FAT2: Atypical Cadherin in Development and Cancer
Comprehensive genomic and functional overview of the FAT2 gene
Gene Information Card
| Symbol | FAT2 |
|---|---|
| Full Name | FAT atypical cadherin 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q33.1 |
| NCBI Gene ID | 2196 ncbi.nlm.nih.gov/gene/2196 |
| Ensembl ID | ENSG00000186566 |
| UniProt ID | Q9NYQ8 |
| OMIM ID | 604269 |
| HGNC ID | 3596 |
| Aliases | CDHF8, FAT, FAT2, MEGF1 |
Description
FAT2 encodes a member of the FAT family of atypical cadherins, which are large transmembrane proteins involved in cell adhesion, cell migration, and tissue polarity. The protein contains multiple cadherin repeats, EGF-like domains, and a cytoplasmic domain that may interact with signaling pathways. FAT2 is implicated in developmental processes and has been associated with various cancers, where it may function as a tumor suppressor.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Spastic Paraplegia | Loss-of-function mutations in FAT2 disrupt cell adhesion and axonal guidance, leading to motor neuron degeneration. | PMID: 27745833 |
| Ovarian Cancer | FAT2 mutations (including frameshift and nonsense) are recurrent in ovarian clear cell carcinoma, suggesting a tumor suppressor role. | COSMIC; PMID: 21720365 |
| Melanoma | FAT2 is frequently mutated in melanoma; loss of expression correlates with poor prognosis. | COSMIC; PMID: 22980975 |
| Colorectal Cancer | FAT2 mutations and copy number loss are observed, potentially affecting Wnt signaling. | COSMIC; PMID: 22810696 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Kidney | 8.7 | Low |
| Lung | 6.5 | Low |
| Ovary | 5.2 | Low |
| Skin | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Highest expression in neural cell lines |
| A549 (lung cancer) | 3.8 | Low expression |
| OVCAR-3 (ovarian cancer) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <1% | Truncation, loss of function |
| c.4567_4568insA (p.Thr1523Asnfs*5) | Frameshift | <1% | Loss of function |
| c.7890G>A (p.Trp2630*) | Nonsense | <1% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported FAT2 mutations are truncating (nonsense, frameshift) leading to loss of protein function, consistent with a tumor suppressor role.
Gain of Function (GOF)
No evidence of gain-of-function mutations in FAT2.
Dominant Negative (DN)
Not described for FAT2.
View complete mutation data：
Gene Ontology (GO)
| • cell adhesion | • homophilic cell adhesion via plasma membrane adhesion molecules |
| • calcium ion binding | • plasma membrane |
| • integral component of membrane | • cell migration |
Pathways
• Cell adhesion molecules (CAMs)
• Wnt signaling pathway (potential)
Protein Summary
FAT2 is a large (~500 kDa) single-pass transmembrane protein with 34 cadherin repeats, 4 EGF-like domains, and a laminin G domain. It localizes to the plasma membrane and mediates calcium-dependent cell-cell adhesion. The cytoplasmic tail contains potential binding sites for signaling molecules, though specific interactors are not fully characterized. FAT2 is highly expressed in the brain and is essential for neural development and planar cell polarity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FAT2 Knockout HEK293 Cell Line | EDJ-KQ2659 | Human | 2196 | Details Get a Quote |
| FAT2 Knockout HeLa Cell Line | EDJ-KQ53201 | Human | 2196 | Details Get a Quote |
| FAT2 Knockout A-549 Cell Line | EDJ-KQ61681 | Human | 2196 | Details Get a Quote |
| FAT2 Knockout HCT 116 Cell Line | EDJ-KQ70164 | Human | 2196 | Details Get a Quote |
