TAF1

Chr X

TATA-box binding protein associated factor 1

Also known as: BA2R, CCG1, CCGS, DYT3, DYT3/TAF1, KAT4, MRXS33, N-TAF1

NCBI Gene: 6872 ENSG00000147133 UniProt: P21675

TAF1 encodes the largest subunit of TFIID, a basal transcription factor that binds core promoter sequences and coordinates RNA polymerase II transcription initiation, and possesses kinase, acetyltransferase, and ubiquitin-conjugating activities. Mutations cause X-linked recessive dystonia-parkinsonism (DYT3) and X-linked syndromic intellectual developmental disorder through loss-of-function mechanisms. The gene is highly intolerant to loss-of-function variants, reflecting its essential role in transcriptional regulation.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDystonia 3, torsion, X-linked

UniProtIntellectual developmental disorder, X-linked, syndromic 33

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.04

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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