 are linked to Inflammatory bowel disease.

• CD40: Tumor necrosis factor receptor superfamily member 5

  Its engagement on B cells and antigen-presenting cells promotes antibody class switching, germinal-center responses, and broader adaptive immune activation. Loss-of-function variants can cause hyper-IgM immunodeficiency, while excessive signaling contributes to autoimmunity and inflammation.

  0 disease-causing and 0 uncertain variants in CD40 are linked to Inflammatory bowel disease.

• IL12B: Interleukin-12 subunit beta

  It provides the p40 subunit shared by IL-12 and IL-23, linking innate immune activation to Th1 and Th17 responses. Biallelic loss-of-function variants impair IFN-gamma-mediated defense against mycobacteria and Salmonella, while therapeutic blockade is effective in several inflammatory diseases.

  0 disease-causing and 0 uncertain variants in IL12B are linked to Inflammatory bowel disease.

• JAK2: Tyrosine-protein kinase JAK2

  It transmits signals from erythropoietin, thrombopoietin, growth hormone, and other cytokine receptors into STAT-dependent transcription. The V617F gain-of-function variant is a major driver of polycythemia vera, essential thrombocythemia, and primary myelofibrosis.

  0 disease-causing and 0 uncertain variants in JAK2 are linked to Inflammatory bowel disease.

Weakly linked (only a few uncertain records): ABCB1 and KRT8.

Where Inflammatory bowel disease variants cluster

• IL10RA Extracellular (positions 22–235): 6 of 7 disease-causing changes, 2.3× more than its size predicts.

Known disease-causing variants in Inflammatory bowel disease

Diseases related to Inflammatory bowel disease

• Type 1 diabetes mellitus, also linked to BACH2 and IL10
• Hyper-IgM syndrome, also linked to CD40
• Acute myeloid leukemia, also linked to JAK2
• Autoinflammatory syndrome, also linked to NOD2
• Blau syndrome, also linked to NOD2
• Thrombocythemia 2, also linked to JAK2
• Regional enteritis, also linked to NOD2
• Essential thrombocythemia, also linked to JAK2
• Hypothyroidism, also linked to BACH2
• Primary myelofibrosis, also linked to JAK2
• Systemic lupus erythematosus, also linked to IL10
• Basal cell carcinoma, also linked to BACH2

Frequently asked questions

Which genes are linked to Inflammatory bowel disease?

In CATVariant, Inflammatory bowel disease is linked to 8 analyzed proteins: IL10RA (Interleukin-10 receptor subunit alpha), NOD2 (Nucleotide-binding oligomerization domain-containing protein 2), IL10 (Interleukin-10), IL23R (Interleukin-23 receptor), BACH2 (Transcription regulator protein BACH2), CD40 (Tumor necrosis factor receptor superfamily member 5) and 2 more.

How many genetic variants are linked to Inflammatory bowel disease?

283 variants: 7 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 221 are of uncertain significance or have conflicting reports.

Which uncertain variants in Inflammatory bowel disease look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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