FRAT1: A Key Regulator of WNT Signaling and Its Role in Cancer
Comprehensive genomic and functional analysis of FRAT1, a WNT pathway modulator implicated in tumorigenesis and developmental processes.
Gene Information Card
| Symbol | FRAT1 |
|---|---|
| Full Name | FRAT regulator of WNT signaling pathway 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 10q24.1 |
| NCBI Gene ID | 10023 ncbi.nlm.nih.gov/gene/10023 |
| Ensembl ID | ENSG00000165879 |
| UniProt ID | Q92837 |
| OMIM ID | 602503 |
| HGNC ID | 3949 |
| Aliases | FRAT, FRAT-1, GSK-3-binding protein, GSK3-binding protein |
Description
FRAT1 (FRAT regulator of WNT signaling pathway 1) encodes a protein that positively regulates the WNT/β-catenin signaling pathway by binding to and inhibiting glycogen synthase kinase-3 (GSK3). This inhibition prevents β-catenin phosphorylation and degradation, leading to its nuclear accumulation and transcriptional activation of WNT target genes. FRAT1 is involved in embryonic development, cell proliferation, and has been implicated in various cancers, including colorectal, breast, and lung cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | FRAT1 overexpression stabilizes β-catenin, driving WNT target gene transcription and tumor progression. | COSMIC, ClinVar |
| Breast Cancer | Increased FRAT1 expression correlates with poor prognosis and promotes metastasis via WNT signaling. | NCBI Gene, PubMed |
| Lung Cancer | FRAT1 amplification and overexpression enhance WNT signaling, contributing to oncogenesis. | COSMIC, PubMed |
| Hepatocellular Carcinoma | FRAT1 upregulation activates β-catenin and promotes cell proliferation. | PubMed |
| Gastric Cancer | FRAT1 overexpression linked to advanced stage and worse survival. | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Brain | 8.5 | Low |
| Colon | 6.3 | Low |
| Breast | 4.1 | Low |
| Lung | 3.9 | Low |
| Liver | 2.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 12.1 | Embryonic kidney; high expression |
| HeLa | 8.7 | Cervical cancer; moderate expression |
| MCF7 | 6.4 | Breast cancer; moderate expression |
| A549 | 5.2 | Lung cancer; low expression |
| HCT116 | 4.8 | Colorectal cancer; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Likely loss of start codon; functional impact unknown |
| c.214C>T (p.Arg72Trp) | Missense | <0.1% | Rare; no known disease association |
| c.487G>A (p.Gly163Ser) | Missense | <0.1% | Rare; no known disease association |
| c.634C>T (p.Arg212*) | Nonsense | <0.1% | Premature stop; likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein, impairing GSK3 binding and WNT signaling regulation.
Gain of Function (GOF)
Amplification or overexpression of FRAT1 enhances WNT signaling, promoting oncogenesis.
Dominant Negative (DN)
No dominant-negative mutations reported in FRAT1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• Wnt/β-catenin signaling (Reactome: R-HSA-201681)
• GSK3B inhibition by FRAT1 (Reactome: R-HSA-3772470)
Protein Summary
FRAT1 is a 279-amino acid protein that functions as a positive regulator of the canonical WNT signaling pathway. It binds directly to GSK3B, displacing axin and preventing β-catenin phosphorylation. This leads to β-catenin stabilization and nuclear translocation, activating transcription of WNT target genes such as MYC and CCND1. FRAT1 is predominantly cytoplasmic and is expressed in testis, brain, and various cancer cell lines. Its overexpression is associated with poor prognosis in several cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FRAT1 Knockout HEK293 Cell Line | EDJ-KQ299 | Human | 10023 | Details Get a Quote |
| FRAT1 Knockout HeLa Cell Line | EDJ-KQ18419 | Human | 10023 | Details Get a Quote |
| FRAT1 Knockout A-549 Cell Line | EDJ-KQ63786 | Human | 10023 | Details Get a Quote |
| FRAT1 Knockout HCT 116 Cell Line | EDJ-KQ72243 | Human | 10023 | Details Get a Quote |
