NLRP1

Chr 17ARAD

NLR family pyrin domain containing 1

Also known as: AIADK, CARD7, CIDED, CLR17.1, DEFCAP, DEFCAP-L/S, JRRP, MSPC

NCBI Gene: 22861ENSG00000091592UniProt: Q9C000

This gene encodes a member of the Ced-4 family of apoptosis proteins. Ced-family members contain a caspase recruitment domain (CARD) and are known to be key mediators of programmed cell death. The encoded protein contains a distinct N-terminal pyrin-like motif, which is possibly involved in protein-protein interactions. This protein interacts strongly with caspase 2 and weakly with caspase 9. Overexpression of this gene was demonstrated to induce apoptosis in cells. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

?Respiratory papillomatosis, juvenile recurrent, congenitalMIM #618803
AR
{Vitiligo-associated multiple autoimmune disease susceptibility 1}MIM #606579
Autoinflammation with arthritis and dyskeratosisMIM #617388
ADAR
Palmoplantar carcinoma, multiple self-healingMIM #615225
AD
301
ClinVar variants
3
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NLRP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
3 Pathogenic / Likely Pathogenic· 177 VUS of 301 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.84LOEUF
pLI 0.000
Z-score 2.60
OE 0.64 (0.49–0.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.49Z-score
OE missense 0.85 (0.80–0.91)
685 obs / 803.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.64 (0.49–0.84)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.80–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.96
0≤1.21.6
LoF obs/exp: 39 / 60.9Missense obs/exp: 685 / 803.8Syn Z: 0.62

ClinVar Variant Classifications

301 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
VUS177
Likely Benign118
Conflicting3
3
Pathogenic
177
VUS
118
Likely Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
3
0
3
Likely Pathogenic
0
0
0
0
0
VUS
9
145
23
0
177
Likely Benign
0
2
32
84
118
Benign
0
0
0
0
0
Conflicting
—3
Total91475884301

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.

Gene2Phenotype Curations

NLRP1-related autoinflammation with arthritis and dyskeratosis

strong
ARUndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

NLRP1-related corneal intraepithelial dyskeratosis

limited
ADUndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Respiratory papillomatosis, juvenile recurrent, congenital

MIM #618803

Molecular basis of disorder known

Autosomal recessive

{Vitiligo-associated multiple autoimmune disease susceptibility 1}

MIM #606579

Molecular basis of disorder known

Autoinflammation with arthritis and dyskeratosis

MIM #617388

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Palmoplantar carcinoma, multiple self-healing

MIM #615225

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases.
Coll RC et al.·Nat Med
2015
Inflammasomes and Cancer.
Karki R et al.·Cancer Immunol Res
2017Review
NLRP1 inflammasome promotes senescence and senescence-associated secretory phenotype.
Muela-Zarzuela I et al.·Inflamm Res
2024
Autoinflammatory Keratinization Diseases-The Concept, Pathophysiology, and Clinical Implications.
Blicharz L et al.·Clin Rev Allergy Immunol
2023Review
Regulation of inflammasome activation.
Man SM et al.·Immunol Rev
2015Review
Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells.
Planès R et al.·Mol Cell
2022
Role of the NLRP1 inflammasome in skin cancer and inflammatory skin diseases.
Calabrese L et al.·Br J Dermatol
2024Review
Inflammasomes-New Contributors to Blood Diseases.
Tomasik J et al.·Int J Mol Sci
2022Review
A clinical update on inflammasomopathies.
Sönmez HE et al.·Int Immunol
2017Review
Role of inflammasomes in Toxoplasma and Plasmodium infections.
Wang ZX et al.·Parasit Vectors
2024Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Retraction: Fexuprazan safeguards the esophagus from hydrochloric acid-induced damage by suppressing NLRP1/Caspase-1/GSDMD pyroptotic pathway.
Frontiers Editorial Office.·Front Immunol
2026🔓 Open Access
MST1 promotes microglial pyroptosis and neuroinflammation in alzheimer's disease by regulating the novel DPP8/NLRP1/Caspase-1/GSDMD-N axis.
Cui D et al.·J Neuroinflammation
2026
Targeting PAK4 promotes Gemcitabine-induced pyroptosis in pancreatic cancer via NLRP1/caspase-3/GSDME axis.
Lu T et al.·Commun Biol
2026🔓 Open Access
Redefining Shiga toxin-induced human cell death as NLRP1- and gasdermin E-mediated pyroptosis.
Ricci-Azevedo R et al.·Proc Natl Acad Sci U S A
2026
TKI-mediated inhibition of NLRP1 inflammasome restores erythropoiesis in DBA syndrome.
Lozano-Gil JM et al.·EMBO Mol Med
2026🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools