Human Gene Module / Chromosome 14 / SUPT16H

SUPT16HSPT16 homolog, facilitates chromatin remodeling subunit

SFARI Gene Score
2S
Strong Candidate, Syndromic Criteria 2.1, Syndromic
Autism Reports / Total Reports
2 / 7
Rare Variants / Common Variants
7 / 0
Aliases
SUPT16H, CDC68,  FACTP140,  SPT16,  SPT16/CDC68
Associated Syndromes
-
Chromosome Band
14q11.2
Associated Disorders
ASD
Relevance to Autism

A de novo missense variant that was predicted to be damaging was identifed in the SUPT16H gene in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. Bina et al., 2020 identified five individuals with de novo variants affecting the SUPT16H gene, all of whom presenting with gross motor delay, delayed or absent speech, and cognitive delay/intellectual disability; two of the five individuals from this study also presented with autistic features. Microdeletions and microduplications involving the CHD8 and SUPT16H genes have also been observed in patients presenting with a spectrum of neurodevelopmental phenotypes, including ASD/autistic features (Drabova et al., 2015; Smyk et al., 2016; Yasin et al., 2019; Smol et al., 2020).

Molecular Function

The SUPT16H gene encodes for a component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II.

SFARI Genomic Platforms
Reports related to SUPT16H (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 Long term follow-up in a patient with a de novo microdeletion of 14q11.2 involving CHD8 Drabova J , et al. (2015) No -
3 Support Novel 14q11.2 microduplication including the CHD8 and SUPT16H genes associated with developmental delay Smyk M , et al. (2016) No -
4 Support A distinct neurodevelopmental syndrome with intellectual disability, autism spectrum disorder, characteristic facies, and macrocephaly is caused by defects in CHD8 Yasin H , et al. (2019) No -
5 Support Neurodevelopmental phenotype associated with CHD8-SUPT16H duplication Smol T , et al. (2019) No -
6 Recent recommendation De novo variants in SUPT16H cause neurodevelopmental disorders associated with corpus callosum abnormalities Bina R , et al. (2020) No Autistic features
7 Support - Mahjani B et al. (2021) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo NA - 31924697 Bina R , et al. (2020)
c.484A>G p.Ile162Val missense_variant De novo NA - 31924697 Bina R , et al. (2020)
c.977A>G p.Tyr326Cys missense_variant Unknown - - 34615535 Mahjani B et al. (2021)
c.1295T>C p.Leu432Pro missense_variant De novo NA - 31924697 Bina R , et al. (2020)
c.1907A>G p.Glu636Gly missense_variant De novo NA - 31924697 Bina R , et al. (2020)
c.2200C>T p.Arg734Trp missense_variant De novo NA - 31924697 Bina R , et al. (2020)
c.2078G>A p.Arg693Gln missense_variant De novo NA Simplex 25363768 Iossifov I et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2S

Strong Candidate, Syndromic

Score Delta: Score remained at 2S

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.

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 0.44702595918186

Ranking 14196/25841 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.
ExAC Score

Score 0.99999960566968

Ranking 252/18225 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
Sanders TADA Score

Score 0.6296690160017

Ranking 814/18665 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).
Zhang D Score

Score 0.31921270044451

Ranking 2451/20870 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.
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