THOC2

Chr XX-linked

THO complex subunit 2

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

NCBI Gene: 57187 ENSG00000125676 UniProt: Q8NI27 OMIM: 300395

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The TREX multiprotein complex binds specifically to spliced mRNAs to facilitate mRNA export. The protein encoded by this gene is a member of the THO complex, a subset of the TREX complex. The encoded protein interacts with the THOC1 protein.[provided by RefSeq, Jun 2010]

OMIM ResearchGenerating clinical summary…

LOFmechanismX-linkedLOEUF 0.082 OMIM phenotypes

Clinical Summary— THOC2

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Gene-Disease Validity (ClinGen)

X-linked complex neurodevelopmental disorder · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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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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ClinVar Variants

19 unique Pathogenic / Likely Pathogenic· 210 VUS of 601 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.08LOEUF

pLI 1.000

Z-score 6.99

OE 0.02 (0.01–0.08)

Highly constrained

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

Missense Constraint?

5.53Z-score

OE missense 0.33 (0.29–0.37)

178 obs / 539.0 exp

Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?

LoF OE?0.02 (0.01–0.08)

0≤0.351.4

Missense OE?0.33 (0.29–0.37)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 1 / 58.9Missense obs/exp: 178 / 539.0Syn Z: 0.20

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongTHOC2-related intellectual developmental disorderOTHERXLR

This gene — mechanism propensity

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

601 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic15

VUS210

Likely Benign42

Benign21

Conflicting3

Pathogenic

Likely Pathogenic

210

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	1	2	0	4
Likely Pathogenic	1	13	1	0	15
VUS	3	193	12	2	210
Likely Benign	0	4	15	23	42
Benign	0	2	11	8	21
Conflicting	—				3
Total	5	213	41	33	295

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

View in ClinVar →

88 pathogenic / likely-pathogenic (of 99) ClinVar copy-number / structural variants overlap THOC2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →