NSMCE3

Chr 15AR

NSE3 component of SMC5/6 complex

Also known as: HCA4, LICS, MAGEG1, MAGEL3, NDNL2, NSE3

NCBI Gene: 56160 ENSG00000185115 UniProt: Q96MG7 OMIM: 608243

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is part of the SMC5-6 chromatin reorganizing complex and is a member of the MAGE superfamily. This is an intronless gene. [provided by RefSeq, May 2011]

OMIM ResearchGenerating clinical summary…

ARLOEUF 1.041 OMIM phenotype

Clinical Summary— NSMCE3

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Gene-Disease Validity (ClinGen)

lung disease, immunodeficiency, and chromosome breakage syndrome; · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.06) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 85 VUS of 191 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.04LOEUF

pLI 0.056

Z-score 1.51

OE 0.40 (0.18–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.33Z-score

OE missense 1.07 (0.95–1.22)

174 obs / 162.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.40 (0.18–1.04)

0≤0.351.4

Missense OE?1.07 (0.95–1.22)

0≤0.61.4

Synonymous OE?1.35

0≤1.21.6

LoF obs/exp: 3 / 7.4Missense obs/exp: 174 / 162.0Syn Z: -2.32

ClinVar Variant Classifications

191 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS85

Likely Benign99

Benign5

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	0	1	0	0	1
VUS	4	79	2	0	85
Likely Benign	0	4	0	95	99
Benign	0	4	0	1	5
Total	4	89	2	96	191

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

View in ClinVar →

97 pathogenic / likely-pathogenic (of 149) ClinVar copy-number / structural variants overlap NSMCE3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →