SIN3A
Chr 15ADSIN3 transcription regulator family member A
Also known as: CHR15DELq24, DEL15Q24, WITKOS
The protein is a transcriptional regulatory protein that mediates gene repression through protein-protein interactions via its paired amphipathic helix domains, including interactions with the Mad-Max transcriptional repressor complex. Loss-of-function mutations cause Witteveen-Kolk syndrome, an autosomal dominant neurodevelopmental disorder. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the disease mechanism.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
300 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 15 | 0 | 1 | 0 | 16 |
Likely Pathogenic | 6 | 1 | 1 | 0 | 8 |
VUS | 1 | 144 | 10 | 0 | 155 |
Likely Benign | 0 | 4 | 26 | 57 | 87 |
Benign | 0 | 1 | 5 | 3 | 9 |
Conflicting | — | 6 | |||
| Total | 22 | 150 | 43 | 60 | 281 |
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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools