THOC1

Chr 18AD

THO complex subunit 1

Also known as: DFNA86, HPR1, P84, P84N5

NCBI Gene: 9984ENSG00000079134UniProt: Q96FV9

Predicted to enable DNA binding activity and RNA binding activity. Involved in mRNA export from nucleus. Located in chromosome, telomeric region; cytoplasm; and nuclear speck. Part of THO complex part of transcription export complex. Implicated in autosomal dominant nonsyndromic deafness 86. [provided by Alliance of Genome Resources, Jul 2025]

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Primary Disease Associations & Inheritance

?Deafness, autosomal dominant 86MIM #620280
AD
0
Active trials
3
Pubs (1 yr)
128
P/LP submissions
1%
P/LP missense
0.23
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— THOC1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
123 unique Pathogenic / Likely Pathogenic· 75 VUS of 227 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — THOC1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 1.000
Z-score 5.26
OE 0.10 (0.05–0.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.58Z-score
OE missense 0.59 (0.52–0.67)
185 obs / 313.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.10 (0.05–0.23)
0≤0.351.4
Missense OE0.59 (0.52–0.67)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 4 / 39.8Missense obs/exp: 185 / 313.4Syn Z: 0.60
DN
0.3594th %ile
GOF
0.4085th %ile
LOF
0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.23

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

227 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic119
Likely Pathogenic4
VUS75
Likely Benign5
119
Pathogenic
4
Likely Pathogenic
75
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
118
0
119
Likely Pathogenic
0
0
4
0
4
VUS
0
49
26
0
75
Likely Benign
0
1
4
0
5
Benign
0
0
0
0
0
Total0511520203

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

View in ClinVar →

Protein Context — Lollipop Plot

THOC1 · protein map & ClinVar variants

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

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