NSMCE1

Chr 16

NSE1 component of SMC5/6 complex

Also known as: NSE1

NCBI Gene: 197370 ENSG00000169189 UniProt: Q8WV22 OMIM: 617263

NSMCE1 encodes a RING-type E3 ubiquitin ligase that functions within the SMC5-SMC6 complex to maintain genome integrity through DNA damage response and homologous recombination-mediated DNA repair. Mutations cause an autosomal recessive primary immunodeficiency characterized by growth retardation, developmental delay, facial dysmorphism, and increased susceptibility to infections. The gene shows tolerance to loss-of-function variants (pLI 0.00002, LOEUF 1.178), consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Enables protein dimerization activity and ubiquitin protein ligase activity. Involved in DNA damage response. Located in nucleoplasm. Part of Smc5-Smc6 complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 1.18

Clinical Summary— NSMCE1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

36 VUS of 45 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?

1.18LOEUF

pLI 0.000

Z-score 1.10

OE 0.68 (0.41–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.56Z-score

OE missense 0.88 (0.76–1.01)

141 obs / 160.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.41–1.18)

0≤0.351.4

Missense OE?0.88 (0.76–1.01)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 9 / 13.3Missense obs/exp: 141 / 160.9Syn Z: 0.02

ClinVar Variant Classifications

45 submitted variants in ClinVar

ClinVar

Classification Summary

VUS36

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	36	0	36
Likely Benign	2	1	3
Benign	0	0	0
Total	38	1	39

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

View in ClinVar →

31 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap NSMCE1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →