Human Gene Module / Chromosome 10 / BTAF1

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

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
5 / 5
Rare Variants / Common Variants
6 / 0
Aliases
BTAF1, MOT1,  TAF(II)170,  TAF172,  TAFII170
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
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.

Reports related to BTAF1 (5 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 -
Rare Variants   (6)
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)
T>C - intron_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
delA - frameshift_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.1241A>T p.Tyr414Phe missense_variant Unknown - Multiplex 25574603 Butler MG , et al. (2015)
- - copy_number_gain Familial Maternal Extended multiplex 22016809 Salyakina D , et al. (2011)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

3

Score Delta: Decreased from 6 to 3.3

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

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.

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.
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
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
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).
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.
CNVs associated with BTAF1(1 CNVs)
10q23.32 3 Deletion 8  /  11
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