NINJ1
Chr 9ninjurin 1
Also known as: NIN1, NINJURIN, hNINJ1
The ninjurin protein mediates plasma membrane rupture during programmed cell death pathways including pyroptosis and necroptosis, and functions as a homophilic adhesion molecule that promotes neurite outgrowth and nerve regeneration. Gain-of-function mutations in NINJ1 cause a dominant neuroinflammatory disorder characterized by recurrent episodes of sterile inflammation affecting the nervous system. The pathogenic mechanism involves excessive plasma membrane rupture leading to release of damage-associated molecular patterns that propagate inflammatory responses.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
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
57 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 | 26 | 0 | 26 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 20 | 3 | 0 | 23 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 20 | 32 | 0 | 52 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NINJ1 · 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