Human Gene Module / Chromosome 19 / SIN3B

SIN3BSIN3 transcription regulator family member B

SFARI Gene Score
2S
Strong Candidate, Syndromic Criteria 2.1, Syndromic
Autism Reports / Total Reports
5 / 7
Rare Variants / Common Variants
11 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
19p13.11
Associated Disorders
ADHD, ASD
Relevance to Autism

De novo missense variants in the SIN3B gene have been identified in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014) and the Autism Sequencing Consortium (Satterstrom et al., 2020), while an inherited protein-truncating variant in this gene was observed in an ASD proband from the iHART cohort (Ruzzo et al., 2019). Latypova et al., 2021 identified nine individuals with heterozygous SIN3B deletions or single-nucleotide variants who presented with a syndrome hallmarked by intellectual disability, developmental delay, and dysmorphic facial features with variably penetrant autism spectrum disorder, congenital malformations, corpus callosum defects, and impaired growth.

Molecular 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.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SIN3B (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
3 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
4 Recent Recommendation - Latypova X et al. (2021) No ASD, ADHD
5 Support - Krgovic D et al. (2022) Yes DD
6 Support - Cirnigliaro M et al. (2023) Yes -
7 Support - Marina Giovannetti et al. (2024) No -
Rare Variants   (11)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 33811806 Latypova X et al. (2021)
c.1747G>A p.Asp583Asn missense_variant De novo - - 35813072 Krgovic D et al. (2022)
c.575C>T p.Thr192Met missense_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.249C>G p.Ile83Met missense_variant De novo - Simplex 33811806 Latypova X et al. (2021)
c.1295C>T p.Ser432Leu missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.58G>A p.Gly20Arg missense_variant Unknown Not maternal - 33811806 Latypova X et al. (2021)
c.1266+335G>A - stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1266+335G>A - stop_gained Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1277G>A p.Trp426Ter stop_gained Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.31del p.Ser11AlafsTer11 frameshift_variant De novo - Multiplex 33811806 Latypova X et al. (2021)
c.1579del p.Leu527SerfsTer13 frameshift_variant Unknown - Unknown 33811806 Latypova X et al. (2021)
Common Variants  

No common variants reported.

SFARI Gene score
2S

Strong Candidate, Syndromic

Score Delta: Score remained at 2S

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2022
icon
2S

Increased from to 2S

Krishnan Probability Score

Score 0.50160173814731

Ranking 2016/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.99223940522256

Ranking 1698/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.94199832143219

Ranking 15141/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.39211174247627

Ranking 1542/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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