NSMCE2

Chr 8AR

NSE2 SUMO ligase component of SMC5/6 complex

Also known as: C8orf36, MMS21, NSE2, ZMIZ7

NCBI Gene: 286053ENSG00000156831UniProt: Q96MF7

This gene encodes a member of a family of E3 small ubiquitin-related modifier (SUMO) ligases that mediates the attachment of a SUMO protein to proteins involved in nuclear transport, transcription, chromosome segregation and DNA repair. The encoded protein is part of the structural maintenance of chromosomes (SMC) 5/6 complex which plays a key role genome maintenance, facilitating chromosome segregation and suppressing mitotic recombination. A knockout of the orthologous mouse gene is lethal prior to embryonic day 10.5. Naturally occurring mutations in this gene, that abolish the SUMO ligase activity, are associated with primordial dwarfism and extreme insulin resistance. [provided by RefSeq, Mar 2017]

Primary Disease Associations & Inheritance

Seckel syndrome 10MIM #617253
AR
0
Active trials
63
Pathogenic / LP
177
ClinVar variants
5
Pubs (1 yr)
0.8
Missense Z
0.86
LOEUF
Clinical Summary— NSMCE2
🧬
Gene-Disease Validity (ClinGen)
Seckel syndrome 10 · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
63 Pathogenic / Likely Pathogenic· 62 VUS of 177 total submissions

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

177 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic1
VUS62
Likely Benign48
Benign3
Conflicting1
62
Pathogenic
1
Likely Pathogenic
62
VUS
48
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
58
0
62
Likely Pathogenic
1
0
0
0
1
VUS
0
45
17
0
62
Likely Benign
0
6
19
23
48
Benign
0
1
2
0
3
Conflicting
—1
Total5529623177

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

View in ClinVar →

NSMCE2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
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