SIN3B

protein-coding

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

Gene summary

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]

MANE transcript

NM_001297595.2

Inheritance

ClinVar variants

P:3U:238B:46

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr19:16,829,398-16,880,353

External References & Databases

Ensembl (ENSG00000127511)

Transcript & Mutation Effects

hg38 • Region Span ~51.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

syndromic intellectual disabilityLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0000508

Submitter: G2P

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

SIN3A-related intellectual disability syndrome due to a point mutationSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0044700

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SIN3B variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 175

not providedTotal: 119

SIN3B-related disorderTotal: 25

Neurodevelopmental disorderTotal: 3

SIN3B-related neurodevelopmental disorderTotal: 1

SIN3B-associated disorderTotal: 1

Congenital ocular colobomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001297595.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	35 clinvar		37
missense			227 clinvar	11 clinvar		238
nonsense		1 clinvar				1
start loss						0
frameshift	1 clinvar		4 clinvar			5
splice donor/acceptor (+/-2bp)	1 clinvar		5 clinvar			6
Total	2	1	238	46	0	287

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001297595.2	RefSeq	NP_001284524.1	19	MANE Select
ENST00000248054.10	Ensembl	ENSP00000248054.4	19	MANE Select
NM_001297597.2	RefSeq	NP_001284526.1	10	Standard
NM_015260.4	RefSeq	NP_056075.1	20	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
sin3b	Danio rerio	Structure: whole organism Quality: decreased behavioural activity abnormal

Gene / Model

Organism

Observed Phenotype

sin3b

Danio rerio

Structure: whole organism

Quality: decreased behavioural activity

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

NoRC negatively regulates rRNA expression
Negative epigenetic regulation of rRNA expression
Epigenetic regulation of gene expression
Gene expression (Transcription)
mets affect on macrophage differentiation

Biological Process

negative regulation of transcription by RNA polymerase II
histone deacetylation
regulation of lipid metabolic process

Molecular Function

chromatin binding
transcription corepressor activity
histone deacetylase activity
protein binding

Cellular Component

chromatin
X chromosome
Y chromosome
XY body
nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379803
Coding exons: 20
Length: 50954
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125748
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.87	454	752	0.603	0.0000525	7619
Missense (PolyPhen)		44	176.97	0.24863		1813
Synonymous	0.175	321	325	0.988	0.0000247	2253
Loss of Function	6.18	5	54.0	0.0927	0.00000240	629

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000096	0.000092	rare
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a transcriptional repressor. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Interacts with MAD-MAX heterodimers by binding to MAD. The heterodimer then represses transcription by tethering SIN3B to DNA. Also forms a complex with FOXK1 which represses transcription. With FOXK1, regulates cell cycle progression probably by repressing cell cycle inhibitor genes expression. {ECO:0000250|UniProtKB:Q62141}.;

Recessive Scores

pRec: 0.117

Intolerance Scores

LoFtool: 0.233
RVIS EVS: -1.37
RVIS percentile EVS: 4.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.944

Gene Damage Prediction

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