NSMCE3
Chr 15ARNSE3 component of SMC5/6 complex
Also known as: HCA4, LICS, MAGEG1, MAGEL3, NDNL2, NSE3
The protein is a component of the SMC5-SMC6 complex that repairs DNA double-strand breaks through homologous recombination and maintains telomeres. Mutations cause lung disease, immunodeficiency, and chromosome breakage syndrome with autosomal recessive inheritance. This syndrome affects multiple organ systems including the respiratory and immune systems, with the underlying chromosome instability reflecting the protein's critical role in DNA repair.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
ClinVar Variant Classifications
339 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 | 1 | 91 | 0 | 92 |
Likely Pathogenic | 0 | 1 | 5 | 0 | 6 |
VUS | 4 | 79 | 46 | 0 | 129 |
Likely Benign | 0 | 4 | 5 | 95 | 104 |
Benign | 0 | 4 | 1 | 1 | 6 |
Conflicting | — | 1 | |||
| Total | 4 | 89 | 148 | 96 | 338 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NSMCE3 · 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 →No open access results found
External Resources
Links to major genomics databases and tools