NLRP12

Chr 19AD

NLR family pyrin domain containing 12

Also known as: CLR19.3, FCAS2, NALP12, PAN6, PYPAF7, RNO, RNO2

NCBI Gene: 91662ENSG00000142405UniProt: P59046

This gene encodes a member of the CATERPILLER family of cytoplasmic proteins. The encoded protein, which contains an N-terminal pyrin domain, a NACHT domain, a NACHT-associated domain, and a C-terminus leucine-rich repeat region, functions as an attenuating factor of inflammation by suppressing inflammatory responses in activated monocytes. Mutations in this gene cause familial cold autoinflammatory syndrome type 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

Primary Disease Associations & Inheritance

Familial cold autoinflammatory syndrome 2MIM #611762
AD
1517
ClinVar variants
2
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NLRP12
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
2 Pathogenic / Likely Pathogenic· 296 VUS of 1517 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
1.35LOEUF
pLI 0.000
Z-score -0.26
OE 1.04 (0.81–1.35)
Tolerant

Highly tolerant — LoF variants common in population

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.
-1.71Z-score
OE missense 1.20 (1.12–1.27)
729 obs / 610.0 exp
Tolerant

Tolerant to missense variation

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.1.04 (0.81–1.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.20 (1.12–1.27)
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.1.19
0≤1.21.6
LoF obs/exp: 41 / 39.3Missense obs/exp: 729 / 610.0Syn Z: -2.50

ClinVar Variant Classifications

1517 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic2
VUS296
Likely Benign91
Conflicting2
2
Likely Pathogenic
296
VUS
91
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
2
0
2
VUS
22
240
32
2
296
Likely Benign
0
0
23
68
91
Benign
0
0
0
0
0
Conflicting
—2
Total222405770391

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NLRP12 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Familial cold autoinflammatory syndrome 2

MIM #611762

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
AIP1 Regulates Ocular Angiogenesis Via NLRP12-ASC-Caspase-8 Inflammasome-Mediated Endothelial Pyroptosis.
Li Y et al.·Adv Sci (Weinh)
2024
The role of NLRP12 in inflammatory diseases.
Huang L et al.·Eur J Pharmacol
2023Review
Association Between Pathogenic Variants in NLRP12 and Autoinflammatory Disease: A Comprehensive Systematic Review.
Vatandoost N et al.·Int J Immunogenet
2025Review
NLRP12-associated systemic autoinflammatory diseases in children.
Wang HF·Pediatr Rheumatol Online J
2022Review
NLRP12-associated autoinflammatory disease in Chinese adult patients: a single-centre study.
Miao J et al.·RMD Open
2023Review
The clinical phenotype and genotype of NLRP12-autoinflammatory disease: a Chinese case series with literature review.
Wang W et al.·World J Pediatr
2020Review
NLRP12 interacts with NLRP3 to block the activation of the human NLRP3 inflammasome.
Coombs JR et al.·Sci Signal
2024
NLRP12 autoinflammatory disease: a Chinese case series and literature review.
Shen M et al.·Clin Rheumatol
2017Review
NLRP12 gene mutations and auto-inflammatory diseases: ever-changing evidence.
Del Porto F et al.·Rheumatology (Oxford)
2020Review
Novel Variant in the NLRP12 Gene: Insights From a Case Report and Systematic Review.
Bouramtane A et al.·Int J Immunogenet
2026Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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