NLRC3

Chr 16

NLR family CARD domain containing 3

Also known as: CLR16.2, NOD3

NCBI Gene: 197358ENSG00000167984UniProt: Q7RTR2

This gene encodes a NOD-like receptor family member. The encoded protein is a cytosolic regulator of innate immunity. This protein directly interacts with stimulator of interferon genes (STING), to prevent its proper trafficking, resulting in disruption of STING-dependent activation of the innate immune response. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

241
ClinVar variants
37
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NLRC3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
37 Pathogenic / Likely Pathogenic· 179 VUS of 241 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.
1.24LOEUF
pLI 0.000
Z-score 0.29
OE 0.95 (0.74–1.24)
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.
-0.49Z-score
OE missense 1.05 (0.99–1.12)
705 obs / 669.1 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.0.95 (0.74–1.24)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (0.99–1.12)
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.1.09
0≤1.21.6
LoF obs/exp: 39 / 41.0Missense obs/exp: 705 / 669.1Syn Z: -1.24

ClinVar Variant Classifications

241 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic1
VUS179
Likely Benign20
Benign5
36
Pathogenic
1
Likely Pathogenic
179
VUS
20
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
36
0
36
Likely Pathogenic
0
0
1
0
1
VUS
0
157
22
0
179
Likely Benign
0
17
0
3
20
Benign
0
3
1
1
5
Total0177604241

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

View in ClinVar →

Protein Context — Lollipop Plot

NLRC3 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Overview of the anti-inflammatory function of the innate immune sensor NLRC3.
Zhao Y et al.·Mol Immunol
2023Review
Mechanism and Application Prospects of NLRC3 Regulating cGAS-STING Pathway in Lung Cancer Immunotherapy.
Wang Q et al.·Int J Med Sci
2024Review
MicroRNA-19b exacerbates systemic sclerosis through promoting Th9 cells.
Lim YJ et al.·Cell Rep
2024
The correlation of NLRC3 expression with the progression and prognosis of hepatocellular carcinoma.
Ma YY et al.·Hum Pathol
2018
NLRC3 is a potential prognostic biomarker that is correlated with immune cell infiltration in lung adenocarcinoma.
Zhuo Y et al.·Sci Rep
2023
Role of NLRC3 in modulating inflammatory responses in neonates.
Zhang M et al.·BMC Pediatr
2025
Rare variants in IFFO1, DTNB, NLRC3 and SLC22A10 associate with Alzheimer's disease CSF profile of neuronal injury and inflammation.
Neumann A et al.·Mol Psychiatry
2022
T-cell hitchhiking nanodrug activates the cGAS-STING signaling pathway for enhanced cancer immunotherapy.
Chen Q et al.·Acta Biomater
2025
[Association of NLRC3 with prognosis and tumor immunity in patients with stage III colorectal cancer].
Wang D et al.·Zhong Nan Da Xue Xue Bao Yi Xue Ban
2019Cohort
The Green Walnut Husks Induces Apoptosis of Colorectal Cancer through Regulating NLRC3/PI3K Pathway.
Chen C et al.·Curr Pharm Des
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Association of NLRC3 gene polymorphism with Graves' disease susceptibility in a Southwest Chinese Han population.
Liang Z et al.·Hum Immunol
2026
Serum NLRC3 levels in systemic lupus erythematosus: correlation with clinical characteristics.
Li W et al.·Clin Exp Rheumatol
2025
Functional characterization of two Caspase-1 transcripts that associated with ASC and NLRC3 in apoptosis and inflammatory response in large yellow croaker Larimichthys crocea.
Hu QY et al.·Fish Shellfish Immunol
2025Functional
A panel incorporating genetic variants of RIN3, NLRC3, and SLX4 shows promise in predicting remission after tofacitinib therapy in rheumatoid arthritis patients.
Chen PK et al.·Clin Exp Rheumatol
2025Cohort
Pseudorabies virus DNA binding to porcine NLRC3 unleashes the activation of the porcine NLRP3 inflammasome.
Li M et al.·Vet Microbiol
2025
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