NLRP1
Chr 17ARADNLR family pyrin domain containing 1
Also known as: AIADK, CARD7, CIDED, CLR17.1, DEFCAP, DEFCAP-L/S, JRRP, MSPC
The NLRP1 protein acts as a sensor component of the NLRP1 inflammasome, recognizing pathogen-associated signals and damage signals to initiate inflammatory responses and pyroptosis through caspase-1 activation. Mutations cause autoinflammation with arthritis and dyskeratosis, palmoplantar carcinoma with multiple self-healing lesions, and juvenile recurrent respiratory papillomatosis, with both autosomal dominant and autosomal recessive inheritance patterns reported. The gene shows low constraint against loss-of-function variants, suggesting tolerance to protein-truncating mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports gain-of-function. 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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
500 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 | 4 | 0 | 4 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 25 | 253 | 19 | 0 | 297 |
Likely Benign | 0 | 1 | 44 | 126 | 171 |
Benign | 0 | 0 | 1 | 0 | 1 |
Conflicting | — | 3 | |||
| Total | 25 | 254 | 68 | 126 | 476 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NLRP1 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools