TRIOBP

protein-coding

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

Gene summary

This gene encodes a protein with an N-terminal pleckstrin homology domain and a C-terminal coiled-coil region. The protein interacts with trio, which is involved with neural tissue development and controlling actin cytoskeleton organization, cell motility and cell growth. The protein also associates with F-actin and stabilizes F-actin structures. Mutations in this gene have been associated with a form of autosomal recessive nonsyndromic deafness. Multiple alternatively spliced transcript variants that would encode different isoforms have been found for this gene, however some transcripts may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Nov 2008]

Previous symbols:

DFNB28

MANE transcript

NM_001039141.3

Inheritance

ClinVar variants

P:125U:513B:323

Top phenotype

Deafness, autosomal recessive 28

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr22:37,697,048-37,776,556

External References & Databases

Ensembl (ENSG00000100106)

Transcript & Mutation Effects

hg38 • Region Span ~79.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive nonsyndromic hearing loss 28STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012355

Submitter: Labcorp Genetics (formerly Invitae)

autosomal recessive nonsyndromic hearing loss 28STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012355

Submitter: PanelApp Australia

hearing loss, autosomal recessiveDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019588

Submitter: ClinGen

autosomal recessive nonsyndromic hearing loss 28DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012355

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

hearing loss, autosomal recessiveSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019588

Submitter: Orphanet

Clinical Genomic Database (CGD)

Deafness, autosomal recessive 28AR

Manifestation: Audiologic/Otolaryngologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 16385457; 16385458; 23226338

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRIOBP variants in ClinVar

16 Conditions Cataloged

not providedTotal: 917

not specifiedTotal: 241

TRIOBP-related disorderTotal: 188

Autosomal recessive nonsyndromic hearing loss 28Total: 137

Inborn genetic diseasesTotal: 96

Hearing impairmentTotal: 9

Rare genetic deafnessTotal: 6

Meniere diseaseTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001039141.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			13 clinvar	217 clinvar	4 clinvar	234
missense		2 clinvar	489 clinvar	94 clinvar	8 clinvar	593
nonsense	29 clinvar	24 clinvar	4 clinvar			57
start loss						0
frameshift	28 clinvar	32 clinvar	1 clinvar			61
splice donor/acceptor (+/-2bp)	1 clinvar	9 clinvar	6 clinvar			16
Total	58	67	513	311	12	961

Highest pathogenic variant AF is 0.000488481

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001039141.3	RefSeq	NP_001034230.1	21	MANE Select
ENST00000644935.1	Ensembl	ENSP00000496394.1	21	MANE Select
NM_007032.5	RefSeq	NP_008963.3	13	Standard
NM_138632.2	RefSeq	NP_619538.2	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell cycle
sensory perception of sound
actin modification
barbed-end actin filament capping
cell division

Molecular Function

GTP-Rho binding
ubiquitin protein ligase binding
myosin II binding
actin filament binding

Cellular Component

nucleus
cytoplasm
microtubule organizing center
focal adhesion
actin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000406386
Coding exons: 21
Length: 79553
Individuals with no LoFs: 125403
Homozygous LoFs: 0
Heterozygous LoFs: 345
Defined: 125748
p: 0.00137

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.196	1396	1.38e+3	1.01	0.0000908	14943
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00084	0.00080	rare
Latino/Admixed American	0.0016	0.0015	notable
Ashkenazi Jewish	0.0023	0.0023	notable
East Asian	0.00053	0.00049	rare
Finnish	0.00073	0.00069	rare
European (Non-Finnish)	0.0017	0.0017	notable
South Asian	0.0013	0.0013	notable
Other	0.0012	0.00098	notable

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.358

Gene Damage Prediction

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