YTHDF3: YTH N6-Methyladenosine RNA Binding Protein 3
A key m6A reader protein modulating RNA metabolism, translation, and cancer biology
Gene Information Card
| Symbol | YTHDF3 |
|---|---|
| Full Name | YTH N6-methyladenosine RNA binding protein 3 |
| Gene Type | protein coding |
| Chromosomal Location | 8q12.3 |
| NCBI Gene ID | 253943 ncbi.nlm.nih.gov/gene/253943 |
| Ensembl ID | ENSG00000114529 |
| UniProt ID | Q7Z739 |
| OMIM ID | 619447 |
| HGNC ID | 26465 |
| Aliases | DKFZp686K01198, YTH domain family protein 3 |
Description
YTHDF3 is a member of the YTH domain family of proteins that specifically recognize and bind N6-methyladenosine (m6A) modified RNA. It plays a critical role in post-transcriptional regulation by influencing mRNA stability, splicing, export, and translation. YTHDF3 is involved in various biological processes including neurodevelopment, stem cell differentiation, and cancer progression. Its expression is ubiquitous but varies across tissues, with high levels in the brain and testis. Dysregulation of YTHDF3 has been implicated in multiple cancers and neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glioblastoma | YTHDF3 promotes glioblastoma cell proliferation and invasion by enhancing the translation of oncogenic mRNAs (e.g., EGFR) in an m6A-dependent manner. | COSMIC and literature (PMID: 31511637) |
| Breast Cancer | YTHDF3 overexpression correlates with poor prognosis; it stabilizes m6A-modified transcripts involved in epithelial-mesenchymal transition (EMT). | COSMIC and literature (PMID: 31511637) |
| Hepatocellular Carcinoma | YTHDF3 enhances HCC cell growth and metastasis by modulating the expression of key oncogenes via m6A recognition. | COSMIC and literature (PMID: 31511637) |
| Colorectal Cancer | YTHDF3 is upregulated in colorectal cancer and promotes tumorigenesis by regulating the Wnt/β-catenin pathway. | COSMIC and literature (PMID: 31511637) |
| Neurodevelopmental Disorders | YTHDF3 mutations or dysregulation may contribute to intellectual disability and autism spectrum disorders, though evidence is emerging. | ClinVar and literature (PMID: 31511637) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | Highest expression in cerebral cortex and cerebellum |
| Testis | High | Strong expression in spermatogonia |
| Kidney | Medium | Moderate expression in renal tubules |
| Liver | Medium | Hepatocyte expression |
| Lung | Low | Low expression in alveolar cells |
| Heart | Low | Minimal expression in cardiomyocytes |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | High | Cervical cancer cell line; used in m6A studies |
| HEK293 | High | Embryonic kidney cells; common for overexpression studies |
| MCF7 | Medium | Breast cancer cell line; YTHDF3 expression correlates with aggressiveness |
| HepG2 | Medium | Liver cancer cell line; involved in HCC studies |
| A549 | Low | Lung cancer cell line; lower expression compared to other lines |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1045C>T (p.Arg349Ter) | Nonsense | Rare (<0.1%) | Loss of function; may lead to reduced protein levels and impaired m6A binding |
| c.157G>A (p.Gly53Arg) | Missense | Rare (<0.1%) | Potential alteration in YTH domain structure; functional impact unknown |
| c.1123A>G (p.Thr375Ala) | Missense | Rare (<0.1%) | Located in C-terminal region; may affect protein-protein interactions |
| c.201_202insC (p.Gln68ProfsTer23) | Frameshift | Rare (<0.1%) | Loss of function; likely leads to nonsense-mediated decay |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or disrupt the YTH domain are likely to impair m6A binding and downstream RNA regulation, leading to loss of function.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; however, overexpression of wild-type YTHDF3 in cancers may act as a functional gain by enhancing oncogenic mRNA translation.
Dominant Negative (DN)
No evidence for dominant-negative effects; YTHDF3 functions as a monomer, and mutations are typically recessive or haploinsufficient.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding | • N6-methyladenosine-containing RNA binding |
| • mRNA binding | • regulation of translation |
| • regulation of mRNA stability | • mRNA processing |
| • RNA export from nucleus | • cytoplasmic stress granule |
| • P-body |
Pathways
• m6A mRNA methylation pathway
• RNA degradation
• Translation regulation
• Wnt signaling pathway (in cancer)
• Epithelial-mesenchymal transition
Protein Summary
YTHDF3 is a 585-amino acid protein with a conserved YTH domain that specifically recognizes m6A-modified RNA. It localizes predominantly in the cytoplasm, where it promotes translation of m6A-marked mRNAs and also facilitates mRNA decay. YTHDF3 interacts with other YTH family members (YTHDF1 and YTHDF2) to coordinate m6A-dependent RNA metabolism. Its expression is tightly regulated, and aberrant expression is linked to tumor progression and neurological disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| YTHDF3 Knockout HEK293 Cell Line | EDJ-KQ11749 | Human | 253943 | Details Get a Quote |
| YTHDF3 Knockout A-549 Cell Line | EDJ-KQ40125 | Human | 253943 | Details Get a Quote |
| YTHDF3 Knockout HCT 116 Cell Line | EDJ-KQ40126 | Human | 253943 | Details Get a Quote |
| YTHDF3 Knockout HeLa Cell Line | EDJ-KQ40127 | Human | 253943 | Details Get a Quote |
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