Human Gene Module / Chromosome X / TAF1

TAF1TATA-box binding protein associated factor 1

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
4 / 17
Rare Variants / Common Variants
64 / 0
Aliases
TAF1, BA2R,  CCG1,  CCGS,  DYT3,  DYT3/TAF1,  KAT4,  N-TAF1,  NSCL2,  OF,  P250,  TAF(II)250,  TAF2A,  TAFII-250,  TAFII250,  XDP
Associated Syndromes
-
Chromosome Band
Xq13.1
Associated Disorders
DD/NDD, ID, EP, EPS, ASD
Relevance to Autism

Rare genetic variants involving TAF1 were identified in affected males from 11 families presenting with an X-linked syndrome characterized by developmental delay, intellectual disability, facial dysmorphic features, generalized hypotonia, and variable neurologic features (O'Rawe et al., 2015); ten of the fourteen probands with TAF1 variants in this report exhibited autistic behaviors.

Molecular Function

The protein encoded by this gene is the largest component and core scaffold of the TFIID basal transcription factor complex. It binds to core promoter sequences encompassing the transcription start site, as well as to activators and other transcriptional regulators, and these interactions affect the rate of transcription initiation. X-linked dystonia-parkinsonism (OMIM 314250) is caused by a retrotransposon insertion in an intron of TAF1 in the Filipino population.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to TAF1 (17 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes Hu H et al. (2016) No -
2 Primary TAF1 Variants Are Associated with Dysmorphic Features, Intellectual Disability, and Neurological Manifestations O'Rawe JA , et al. (2015) No Autistic behaviors
3 Support High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing Martnez F , et al. (2016) No -
4 Support TAF1, associated with intellectual disability in humans, is essential for embryogenesis and regulates neurodevelopmental processes in zebrafish Gudmundsson S , et al. (2019) No -
5 Support Missense variants in TAF1 and developmental phenotypes: challenges of determining pathogenicity Cheng H , et al. (2019) No -
6 Support Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability Chevarin M et al. (2020) No Marfanoid habitus
7 Support A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders Suzuki T et al. (2020) No -
8 Support A novel variant in TAF1 affects gene expression and is associated with X-linked TAF1 intellectual disability syndrome Hurst SE et al. (2018) No DD, ID, stereotypy
9 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes ID
10 Support - Alonso-Gonzalez A et al. (2021) Yes -
11 Support - Taşkıran EZ et al. (2021) No Epilepsy/seizures, autistic features
12 Support - Zou D et al. (2021) Yes -
13 Support - Bruno LP et al. (2021) No -
14 Support - Zhou X et al. (2022) Yes -
15 Support - Giovenino C et al. (2023) No ID
16 Support - Spataro N et al. (2023) No Learning disability, autistic features
17 Support - Bartolomaeus T et al. (2023) No -
Rare Variants   (64)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain De novo - Simplex 26637982 O'Rawe JA , et al. (2015)
c.281A>G p.Asn94Ser missense_variant Unknown - - 34145886 Zou D et al. (2021)
c.454G>T p.Asp152Tyr missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.482C>T p.Pro161Leu missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1156G>A p.Gly386Ser missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2524C>T p.Arg842Trp missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2933C>T p.Thr978Met missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1745G>A p.Arg582Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1962G>C p.Glu654Asp missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2480G>A p.Arg827Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2T>C p.Met1? initiator_codon_variant Unknown - - 33004838 Wang T et al. (2020)
c.4196G>A p.Arg1399His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.4196G>T p.Arg1399Leu missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.4991C>A p.Thr1664Lys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.4454A>G p.His1485Arg missense_variant De novo - - 31646703 Cheng H , et al. (2019)
c.4580C>T p.Ala1527Val missense_variant De novo - - 31646703 Cheng H , et al. (2019)
c.3760C>T p.Arg1254Trp missense_variant Familial - - 31646703 Cheng H , et al. (2019)
c.2926G>C p.Asp976His missense_variant De novo - - 27620904 Martnez F , et al. (2016)
c.29_53dup p.Ala19AspfsTer50 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.1580A>G p.Asp527Gly missense_variant De novo - Simplex 31646703 Cheng H , et al. (2019)
c.2668C>T p.Arg890Cys missense_variant De novo - Simplex 31646703 Cheng H , et al. (2019)
c.2954C>T p.Ser985Phe missense_variant De novo - Simplex 31646703 Cheng H , et al. (2019)
c.2039G>A p.Gly680Asp missense_variant De novo - Unknown 31646703 Cheng H , et al. (2019)
c.613A>G p.Ser205Gly missense_variant Familial Maternal - 31646703 Cheng H , et al. (2019)
c.862C>T p.Arg288Cys missense_variant Familial Maternal - 31646703 Cheng H , et al. (2019)
c.952G>A p.Ala318Thr missense_variant Familial Maternal - 31646703 Cheng H , et al. (2019)
c.3035C>T p.Thr1012Ile missense_variant De novo - Simplex 31646703 Cheng H , et al. (2019)
c.3568C>T p.Arg1190Cys missense_variant De novo - Simplex 31646703 Cheng H , et al. (2019)
c.4442A>T p.Asn1481Ile missense_variant De novo - Simplex 31646703 Cheng H , et al. (2019)
c.4033G>A p.Val1345Ile missense_variant De novo - Unknown 31646703 Cheng H , et al. (2019)
c.4151A>G p.His1384Arg missense_variant De novo - Simplex 34948243 Bruno LP et al. (2021)
c.1297G>A p.Asp433Asn missense_variant Familial Maternal - 31646703 Cheng H , et al. (2019)
c.1825A>G p.Ile609Val missense_variant Familial Maternal - 31646703 Cheng H , et al. (2019)
c.2833G>A p.Asp945Asn missense_variant Familial Maternal - 31646703 Cheng H , et al. (2019)
c.1514T>A p.Ile505Asn missense_variant De novo - Simplex 26637982 O'Rawe JA , et al. (2015)
c.2419T>C p.Cys807Arg missense_variant De novo - Simplex 26637982 O'Rawe JA , et al. (2015)
c.2926G>C p.Asp976His missense_variant De novo - Simplex 26637982 O'Rawe JA , et al. (2015)
- - copy_number_gain Familial Maternal Extended multiplex 26637982 O'Rawe JA , et al. (2015)
c.180+2T>G - splice_site_variant De novo - Simplex 33431980 Alonso-Gonzalez A et al. (2021)
c.4726A>G p.Lys1576Glu missense_variant Familial Maternal - 31646703 Cheng H , et al. (2019)
c.5659A>T p.Ser1887Cys missense_variant Familial Maternal - 31646703 Cheng H , et al. (2019)
c.5370G>C p.Glu1790Asp missense_variant Unknown - Multiplex 31646703 Cheng H , et al. (2019)
c.3736C>T p.Arg1246Trp missense_variant De novo - Simplex 26637982 O'Rawe JA , et al. (2015)
c.4355G>A p.Arg1452His missense_variant De novo - Simplex 26637982 O'Rawe JA , et al. (2015)
c.4549A>C p.Asn1517His missense_variant De novo - Simplex 26637982 O'Rawe JA , et al. (2015)
c.1251_1253del p.Leu418del inframe_deletion Familial Maternal - 31646703 Cheng H , et al. (2019)
c.2180G>C p.Arg727Pro missense_variant Familial Maternal Simplex 31646703 Cheng H , et al. (2019)
c.2617T>G p.Phe873Val missense_variant Familial Maternal Simplex 31646703 Cheng H , et al. (2019)
c.2834A>T p.Asp945Val missense_variant Familial Maternal Simplex 32530565 Suzuki T et al. (2020)
c.4052T>A p.Ile1351Asn missense_variant Familial Maternal Unknown 31646703 Cheng H , et al. (2019)
c.4735A>G p.Asn1579Asp missense_variant Familial Maternal Simplex 32714589 Hurst SE et al. (2018)
c.4190G>A p.Arg1397Gln missense_variant Familial Maternal Multiplex 31646703 Cheng H , et al. (2019)
c.4442A>G p.Asn1481Ser missense_variant Familial Maternal Multiplex 31646703 Cheng H , et al. (2019)
c.4276A>G p.Met1426Val missense_variant Familial Maternal Multiplex 36980980 Spataro N et al. (2023)
c.3708A>G p.Gln1236= splice_site_variant Familial Maternal Simplex 26637982 O'Rawe JA , et al. (2015)
c.1786C>T p.Pro596Ser missense_variant Familial Maternal Multiplex 26637982 O'Rawe JA , et al. (2015)
c.745G>A p.Gly249Arg missense_variant Familial Maternal Multiplex 36879111 Giovenino C et al. (2023)
c.4010T>C p.Ile1337Thr missense_variant Familial Maternal Multiplex 26637982 O'Rawe JA , et al. (2015)
c.4130G>A p.Arg1377Gln missense_variant Familial Maternal Multiplex 32277047 Chevarin M et al. (2020)
c.1477A>G p.Asn493Asp missense_variant Familial Maternal Multi-generational 25644381 Hu H et al. (2016)
c.3568C>T p.Arg1190Cys missense_variant Familial Maternal Multi-generational 25644381 Hu H et al. (2016)
c.2590C>T p.Arg864Trp missense_variant Familial Maternal Multiplex 37460657 Bartolomaeus T et al. (2023)
c.4603A>G p.Lys1535Glu missense_variant Familial Maternal Multiplex 33739554 Taşkıran EZ et al. (2021)
c.3568C>T p.Arg1190Cys missense_variant Familial Maternal Multi-generational 31341187 Gudmundsson S , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Rare genetic variants involving TAF1 were identified in affected males from 11 families presenting with an X-linked syndrome characterized by developmental delay, intellectual disability, facial dysmorphic features, generalized hypotonia, and variable neurologic features (O'Rawe et al., 2015); ten of the fourteen probands with TAF1 variants in this report exhibited autistic behaviors. Variants in this gene had previously been shown to segregate with X-linked intellectual disability in two multi-generational pedigrees (Hu et al., 2015). Clinical phenotyping of 24 novel individuals with TAF1 missense variants using standardized Human Phenotype Ontology (HPO) terminology in Cheng et al., 2019 found that four individuals were reported to display "Autistic behavior" (HP:0000729).

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
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."

4/1/2021
S
icon
S

Score remained at S

Description

Rare genetic variants involving TAF1 were identified in affected males from 11 families presenting with an X-linked syndrome characterized by developmental delay, intellectual disability, facial dysmorphic features, generalized hypotonia, and variable neurologic features (O'Rawe et al., 2015); ten of the fourteen probands with TAF1 variants in this report exhibited autistic behaviors. Variants in this gene had previously been shown to segregate with X-linked intellectual disability in two multi-generational pedigrees (Hu et al., 2015). Clinical phenotyping of 24 novel individuals with TAF1 missense variants using standardized Human Phenotype Ontology (HPO) terminology in Cheng et al., 2019 found that four individuals were reported to display "Autistic behavior" (HP:0000729).

Reports Added
[Diagnostic yield of whole-exome sequencing in non-syndromic intellectual disability2021]
1/1/2021
S
icon
S

Score remained at S

Description

Rare genetic variants involving TAF1 were identified in affected males from 11 families presenting with an X-linked syndrome characterized by developmental delay, intellectual disability, facial dysmorphic features, generalized hypotonia, and variable neurologic features (O'Rawe et al., 2015); ten of the fourteen probands with TAF1 variants in this report exhibited autistic behaviors. Variants in this gene had previously been shown to segregate with X-linked intellectual disability in two multi-generational pedigrees (Hu et al., 2015). Clinical phenotyping of 24 novel individuals with TAF1 missense variants using standardized Human Phenotype Ontology (HPO) terminology in Cheng et al., 2019 found that four individuals were reported to display "Autistic behavior" (HP:0000729).

Reports Added
[Exploring the biological role of postzygotic and germinal de novo mutations in ASD2021]
10/1/2020
S
icon
S

Score remained at S

Description

Rare genetic variants involving TAF1 were identified in affected males from 11 families presenting with an X-linked syndrome characterized by developmental delay, intellectual disability, facial dysmorphic features, generalized hypotonia, and variable neurologic features (O'Rawe et al., 2015); ten of the fourteen probands with TAF1 variants in this report exhibited autistic behaviors. Variants in this gene had previously been shown to segregate with X-linked intellectual disability in two multi-generational pedigrees (Hu et al., 2015). Clinical phenotyping of 24 novel individuals with TAF1 missense variants using standardized Human Phenotype Ontology (HPO) terminology in Cheng et al., 2019 found that four individuals were reported to display "Autistic behavior" (HP:0000729).

Reports Added
[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
7/1/2020
S
icon
S

Score remained at S

Description

Rare genetic variants involving TAF1 were identified in affected males from 11 families presenting with an X-linked syndrome characterized by developmental delay, intellectual disability, facial dysmorphic features, generalized hypotonia, and variable neurologic features (O'Rawe et al., 2015); ten of the fourteen probands with TAF1 variants in this report exhibited autistic behaviors. Variants in this gene had previously been shown to segregate with X-linked intellectual disability in two multi-generational pedigrees (Hu et al., 2015). Clinical phenotyping of 24 novel individuals with TAF1 missense variants using standardized Human Phenotype Ontology (HPO) terminology in Cheng et al., 2019 found that four individuals were reported to display "Autistic behavior" (HP:0000729).

Reports Added
[A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders2020] [A novel variant in TAF1 affects gene expression and is associated with X-linked TAF1 intellectual disability syndrome2018]
4/1/2020
S
icon
S

Score remained at S

Description

Rare genetic variants involving TAF1 were identified in affected males from 11 families presenting with an X-linked syndrome characterized by developmental delay, intellectual disability, facial dysmorphic features, generalized hypotonia, and variable neurologic features (O'Rawe et al., 2015); ten of the fourteen probands with TAF1 variants in this report exhibited autistic behaviors. Variants in this gene had previously been shown to segregate with X-linked intellectual disability in two multi-generational pedigrees (Hu et al., 2015). Clinical phenotyping of 24 novel individuals with TAF1 missense variants using standardized Human Phenotype Ontology (HPO) terminology in Cheng et al., 2019 found that four individuals were reported to display "Autistic behavior" (HP:0000729).

Reports Added
[Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability2020]
10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Rare genetic variants involving TAF1 were identified in affected males from 11 families presenting with an X-linked syndrome characterized by developmental delay, intellectual disability, facial dysmorphic features, generalized hypotonia, and variable neurologic features (O'Rawe et al., 2015); ten of the fourteen probands with TAF1 variants in this report exhibited autistic behaviors. Variants in this gene had previously been shown to segregate with X-linked intellectual disability in two multi-generational pedigrees (Hu et al., 2015). Clinical phenotyping of 24 novel individuals with TAF1 missense variants using standardized Human Phenotype Ontology (HPO) terminology in Cheng et al., 2019 found that four individuals were reported to display "Autistic behavior" (HP:0000729).

Reports Added
[Missense variants in TAF1 and developmental phenotypes: challenges of determining pathogenicity.2019] [New Scoring Scheme]
7/1/2019
S
icon
S

Score remained at S

Description

Rare genetic variants involving TAF1 were identified in affected males from 11 families presenting with an X-linked syndrome characterized by developmental delay, intellectual disability, facial dysmorphic features, generalized hypotonia, and variable neurologic features (O'Rawe et al., 2015); ten of the fourteen probands with TAF1 variants in this report exhibited autistic behaviors. Variants in this gene had previously been shown to segregate with X-linked intellectual disability in two multi-generational pedigrees (Hu et al., 2015).

Reports Added
[TAF1, associated with intellectual disability in humans, is essential for embryogenesis and regulates neurodevelopmental processes in zebrafish.2019]
10/1/2016
S
icon
S

Score remained at S

Description

Rare genetic variants involving TAF1 were identified in affected males from 11 families presenting with an X-linked syndrome characterized by developmental delay, intellectual disability, facial dysmorphic features, generalized hypotonia, and variable neurologic features (O'Rawe et al., 2015); ten of the fourteen probands with TAF1 variants in this report exhibited autistic behaviors. Variants in this gene had previously been shown to segregate with X-linked intellectual disability in two multi-generational pedigrees (Hu et al., 2015).

Reports Added
[High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing.2016]
Krishnan Probability Score

Score 0.43675359406646

Ranking 20307/25841 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 0.99999975577346

Ranking 228/18225 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 0.947694236799

Ranking 17380/18665 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 0.34645329974797

Ranking 2063/20870 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
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
TAF7L Transcription initiation factor TFIID subunit 7-like Human Protein Binding 54457 Q5H9L4-2
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