FAT1 (FAT tumor suppressor homolog 1 (Drosophila))

2011-02-01   Kunzang Chosdol , Bhawana Dikshit , Subrata Sinha 

Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India





FAT1 gene is located on the chromosome 4q35.2 (Accession: NC_000004.11). The total length of the gene is 136050 bases (187509746 bp to 187630981 bp from pter) of reverse strand. There are 27 exons.
An alternate assembly suggested to be starting from 187745931 bp to 187881981 bp from pter.


The length of the transcript is 14773 bps made from 27 exons (Accession: NM_005245.3).


FAT tumor suppressor homolog 1 (Drosophila) pseudogene 1 (FAT1P1).
Other name: dJ697P8.1; sequence accession ID: AL050403; location chromosome: 20p12.2.



Known protein coding gene.

Protein names
Recommended name: protocadherin Fat 1.
Alternative names: Cadherin-related tumor suppressor homolog, Protein fat homolog, Cadherin family member 7.


4588 aa (Accession: NP_005236.2).


Expressed in epithelial, endothelial and smooth muscle cells.


Cell membrane; single-pass type I membrane protein.


Could function as a cell-adhesion molecule, cell signalling molecule, and have a role in cell migration.
Fat in Drosophila acts via SWH signalling pathway as tumour suppressor gene. Homolog of SWH pathway molecules are present in human, so there is a possibility of acting FAT1 as an upstream regulator of SWH pathway in human.
In human, FAT1 expression is highest at the embryonic stages and diminishes later in adult life. In human fetal tissues, high levels of FAT1 transcripts were found in kidney, lungs, and eye epithelia, and the expression was found to be down regulated in the corresponding adult tissues, indicating the role of FAT1 in organ development. FAT1 also has a role in cell migration (Moeller et al., 2004; Tanoue and Takeichi, 2004) and found to be up-regulated in migrating cells, also crucial for efficient wound healing (Braun et al., 2007).
In Drosophila, fat is an upstream regulator of the Salvador-Wart-Hippo (SWH) signaling pathway (Cho et al., 2006; Bennett and Harvey, 2006). The signalling molecules of SWH pathway are conserved in mammals (figure below) but the role of FAT1 as an apical regulator of SWH pathway in human has not yet been established.
Atlas Image
Salvador-Warts-Hippo pathway. Mammalian hippo signaling pathway shows homology with Drosophila pathway proteins (depicted in similar color and shape).
In Drosophila fat (ft) interacts with core kinase cascade via Expanded (Ex). The core kinase cascade includes kinase Hippo (hpo), adaptor proteins mats and Salvador (Sav) and kinase Warts. The core kinase cascade inhibits phosphorylation of transcriptional co-activator Yorkie (Yki) causing its translocation to nucleus where it binds to transcriptional activator Scalloped (Sd) and modulates gene expression.
In mammals, whether FAT1 is involved in hippo pathway regulation is not clear. The effector molecule, phospho-YAP, is reported to interact with p73 in the nucleus and promotes cell death. There is no p73 homolog known to be reported in Drosophila. YAP is also found to interact with other transcription factors and modulate gene expression, thus, the outcome of hippo pathway is context dependent.


Paralogs for FAT1 gene: FAT2, FAT3, FAT4.
OrganismGeneLocusDescriptionSimilarity to human FAT1
(Canis familiaris)
FAT1Chr. 16FAT tumor suppressor homolog 1 (Drosophila)86.95(n), 91.17(a)
(Sus scrofa)
FAT1Chr. 17FAT tumor suppressor homolog 1 (Drosophila)86(n), 90(a)
(Bos Taurus)
FAT1Chr. 27FAT tumor suppressor homolog 1 (Drosophila)84.18(n) 89.93(a)
(Rattus norvegicus)
Fat1Chr. 16q11FAT tumor suppressor homolog 1 (Drosophila)82.93(n) 88.16(a)
(Mus musculus)
Fat1Chr. 8
(25.00 cM)
FAT tumor suppressor homolog 1 (Drosophila)82.51(n) 88.14(a)
(Gallus gallus)
FATChr. 4FAT tumor suppressor homolog 1 (Drosophila)76.35(n) 81.43(a)
(Danio rerio)
fat1Chr. 1FAT tumor suppressor homolog 164.68(n) 64.82(a)
Fruit fly
(Drosophila melanogaster)
ft and fat2Chr. 2L (ft) Chr. 3L (fat2)fat and fat2ft - 42.8(n) 42(a),
fat2 - 47.99(n) 39.02(a)
(Caenorhabditis elegans)
cdh-4Chr. IIICadherin family44.19(n) 30.89(a)
African malaria mosquito
(Anopheles gambiae)
AgaP_AGAP011526Chr. 3LAGAP011526-PA48.06(n) 39.5(a)
Orthologs for FAT1 gene from other species.



No known mutations. Single nucleotide polymorphism (SNPs): gene: FAT1 (ENSG00000083857).

Implicated in

Entity name
Various cancers
FAT1, a member of the cadherin gene family, is homologue of Drosophila tumour suppressor gene fat. In Drosophila, fat gene is important in controlling cell proliferation during development and any defect in the expression of fat would lead to tumor development (Bryant et al., 1988). Dunne et al. (1995) have identified the human homologue and studied the tissue distribution of FAT transcripts in adult and fetal tissues.
Loss of heterozygosity and altered expression of FAT1 has been found in human glial tumors (Chosdol et al., 2009). Homozygous deletion of FAT1 gene was detected in oral cancer (Nakaya et al., 2007). Kwaepila et al. (2006) found higher FAT1 expression in more malignant form of breast cancer tissues by immunohistochemistry (IHC). There are studies showing LOH and/or deletion of the chromosome 4q34-35 region (which harbors FAT gene) in many tumors including gliomas. LOH was found in grade IV gliomas using microsatellite markers (Hu et al., 2002), though the gene itself has not been implicated. Other tumors like small cell lung carcinoma (Cho et al., 2002), hepatocellular carcinoma (Zhang et al., 2005; Chang et al., 2002) and cervical carcinoma (Backsch et al., 2005) etc showed alterations/LOH in the chromosomal 4q34-q35 locus and significant association of 4q34-q35 region with increased risk of progression of these tumors was suggested. Since the FAT gene is located in this region it may have an important role to play in the development and progression of these tumors.
Entity name
Astrocytic tumour
Loss of heterozygosity and altered expression of FAT1 in astrocytic tumors (Chosdol et al., 2009).
Entity name
Breast cancer
Increased FAT1 expression contributes to loss of duct formation, and increased cell migration and invasion in breast cancer (Kwaepila et al., 2006).
Entity name
Oral cancer
Homozygous deletion of FAT in the cell lines and in primary oral cancers was studied. Homozygous deletion hot spots were observed in exon 1 (9/20, 45%) and exon 4 (7/20, 35%). The methylation status of the FAT CpG island in squamous cell carcinomas correlated negatively with its expression. Mutations in FAT is suggested as an important factor in the development of oral cancer. Moreover, loss of gene expression was identified in other types of squamous cell carcinoma (Nakaya et al., 2007).
Entity name
Psychiatric disorders
Bipolar disorder: a positional cloning strategy, combined with association analysis have provided evidence that a cadherin gene, FAT, confers susceptibility to bipolar disorder (Blair et al., 2006).
Entity name
Cell migration
FAT1 is known to play role in cell migration. FAT1 knockdown decreases cell migration in vascular smooth muscle cells (Hou et al., 2006; Hou and Sibinga, 2009). FAT1 plays an integrative role in regulating cell migration by participating in Ena/VASP-dependent regulation of cytoskeletal dynamics (Moeller et al., 2004).


Pubmed IDLast YearTitleAuthors
158388432005A region on human chromosome 4 (q35.1-->qter) induces senescence in cell hybrids and is involved in cervical carcinogenesis.Backsch C et al
170458012006Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway.Bennett FC et al
164021352006Positional cloning, association analysis and expression studies provide convergent evidence that the cadherin gene FAT contains a bipolar disorder susceptibility allele.Blair IP et al
175000542007Differentially spliced isoforms of FAT1 are asymmetrically distributed within migrating cells.Braun GS et al
34170511988Mutations at the fat locus interfere with cell proliferation control and epithelial morphogenesis in Drosophila.Bryant PJ et al
120481652002Assessment of chromosomal losses and gains in hepatocellular carcinoma.Chang J et al
169809762006Delineation of a Fat tumor suppressor pathway.Cho E et al
119712072002Identification of tumor suppressor loci on the long arm of chromosome 4 in primary small cell lung cancers.Cho ES et al
191262442009Frequent loss of heterozygosity and altered expression of the candidate tumor suppressor gene 'FAT' in human astrocytic tumors.Chosdol K et al
107414172000Cloning and expression throughout mouse development of mfat1, a homologue of the Drosophila tumour suppressor gene fat.Cox B et al
157490762005Cloning and expression of the large zebrafish protocadherin gene, Fat.Down M et al
85864201995Molecular cloning and tissue expression of FAT, the human homologue of the Drosophila fat gene that is located on chromosome 4q34-q35 and encodes a putative adhesion molecule.Dunne J et al
166825282006The Fat1 cadherin integrates vascular smooth muscle cell growth and migration signals.Hou R et al
191313402009Atrophin proteins interact with the Fat1 cadherin and regulate migration and orientation in vascular smooth muscle cells.Hou R et al
122152922002Chromosome 14q may harbor multiple tumor suppressor genes in primary glioblastoma multiforme.Hu J et al
168652402006Comparative integromics on FAT1, FAT2, FAT3 and FAT4.Katoh Y et al
165816522006Immunohistological localisation of human FAT1 (hFAT) protein in 326 breast cancers. Does this adhesion molecule have a role in pathogenesis?Kwaepila N et al
159227302005Processing of the human protocadherin Fat1 and translocation of its cytoplasmic domain to the nucleus.Magg T et al
153432702004Protocadherin FAT1 binds Ena/VASP proteins and is necessary for actin dynamics and cell polarization.Moeller MJ et al
173256622007Identification of homozygous deletions of tumor suppressor gene FAT in oral cancer using CGH-array.Nakaya K et al
100727901999Expression of the rat homologue of the Drosophila fat tumour suppressor gene.Ponassi M et al
169796242006The intracellular domain of the human protocadherin hFat1 interacts with Homer signalling scaffolding proteins.Schreiner D et al
151483052004Mammalian Fat1 cadherin regulates actin dynamics and cell-cell contact.Tanoue T et al
159181852005Clinicopathological significance of loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in China.Zhang SH et al

Other Information

Locus ID:

NCBI: 2195
MIM: 600976
HGNC: 3595
Ensembl: ENSG00000083857


dbSNP: 2195
ClinVar: 2195
TCGA: ENSG00000083857


Gene IDTranscript IDUniprot

Expression (GTEx)


Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
283665572017FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK/ERK signaling pathway in esophageal squamous cell cancer.31
269056942016FAT1 mutations cause a glomerulotubular nephropathy.30
245502272014Genetic lesions associated with chronic lymphocytic leukemia chemo-refractoriness.28
216178782011Human FAT1 cadherin controls cell migration and invasion of oral squamous cell carcinoma through the localization of β-catenin.26
221165502012The Fat1 cadherin is overexpressed and an independent prognostic factor for survival in paired diagnosis-relapse samples of precursor B-cell acute lymphoblastic leukemia.26
173256622007Identification of homozygous deletions of tumor suppressor gene FAT in oral cancer using CGH-array.25
305143092018CircFAT1 sponges miR-375 to promote the expression of Yes-associated protein 1 in osteosarcoma cells.23
216807322011Dual processing of FAT1 cadherin protein by human melanoma cells generates distinct protein products.18
299853912018Assembly and activation of the Hippo signalome by FAT1 tumor suppressor.18
229865332013FAT1 acts as an upstream regulator of oncogenic and inflammatory pathways, via PDCD4, in glioma cells.17


Kunzang Chosdol ; Bhawana Dikshit ; Subrata Sinha

FAT1 (FAT tumor suppressor homolog 1 (Drosophila))

Atlas Genet Cytogenet Oncol Haematol. 2011-02-01

Online version: http://atlasgeneticsoncology.org/gene/40533/fat1