THOC6

Chr 16AR

THO complex subunit 6

Also known as: MMRFCGU, WDR58, fSAP35

NCBI Gene: 79228 ENSG00000131652 UniProt: Q86W42 OMIM: 615403

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 OMIM 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 OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.671 OMIM phenotype

Clinical Summary— THOC6

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Gene-Disease Validity (ClinGen)

THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

27 unique Pathogenic / Likely Pathogenic· 69 VUS of 141 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — THOC6

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?

0.67LOEUF

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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveTHOC6-related Beaulieu-Boycott-Innes syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6550th %ile

GOF

0.5072th %ile

LOF

0.3549th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

141 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10

Likely Pathogenic17

VUS69

Likely Benign21

Benign4

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	8	2	0	0	10
Likely Pathogenic	12	5	0	0	17
VUS	1	65	3	0	69
Likely Benign	0	3	3	15	21
Benign	0	0	2	2	4
Conflicting	—				1
Total	21	75	8	17	122

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

View in ClinVar →

35 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap THOC6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →