ALYREF: A Key RNA Export Adaptor in Gene Expression
Comprehensive genomic and functional overview of ALYREF, a THO complex subunit involved in mRNA export and implicated in cancer and developmental disorders.
Gene Information Card
| Symbol | ALYREF |
|---|---|
| Full Name | Aly/REF export factor |
| Gene Type | Protein coding |
| Chromosomal Location | 17q25.3 |
| NCBI Gene ID | 10189 ncbi.nlm.nih.gov/gene/10189 |
| Ensembl ID | ENSG00000183684 |
| UniProt ID | Q86V81 |
| OMIM ID | 604830 |
| HGNC ID | 11697 |
| Aliases | ALY, THOC4, BEF, REF |
Description
ALYREF (Aly/REF export factor) encodes a member of the THO complex, which is part of the TREX complex essential for mRNA export from the nucleus to the cytoplasm. The protein binds to spliced mRNA and facilitates its translocation through the nuclear pore. ALYREF is involved in transcriptional elongation, RNA processing, and genome stability. It is ubiquitously expressed and plays a critical role in cellular proliferation and differentiation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | ALYREF overexpression enhances mRNA export of oncogenic transcripts, promoting tumor growth. | ClinVar, COSMIC |
| Colorectal cancer | Somatic mutations and copy number gains in ALYREF correlate with poor prognosis and metastasis. | COSMIC, PubMed |
| Hepatocellular carcinoma | Upregulation of ALYREF increases export of cell cycle mRNAs, driving proliferation. | PubMed |
| Developmental delay (rare) | Heterozygous loss-of-function variants in ALYREF are associated with intellectual disability and microcephaly. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Lymph node | 22.1 | High |
| Bone marrow | 19.8 | High |
| Brain | 12.3 | Medium |
| Liver | 9.7 | Medium |
| Heart | 6.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 24.1 | Embryonic kidney; high expression |
| HeLa | 21.5 | Cervical carcinoma; high expression |
| HepG2 | 18.3 | Hepatocellular carcinoma; moderate expression |
| K562 | 15.7 | Leukemia; moderate expression |
| MCF7 | 12.9 | Breast cancer; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.287A>G (p.Asn96Ser) | Missense | <0.01% | Reduced RNA binding affinity; reported in developmental delay |
| c.502C>T (p.Arg168Trp) | Missense | <0.01% | Loss of nuclear export function; associated with intellectual disability |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Complete loss of protein; likely pathogenic |
| c.724_725insA (p.Thr242Asnfs*5) | Frameshift | <0.01% | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift variants in the RNA-binding domain impair mRNA export, leading to reduced cell proliferation and developmental defects.
Gain of Function (GOF)
Amplification or overexpression in cancers enhances oncogenic mRNA export, promoting tumorigenesis.
Dominant Negative (DN)
Not reported for ALYREF; heterozygous loss-of-function likely leads to haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003723 – RNA binding | • GO:0005654 – nucleoplasm |
| • GO:0006406 – mRNA export from nucleus | • GO:0006397 – mRNA processing |
| • GO:0008380 – RNA splicing | • GO:0030529 – intracellular ribonucleoprotein complex |
| • GO:0045296 – cadherin binding |
Pathways
• mRNA export from nucleus (Reactome: R-HSA-164843)
• Processing of Capped Intron-Containing Pre-mRNA (Reactome: R-HSA-72163)
• TREX complex pathway (Reactome: R-HSA-164952)
Protein Summary
ALYREF is a 257-amino-acid protein (UniProt Q86V81) containing an N-terminal RNA recognition motif (RRM) and a C-terminal arginine-rich region. It shuttles between nucleus and cytoplasm, binding to spliced mRNA and recruiting the export receptor NXF1. The protein is part of the TREX complex, coupling transcription elongation to mRNA export. Post-translational modifications include arginine methylation, which modulates its RNA-binding activity. ALYREF is essential for cell viability and its dysregulation contributes to cancer and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID |
|---|
