Human Gene Module / Chromosome 10 / BTAF1

BTAF1RNA polymerase II, B-TFIID transcription factor-associated, 170kDa (Mot1 homolog, S. cerevisiae)

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
9 / 9
Rare Variants / Common Variants
15 / 0
Aliases
BTAF1, MOT1,  TAF(II)170,  TAF172,  TAFII170
Associated Syndromes
-
Chromosome Band
10q23.32
Associated Disorders
ASD
Relevance to Autism

A rare duplication in the BTAF1 gene has been identified with ASD (Salyakina et al., 2011).

Molecular Function

This gene encodes a TAF (TATA box-binding protein-associated factor), which associates with TBP (TATA box-binding protein) to form the B-TFIID complex that is required for transcription initiation of genes by RNA polymerase II. This TAF has DNA-dependent ATPase activity, which drives the dissociation of TBP from DNA, freeing the TBP to associate with other TATA boxes or TATA-less promoters.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to BTAF1 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Copy number variants in extended autism spectrum disorder families reveal candidates potentially involved in autism risk Salyakina D , et al. (2011) Yes AS
2 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Support Whole exome sequencing in females with autism implicates novel and candidate genes Butler MG , et al. (2015) Yes -
4 Recent Recommendation Low load for disruptive mutations in autism genes and their biased transmission Iossifov I , et al. (2015) Yes -
5 Support A Statistical Framework for Mapping Risk Genes from De Novo Mutations in Whole-Genome-Sequencing Studies Liu Y , et al. (2018) Yes -
6 Support Recessive gene disruptions in autism spectrum disorder Doan RN , et al. (2019) Yes -
7 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
8 Support - Zhou X et al. (2022) Yes -
9 Support - Wang J et al. (2023) Yes -
Rare Variants   (15)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - splicing_variant De novo - - 29754769 Liu Y , et al. (2018)
- - loss_of_function_variant De novo - - 29754769 Liu Y , et al. (2018)
c.3199+4T>C - splice_region_variant De novo - - 35982159 Zhou X et al. (2022)
c.2612C>T p.Pro871Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.5122G>A p.Val1708Ile missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.4710+20T>C - intron_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.3705A>G p.Gln1235%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1651-2A>T - splice_site_variant Unknown - Unknown 31209396 Doan RN , et al. (2019)
c.2396A>G p.Asn799Ser missense_variant De novo - - 31452935 Feliciano P et al. (2019)
c.1405-11_1424del - splice_site_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.4612T>C p.Ser1538Pro missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.740G>A p.Arg247Gln missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.1241A>T p.Lys414Ile missense_variant Unknown - Multiplex 25574603 Butler MG , et al. (2015)
- - copy_number_gain Familial Maternal Extended multiplex 22016809 Salyakina D , et al. (2011)
c.1469del p.Thr490LysfsTer5 frameshift_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Exonic duplications encompassing FGFBP3 and BTAF1 have been reported (PMIDs 22016809 and 22241657; Decipher Patient 252137) that were not present in >10,000 controls. A de novo frameshift variant in the BTAF1 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. TADA-Annotations (TADA-A) analysis of whole-genome sequencing data from five studies with a total of 314 ASD-affected subjects in Liu et al., 2018 identified BTAF1 as an ASD risk gene with a false discovery rate (FDR) < 0.3; among the de novo variants associated with this gene in ASD subjects was a loss-of-function variant and a splicing SNV.

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

Exonic duplications encompassing FGFBP3 and BTAF1 have been reported (PMIDs 22016809 and 22241657; Decipher Patient 252137) that were not present in >10,000 controls. A de novo frameshift variant in the BTAF1 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. TADA-Annotations (TADA-A) analysis of whole-genome sequencing data from five studies with a total of 314 ASD-affected subjects in Liu et al., 2018 identified BTAF1 as an ASD risk gene with a false discovery rate (FDR) < 0.3; among the de novo variants associated with this gene in ASD subjects was a loss-of-function variant and a splicing SNV.

Reports Added
[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

Exonic duplications encompassing FGFBP3 and BTAF1 have been reported (PMIDs 22016809 and 22241657; Decipher Patient 252137) that were not present in >10,000 controls. A de novo frameshift variant in the BTAF1 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. TADA-Annotations (TADA-A) analysis of whole-genome sequencing data from five studies with a total of 314 ASD-affected subjects in Liu et al., 2018 identified BTAF1 as an ASD risk gene with a false discovery rate (FDR) < 0.3; among the de novo variants associated with this gene in ASD subjects was a loss-of-function variant and a splicing SNV.

Reports Added
[Recessive gene disruptions in autism spectrum disorder.2019]
7/1/2018
6
icon
3

Decreased from 6 to 3

Description

Exonic duplications encompassing FGFBP3 and BTAF1 have been reported (PMIDs 22016809 and 22241657; Decipher Patient 252137) that were not present in >10,000 controls. A de novo frameshift variant in the BTAF1 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. TADA-Annotations (TADA-A) analysis of whole-genome sequencing data from five studies with a total of 314 ASD-affected subjects in Liu et al., 2018 identified BTAF1 as an ASD risk gene with a false discovery rate (FDR) < 0.3; among the de novo variants associated with this gene in ASD subjects was a loss-of-function variant and a splicing SNV.

1/1/2016
6
icon
6

Decreased from 6 to 6

Description

Exonic duplications encompassing FGFBP3 and BTAF1 have been reported (PMIDs 22016809 and 22241657; Decipher Patient 252137) that were not present in >10,000 controls.

Reports Added
[Copy number variants in extended autism spectrum disorder families reveal candidates potentially involved in autism risk.2011] [Whole exome sequencing in females with autism implicates novel and candidate genes.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Low load for disruptive mutations in autism genes and their biased transmission.2015]
1/1/2015
6
icon
6

Decreased from 6 to 6

Description

Exonic duplications encompassing FGFBP3 and BTAF1 have been reported (PMIDs 22016809 and 22241657; Decipher Patient 252137) that were not present in >10,000 controls.

Reports Added
[Whole exome sequencing in females with autism implicates novel and candidate genes.2015]
7/1/2014
No data
icon
6

Increased from No data to 6

Description

Exonic duplications encompassing FGFBP3 and BTAF1 have been reported (PMIDs 22016809 and 22241657; Decipher Patient 252137) that were not present in >10,000 controls.

4/1/2014
No data
icon
6

Increased from No data to 6

Description

Exonic duplications encompassing FGFBP3 and BTAF1 have been reported (PMIDs 22016809 and 22241657; Decipher Patient 252137) that were not present in >10,000 controls.

Krishnan Probability Score

Score 0.48280797952189

Ranking 7768/25841 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 0.9999999999383

Ranking 66/18225 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
Iossifov Probability Score

Score 0.933

Ranking 107/239 scored genes


[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists 239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This probability metric combines the evidence from de novo likely-gene- disrupting and missense mutations and assesses it against the background mutation rate in unaffected individuals from the University of Washington’s Exome Variant Sequence database (evs.gs.washington.edu/EVS/). The list of probability scores can be found here: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/- /DCSupplemental/pnas.1516376112.sd02.xlsx
Original Source
Sanders TADA Score

Score 0.77526755133545

Ranking 1839/18665 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 0.58547520481862

Ranking 126/20870 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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