Familial cold autoinflammatory syndrome 3: genes and variants

Genes linked to Familial cold autoinflammatory syndrome 3

• PLCG2: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2

  It generates IP3 and diacylglycerol downstream of immune receptors, triggering intracellular calcium release and protein-kinase-C signaling in B cells and myeloid cells. Gain-of-function variants cause autoinflammatory and antibody-deficiency syndromes, while somatic mutations can mediate resistance to BTK inhibitors.

  3 disease-causing and 596 uncertain variants in PLCG2 are linked to Familial cold autoinflammatory syndrome 3.

• NLRP3: NACHT, LRR and PYD domains-containing protein 3

  It assembles a widely used inflammasome in response to diverse danger signals, driving caspase-1 activation and release of IL-1beta and IL-18. Gain-of-function variants cause cryopyrin-associated periodic syndromes, while excessive activation contributes to common inflammatory diseases.

  1 disease-causing and 2 uncertain variants in NLRP3 are linked to Familial cold autoinflammatory syndrome 3.

Known disease-causing variants in Familial cold autoinflammatory syndrome 3

Same protein, different disease

• Cryopyrin associated periodic syndrome is also caused by NLRP3 variants; they fall mostly in different places as the Familial cold autoinflammatory syndrome 3 variants (15 disease-causing).
• Autoinflammatory syndrome is also caused by NLRP3 variants; they fall mostly in different places as the Familial cold autoinflammatory syndrome 3 variants (7 disease-causing).
• Chronic infantile neurological, cutaneous and articular syndrome is also caused by NLRP3 variants; they fall mostly in different places as the Familial cold autoinflammatory syndrome 3 variants (5 disease-causing).
• Familial amyloid nephropathy with urticaria AND deafness is also caused by NLRP3 variants; they fall mostly in different places as the Familial cold autoinflammatory syndrome 3 variants (4 disease-causing).

Diseases related to Familial cold autoinflammatory syndrome 3

• Alzheimer disease, also linked to PLCG2
• Autosomal dominant nonsyndromic hearing loss, also linked to NLRP3
• Cryopyrin associated periodic syndrome, also linked to NLRP3
• Autoinflammatory syndrome, also linked to NLRP3
• Chronic infantile neurological, cutaneous and articular syndrome, also linked to NLRP3
• Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation, also linked to PLCG2
• Keratitis fugax hereditaria, also linked to NLRP3

Frequently asked questions

Which genes are linked to Familial cold autoinflammatory syndrome 3?

In CATVariant, Familial cold autoinflammatory syndrome 3 is linked to 2 analyzed proteins: PLCG2 (1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2) and NLRP3 (NACHT, LRR and PYD domains-containing protein 3).

How many genetic variants are linked to Familial cold autoinflammatory syndrome 3?

658 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 598 are of uncertain significance or have conflicting reports.

Which uncertain variants in Familial cold autoinflammatory syndrome 3 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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