SIN3A: Transcriptional Regulatory Hub in Development and Disease
A comprehensive biomedical overview of the SIN3A gene, its protein product, associated diseases, expression, mutations, and functional classification.
Gene Information Card
| Symbol | SIN3A |
|---|---|
| Full Name | SIN3 transcription regulator family member A |
| Gene Type | protein-coding |
| Chromosomal Location | 15q24.2 |
| NCBI Gene ID | 25942 ncbi.nlm.nih.gov/gene/25942 |
| Ensembl ID | ENSG00000169375 |
| UniProt ID | Q96ST3 |
| OMIM ID | 607776 |
| HGNC ID | 10853 |
| Aliases | SIN3, SIN3A, SIN3B, KIAA0700, DKFZp686B24102 |
Description
SIN3A encodes a transcriptional regulatory protein that serves as a scaffold for the SIN3/HDAC (histone deacetylase) complex. This complex represses gene expression by deacetylating histones and recruiting other chromatin-modifying enzymes. SIN3A is involved in diverse processes including cell cycle control, differentiation, and development. It is ubiquitously expressed and plays critical roles in both normal physiology and disease, particularly in cancer and neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Witteveen-Kolk syndrome (WITKOS) | Loss-of-function mutations in SIN3A lead to haploinsufficiency, disrupting transcriptional repression and causing neurodevelopmental abnormalities. | OMIM #613406 |
| Intellectual disability | De novo SIN3A mutations are associated with intellectual disability, often with autism spectrum disorder features. | ClinVar, PMID: 27573165 |
| Cancer (various) | SIN3A acts as a tumor suppressor in some contexts (e.g., breast, lung) by repressing oncogenes; loss of function promotes proliferation. | COSMIC, PMID: 23382219 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Heart | 8.2 | Medium |
| Liver | 6.1 | Medium |
| Kidney | 7.8 | Medium |
| Testis | 15.3 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | High expression |
| HeLa | 11.5 | High expression |
| K562 | 9.8 | Medium expression |
| MCF7 | 10.1 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2083C>T (p.Arg695*) | Nonsense | Rare | Loss of function; truncation of SIN3A protein |
| c.1124_1125del (p.Glu375Glyfs*12) | Frameshift | Rare | Loss of function; premature stop codon |
| c.2560G>A (p.Gly854Arg) | Missense | Rare | Likely loss of function; disrupts protein interaction |
Mutation functional classification
Loss of Function (LOF)
Most SIN3A disease-associated mutations are loss-of-function, leading to haploinsufficiency or dominant-negative effects.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in SIN3A.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner by disrupting complex assembly.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Notch signaling pathway (KEGG: hsa04330)
• Transcriptional misregulation in cancer (KEGG: hsa05202)
• Chromatin modifying enzymes (Reactome: R-HSA-3247509)
Protein Summary
SIN3A is a 1273-amino-acid protein that functions as a scaffold for the SIN3/HDAC complex. It contains paired amphipathic helix (PAH) domains that mediate protein-protein interactions, and a histone deacetylase interaction domain (HID). SIN3A does not directly bind DNA but is recruited to promoters via transcription factors. It represses transcription by deacetylating histones, leading to chromatin compaction. The protein is widely expressed and essential for development.
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