THOC1

Chr 18AD

THO complex subunit 1

Also known as: DFNA86, HPR1, P84, P84N5

The THOC1 protein is a component of the THO complex that couples mRNA transcription, processing and nuclear export, and is required for efficient export of polyadenylated RNA from the nucleus to the cytoplasm. Mutations cause autosomal dominant nonsyndromic deafness 86, which affects hearing without other systemic features. THOC1 is highly constrained against loss-of-function variants, indicating that such variants are likely to be pathogenic when they occur.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismADLOEUF 0.231 OMIM phenotype
Clinical SummaryTHOC1
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 1.000
Z-score 5.26
OE 0.10 (0.050.23)
Highly constrained

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

Missense Constraint
2.58Z-score
OE missense 0.59 (0.520.67)
185 obs / 313.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.10 (0.050.23)
00.351.4
Missense OE0.59 (0.520.67)
00.61.4
Synonymous OE0.93
01.21.6
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

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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