SIN3B

Chr 19

SIN3 transcription regulator family member B

NCBI Gene: 23309ENSG00000127511UniProt: O75182

Predicted to enable transcription corepressor activity. Predicted to be involved in cardiac muscle tissue development; negative regulation of transcription by RNA polymerase II; and skeletal muscle tissue development. Predicted to be located in nucleus. Predicted to be part of Sin3-type complex. Predicted to be active in chromatin. [provided by Alliance of Genome Resources, Jul 2025]

287
ClinVar variants
11
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SIN3B
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 234 VUS of 287 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.20LOEUF
pLI 1.000
Z-score 6.18
OE 0.09 (0.05–0.20)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
3.87Z-score
OE missense 0.60 (0.56–0.65)
454 obs / 752.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.09 (0.05–0.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.60 (0.56–0.65)
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.0.99
0≤1.21.6
LoF obs/exp: 5 / 54.0Missense obs/exp: 454 / 752.4Syn Z: 0.18

ClinVar Variant Classifications

287 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic2
VUS234
Likely Benign36
Benign3
Conflicting3
9
Pathogenic
2
Likely Pathogenic
234
VUS
36
Likely Benign
3
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
8
0
9
Likely Pathogenic
0
0
2
0
2
VUS
5
219
10
0
234
Likely Benign
0
8
6
22
36
Benign
0
0
1
2
3
Conflicting
—3
Total62272724287

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

View in ClinVar →

Protein Context — Lollipop Plot

SIN3B · protein map & ClinVar variants

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

Gene2Phenotype Curations

SIN3B-related syndromic intellectual disability and autism spectrum disorder

limited
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The potential of targeting Sin3B and its associated complexes for cancer therapy.
Cantor DJ et al.·Expert Opin Ther Targets
2017Review
Myt1l safeguards neuronal identity by actively repressing many non-neuronal fates.
Mall M et al.·Nature
2017
miR-96-5p expression is sufficient to induce and maintain the senescent cell fate in the absence of stress.
Santiago FE et al.·Proc Natl Acad Sci U S A
2024
Emerging Roles of Epigenetic Regulator Sin3 in Cancer.
Bansal N et al.·Adv Cancer Res
2016Review
Haploinsufficiency of the Sin3/HDAC corepressor complex member SIN3B causes a syndromic intellectual disability/autism spectrum disorder.
Latypova X et al.·Am J Hum Genet
2021
Interaction between the transcriptional corepressor Sin3B and voltage-gated sodium channels modulates functional channel expression.
Vega AV et al.·Sci Rep
2013Functional
Differential Complex Formation via Paralogs in the Human Sin3 Protein Interaction Network.
Adams MK et al.·Mol Cell Proteomics
2020
High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing.
Martínez F et al.·J Med Genet
2017
A homozygous RNF220 mutation leads to male infertility with small-headed sperm.
Jiang X et al.·Gene
2019Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Intragenic loss-of-function variants in transcription factors MAZ, FOXP1 and SIN3B in colobomatous microphthalmia.
Seese SE et al.·J Med Genet
2026
Knockout of SIN3B modulates transcriptional programs and cell survival in cutaneous melanoma.
Alcantara Sekimoto Matsuyama LS et al.·Pharmacol Res
2025
SIN3B Loss Heats up Cold Tumor Microenvironment to Boost Immunotherapy in Pancreatic Cancer.
Zhang Z et al.·Adv Sci (Weinh)
2024🔓 Open Access
Chromatin accessibility and cell cycle progression are controlled by the HDAC-associated Sin3B protein in murine hematopoietic stem cells.
Calderon A et al.·Epigenetics Chromatin
2024🔓 Open Access
Chromatin-Associated SIN3B Protects Cancer Cells from Genotoxic Stress-Induced Apoptosis and Dictates DNA Damage Repair Pathway Choice.
Morales-Valencia J et al.·Mol Cancer Res
2023
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