FAT1 Gene - FAT Atypical Cadherin 1
Comprehensive genomic and functional overview of the FAT1 gene, a tumor suppressor and planar cell polarity regulator.
Gene Information Card
| Symbol | FAT1 |
|---|---|
| Full Name | FAT atypical cadherin 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 4q35.2 |
| NCBI Gene ID | 2195 ncbi.nlm.nih.gov/gene/2195 |
| Ensembl ID | ENSG00000083857 |
| UniProt ID | Q14517 |
| OMIM ID | 600976 |
| HGNC ID | 3595 |
| Aliases | CDHF7, CDHR8, FAT, ME5, hFat1 |
Description
FAT1 encodes a protocadherin that functions as a tumor suppressor and regulator of planar cell polarity (PCP). It is involved in cell-cell adhesion, migration, and Hippo signaling. Loss-of-function mutations are recurrent in multiple cancers, including glioblastoma, head and neck squamous cell carcinoma, and colorectal cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glioblastoma | Loss of FAT1 disrupts Hippo signaling and promotes YAP/TAZ nuclear localization, driving proliferation. | COSMIC; ClinVar |
| Head and Neck Squamous Cell Carcinoma | Recurrent truncating mutations lead to loss of tumor suppressor function and increased invasion. | COSMIC; ClinVar |
| Colorectal Cancer | FAT1 frameshift and nonsense mutations are associated with microsatellite instability and poor prognosis. | COSMIC; ClinVar |
| Hereditary Cancer Predisposition | Germline FAT1 variants are implicated in a subset of familial cancer syndromes. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 15.2 | Medium |
| Colon | 9.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| U-87 MG (glioblastoma) | 18.4 | High expression; consistent with glial origin |
| A549 (lung carcinoma) | 7.2 | Moderate expression |
| HCT 116 (colorectal carcinoma) | 5.8 | Low expression; often lost in tumors |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | 3.2% in HNSCC | Loss of function; truncation of cadherin repeats |
| c.789_790del (p.Glu264fs) | Frameshift | 2.1% in colorectal cancer | Loss of function; premature stop |
| c.4567G>A (p.Gly1523Arg) | Missense | 0.8% in glioblastoma | Unknown; likely damaging (PolyPhen-2) |
Mutation functional classification
Loss of Function (LOF)
Recurrent nonsense and frameshift mutations truncate the protein, abrogating cadherin repeats and intracellular domain, leading to loss of tumor suppression.
Gain of Function (GOF)
Not established; no activating mutations reported in FAT1.
Dominant Negative (DN)
Possible for missense variants that disrupt homodimerization or ligand binding, but not well characterized.
View complete mutation data：
Gene Ontology (GO)
| • cell adhesion (GO:0007155) | • planar cell polarity (GO:0001738) |
| • Hippo signaling (GO:0035329) | • cadherin binding (GO:0045296) |
| • negative regulation of cell proliferation (GO:0008285) |
Pathways
• Hippo signaling pathway (KEGG: hsa04390)
• Planar cell polarity pathway (Reactome: R-HSA-4086400)
• Cell-cell junction organization (Reactome: R-HSA-421270)
Protein Summary
FAT1 is a large transmembrane protocadherin (approx. 4588 amino acids) with 34 cadherin repeats, a transmembrane domain, and a cytoplasmic tail that interacts with β-catenin and Hippo pathway components. It mediates calcium-dependent cell adhesion and regulates cell polarity and proliferation. Loss of FAT1 is oncogenic in multiple tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FAT1 Knockout HEK293 Cell Line | EDJ-KQ3823 | Human | 2195 | Details Get a Quote |
| FAT1 Knockout A-549 Cell Line | EDJ-KQ25964 | Human | 2195 | Details Get a Quote |
| FAT1 Knockout HCT 116 Cell Line | EDJ-KQ25965 | Human | 2195 | Details Get a Quote |
| FAT1 Knockout HeLa Cell Line | EDJ-KQ25966 | Human | 2195 | Details Get a Quote |
| Fat1 Knockout 4T1 Cell Line | EDJ-KZ243 | Mouse | 14107 | Details Get a Quote |
| Fat1 Knockout ID8 Cell Line | EDJ-KZ244 | Mouse | 14107 | Details Get a Quote |
| Fat1 Knockout MC-38 Cell Line | EDJ-KZ245 | Mouse | 2195 | Details Get a Quote |
