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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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FAT2
FAT atypical cadherin 2
Chromosome 5 · 5q33.1
NCBI Gene: 2196Ensembl: ENSG00000086570.13HGNC: HGNC:3596UniProt: Q6PIA2
23PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
epithelial cell migrationadherens junctioncell-substrate adhesionextracellular exosomeAutosomal dominant cerebellar ataxia type 1vaginal cancermetabolic diseasebrain aneurysm
✦AI Summary

FAT2 (FAT atypical cadherin 2) is a cell adhesion molecule that plays critical roles in cellular migration, synaptic integrity, and cerebellar function. FAT2 directly binds Cbln1, a secreted molecule essential for synapse formation and plasticity at Purkinje cell synapses 1. This interaction is crucial for maintaining synaptic strength of parallel fiber synapses in the cerebellum, as Fat2 deletion mice show selective weakening of these synapses and impaired motor behaviors 1. The protein is involved in regulation of cell migration and may mediate organization of parallel fibers during cerebellar development 2. In disease contexts, FAT2 mutations are associated with spinocerebellar ataxia 45 (SCA45), an autosomal dominant cerebellar ataxia 3. FAT2 is frequently mutated in esophageal squamous cell carcinoma, where it contributes to dysregulation of the Hippo signaling pathway 45. Interestingly, in uterine corpus endometrial carcinoma, FAT2 mutations are associated with better prognosis and enhanced responsiveness to immunotherapy 6. Recent research has identified FAT2 as a potential therapeutic target in squamous cancers, where it regulates cell growth and adhesion through integrin-PI3K signaling 7.

Sources cited
1
FAT2 directly binds Cbln1 and is essential for synaptic integrity and motor behaviors
PMID: 40393806
2
FAT2 mutations cause spinocerebellar ataxia 45
PMID: 37479376
3
FAT2 is frequently mutated in esophageal squamous cell carcinoma affecting Hippo pathway
PMID: 25151357
4
FAT2 mutations identified in esophageal squamous cell carcinoma
PMID: 24686850
5
FAT2 mutations associated with better prognosis in uterine corpus endometrial carcinoma
PMID: 36812126
6
FAT2 identified as therapeutic target regulating cell growth and adhesion in squamous cancers
PMID: 41579862
Disease Associationsⓘ21
Autosomal dominant cerebellar ataxia type 1Open Targets
0.44Moderate
vaginal cancerOpen Targets
0.37Weak
metabolic diseaseOpen Targets
0.32Weak
brain aneurysmOpen Targets
0.30Weak
ParalysisOpen Targets
0.18Weak
cerebellar ataxiaOpen Targets
0.12Weak
neoplasmOpen Targets
0.06Suggestive
non-small cell lung carcinomaOpen Targets
0.04Suggestive
gastric cancerOpen Targets
0.04Suggestive
esophageal adenocarcinomaOpen Targets
0.04Suggestive
Abruptio PlacentaeOpen Targets
0.03Suggestive
lung adenocarcinomaOpen Targets
0.03Suggestive
Barrett's esophagusOpen Targets
0.03Suggestive
liver diseaseOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
breast carcinomaOpen Targets
0.02Suggestive
glioblastoma multiformeOpen Targets
0.01Suggestive
hepatocellular carcinomaOpen Targets
0.01Suggestive
urinary bladder carcinomaOpen Targets
0.01Suggestive
squamous cell lung carcinomaOpen Targets
0.01Suggestive
Spinocerebellar ataxia 45UniProt
Pathogenic Variants1
NM_001447.3(FAT2):c.3632A>C (p.Glu1211Ala)Likely pathogenic
Spinocerebellar ataxia 45
★☆☆☆2024→ Residue 1211
View on ClinVar ↗
Related Genes
FJX1Protein interaction76%DSC3Shared pathway50%CDH16Shared pathway50%DSG4Shared pathway43%CDHR1Shared pathway38%CDHR5Shared pathway38%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
59%
Ovary
53%
Liver
31%
Brain
21%
Heart
11%
Gene Interaction Network
Click a node to explore
FAT2FJX1DSC3CDH16DSG4CDHR1CDHR5
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q6PIA2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.55Moderately Constrained
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.48 [0.42–0.55]
RankingsWhere FAT2 stands among ~20K protein-coding genes
  • #13,417of 20,598
    Most Researched23
  • #5,341of 5,498
    Most Pathogenic Variants1
  • #3,569of 17,882
    Most Constrained (LOEUF)0.55 · top quartile
Genes detectedFAT2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Autosomal dominant cerebellar ataxias: new genes and progress towards treatments.
PMID: 37479376
Lancet Neurol · 2023
1.00
2
Genetic landscape of esophageal squamous cell carcinoma.
PMID: 25151357
Nat Genet · 2014
0.90
3
Genomic and molecular characterization of esophageal squamous cell carcinoma.
PMID: 24686850
Nat Genet · 2014
0.80
4
Atypical Cadherin FAT2 Is Required for Synaptic Integrity and Motor Behaviors.
PMID: 40393806
J Neurosci · 2025
0.70
5
FAT2 mutation is associated with better prognosis and responsiveness to immunotherapy in uterine corpus endometrial carcinoma.
PMID: 36812126
Cancer Med · 2023
0.60