THOC5

Chr 22

THO complex subunit 5

Also known as: C22orf19, Fmip, PK1.3, fSAP79

NCBI Gene: 8563ENSG00000100296UniProt: Q13769

Predicted to enable mRNA binding activity. Involved in mRNA export from nucleus and monocyte differentiation. Located in chromosome, telomeric region and nucleoplasm. Part of THO complex part of transcription export complex. Implicated in breast carcinoma. [provided by Alliance of Genome Resources, Jul 2025]

114
ClinVar variants
26
Pathogenic / LP
0.05
pLI score
0
Active trials
Clinical Summary— THOC5
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 63 VUS of 114 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.43LOEUF
pLI 0.045
Z-score 4.42
OE 0.26 (0.16–0.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.73Z-score
OE missense 0.75 (0.69–0.83)
296 obs / 392.7 exp
Tolerant

Mild missense constraint

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.0.26 (0.16–0.43)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.69–0.83)
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.0.91
0≤1.21.6
LoF obs/exp: 11 / 41.9Missense obs/exp: 296 / 392.7Syn Z: 0.88

ClinVar Variant Classifications

114 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic1
VUS63
Likely Benign1
Benign2
25
Pathogenic
1
Likely Pathogenic
63
VUS
1
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
25
0
25
Likely Pathogenic
0
0
1
0
1
VUS
0
60
3
0
63
Likely Benign
0
0
0
1
1
Benign
0
1
0
1
2
Total06129292

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

View in ClinVar →

Protein Context — Lollipop Plot

THOC5 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
mRNA export protein THOC5 as a tool for identification of target genes for cancer therapy.
Tran DD et al.·Cancer Lett
2016Review
The host genes influencing Clostridioides difficile infection and the potential role of intestinal Lactobacillus acidophilus: a Mendelian randomization and animal model study.
Sun Y et al.·Front Cell Infect Microbiol
2025Functional
THO Complex-Dependent Posttranscriptional Control Contributes to Vascular Smooth Muscle Cell Fate Decision.
Yuan X et al.·Circ Res
2018
Integrated bioinformatic analysis of RNA binding proteins in hepatocellular carcinoma.
Wang L et al.·Aging (Albany NY)
2020
THOC5: a novel gene involved in HDL-cholesterol metabolism.
Keller M et al.·J Lipid Res
2013
Clinical and functional characterization of recurrent missense variants implicated in THOC6-related intellectual disability.
Mattioli F et al.·Hum Mol Genet
2019Functional
Identification of an individualized RNA binding protein-based prognostic signature for diffuse large B-cell lymphoma.
Xie Y et al.·Cancer Med
2021
NTF2-like domain of Tap plays a critical role in cargo mRNA recognition and export.
Katahira J et al.·Nucleic Acids Res
2015
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