Human Gene Module / Chromosome 7 / TAF6

TAF6TATA-box binding protein associated factor 6

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
7 / 7
Rare Variants / Common Variants
12 / 0
Aliases
TAF6, ALYUS,  MGC:8964,  TAF(II)70,  TAF(II)80,  TAF2E,  TAFII-70,  TAFII-80,  TAFII70,  TAFII80,  TAFII85
Associated Syndromes
-
Chromosome Band
7q22.1
Associated Disorders
-
Relevance to Autism

Two de novo missense variants in the TAF6 gene had previously been identified in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014). Two additional de novo missense variants in this gene were identified by whole genome sequencing in two ASD probands as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of four de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), TAF6 was determined to be an ASD candidate gene in Yuen et al., 2017.

Molecular Function

Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. The TAF6 gene encodes one of the smaller subunits of TFIID that binds weakly to TBP but strongly to TAF1, the largest subunit of TFIID.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to TAF6 (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 Recent Recommendation Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
3 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
4 Support - Zhou X et al. (2022) Yes -
5 Support - Yuan B et al. (2023) Yes -
6 Support - Wang J et al. (2023) Yes -
7 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (12)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.49G>C p.Glu17Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.260A>G p.Asp87Gly missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.565G>A p.Ala189Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1343G>A p.Arg448Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.796G>T p.Glu266Ter missense_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.323T>C p.Ile108Thr missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.439A>G p.Lys147Glu missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.420_421insAGGG p.Leu141GlyfsTer6 frameshift_variant De novo - - 36881370 Yuan B et al. (2023)
c.52+2T>C - splice_site_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.248_249insACCG p.Leu84ProfsTer6 frameshift_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.260A>G;c.371A>G p.His87Arg;p.His124Arg missense_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.907G>T p.Gly303Trp missense_variant De novo - Multiplex (monozygotic twins) 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two de novo missense variants in the TAF6 gene had previously been identified in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014). Two additional de novo missense variants in this gene were identified by whole genome sequencing in two ASD probands as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of four de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), TAF6 was determined to be an ASD candidate gene in Yuen et al., 2017.

Score Delta: Score remained at 2

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Two de novo missense variants in the TAF6 gene had previously been identified in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014). Two additional de novo missense variants in this gene were identified by whole genome sequencing in two ASD probands as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of four de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), TAF6 was determined to be an ASD candidate gene in Yuen et al., 2017.

Reports Added
[New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

Two de novo missense variants in the TAF6 gene had previously been identified in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014). Two additional de novo missense variants in this gene were identified by whole genome sequencing in two ASD probands as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of four de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), TAF6 was determined to be an ASD candidate gene in Yuen et al., 2017.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
4/1/2017
icon
3

Increased from to 3

Description

Two de novo missense variants in the TAF6 gene had previously been identified in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014). Two additional de novo missense variants in this gene were identified by whole genome sequencing in two ASD probands as part of the MSSNG initiative in Yuen et al., 2017. Based on the discovery of four de novo missense variants in ASD cases, a z-score > 2.0 for missense mutations, and a higher-than expected mutation rate (a false discovery rate < 15%), TAF6 was determined to be an ASD candidate gene in Yuen et al., 2017.

Krishnan Probability Score

Score 0.49149013265148

Ranking 5503/25841 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 0.0006741652166016

Ranking 12038/18225 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 0.79546859395929

Ranking 2132/18665 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 -0.063541313793689

Ranking 10919/20870 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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