PYCARD
Chr 16PYD and CARD domain containing
Also known as: ASC, CARD5, TMS, TMS-1, TMS1
The protein functions as a key adapter in inflammasome assembly and caspase-mediated apoptosis, mediating innate immune responses and inflammatory signaling pathways. Mutations cause autoinflammatory disorders with autosomal recessive inheritance, typically presenting with early-onset recurrent fever, skin rash, and arthritis. The gene shows low constraint to loss-of-function variants (pLI 0.0002, LOEUF 1.9), consistent with recessive inheritance patterns.
Some data sources returned errors (1)
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
39 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 9 | 0 | 9 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 13 | 7 | 0 | 20 |
Likely Benign | 0 | 0 | 0 | 1 | 1 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 0 | 13 | 17 | 2 | 32 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PYCARD · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Health-related Quality of Life, Electrocardiographic and Holter Findings in Children With Familial Mediterranean Fever
ACTIVE NOT RECRUITINGEvaluation of Canakinumab in High-Risk Former-Smokers
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools