THOC5: A Key Component of the THO Complex in mRNA Export and Cellular Homeostasis
Comprehensive genomic, transcriptomic, and proteomic analysis of THOC5 (THO complex subunit 5) with clinical relevance in cancer and developmental disorders.
Gene Information Card
| Symbol | THOC5 |
|---|---|
| Full Name | THO complex subunit 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q12.2 |
| NCBI Gene ID | 8563 ncbi.nlm.nih.gov/gene/8563 |
| Ensembl ID | ENSG00000100242 |
| UniProt ID | Q13769 |
| OMIM ID | 612361 |
| HGNC ID | 19074 |
| Aliases | C22orf19, fSAP79, FMIP, NIF-1, NIF1, THO complex 5 |
Description
THOC5 encodes a subunit of the THO complex, which is part of the TREX (transcription/export) complex. This complex is essential for efficient mRNA export from the nucleus to the cytoplasm, coupling transcription, processing, and export. THOC5 is involved in cellular processes including cell cycle regulation, DNA damage response, and maintenance of genomic stability. Mutations and altered expression of THOC5 have been implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of THOC5 promotes mRNA export of oncogenic transcripts, enhancing proliferation and metastasis. | ClinVar, COSMIC |
| Colorectal cancer | THOC5 upregulation correlates with poor prognosis; involved in Wnt/β-catenin signaling. | COSMIC, PubMed |
| Hepatocellular carcinoma | THOC5 depletion reduces cell viability and induces apoptosis via impaired mRNA export. | COSMIC, PubMed |
| Developmental delay / intellectual disability | De novo missense variants in THOC5 associated with neurodevelopmental phenotypes. | ClinVar, OMIM |
| Acute myeloid leukemia | THOC5 fusion transcripts (e.g., with NUP98) reported in rare cases. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | High |
| Lymph node | 12.8 | High |
| Bone marrow | 11.5 | High |
| Brain | 8.3 | Medium |
| Liver | 6.1 | Medium |
| Heart | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.4 | Embryonic kidney; high expression |
| HeLa | 14.2 | Cervical carcinoma; moderate-high |
| MCF7 | 12.1 | Breast cancer; moderate |
| HepG2 | 9.8 | Hepatocellular carcinoma; moderate |
| K562 | 7.5 | Leukemia; low-moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon; likely loss of function |
| c.287C>T (p.Pro96Leu) | Missense | Rare | ClinVar: uncertain significance; possibly damaging |
| c.1045C>T (p.Arg349Trp) | Missense | Rare | ClinVar: likely pathogenic; associated with developmental delay |
| c.1234_1235insA (p.Thr412Asnfs*3) | Frameshift | Rare | Loss of function; truncation |
| c.1567G>A (p.Glu523Lys) | Missense | Rare | COSMIC: somatic; breast cancer |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations leading to truncated protein or nonsense-mediated decay; associated with developmental disorders.
Gain of Function (GOF)
Overexpression or amplification in cancers; not clearly linked to specific gain-of-function mutations.
Dominant Negative (DN)
Not well characterized; some missense variants may interfere with THO complex assembly.
View complete mutation data：
Gene Ontology (GO)
| • mRNA export from nucleus (GO:0006406) | • RNA splicing (GO:0008380) |
| • nucleoplasm (GO:0005654) | • nucleus (GO:0005634) |
| • protein binding (GO:0005515) | • RNA binding (GO:0003723) |
| • THO complex part of TREX complex (GO:0000448) |
Pathways
• TREX complex pathway (mRNA export)
• Spliceosome pathway
• mRNA surveillance pathway
• Wnt signaling pathway (via β-catenin stabilization)
Protein Summary
THOC5 (THO complex subunit 5) is a 683-amino acid protein (UniProt Q13769) that localizes to the nucleus and nucleoplasm. It is a core component of the THO/TREX complex, which couples transcription elongation to mRNA export. The protein contains a conserved THOC5 domain and interacts with RNA and other TREX subunits (e.g., THOC2, THOC3). THOC5 is essential for cell viability; its depletion leads to nuclear retention of poly(A)+ RNA and impaired cell proliferation. Post-translational modifications include phosphorylation, which may regulate its function in cell cycle and DNA damage response.
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