Human Gene Module / Chromosome 7 / TRRAP

TRRAPtransformation/transcription domain associated protein

Score
4S
Minimal Evidence, Syndromic Criteria 4.1, Syndromic
Autism Reports / Total Reports
3 / 8
Rare Variants / Common Variants
44 / 0
Aliases
TRRAP, PAF350/400,  PAF400,  STAF40,  TR-AP,  Tra1
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
7q22.1
Associated Disorders
ASD
Relevance to Autism

A de novo loss-of-function variant and multiple de novo missense variants in the TRRAP gene have been observed in ASD probands (Iossifov et al., 2014; Yuen et al., 2017), while multiple de novo missense variants in this gene have also been identified in probands with unspecified developmental disorders (Deciphering Developmental Disorders Study 2017) or epilepsy (Epi4K Consortium 2013). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified TRRAP as a gene with an excess of missense variants (false discovery rata < 5%, count >1) (Coe et al., 2018). Cogne et al., 2019 reported 24 individuals with 17 distinct de novo or apparently de novo missense variants that presented with two distinct clinical spectra: the first was a complex multi-systemic syndrome associated with various malformations of the brain, heart, kidneys and genitourinary system and a wide range of intellectual functioning in individuals with variants clustered between animo acids 1031 and 1159; the second spectrum manifested with autism spectrum disorder and/or intellectual disability and epilepsy in individuals with variants outside of this region.

Molecular Function

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.

Reports related to TRRAP (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support De novo mutations in epileptic encephalopathies. Epi4K Consortium , et al. (2013) No -
2 Primary The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
3 Support Prevalence and architecture of de novo mutations in developmental disorders. Deciphering Developmental Disorders Study (2017) No -
4 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. C Yuen RK , et al. (2017) Yes -
5 Support De novo variant of TRRAP in a patient with very early onset psychosis in the context of non-verbal learning disability and obsessive-compulsive dis... Mavros CF , et al. (2018) No -
6 Recent Recommendation Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity. Coe BP , et al. (2018) No -
7 Support Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model. Guo H , et al. (2018) Yes -
8 Recent Recommendation Missense Variants in the Histone Acetyltransferase Complex Component Gene TRRAP Cause Autism and Syndromic Intellectual Disability. Cogn B , et al. (2019) No ASD
Rare Variants   (44)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.11270G>A p.Arg3757Gln missense_variant De novo - Simplex 23934111 Epi4K Consortium , et al. (2013)
c.1195G>A p.Val399Ile missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.5575C>T p.Arg1859Cys missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.11461C>T p.Arg3821Cys missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.5596T>A p.Trp1866Arg missense_variant De novo - - 28135719 Deciphering Developmental Disorders Study (2017)
c.5598G>T p.Trp1866Cys missense_variant De novo - - 28135719 Deciphering Developmental Disorders Study (2017)
c.4634C>T p.Ala1545Val missense_variant De novo - - 28135719 Deciphering Developmental Disorders Study (2017)
c.10096C>G p.His3366Asp missense_variant De novo - - 28135719 Deciphering Developmental Disorders Study (2017)
c.3337G>A p.Val1113Met missense_variant De novo - - 28135719 Deciphering Developmental Disorders Study (2017)
c.7697C>G p.Ala2566Gly missense_variant De novo - - 28135719 Deciphering Developmental Disorders Study (2017)
c.3311A>G p.Glu1104Gly missense_variant De novo - - 28135719 Deciphering Developmental Disorders Study (2017)
c.7950_7951insAGATAAG p.Glu2651ArgfsTer2 frameshift_variant De novo - Simplex 28263302 C Yuen RK , et al. (2017)
c.310G>A p.Glu104Lys missense_variant De novo - Simplex 28263302 C Yuen RK , et al. (2017)
c.3652G>A p.Ala1218Thr missense_variant De novo - Simplex 28263302 C Yuen RK , et al. (2017)
c.5957G>A p.Arg1986Gln missense_variant De novo - - 30424743 Mavros CF , et al. (2018)
c.10775C>G p.Ser3592Cys missense_variant Familial Maternal Simplex 30564305 Guo H , et al. (2018)
c.7090C>T p.Leu2364Phe missense_variant Familial Paternal Simplex 30564305 Guo H , et al. (2018)
c.3761C>A p.Ser1254Tyr missense_variant Familial Paternal Simplex 30564305 Guo H , et al. (2018)
c.2087G>A p.Arg696His missense_variant Unknown - Simplex 30564305 Guo H , et al. (2018)
c.2413C>T p.Leu805Phe missense_variant De novo - Simplex 30827496 Cogn B , et al. (2019)
c.2580C>G p.Phe860Leu missense_variant De novo - Simplex 30827496 Cogn B , et al. (2019)
c.2678G>T p.Arg893Leu missense_variant De novo - Simplex 30827496 Cogn B , et al. (2019)
c.3093T>G p.Ile1031Met missense_variant De novo - Simplex 30827496 Cogn B , et al. (2019)
c.3104G>A p.Arg1035Gln missense_variant De novo - Simplex 30827496 Cogn B , et al. (2019)
c.3111C>A p.Ser1037Arg missense_variant De novo - Multi-generational 30827496 Cogn B , et al. (2019)
c.3127G>A p.Ala1043Thr missense_variant De novo - Simplex 30827496 Cogn B , et al. (2019)
c.3127G>A p.Ala1043Thr missense_variant De novo - Simplex 30827496 Cogn B , et al. (2019)
c.3127G>A p.Ala1043Thr missense_variant De novo - Simplex 30827496 Cogn B , et al. (2019)
c.3127G>A p.Ala1043Thr missense_variant De novo - Simplex 30827496 Cogn B , et al. (2019)
c.3127G>A p.Ala1043Thr missense_variant De novo - - 30827496 Cogn B , et al. (2019)
c.3311A>G p.Glu1104Gly missense_variant De novo - Simplex 30827496 Cogn B , et al. (2019)
c.3316G>A p.Glu1106Lys missense_variant De novo - Multiplex 30827496 Cogn B , et al. (2019)
c.3316G>A p.Glu1106Lys missense_variant Unknown Not maternal Simplex 30827496 Cogn B , et al. (2019)
c.3331G>T p.Gly1111Trp missense_variant De novo - Simplex 30827496 Cogn B , et al. (2019)
c.3475G>A p.Gly1159Arg missense_variant De novo - Simplex 30827496 Cogn B , et al. (2019)
c.5596T>A p.Trp1866Arg missense_variant De novo - Simplex 30827496 Cogn B , et al. (2019)
c.5598G>T p.Trp1866Cys missense_variant De novo - Simplex 30827496 Cogn B , et al. (2019)
c.5647G>A p.Gly1883Arg missense_variant De novo - Simplex 30827496 Cogn B , et al. (2019)
c.5647G>A p.Gly1883Arg missense_variant De novo - Multi-generational 30827496 Cogn B , et al. (2019)
c.5795C>T p.Pro1932Leu missense_variant Familial Maternal Multiplex 30827496 Cogn B , et al. (2019)
c.11270G>A p.Arg3757Gln missense_variant De novo - Extended multiplex 30827496 Cogn B , et al. (2019)
c.2575G>A p.Asp859Asn missense_variant Unknown - Multi-generational 30827496 Cogn B , et al. (2019)
c.4465G>A p.Asp1489Asn missense_variant De novo - Simplex 30827496 Cogn B , et al. (2019)
c.6415T>C p.Trp2139Arg missense_variant De novo - - 30827496 Cogn B , et al. (2019)
Common Variants  

No common variants reported.

CNVs associated with TRRAP(1 CNVs)
7q22.1 21 Deletion-Duplication 37  /  143
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