ClinGen Dosage Sensitivity Curation Page

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  • Curation Status: Complete

Location Information

Select assembly: (NC_000007.13) (NC_000007.14)
Evidence for haploinsufficiency phenotype
PubMed ID Description
28263302 Yuen et al (2017) identified a de novo frameshift mutation in an autism patient using whole genome sequencing (supplementary table 4)
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)

Haploinsufficiency phenotype 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 score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

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)