TRRAP

Chr 7AD

transformation/transcription domain associated protein

Also known as: DEDDFA, DFNA75, PAF350/400, PAF400, STAF40, TR-AP, Tra1

NCBI Gene: 8295 ENSG00000196367 UniProt: Q9Y4A5 OMIM: 603015

The encoded protein is an adapter protein that recruits histone acetyltransferase complexes to chromatin for transcription activation and is required for MYC-, p53-, and E2F-mediated gene expression. Mutations cause autosomal dominant developmental delay with or without dysmorphic features and autism, as well as autosomal dominant deafness. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.06), indicating that heterozygous loss is likely pathogenic.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a large multidomain protein of the phosphoinositide 3-kinase-related kinases (PIKK) family. The encoded protein is a common component of many histone acetyltransferase (HAT) complexes and plays a role in transcription and DNA repair by recruiting HAT complexes to chromatin. Deregulation of this gene may play a role in several types of cancer including glioblastoma multiforme. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Deafness, autosomal dominant 75MIM #618778

Developmental delay with or without dysmorphic facies and autismMIM #618454

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder with or without congenital anomalies · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.06

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

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GeneReview available — TRRAP