THOC6

Chr 16AR

THO complex subunit 6

Also known as: MMRFCGU, WDR58, fSAP35

NCBI Gene: 79228ENSG00000131652UniProt: Q86W42

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]

Primary Disease Associations & Inheritance

Beaulieu-Boycott-Innes syndromeMIM #613680
AR
165
ClinVar variants
60
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— THOC6
🧬
Gene-Disease Validity (ClinGen)
THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
60 Pathogenic / Likely Pathogenic· 77 VUS of 165 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.67LOEUF
pLI 0.000
Z-score 2.81
OE 0.40 (0.24–0.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.40Z-score
OE missense 1.08 (0.97–1.21)
223 obs / 206.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.40 (0.24–0.67)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.08 (0.97–1.21)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.20
0≤1.21.6
LoF obs/exp: 10 / 25.2Missense obs/exp: 223 / 206.8Syn Z: -1.47

ClinVar Variant Classifications

165 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45
Likely Pathogenic15
VUS77
Likely Benign21
Benign4
Conflicting3
45
Pathogenic
15
Likely Pathogenic
77
VUS
21
Likely Benign
4
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
2
39
0
45
Likely Pathogenic
7
3
5
0
15
VUS
1
64
12
0
77
Likely Benign
0
3
3
15
21
Benign
0
0
2
2
4
Conflicting
—3
Total12726117165

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

View in ClinVar →

Protein Context — Lollipop Plot

THOC6 · protein map & ClinVar variants

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

Gene2Phenotype Curations

THOC6-related Beaulieu-Boycott-Innes syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Beaulieu-Boycott-Innes syndrome

MIM #613680

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — THOC6
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Nuclear farnesoid X receptor protects against bone loss by driving osteoblast differentiation through stabilizing RUNX2.
Dong Q et al.·Bone Res
2025
Biallelic THOC6 pathogenic variants: Prenatal phenotype and review of the literature.
Ruaud L et al.·Birth Defects Res
2022Review
Clinical and functional characterization of recurrent missense variants implicated in THOC6-related intellectual disability.
Mattioli F et al.·Hum Mol Genet
2019Functional
Novel CNS malformations and skeletal anomalies in a patient with Beaulieu-boycott-Innes syndrome.
Accogli A et al.·Am J Med Genet A
2018Review
A truncating variant in the THOC6 gene with new findings in a patient with Beaulieu-Boycott-Innes syndrome.
Kiraz A et al.·Am J Med Genet A
2022Case report
THOC6 is a novel biomarker of glioma and a target of anti-glioma drugs: An analysis based on bioinformatics and molecular docking.
Wei C et al.·Medicine (Baltimore)
2024
Autosomal recessive mutations in THOC6 cause intellectual disability: syndrome delineation requiring forward and reverse phenotyping.
Amos JS et al.·Clin Genet
2017Case report
Proteinuria in Two Sisters with Beaulieu-Boycott-Innes Syndrome, A Case Report.
Hassanvand Amouzadeh M et al.·Iran J Kidney Dis
2020Case report
First report of THOC6 related intellectual disability (Beaulieu Boycott Innes syndrome) in two siblings from India.
Gupta N et al.·Eur J Med Genet
2020Case report
Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.
Anazi S et al.·Mol Psychiatry
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools