Cryopyrin associated periodic syndrome: genes and variants

Genes linked to Cryopyrin associated periodic syndrome

• 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.

  15 disease-causing and 2 uncertain variants in NLRP3 are linked to Cryopyrin associated periodic syndrome.

• IL1B: Interleukin-1 beta

  After inflammasome-mediated processing, it drives fever, leukocyte recruitment, and local inflammatory responses to infection or tissue damage. Excess production contributes to multiple autoinflammatory diseases and can be therapeutically suppressed by blocking IL-1 signaling.

  0 disease-causing and 0 uncertain variants in IL1B are linked to Cryopyrin associated periodic syndrome.

Where Cryopyrin associated periodic syndrome variants cluster

• NLRP3 NACHT (positions 220–536): 14 of 15 disease-causing changes, 3.0× more than its size predicts.

Known disease-causing variants in Cryopyrin associated periodic syndrome

Same protein, different disease

• Chronic infantile neurological, cutaneous and articular syndrome is also caused by NLRP3 variants; they fall mostly in different places as the Cryopyrin associated periodic syndrome 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 Cryopyrin associated periodic syndrome variants (4 disease-causing).

Diseases related to Cryopyrin associated periodic syndrome

• Autosomal dominant nonsyndromic hearing loss, also linked to NLRP3
• Autoinflammatory syndrome, also linked to NLRP3
• Familial Mediterranean fever, also linked to IL1B
• Chronic infantile neurological, cutaneous and articular syndrome, also linked to NLRP3
• Familial cold autoinflammatory syndrome 3, also linked to NLRP3
• Keratitis fugax hereditaria, also linked to NLRP3

Frequently asked questions

Which genes are linked to Cryopyrin associated periodic syndrome?

In CATVariant, Cryopyrin associated periodic syndrome is linked to 2 analyzed proteins: NLRP3 (NACHT, LRR and PYD domains-containing protein 3) and IL1B (Interleukin-1 beta).

How many genetic variants are linked to Cryopyrin associated periodic syndrome?

21 variants: 15 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 2 are of uncertain significance or have conflicting reports.

Which uncertain variants in Cryopyrin associated periodic syndrome 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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