RIPK2
Chr 8receptor interacting serine/threonine kinase 2
Also known as: CARD3, CARDIAK, CCK, GIG30, RICK, RIP2
This gene encodes a serine/threonine protein kinase that serves as a key effector in NOD1 and NOD2 innate immune signaling pathways, functioning as a scaffolding protein that activates NF-kappa-B transcription and immune responses to bacterial peptidoglycans. Mutations cause early-onset inflammatory bowel disease and immunodeficiency, following an autosomal recessive inheritance pattern. The gene shows high constraint against loss-of-function variants (LOEUF 0.441), indicating that complete loss of protein function is likely deleterious.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
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
117 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 | 33 | 0 | 33 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 46 | 8 | 0 | 54 |
Likely Benign | 0 | 4 | 0 | 1 | 5 |
Benign | 0 | 1 | 2 | 1 | 4 |
| Total | 0 | 51 | 43 | 2 | 96 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RIPK2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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