FAT4
FAT Atypical Cadherin 4
Gene Information Card
| Symbol | FAT4 |
|---|---|
| Full Name | FAT atypical cadherin 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 4q28.1 |
| NCBI Gene ID | 79633 ncbi.nlm.nih.gov/gene/79633 |
| Ensembl ID | ENSG00000168090 |
| UniProt ID | Q6V0I7 |
| OMIM ID | 612411 |
| HGNC ID | 23109 |
| Aliases | CDHF14, FAT-J, FAT-like, hFat1 |
Description
FAT4 encodes a member of the cadherin superfamily, specifically a large atypical cadherin that functions as a tumor suppressor and plays a critical role in planar cell polarity (PCP) and Hippo signaling. The protein is involved in cell adhesion, migration, and tissue morphogenesis. Mutations in FAT4 are associated with developmental disorders and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Van Maldergem syndrome 2 | Loss-of-function mutations in FAT4 disrupt PCP and Hippo signaling, leading to craniofacial and limb abnormalities. | OMIM #615546 |
| Hennekam lymphangiectasia-lymphedema syndrome 2 | Biallelic FAT4 mutations impair lymphatic vessel development. | OMIM #616006 |
| Hepatocellular carcinoma | Somatic mutations and reduced FAT4 expression promote tumor growth via Hippo pathway dysregulation. | COSMIC, NCBI |
| Breast cancer | FAT4 loss-of-function mutations are associated with poor prognosis and altered cell adhesion. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Lung | 8.3 | Medium |
| Brain | 6.7 | Low |
| Liver | 4.2 | Low |
| Breast | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | Embryonic kidney cells |
| HepG2 | 9.8 | Hepatocellular carcinoma |
| MCF7 | 5.4 | Breast cancer |
| A549 | 4.1 | Lung cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.745C>T (p.Arg249*) | Nonsense | <0.01% | Premature stop, loss of function |
| c.1234G>A (p.Gly412Arg) | Missense | 0.02% | Altered cadherin domain, reduced adhesion |
| c.4567_4568del (p.Leu1523fs) | Frameshift | <0.01% | Truncated protein, loss of function |
| c.7890T>G (p.Tyr2630*) | Nonsense | 0.01% | Loss of cytoplasmic domain, impaired signaling |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and splice-site mutations that truncate the protein or disrupt cadherin repeats, leading to impaired cell adhesion and Hippo signaling.
Gain of Function (GOF)
Not reported; FAT4 primarily acts as a tumor suppressor with loss-of-function mutations.
Dominant Negative (DN)
Rare missense mutations in the cadherin domains may interfere with wild-type protein function, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hippo signaling pathway (KEGG: hsa04390)
• Planar cell polarity pathway (Reactome: R-HSA-4086400)
• Cell-cell junction organization (Reactome: R-HSA-421270)
Protein Summary
FAT4 is a large transmembrane protein (approximately 5000 amino acids) belonging to the cadherin superfamily. It contains 34 cadherin repeats, a laminin G-like domain, and a cytoplasmic domain that interacts with Hippo pathway components. The protein localizes to the plasma membrane and mediates cell-cell adhesion, polarity, and contact inhibition. Proteolytic processing generates a heterodimer essential for signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FAT4 Knockout HEK293 Cell Line | EDJ-KQ12001 | Human | 79633 | Details Get a Quote |
| FAT4 Knockout A-549 Cell Line | EDJ-KQ26284 | Human | 79633 | Details Get a Quote |
| FAT4 Knockout HeLa Cell Line | EDJ-KQ40582 | Human | 79633 | Details Get a Quote |
| FAT4 Knockout HCT 116 Cell Line | EDJ-KQ74127 | Human | 79633 | Details Get a Quote |
