THOC7

Chr 3

THO complex subunit 7

Also known as: NIF3L1BP1, fSAP24, hTREX30

NCBI Gene: 80145 ENSG00000163634 UniProt: Q6I9Y2 OMIM: 611965

The THOC7 protein is a component of the TREX complex that couples mRNA transcription, processing and nuclear export, and is required for efficient export of polyadenylated RNA from the nucleus to the cytoplasm. Mutations cause autosomal recessive intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies. This gene has moderate constraint against loss-of-function variants and is associated with a GeneReviews entry indicating established clinical significance.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable RNA binding activity. Involved in mRNA export from nucleus. Located in chromosome, telomeric region; cytosol; and nuclear speck. Part of THO complex part of transcription export complex. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.82

Clinical Summary— THOC7

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

24 VUS of 34 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — THOC7

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?

0.82LOEUF

pLI 0.006

Z-score 2.06

OE 0.42 (0.23–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.09Z-score

OE missense 0.70 (0.58–0.85)

76 obs / 107.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.23–0.82)

0≤0.351.4

Missense OE?0.70 (0.58–0.85)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 6 / 14.4Missense obs/exp: 76 / 107.9Syn Z: -0.60

This gene — mechanism propensity

0.75top 25%

GOF

0.6247th %ile

LOF

0.2680th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

34 submitted variants in ClinVar

ClinVar

Classification Summary

VUS24

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	24	24
Likely Benign	0	0
Benign	0	0
Total	24	24

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap THOC7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →