THOC5
protein-codingTHO complex subunit 5, the group of THO complex
Gene summary
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]
- C22orf19
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~49.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to THOC5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003678.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 1 | 4 | ||
| missense | 69 | 1 | 70 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 77 | 1 | 2 | 80 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003669.4 | 19 | MANE Select | |
| Ensembl | ENSP00000420306.1 | 19 | MANE Select | |
| RefSeq | NP_001002877.1 | 19 | Standard | |
| RefSeq | NP_001002878.1 | 19 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- RNA transport - Homo sapiens (human)
- Gene expression (Transcription)
- RNA Polymerase II Transcription
- Metabolism of RNA
- Cleavage of Growing Transcript in the Termination Region
Biological Process
- RNA export from nucleus
- mRNA export from nucleus
- RNA splicing
- monocyte differentiation
- mRNA 3'-end processing
Molecular Function
- mRNA binding
- protein binding
Cellular Component
- nuclear chromosome
- transcription export complex
- THO complex
- THO complex part of transcription export complex
- nuclear chromosome, telomeric region
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000490103
- Coding exons
- 19
- Length
- 49338
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 125748
- p
- 0.0000915
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.73 | 296 | 393 | 0.754 | 0.0000220 | 4512 |
| Missense (PolyPhen) | 45 | 61.81 | 0.72804 | 808 | ||
| Synonymous | 0.879 | 140 | 154 | 0.910 | 0.00000880 | 1260 |
| Loss of Function | 4.42 | 11 | 41.9 | 0.263 | 0.00000210 | 491 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00012 | 0.00012 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway. The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production. THOC5 in conjunction with ALYREF/THOC4 functions in NXF1-NXT1 mediated nuclear export of HSP70 mRNA; both proteins enhance the RNA binding activity of NXF1 and are required for NXF1 localization to the nuclear rim. Involved in transcription elongation and genome stability. Involved in alternative polyadenylation site choice by recruiting CPSF6 to 5' region of target genes; probably mediates association of the TREX and CFIm complexes.;
Recessive Scores
- pRec
- 0.0985
Intolerance Scores
- LoFtool
- 0.676
- RVIS EVS
- 0.22
- RVIS percentile EVS
- 68.38
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.554
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |