SIN3A

SIN3 transcription regulator family member A, the group of SIN3 histone deacetylase complex subunits|EMSY complex

Basic information

Region (hg38): 15:75369378-75455842

Links

ENSG00000169375 ∙ NCBI:25942 ∙ OMIM:607776 ∙ HGNC:19353 ∙ Uniprot:Q96ST3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism, susceptibility to, 15 (Strong), mode of inheritance: AD
• chromosome 15q24 deletion syndrome (Strong), mode of inheritance: AD
• SIN3A-related intellectual disability syndrome due to a point mutation (Supportive), mode of inheritance: AD
• congenital diaphragmatic hernia (Limited), mode of inheritance: AD
• chromosome 15q24 deletion syndrome (Strong), mode of inheritance: AD
• SIN3A-related intellectual disability syndrome (Definitive), mode of inheritance: AD
• SIN3A-related intellectual disability syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Witteveen-Kolk syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	27399968

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SIN3A gene.

• not provided (293 variants)
• SIN3A-related intellectual disability syndrome due to a point mutation (51 variants)
• Inborn genetic diseases (34 variants)
• not specified (9 variants)
• SIN3A-related intellectual disability syndrome (4 variants)
• See cases (4 variants)
• SIN3A-related condition (3 variants)
• Autism;Intellectual disability (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIN3A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	79	8	91
missense		6	150	8	1	165
nonsense	14	6	1			21
start loss						0
frameshift	19	7	1			27
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)	2	5				7
splice region		2	5	11	5	23
non coding	1		2	18	7	28
Total	36	25	161	105	16

Variants in SIN3A

This is a list of pathogenic ClinVar variants found in the SIN3A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-75371996-C-T			Uncertain significance (Jun 03, 2023)
15-75372002-C-T			Uncertain significance (Jul 01, 2022)
15-75372007-T-C			Uncertain significance (Nov 30, 2022)
15-75372009-GACACGAT-G		SIN3A-related intellectual disability syndrome due to a point mutation	Likely pathogenic (Oct 04, 2022)
15-75372042-G-C			Likely benign (Oct 22, 2023)
15-75372063-G-A			Likely benign (Dec 06, 2023)
15-75372066-A-G			Likely benign (Oct 14, 2022)
15-75372068-A-G			Uncertain significance (Sep 01, 2022)
15-75372085-A-G			Uncertain significance (Apr 24, 2022)
15-75372099-G-A			Likely benign (May 01, 2022)
15-75372120-T-C			Likely benign (Oct 03, 2023)
15-75372130-C-T			Uncertain significance (Aug 22, 2022)
15-75372131-G-A			Conflicting classifications of pathogenicity (Jan 15, 2024)
15-75372132-G-C			Likely benign (Mar 06, 2018)
15-75372148-G-C		SIN3A-related intellectual disability syndrome due to a point mutation	Uncertain significance (Mar 24, 2022)
15-75372158-C-T			Uncertain significance (Dec 28, 2023)
15-75372160-AC-A			Uncertain significance (Jan 05, 2018)
15-75372161-C-T		SIN3A-related intellectual disability syndrome due to a point mutation	Uncertain significance (Jan 12, 2021)
15-75372162-C-G		Inborn genetic diseases	Uncertain significance (Sep 29, 2023)
15-75372165-G-A			Benign (Jul 16, 2023)
15-75372177-C-G		Inborn genetic diseases	Uncertain significance (Aug 26, 2022)
15-75372181-T-C		SIN3A-related intellectual disability syndrome due to a point mutation	Uncertain significance (Mar 19, 2021)
15-75372187-C-T		SIN3A-related intellectual disability syndrome due to a point mutation	Uncertain significance (Jul 29, 2021)
15-75372199-C-T			Uncertain significance (Oct 03, 2023)
15-75372218-CAG-C			Likely benign (Jan 19, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SIN3A	protein_coding	protein_coding	ENST00000394947	20	86464

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.04e-10	125744	0	3	125747	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.39	386	717	0.538	0.0000403	8373
Missense in Polyphen		61	239.21	0.25501		2972
Synonymous	0.193	262	266	0.985	0.0000144	2446
Loss of Function	7.50	1	67.4	0.0148	0.00000379	738

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a transcriptional repressor. Corepressor for REST. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Also interacts with MXD1-MAX heterodimers to repress transcription by tethering SIN3A to DNA. Acts cooperatively with OGT to repress transcription in parallel with histone deacetylation. Involved in he control of the circadian rhythms. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation. Cooperates with FOXK1 to regulate cell cycle progression probably by repressing cell cycle inhibitor genes expression (By similarity). {ECO:0000250|UniProtKB:Q60520, ECO:0000269|PubMed:12150998}.
• Pathway: Huntington,s disease - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Androgen receptor signaling pathway;Retinoblastoma (RB) in Cancer;MECP2 and Associated Rett Syndrome;TGF-beta Signaling Pathway;Hedgehog Signaling Pathway;NoRC negatively regulates rRNA expression;Negative epigenetic regulation of rRNA expression;Epigenetic regulation of gene expression;Gene expression (Transcription);mets affect on macrophage differentiation;Generic Transcription Pathway;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Metabolism of lipids;Factors involved in megakaryocyte development and platelet production;RNA Polymerase II Transcription;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;Metabolism;AndrogenReceptor;Hemostasis;C-MYB transcription factor network;Transcriptional regulation by RUNX1;Regulation of Telomerase;Signaling events mediated by HDAC Class I;Hedgehog signaling events mediated by Gli proteins;Regulation of nuclear SMAD2/3 signaling (Consensus)

Recessive Scores

• pRec: 0.372

Intolerance Scores

• rvis_EVS: -1.39
• rvis_percentile_EVS: 4.27

Haploinsufficiency Scores

• pHI: 0.925
• hipred: Y
• hipred_score: 0.786
• ghis: 0.620

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sin3a
• Phenotype: normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;in utero embryonic development;activation of innate immune response;positive regulation of defense response to virus by host;hematopoietic progenitor cell differentiation;DNA replication;protein deacetylation;aging;regulation of hormone levels;positive regulation of G2/M transition of mitotic cell cycle;histone deacetylation;regulation of lipid metabolic process;positive regulation of chromatin silencing;cellular protein localization;negative regulation of circadian rhythm;negative regulation of apoptotic process;regulation of transcription from RNA polymerase II promoter in response to oxidative stress;regulation of megakaryocyte differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;rhythmic process;response to methylglyoxal;cellular response to glucose stimulus;negative regulation of protein localization to nucleus;negative regulation of histone H3-K27 acetylation;cellular response to dopamine;negative regulation of transcription regulatory region DNA binding
• Cellular component: kinetochore;chromatin;nucleus;nucleoplasm;transcription factor complex;nucleolus;Sin3 complex;transcriptional repressor complex
• Molecular function: transcription regulatory region sequence-specific DNA binding;RNA polymerase II activating transcription factor binding;RNA polymerase II repressing transcription factor binding;chromatin binding;DNA-binding transcription factor activity;transcription corepressor activity;RNA binding;histone deacetylase activity;protein binding;protein deacetylase activity;protein-containing complex binding