THOC6

Chr 16

THO complex subunit 6

Also known as: MMRFCGU, WDR58, fSAP35

NCBI Gene: 79228 ENSG00000131652 UniProt: Q86W42

The protein is a subunit of the THO complex that coordinates transcription with mRNA processing and export from the nucleus. Mutations cause Beaulieu-Boycott-Innes syndrome, a neurodevelopmental disorder inherited in an autosomal recessive pattern. The pathogenic mechanism involves disruption of the transcription-export machinery critical for proper mRNA metabolism.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a subunit of the multi-protein THO complex, which is involved in coordination between transcription and mRNA processing. The THO complex is a component of the TREX (transcription/export) complex, which is involved in transcription and export of mRNAs. A missense mutation in this gene is associated with a neurodevelopmental disorder called Beaulieu-Boycott-Innes syndrome. [provided by RefSeq, Dec 2016]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtBeaulieu-Boycott-Innes syndrome

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome · AR · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.67

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — THOC6

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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?

0.67LOEUF

pLI 0.000

Z-score 2.81

OE 0.40 (0.24–0.67)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.40Z-score

OE missense 1.08 (0.97–1.21)

223 obs / 206.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.40 (0.24–0.67)

0≤0.351.4

Missense OE?1.08 (0.97–1.21)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 10 / 25.2Missense obs/exp: 223 / 206.8Syn Z: -1.47

Background carrier burden — how many people carry a rare variant somewhere in THOC6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

504 rare PASS variants

Rare truncating (LoF)

1 in 2,100

86 rare PASS variants

Rare synonymous (reference)

1 in 180

207 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for THOC6. 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 110	1 in 2,400
South Asian	~43k	1 in 140	1 in 1,400
Remaining (unassigned)	~30k	1 in 99	1 in 2,200
European (Finnish)	~27k	1 in 440	≈ 1 in 13,000
Admixed American	~22k	1 in 120	≈ 1 in 11,000
African / African American	~21k	1 in 90	1 in 1,400
East Asian	~20k	1 in 130	1 in 1,000
Ashkenazi Jewish	~13k	1 in 390	none seen
Middle Eastern	~2,884	1 in 140	≈ 1 in 2,900

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): All 13 coding exons well covered in gnomAD exomes and genomes.? see exons ↓