TRIOBP

Chr 22AR

TRIO and F-actin binding protein

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

NCBI Gene: 11078ENSG00000100106UniProt: Q9H2D6OMIM: 609761

The protein regulates actin cytoskeletal organization by directly binding and stabilizing filamentous F-actin and preventing its depolymerization, and is essential for correct mitotic progression. Mutations cause autosomal recessive nonsyndromic deafness (DFNB28). The gene shows high tolerance to loss-of-function variants (very low pLI), consistent with its autosomal recessive inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.711 OMIM phenotype
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
50 unique Pathogenic / Likely Pathogenic· 205 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — TRIOBP
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.71LOEUF
pLI 0.000
Z-score 4.07
OE 0.58 (0.47–0.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.20Z-score
OE missense 1.01 (0.97–1.06)
1396 obs / 1375.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.58 (0.47–0.71)
0≤0.351.4
Missense OE1.01 (0.97–1.06)
0≤0.61.4
Synonymous OE0.94
0≤1.21.6
LoF obs/exp: 63 / 108.8Missense obs/exp: 1396 / 1375.5Syn Z: 1.20
DN
0.6841th %ile
GOF
0.4973th %ile
LOF
0.4233th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
LOF96% of P/LP variants are LoF

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic14
VUS205
Likely Benign164
Benign46
Conflicting7
36
Pathogenic
14
Likely Pathogenic
205
VUS
164
Likely Benign
46
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
34
0
2
0
36
Likely Pathogenic
14
0
0
0
14
VUS
2
189
12
2
205
Likely Benign
0
13
58
93
164
Benign
0
4
40
2
46
Conflicting
—7
Total5020611297472

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients