THOC2

Chr XX-linked

THO complex subunit 2

Also known as: AMC7, CXorf3, MRX12, MRX35, THO2, XLID12, dJ506G2.1, hTREX120

The protein is a member of the THO complex that binds to spliced mRNAs and facilitates their export from the nucleus. Loss-of-function mutations cause X-linked intellectual developmental disorder (Kumar type) and X-linked arthrogryposis multiplex congenita type 7. The inheritance pattern is X-linked, with the mechanism of pathogenicity being loss of function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismX-linkedLOEUF 0.082 OMIM phenotypes
Clinical SummaryTHOC2
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Gene-Disease Validity (ClinGen)
X-linked complex neurodevelopmental disorder · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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.
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GeneReview available — THOC2
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 6.99
OE 0.02 (0.010.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
5.53Z-score
OE missense 0.33 (0.290.37)
178 obs / 539.0 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.02 (0.010.08)
00.351.4
Missense OE0.33 (0.290.37)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 1 / 58.9Missense obs/exp: 178 / 539.0Syn Z: 0.20
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongTHOC2-related intellectual developmental disorderOTHERXLR
DN
0.15100th %ile
GOF
0.2099th %ile
LOF
0.88top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.08

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

THOC2 · 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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