SMC1B

Chr 22

structural maintenance of chromosomes 1B

Also known as: SMC1BETA, SMC1L2

NCBI Gene: 27127ENSG00000077935UniProt: Q8NDV3

SMC1L2 belongs to a family of proteins required for chromatid cohesion and DNA recombination during meiosis and mitosis (3:Revenkova et al., 2001 [PubMed 11564881]).[supplied by OMIM, Mar 2008]

239
ClinVar variants
70
Pathogenic / LP
0.10
pLI score
0
Active trials
Clinical Summary— SMC1B
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
70 Pathogenic / Likely Pathogenic· 135 VUS of 239 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.36LOEUF
pLI 0.104
Z-score 5.92
OE 0.24 (0.16–0.36)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.95Z-score
OE missense 0.78 (0.72–0.84)
486 obs / 622.6 exp
Tolerant

Mild missense constraint

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.0.24 (0.16–0.36)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.72–0.84)
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.0.92
0≤1.21.6
LoF obs/exp: 17 / 70.8Missense obs/exp: 486 / 622.6Syn Z: 0.97

ClinVar Variant Classifications

239 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic68
Likely Pathogenic2
VUS135
Likely Benign10
Benign7
68
Pathogenic
2
Likely Pathogenic
135
VUS
10
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
68
0
68
Likely Pathogenic
0
1
1
0
2
VUS
0
131
4
0
135
Likely Benign
0
5
1
4
10
Benign
0
2
2
3
7
Total0139767222

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

View in ClinVar →

Protein Context — Lollipop Plot

SMC1B · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
RNA immunoprecipitation identifies novel targets of DAZL in human foetal ovary.
Rosario R et al.·Mol Hum Reprod
2017
Identification of an SMC1B Mutation Associated With Necrozoospermia and Failure of Testi-ICSI : SMC1B Mutation Associated With Necrozoospermia.
Zhao G et al.·Reprod Sci
2025Case report
Novel 2 Gene Signatures Associated With Breast Cancer Proliferation: Insights From Predictive Differential Gene Expression Analysis.
Ibrahim A et al.·Mod Pathol
2024
Ectopic expression of meiotic cohesin generates chromosome instability in cancer cell line.
Boukaba A et al.·Proc Natl Acad Sci U S A
2022
Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy.
Balbás-Martínez C et al.·Nat Genet
2013
A let-7 microRNA polymorphism in the KRAS 3'-UTR is prognostic in oropharyngeal cancer.
De Ruyck K et al.·Cancer Epidemiol
2014
Identification of potential prognostic biomarkers in vulval squamous cell carcinoma based on human papillomavirus infection Status-Analysis of GSE183454.
Xi R et al.·J Obstet Gynaecol
2023
Carob extract induces spermatogenesis in an infertile mouse model via upregulation of Prm1, Plzf, Bcl-6b, Dazl, Ngn3, Stra8, and Smc1b.
Ghorbaninejad Z et al.·J Ethnopharmacol
2023Functional
A novel non-invasive mRNA-lncRNA biomarker panel for accurate prediction of cervical squamous cell carcinoma and adenocarcinoma.
Cen Y et al.·J Gynecol Oncol
2025
MicroRNA-related genetic variations as predictors for risk of second primary tumor and/or recurrence in patients with early-stage head and neck cancer.
Zhang X et al.·Carcinogenesis
2010Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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