SIN3A

Chr 15AD

SIN3 transcription regulator family member A

Also known as: CHR15DELq24, DEL15Q24, WITKOS

NCBI Gene: 25942ENSG00000169375UniProt: Q96ST3

The protein encoded by this gene is a transcriptional regulatory protein. It contains paired amphipathic helix (PAH) domains, which are important for protein-protein interactions and may mediate repression by the Mad-Max complex. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Witteveen-Kolk syndromeMIM #613406
AD
840
ClinVar variants
17
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— SIN3A
⚡
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
17 Pathogenic / Likely Pathogenic· 105 VUS of 840 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.07LOEUF
pLI 1.000
Z-score 7.50
OE 0.01 (0.00–0.07)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
4.39Z-score
OE missense 0.54 (0.49–0.59)
386 obs / 717.0 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.0.01 (0.00–0.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.54 (0.49–0.59)
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.0.98
0≤1.21.6
LoF obs/exp: 1 / 67.4Missense obs/exp: 386 / 717.0Syn Z: 0.19

ClinVar Variant Classifications

840 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic7
VUS105
Likely Benign54
Benign1
Conflicting4
10
Pathogenic
7
Likely Pathogenic
105
VUS
54
Likely Benign
1
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
2
0
10
Likely Pathogenic
2
2
3
0
7
VUS
1
99
5
0
105
Likely Benign
0
3
17
34
54
Benign
0
0
1
0
1
Conflicting
—4
Total111042834181

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

View in ClinVar →

Protein Context — Lollipop Plot

SIN3A · protein map & ClinVar variants

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

Gene2Phenotype Curations

SIN3A-related syndromic intellectual disability

strong
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

Witteveen-Kolk syndrome

MIM #613406

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Understanding the role of ten-eleven translocation family proteins in kidney diseases.
Zhang Y et al.·Biochem Soc Trans
2024Review
Orphan nuclear receptor NR4A1 regulates transforming growth factor-β signaling and fibrosis.
Palumbo-Zerr K et al.·Nat Med
2015
Chromosome 15q24 microdeletion syndrome.
Magoulas PL et al.·Orphanet J Rare Dis
2012Review
SIN3A Defects Associated with Syndromic Congenital Hypogonadotropic Hypogonadism: An Overlap with Witteveen-Kolk Syndrome.
Schnöll C et al.·Neuroendocrinology
2023
Emerging Roles of Epigenetic Regulator Sin3 in Cancer.
Bansal N et al.·Adv Cancer Res
2016Review
Suppressors of Break-Induced Replication in Human Cells.
Rider SD Jr et al.·Genes (Basel)
2023
Systems biomarkers for papillary thyroid cancer prognosis and treatment through multi-omics networks.
Gulfidan G et al.·Arch Biochem Biophys
2022Meta-analysis
MeCP2 phosphorylation in the brain: from transcription to behavior.
Damen D et al.·Biol Chem
2013Review
Epigenetic landscape of amphetamine and methamphetamine addiction in rodents.
Godino A et al.·Epigenetics
2015Review
A Series of Patients with Genodermatoses in a Reference Service for Rare Diseases: Results from the Brazilian Rare Genomes Project.
Steiner CE et al.·Genes (Basel)
2025Cohort
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
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools