THOC6: A Key Component of the THO Complex and Its Role in Neurodevelopmental Disorders
Comprehensive genomic and functional analysis of THOC6, associated with THOC6-related intellectual disability and microcephaly.
Gene Information Card
| Symbol | THOC6 |
|---|---|
| Full Name | THO complex subunit 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 79228 ncbi.nlm.nih.gov/gene/79228 |
| Ensembl ID | ENSG00000131669 |
| UniProt ID | Q86W42 |
| OMIM ID | 615403 |
| HGNC ID | 28369 |
| Aliases | fSAP35, NIF3L1BP1, THO complex subunit 6 homolog |
Description
THOC6 encodes a subunit of the THO complex, which is part of the larger TREX (transcription/export) complex. The THO complex is involved in transcription elongation, mRNA export from the nucleus, and genome stability. Mutations in THOC6 cause autosomal recessive intellectual disability with microcephaly (THOC6-related intellectual disability syndrome). The protein is ubiquitously expressed and localizes to the nucleus.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| THOC6-related intellectual disability syndrome (autosomal recessive intellectual disability with microcephaly) | Loss-of-function mutations in THOC6 impair THO complex assembly, leading to defective mRNA export and transcription elongation, resulting in neurodevelopmental deficits. | Multiple reports in OMIM (615403) and ClinVar; biallelic pathogenic variants identified in affected individuals. |
| Microcephaly | Disrupted THO complex function affects neural progenitor cell proliferation and survival, contributing to reduced brain size. | Observed in patients with THOC6 mutations; documented in OMIM and literature. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 10.2 | Medium |
| Lymph node | 8.9 | Medium |
| Liver | 7.1 | Low |
| Kidney | 6.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.3 | High expression in embryonic kidney cells |
| HeLa | 12.1 | Moderate expression in cervical cancer cells |
| K562 | 9.4 | Moderate expression in leukemia cells |
| HepG2 | 7.8 | Low expression in liver cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.662G>A (p.Arg221Gln) | Missense | Rare | Loss of function; disrupts THO complex interaction |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; prevents translation initiation |
| c.325C>T (p.Arg109*) | Nonsense | Rare | Loss of function; premature truncation |
| c.472_473del (p.Leu158Glufs*2) | Frameshift | Rare | Loss of function; frameshift and premature stop |
Mutation functional classification
Loss of Function (LOF)
Most THOC6 mutations are loss-of-function (nonsense, frameshift, missense affecting protein stability or complex assembly), leading to haploinsufficiency or complete loss of THO complex activity.
Gain of Function (GOF)
No gain-of-function mutations reported for THOC6.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • mRNA export from nucleus (GO:0006406) | • transcription elongation from RNA polymerase II promoter (GO:0006368) |
| • THO complex (GO:0000347) | • nucleus (GO:0005634) |
| • protein binding (GO:0005515) |
Pathways
• TREX complex pathway (mRNA export)
• RNA polymerase II transcription elongation
Protein Summary
THOC6 is a 35 kDa nuclear protein that forms part of the THO complex, which is essential for coupling transcription elongation with mRNA export. The protein contains a conserved domain that mediates interactions with other THO subunits (THOC1, THOC2, THOC5, THOC7). Loss of THOC6 leads to nuclear retention of mRNA and transcription defects, particularly affecting genes critical for neurodevelopment.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| THOC6 Knockout HEK293 Cell Line | EDJ-KQ15725 | Human | 79228 | Details Get a Quote |
| THOC6 Knockout A-549 Cell Line | EDJ-KQ45404 | Human | 79228 | Details Get a Quote |
| THOC6 Knockout HCT 116 Cell Line | EDJ-KQ46639 | Human | 79228 | Details Get a Quote |
| THOC6 Knockout HeLa Cell Line | EDJ-KQ46640 | Human | 79228 | Details Get a Quote |
