GeneBe

TAF1

protein-coding

TATA-box binding protein associated factor 1, the group of Bromodomain containing|General transcription factor IID complex subunits |Lysine acetyltransferases

Gene summary

Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is the basal transcription factor 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. This gene encodes the largest subunit of TFIID. This subunit binds to core promoter sequences encompassing the transcription start site. It also binds to activators and other transcriptional regulators, and these interactions affect the rate of transcription initiation. This subunit contains two independent protein kinase domains at the N- and C-terminals, but also possesses acetyltransferase activity and can act as a ubiquitin-activating/conjugating enzyme. Mutations in this gene result in Dystonia 3, torsion, X-linked, a dystonia-parkinsonism disorder. Alternative splicing of this gene results in multiple transcript variants. This gene is part of a complex transcription unit (TAF1/DYT3), wherein some transcript variants share exons with TAF1 as well as additional downstream DYT3 exons. [provided by RefSeq, Oct 2013]

Previous symbols:
  • TAF2A
  • BA2R
  • CCG1
  • CCGS
  • DYT3

MANE transcript

NM_004606.5

Inheritance

XL

ClinVar variants

P:46U:608B:202

Top phenotype

Dystonia 3, torsion, X-linked; Mental retardation, X-linked, syndromic 33

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:71,366,136-71,532,374

External References & Databases

Ensembl (ENSG00000147133)NCBI Gene (6872)OMIM (313650)HGNC:11535GenCCUniProt (P21675)AlphaFoldClinVar (TAF1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~166.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder, X-linked, syndromic 33STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010500

Submitter: Labcorp Genetics (formerly Invitae)

intellectual developmental disorder, X-linked, syndromic 33DEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010500

Submitter: Illumina

X-linked dystonia-parkinsonismMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0010747

Submitter: Genomics England PanelApp

X-linked dystonia-parkinsonismLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0010747

Submitter: Labcorp Genetics (formerly Invitae)

X-linked dystonia-parkinsonismSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010747

Submitter: Ambry Genetics

intellectual developmental disorder, X-linked, syndromic 33STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010500

Submitter: Ambry Genetics

X-linked dystonia-parkinsonismSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010747

Submitter: Orphanet

X-linked intellectual disability-global development delay-facial dysmorphism-sacral caudal remnant syndromeSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0018823

Submitter: Orphanet

intellectual developmental disorder, X-linked, syndromic 33STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010500

Submitter: PanelApp Australia

intellectual developmental disorder, X-linked, syndromic 33DEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010500

Submitter: G2P

X-linked dystonia-parkinsonismSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010747

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Dystonia 3, torsion, X-linked; Mental retardation, X-linked, syndromic 33XL

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: Neurologic

Rationale: Dystonia 3, torsion, X-linked may be responsive to levodopa

Refs: 15596620; 17273961; 26637982Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TAF1 variants in ClinVar

16 Conditions Cataloged
not providedTotal: 635
Intellectual disability, X-linked, syndromic 33Total: 107
Inborn genetic diseasesTotal: 93
not specifiedTotal: 88
TAF1-related disorderTotal: 48
X-linked dystonia-parkinsonismTotal: 20
Abnormal heart morphologyTotal: 16
Intellectual disabilityTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004606.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
29
clinvar
131
clinvar
21
clinvar
 182
missense
9
clinvar
33
clinvar
497
clinvar
40
clinvar
10
clinvar
 589
nonsense
22
clinvar
 22
start loss
1
clinvar
1
clinvar
 2
frameshift
1
clinvar
3
clinvar
 4
splice donor/acceptor (+/-2bp)
1
clinvar
56
clinvar
 57
Total93760817131856

Highest pathogenic variant AF is 0.000001653312

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004606.5RefSeqNP_004597.338MANE Select
ENST00000423759.6EnsemblENSP00000406549.238MANE Select
NM_001286074.2RefSeqNP_001273003.239Standard
NM_001440852.1RefSeqNP_001427781.139Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
taf1Danio rerio

Structure: optic tectum

Quality: decreased area

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Basal transcription factors - Homo sapiens (human)
  • MECP2 and Associated Rett Syndrome
  • Disease
  • Gene expression (Transcription)
  • hypoxia and p53 in the cardiovascular system

Biological Process

  • protein polyubiquitination
  • DNA-templated transcription, initiation
  • regulation of transcription, DNA-templated
  • transcription by RNA polymerase II
  • transcription initiation from RNA polymerase II promoter

Molecular Function

  • DNA-binding transcription factor activity, RNA polymerase II-specific
  • p53 binding
  • transcription coactivator activity
  • histone acetyltransferase activity
  • protein serine/threonine kinase activity

Cellular Component

  • nuclear chromatin
  • nucleus
  • nucleoplasm
  • transcription factor complex
  • transcription factor TFIID complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000276072
Coding exons
38
Length
166111
Individuals with no LoFs
125612
Homozygous LoFs
3
Heterozygous LoFs
14
Defined
125629
p
0.0000677
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense5.493267480.4360.000059612563
Missense (PolyPhen)82312.020.26285365
Synonymous-1.072722501.090.00001823522
Loss of Function7.69068.90.000.000005381203

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish0.000540.00040rare
East Asian0.000790.00060rare
Finnish00.0absent
European (Non-Finnish)0.0000120.0000088rare
South Asian0.0000520.000033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Largest component and core scaffold of the TFIID basal transcription factor complex (PubMed:25412659, PubMed:27007846). Contains novel N- and C-terminal Ser/Thr kinase domains which can autophosphorylate or transphosphorylate other transcription factors. Phosphorylates TP53 on 'Thr-55' which leads to MDM2- mediated degradation of TP53. Phosphorylates GTF2A1 and GTF2F1 on Ser residues. Possesses DNA-binding activity (PubMed:25412659). Essential for progression of the G1 phase of the cell cycle (PubMed:11278496, PubMed:15053879, PubMed:2038334, PubMed:8450888, PubMed:8625415, PubMed:9660973, PubMed:9858607). Exhibits histone acetyltransferase activity towards histones H3 and H4 (PubMed:15870300). {ECO:0000269|PubMed:11278496, ECO:0000269|PubMed:15053879, ECO:0000269|PubMed:15870300, ECO:0000269|PubMed:2038334, ECO:0000269|PubMed:25412659, ECO:0000269|PubMed:27007846, ECO:0000269|PubMed:8450888, ECO:0000269|PubMed:8625415, ECO:0000269|PubMed:9660973, ECO:0000269|PubMed:9858607}.;
Disease
DISEASE: Dystonia 3, torsion, X-linked (DYT3) [MIM:314250]: A X- linked dystonia-parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DYT3 is characterized by severe progressive torsion dystonia followed by parkinsonism. It has a well-defined pathology of extensive neuronal loss and mosaic gliosis in the striatum (caudate nucleus and putamen) which appears to resemble that in Huntington disease. {ECO:0000269|PubMed:12928496, ECO:0000269|PubMed:17273961}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Mental retardation, X-linked, syndromic, 33 (MRXS33) [MIM:300966]: A mental retardation syndrome characterized by intellectual deficit, delayed psychomotor development, delayed speech and language, and characteristic facial features. Mental retardation is defined by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:26637982}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.180

Intolerance Scores

LoFtool
0.152
RVIS EVS
-0.42
RVIS percentile EVS
25.73

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
1.00

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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