NSMCE2

Chr 8AR

NSE2 SUMO ligase component of SMC5/6 complex

Also known as: C8orf36, MMS21, NSE2, ZMIZ7

NCBI Gene: 286053ENSG00000156831UniProt: Q96MF7OMIM: 617246

The protein functions as an E3 SUMO ligase within the SMC5-SMC6 complex, mediating DNA double-strand break repair by homologous recombination, telomere maintenance, and sister chromatid cohesion during mitosis. Biallelic mutations cause Seckel syndrome 10, characterized by primordial dwarfism and extreme insulin resistance with prenatal onset. This follows autosomal recessive inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.861 OMIM phenotype
Clinical Summary— NSMCE2
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Gene-Disease Validity (ClinGen)
Seckel syndrome 10 · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.038
Z-score 1.88
OE 0.38 (0.18–0.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.82Z-score
OE missense 0.80 (0.69–0.94)
109 obs / 135.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.18–0.86)
0≤0.351.4
Missense OE0.80 (0.69–0.94)
0≤0.61.4
Synonymous OE1.07
0≤1.21.6
LoF obs/exp: 4 / 10.6Missense obs/exp: 109 / 135.7Syn Z: -0.36

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

NSMCE2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients