TRRAP

transformation/transcription domain associated protein, the group of SAGA complex|Tip60/Nua4 histone acetyltransferase complex subunits|Armadillo like helical domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 7:98877933-99050831

Links

ENSG00000196367 ∙ NCBI:8295 ∙ OMIM:603015 ∙ HGNC:12347 ∙ Uniprot:Q9Y4A5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• developmental delay with or without dysmorphic facies and autism (Moderate), mode of inheritance: AD
• hearing loss, autosomal dominant 75 (Limited), mode of inheritance: AD
• developmental delay with or without dysmorphic facies and autism (Definitive), mode of inheritance: AD
• developmental delay with or without dysmorphic facies and autism (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder with or without congenital anomalies (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental delay with or without dysmorphic facies and autism	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Renal	23042115; 30424743; 31231791

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRRAP gene.

• not provided (3 variants)
• Developmental delay with or without dysmorphic facies and autism (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRRAP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			12	456	47	515
missense	4	12	580	64	42	702
nonsense		1	6			7
start loss						0
frameshift			9			9
inframe indel			9	1		10
splice donor/acceptor (+/-2bp)		1	5			6
splice region			27	59	21	107
non coding		1	4	184	88	277
Total	4	15	625	705	177

Variants in TRRAP

This is a list of pathogenic ClinVar variants found in the TRRAP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-98881057-A-G			Benign (May 22, 2021)
7-98881156-G-A		Inborn genetic diseases • TRRAP-related disorder	Likely benign (Jun 10, 2023)
7-98881178-A-G			Uncertain significance (Dec 11, 2023)
7-98881179-C-T			Likely benign (Sep 06, 2022)
7-98881182-T-C			Uncertain significance (Feb 06, 2023)
7-98881188-A-C		TRRAP-related disorder	Uncertain significance (Sep 25, 2022)
7-98881199-T-C		TRRAP-related disorder	Likely benign (May 10, 2019)
7-98881202-A-C			Uncertain significance (May 29, 2021)
7-98881202-A-T			Uncertain significance (Jun 17, 2020)
7-98881209-A-G		Developmental delay with or without dysmorphic facies and autism	Uncertain significance (May 14, 2020)
7-98881229-G-C			Uncertain significance (Jan 31, 2023)
7-98881231-T-C			Likely benign (Sep 27, 2023)
7-98881966-C-T			Likely benign (Dec 11, 2023)
7-98881967-G-A			Likely benign (Aug 22, 2022)
7-98881971-A-G			Likely benign (Nov 19, 2023)
7-98881978-A-G		Developmental delay with or without dysmorphic facies and autism	Uncertain significance (Jan 01, 2019)
7-98882016-A-T			Uncertain significance (Jan 16, 2023)
7-98882027-A-G			Uncertain significance (Jan 11, 2023)
7-98882032-C-T			Benign (Jan 30, 2024)
7-98882033-A-G			Likely benign (Dec 22, 2023)
7-98882084-G-A			Benign (May 15, 2021)
7-98890314-CT-C			Likely benign (Dec 11, 2023)
7-98890318-T-C			Likely benign (Mar 04, 2023)
7-98890330-A-C			Likely benign (Jul 08, 2022)
7-98890342-C-T		Inborn genetic diseases	Likely benign (Oct 27, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRRAP	protein_coding	protein_coding	ENST00000359863	71	135311

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.30e-28	125728	0	19	125747	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	8.17	1191	2.29e+3	0.520	0.000147	25405
Missense in Polyphen		200	647.77	0.30875		7151
Synonymous	-2.45	1038	942	1.10	0.0000674	7531
Loss of Function	12.6	6	197	0.0305	0.0000106	2182

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000623	0.0000615
Middle Eastern	0.000109	0.000109
South Asian	0.000223	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. Also involved in transcription activation mediated by the adenovirus E1A, a viral oncoprotein that deregulates transcription of key genes. Probably acts by linking transcription factors such as E1A, MYC or E2F1 to HAT complexes such as STAGA thereby allowing transcription activation. Probably not required in the steps following histone acetylation in processes of transcription activation. May be required for the mitotic checkpoint and normal cell cycle progression. Component of a SWR1- like complex that specifically mediates the removal of histone H2A.Z/H2AFZ from the nucleosome. {ECO:0000269|PubMed:11418595, ECO:0000269|PubMed:12138177, ECO:0000269|PubMed:12660246, ECO:0000269|PubMed:12743606, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:17967892, ECO:0000269|PubMed:24463511, ECO:0000269|PubMed:9708738}.
• Disease: DISEASE: Note=TRRAP mutation Phe-722 has been frequently found in cutaneous malignant melanoma, suggesting that TRRAP may play a role in the pathogenesis of melanoma. {ECO:0000269|PubMed:21499247}.
• Pathway: HTLV-I infection - Homo sapiens (human);Signaling by WNT;Signal Transduction;multi-step regulation of transcription by pitx2;Post-translational protein modification;Metabolism of proteins;Chromatin modifying enzymes;HATs acetylate histones;Ub-specific processing proteases;Deubiquitination;Chromatin organization;C-MYC pathway;Direct p53 effectors;Regulation of nuclear beta catenin signaling and target gene transcription;Validated targets of C-MYC transcriptional activation;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT;E2F transcription factor network (Consensus)

Recessive Scores

• pRec: 0.527

Intolerance Scores

• loftool: 0.0406
• rvis_EVS: -6.14
• rvis_percentile_EVS: 0.04

Haploinsufficiency Scores

• pHI: 0.901
• hipred: Y
• hipred_score: 0.859
• ghis: 0.697

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.862

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Trrap
• Phenotype: vision/eye phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: DNA repair;regulation of transcription, DNA-templated;histone acetylation;histone deubiquitination;protein deubiquitination;histone H4 acetylation;histone H2A acetylation;beta-catenin-TCF complex assembly
• Cellular component: SAGA complex;PCAF complex;Swr1 complex;nucleus;nucleoplasm;Golgi apparatus;STAGA complex;transcription factor TFTC complex;NuA4 histone acetyltransferase complex
• Molecular function: transcription coregulator activity;protein binding;thiol-dependent ubiquitinyl hydrolase activity