THOC1

Chr 18AD

THO complex subunit 1

Also known as: DFNA86, HPR1, P84, P84N5

NCBI Gene: 9984 ENSG00000079134 UniProt: Q96FV9 OMIM: 606930

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.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

Enables identical protein 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, Jun 2026]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Deafness, autosomal dominant 86MIM #620280

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.23

LOEUF· LoF intol.

LOF

Mechanism· predicted

📖

GeneReview available — THOC1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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 OE?0.10 (0.05–0.23)

0≤0.351.4

Missense OE?0.59 (0.52–0.67)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 4 / 39.8Missense obs/exp: 185 / 313.4Syn Z: 0.60

Background carrier burden — how many people carry a rare variant somewhere in THOC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

593 rare PASS variants

Rare truncating (LoF)

1 in 2,100

108 rare PASS variants

Rare synonymous (reference)

1 in 200

258 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for THOC1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 250	1 in 2,500
South Asian	~43k	1 in 130	1 in 1,400
Remaining (unassigned)	~30k	1 in 180	1 in 2,700
European (Finnish)	~27k	1 in 380	1 in 3,700
Admixed American	~22k	1 in 130	1 in 500
African / African American	~21k	1 in 200	1 in 1,900
East Asian	~20k	1 in 170	1 in 2,200
Ashkenazi Jewish	~13k	1 in 480	1 in 760
Middle Eastern	~2,884	1 in 190	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 16 of 21 coding exons well covered in gnomAD exomes; exons 5, 6, 8, 10, 11 marginal. Genomes: all 21.? see exons ↓