NEXN
Chr 1ADARnexilin F-actin binding protein
Also known as: CDM2M, CMH20, NELIN
This gene encodes a filamentous actin-binding protein essential for maintaining Z line and sarcomere integrity in cardiac muscle and regulating cell migration through cytoskeletal interactions. Mutations cause dilated cardiomyopathy (both autosomal dominant and recessive forms) and hypertrophic cardiomyopathy. The gene shows both autosomal dominant and autosomal recessive inheritance patterns depending on the specific cardiomyopathy subtype.
Primary Disease Associations & Inheritance
Limited evidence — not for standalone diagnostic reporting
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports dominant-negative. 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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
500 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 | 10 | 0 | 18 | 0 | 28 |
Likely Pathogenic | 6 | 0 | 2 | 0 | 8 |
VUS | 22 | 238 | 26 | 4 | 290 |
Likely Benign | 0 | 6 | 37 | 89 | 132 |
Benign | 0 | 0 | 10 | 0 | 10 |
Conflicting | — | 18 | |||
| Total | 38 | 244 | 93 | 93 | 486 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NEXN · 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