NSMCE3

Chr 15

NSE3 component of SMC5/6 complex

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

NCBI Gene: 56160ENSG00000185115UniProt: Q96MG7

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]

Primary Disease Associations & Inheritance

UniProtLung disease, immunodeficiency, and chromosome breakage syndrome
338
ClinVar variants
98
Pathogenic / LP
0.06
pLI score
0
Active trials
Clinical Summary— NSMCE3
🧬
Gene-Disease Validity (ClinGen)
lung disease, immunodeficiency, and chromosome breakage syndrome; · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.06) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
98 Pathogenic / Likely Pathogenic· 129 VUS of 338 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.33Z-score
OE missense 1.07 (0.95–1.22)
174 obs / 162.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.40 (0.18–1.04)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.07 (0.95–1.22)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.35
0≤1.21.6
LoF obs/exp: 3 / 7.4Missense obs/exp: 174 / 162.0Syn Z: -2.32

ClinVar Variant Classifications

338 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic92
Likely Pathogenic6
VUS129
Likely Benign104
Benign6
Conflicting1
92
Pathogenic
6
Likely Pathogenic
129
VUS
104
Likely Benign
6
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
91
0
92
Likely Pathogenic
0
1
5
0
6
VUS
3
77
49
0
129
Likely Benign
0
4
5
95
104
Benign
0
4
1
1
6
Conflicting
—1
Total38715196338

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.

Gene2Phenotype Curations

NSMCE3-related distinct DNA breakage syndrome

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools