TRIOBP

Chr 22

TRIO and F-actin binding protein

Also known as: DFNB28, HRIHFB2122, TAP68, TARA, dJ37E16.4

NCBI Gene: 11078ENSG00000100106UniProt: Q9H2D6

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]

Primary Disease Associations & Inheritance

UniProtDeafness, autosomal recessive, 28
672
ClinVar variants
65
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TRIOBP
🧬
Gene-Disease Validity (ClinGen)
hearing loss, autosomal recessive · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
65 Pathogenic / Likely Pathogenic· 315 VUS of 672 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.71LOEUF
pLI 0.000
Z-score 4.07
OE 0.58 (0.47–0.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.20Z-score
OE missense 1.01 (0.97–1.06)
1396 obs / 1375.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.58 (0.47–0.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.97–1.06)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 63 / 108.8Missense obs/exp: 1396 / 1375.5Syn Z: 1.20

ClinVar Variant Classifications

672 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic18
VUS315
Likely Benign210
Benign54
Conflicting28
47
Pathogenic
18
Likely Pathogenic
315
VUS
210
Likely Benign
54
Benign
28
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
21
0
26
0
47
Likely Pathogenic
10
0
8
0
18
VUS
1
285
22
7
315
Likely Benign
0
27
71
112
210
Benign
0
7
43
4
54
Conflicting
—28
Total32319170123672

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TRIOBP · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — TRIOBP
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Emerging roles of TRIO and F-actin-binding protein in human diseases.
Park S et al.·Cell Commun Signal
2018Review
The genomic landscape of Ménière's disease: a path to endolymphatic hydrops.
Fisch KM et al.·BMC Genomics
2024
Aggregation of the protein TRIOBP-1 and its potential relevance to schizophrenia.
Bradshaw NJ et al.·PLoS One
2014
Whole exome sequencing identifies TRIOBP pathogenic variants as a cause of post-lingual bilateral moderate-to-severe sensorineural hearing loss.
Pollak A et al.·BMC Med Genet
2017
A New Pathogenic Variant in the TRIOBP Associated with Profound Deafness Is Remediable with Cochlear Implantation.
Tekin AM et al.·Audiol Neurootol
2021
Broadening the phenotype of DFNB28: Mutations in TRIOBP are associated with moderate, stable hereditary hearing impairment.
Wesdorp M et al.·Hear Res
2017Case report
Elucidation of repeat motifs R1- and R2-related TRIOBP variants in autosomal recessive nonsyndromic hearing loss DFNB28 among indigenous South African individuals.
Kabahuma RI et al.·Mol Genet Genomic Med
2022
A novel mutation in TRIOBP gene leading to congenital deafness in a Chinese family.
Zhou B et al.·BMC Med Genet
2020Case report
Analysis of TRIOBP gene in non-syndromic deafness: A case report.
Zhou H et al.·Medicine (Baltimore)
2024Case report
Variant analysis of 92 Chinese Han families with hearing loss.
Jin X et al.·BMC Med Genomics
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools