TRIOBP

TRIO and F-actin binding protein, the group of Pleckstrin homology domain containing

Basic information

Region (hg38): 22:37697047-37776556

Previous symbols: [ "DFNB28" ]

Links

ENSG00000100106 ∙ NCBI:11078 ∙ OMIM:609761 ∙ HGNC:17009 ∙ Uniprot:Q9H2D6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 28 (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 28 (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 28 (Definitive), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• hearing loss, autosomal recessive (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 28	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	16385457; 16385458; 23226338

ClinVar

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

• not provided (661 variants)
• not specified (171 variants)
• Autosomal recessive nonsyndromic hearing loss 28 (75 variants)
• Inborn genetic diseases (46 variants)
• Hearing impairment (9 variants)
• TRIOBP-related condition (6 variants)
• Deafness (1 variants)
• Nonsyndromic genetic hearing loss (1 variants)
• Hearing loss, autosomal recessive (1 variants)
• TRIOBP-related hearing loss (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRIOBP 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			10	119	12	141
missense			298	53	29	380
nonsense	13	8	4	1		26
start loss						0
frameshift	8	9	1			18
inframe indel			10	1	2	13
splice donor/acceptor (+/-2bp)	1	6				7
splice region			5	7	2	14
non coding			8	87	51	146
Total	22	23	331	261	94

Highest pathogenic variant AF is 0.0000920

Variants in TRIOBP

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

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

Position	Type	Phenotype	Significance	ClinVar
22-37701177-G-C			Likely benign (Dec 31, 2018)
22-37701198-T-TAA			Benign (Oct 02, 2019)
22-37701352-C-G		not specified • Autosomal recessive nonsyndromic hearing loss 28	Benign (Sep 10, 2021)
22-37701363-A-G		not specified • TRIOBP-related disorder	Conflicting classifications of pathogenicity (Jul 08, 2019)
22-37701406-A-G			Uncertain significance (Jul 08, 2020)
22-37701429-C-T		not specified	Uncertain significance (Nov 22, 2017)
22-37701458-G-A			Likely benign (Sep 17, 2023)
22-37701461-C-T		not specified	Likely benign (Sep 20, 2023)
22-37701476-C-G		not specified	Uncertain significance (Oct 11, 2015)
22-37701495-A-G			Benign/Likely benign (Oct 05, 2023)
22-37701731-T-A			Benign (Jul 10, 2018)
22-37701735-T-G			Likely benign (Jul 10, 2018)
22-37710101-C-T			Benign (Jul 09, 2018)
22-37710218-T-G			Benign (Jul 09, 2018)
22-37710250-C-T			Likely benign (Feb 04, 2019)
22-37710252-A-T			Benign (Jul 09, 2018)
22-37710279-C-T			Likely benign (Dec 31, 2018)
22-37710353-G-A			Likely benign (Jun 24, 2018)
22-37710372-G-T			Likely benign (Jan 06, 2020)
22-37710392-C-T			Likely benign (Jul 01, 2018)
22-37710415-A-T		not specified	Uncertain significance (May 16, 2017)
22-37710430-C-T			Uncertain significance (May 25, 2017)
22-37710443-C-G		Autosomal recessive nonsyndromic hearing loss 28	Likely pathogenic (Feb 26, 2019)
22-37710446-GTGCTGAGGTGCCCTAC-G		Rare genetic deafness	Likely pathogenic (Nov 03, 2022)
22-37710466-G-A		Autosomal recessive nonsyndromic hearing loss 28	Uncertain significance (Aug 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRIOBP	protein_coding	protein_coding	ENST00000406386	21	79553

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.02e-28	1.00	125403	0	345	125748	0.00137

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.196	1396	1.38e+3	1.01	0.0000908	14943
Missense in Polyphen		465	462.63	1.0051		4809
Synonymous	1.20	532	568	0.936	0.0000351	5092
Loss of Function	4.07	63	109	0.579	0.00000772	1025

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00245	0.00241
Ashkenazi Jewish	0.00231	0.00228
East Asian	0.000529	0.000489
Finnish	0.000727	0.000693
European (Non-Finnish)	0.00171	0.00165
Middle Eastern	0.000529	0.000489
South Asian	0.00129	0.00127
Other	0.00123	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May regulate actin cytoskeletal organization, cell spreading and cell contraction by directly binding and stabilizing filamentous F-actin. The localized formation of TARA and TRIO complexes coordinates the amount of F-actin present in stress fibers. May also serve as a linker protein to recruit proteins required for F-actin formation and turnover. {ECO:0000269|PubMed:18194665}.
• Disease: DISEASE: Deafness, autosomal recessive, 28 (DFNB28) [MIM:609823]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:16385457, ECO:0000269|PubMed:16385458}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• loftool: 0.171
• rvis_EVS: 2.97
• rvis_percentile_EVS: 99.18

Haploinsufficiency Scores

• pHI: 0.253
• hipred: N
• hipred_score: 0.270
• ghis: 0.446

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.358

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Triobp
• 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); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype

Gene ontology

• Biological process: cell cycle;sensory perception of sound;actin modification;barbed-end actin filament capping;cell division;auditory receptor cell stereocilium organization;positive regulation of substrate adhesion-dependent cell spreading
• Cellular component: nucleus;cytoplasm;microtubule organizing center;focal adhesion;actin cytoskeleton;midbody
• Molecular function: GTP-Rho binding;ubiquitin protein ligase binding;myosin II binding;actin filament binding