TRRAP

Gene Facts

• HGNC Symbol: TRRAP (HGNC:12347)
• HGNC Name: transformation/transcription domain associated protein
• Gene type: protein-coding gene
• Locus type: gene with protein product
• Previous symbols: No previous names found
• Alias symbols: TR-AP, PAF400, Tra1
• %HI: 19.5
• pLI: 1
• LOEUF: 0.12
• Cytoband: 7q22.1
• Genomic Coordinates:

  GRCh37/hg19:	chr7:98476155-98610864
  GRCh38/hg38:	chr7:98878532-99013241

• MANE Select Transcript: NM_001375524.1 ENST00000456197.2
• Function: Adapter protein, which is found in various multiprotein chromatin complexes with histone acetyltransferase activity (HAT), which gives a specific tag for epigenetic transcription activation. Component of the NuA4 histone acetyltransferase complex which is responsible for acetylation of nucleosomal histones H4 and H2A. Plays a central role in MYC transcription activation, and also participates in cell transformation by MYC. Required for p53/TP53-, E2F1- and E2F4- mediated transcription activation... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

• Dosage ID: ISCA-13536
• ClinGen Curation ID: CCID:008051
• Curation Status: Complete
• Issue Type: Dosage Curation - Gene
• Haploinsufficiency: Little Evidence for Haploinsufficiency (1)
• Triplosensitivity: No Evidence for Triplosensitivity (0)
• Last Evaluated: 04/24/2019

Haploinsufficiency (HI) Score Details

• HI Score: 1
• HI Evidence Strength: Little Evidence for Haploinsufficiency

HI Disease

• Complex Neurodevelopmental Disorder

HI Evidence

• PUBMED: 28263302
  Yuen et al (2017) identified a de novo frameshift mutation in an autism patient using whole genome sequencing (supplementary table 4)
• PUBMED: 23042115
  Xu et al (2012) described a de novo splice site mutation in an adult male patient with schizophrenia. In addition, the authors identified a de novo missense variant in an adult female patient with schizophrenia (Table 3 and Supplementary Table 5)

• HI Evidence Comments: TRRAP (Transformation/transcription domain-associated protein) encodes a large multidomain protein of the phosphoinositide 3-kinase-related kinases (PIKK) family. The encoded protein has transferase activity, transferring phosphorus-containing groups and transcription coactivator activity. A de novo frameshift variant has been reported in a patient with autism (PMID: 28263302). Further, a de novo splice site variant and a de novo missense variant have been identified in patients with schizophrenia (PMID: 23042115). Currently, partial or whole deletions of TRRAP have not yet been reported. Additional publications: 1) Xu et al (2011) PMID: 21822266 (1 de novo missense variant in a patient with schizophrenia) 2) Sanders et al (2012) PMID: 22495306 (1 de novo missense variant in a patient with autism) 3) Wang et al., (2016) PMID: 27824329 (2 de novo missense variants in patients with autism) 4) Deciphering Developmental Disorders Study (2017) PMID: 28135719 (Several de novo missense variants in patients with developmental delays)

Triplosensitivity (TS) Score Details

• TS Score: 0
• TS Evidence Strength: No Evidence for Triplosensitivity
• TS Evidence Comments: At this time there is no evidence that supports the triplosensitivity of TRRAP. DECIPHER: There are two overlapping copy number gains involving TRRAP: 1) Patient 277488 (Short attention span and specific learning disability) (likely benign) 2) Patient 289542 (Abnormalities of the hand & foot) (uncertain) One publication: Aury-Landas et al (2013) PMID: 23612572 (A 169 kb duplication of whole TRRAP & part of TMEM130 in a patient with Li-Fraumeni syndrome with brain tumor)