FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: obesity, susceptibility to (postulated), Hippo signaling pathway
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General Information
Name
obesity, susceptibility to (postulated), Hippo signaling pathway
FlyBase ID
FBhh0001417
Disease Ontology Term
Parent Disease
OMIM
Overview

In a genomic study of variants associated with obesity in humans, variants associated with the human gene DCHS1 were identified. DCHS1 encodes a calcium-dependent cell-cell adhesion molecule. There is a single orthologous gene in Drosophila, ds. Ubiquitous knockdown of ds, effected by RNAi, results in a significant increase in triacylglyceride (TAG) level, measured as the ratio of TAG to protein.

Dmel\ds is known to be a regulator of the Hippo signaling pathway. Additional genes involving in the Hippo signaling pathway were assessed in flies: Dmel\ft (orthologous to human FAT4); Dmel\fj (orthologou to human FJX1); Dmel\hpo (orthologous to human STK3 and STK4); ubiquitous knockdown of each of these genes results in a significant increase in triacylglyceride level. Results support the hypothesis that Hippo pathway activity in the nervous system regulates adiposity in Drosophila.

Using an independent cohort, an additional human gene, TAOK2, was implicated in development of obesity. The Drosophila ortholog, Tao is also a regulator of the Hippo signaling pathway. Ubiquitous knockdown of Tao, effected by RNAi, also results in a significant increase in triacylglyceride level.

A number of the related human genes have been introduced into flies, but have not been assessed in the context of this disease model: Hsap\FAT4, Hsap\STK3, Hsap\STK4, Hsap\TAOK2.

[updated Dec. 2021 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: obesity, susceptibility to (fly models overview)
Symptoms and phenotype

Obesity is an abnormal accumulation of body fat, usually 20% or more over an individual's ideal body weight. Obesity is associated with increased risk of illness, disability, and death. (http://medical-dictionary.thefreedictionary.com/obesity).

The development of obesity is recognized as having both genetic and environmental components (https://www.sciencelearn.org.nz/resources/203-obesity-genetic-or-environmental).

Specific Disease Summary: obesity, susceptibility to (postulated), Hippo signaling pathway
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information

STK3 and STK4 encode serine/threonine protein kinases that are core components of the Hippo signaling pathway. [Gene Cards, STK3, STK4; 2021.12.15]

TAOK2 encodes a serine/threonine protein kinase that is involved in many different processes. [Gene Cards, TAOK2; 2021.12.15]

DCHS1 and FAT4 encode calcium-dependent cell-cell adhesion molecules of the cadherin family. [Gene Cards, DCHS1, FAT4; 2021.12.15]

The FJX1 gene is not well characterized in human. [Gene Cards, FJX1; 2021.12.15] The Drosophila gene fj has been shown to modulate activity of ft and ds (FBrf0205751, FBrf0210769).

External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to one: 2 human genes to 1 Drosophila gene.

Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

One to one: 1 human gene to 1 Drosophila gene.

Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

One to one: 1 human gene to 1 Drosophila gene.

Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to one: 2 human genes to 1 Drosophila gene

Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to one: 2 human genes to 1 Drosophila gene.

Human gene (HGNC)
Symbol / Name
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to one: 3 human genes to 1 Drosophila gene.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (5)
    Gene Groups / Pathways
    Comments on ortholog(s)

    High-scoring ortholog of human DCHS1; moderate-scoring ortholog of DCHS2.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Gene Snapshot
    fat (ft) is a tumor suppressor gene that encodes a large cadherin family transmembrane protein. It functions in the Hippo signaling pathway (as a receptor) and the Dachsous-Fat planar cell polarity pathway (as a transmembrane component). [Date last reviewed: 2019-03-07]
    Gene Groups / Pathways
    Comments on ortholog(s)

    High-scoring ortholog of human FAT4.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Gene Snapshot
    four-jointed (fj) encodes a type II transmembrane kinase. Through phosphorylation of the atypical cadherins encoded by ft and ds, it regulates control of planar polarity in epithelia and also growth via the Hippo/Warts pathway. [Date last reviewed: 2019-03-07]
    Cellular component (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    High-scoring ortholog of human FJX1.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Gene Snapshot
    hippo (hpo) encodes a kinase in the Salvador-Warts-Hippo pathway. It controls tissue growth by controlling cell growth, proliferation and apoptosis. It has several roles in post-mitotic cells including fate specification of photoreceptors and tiling of dendritic neurons. [Date last reviewed: 2019-03-07]
    Gene Groups / Pathways
    Comments on ortholog(s)

    High-scoring ortholog of human STK3 and STK4.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Gene Snapshot
    Tao (Tao) encodes a Ser/Thr kinase belonging to the Mst/Ste20 family. It is implicated in the Hippo and PAR-1 pathways. It contributes to restriction of tissue growth during development, regulation of microtubule dynamics, neuronal polarity, neural development, ethanol-stimulated behavioral response, and apoptosis. [Date last reviewed: 2019-03-14]
    Gene Groups / Pathways
    Comments on ortholog(s)

    Moderate- to high-scoring ortholog of human TAOK1, TAOK2, TAOK3.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (130 groups)
      protein-protein
      Interacting group
      Assay
      References
      colocalization, fluorescence microscopy, inferred by author
      anti bait coimmunoprecipitation, anti tag western blot, colocalization, fluorescence microscopy, inferred by author
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, western blot, colocalization, fluorescence microscopy, inferred by author, anti tag western blot
      enzymatic study, autoradiography, anti tag coimmunoprecipitation, anti tag western blot
      affinity technology, enzymatic reaction, ultraviolet-visible spectroscopy, inferred by author, anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, colocalization, fluorescence microscopy, bead aggregation assay
      anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
      anti tag coimmunoprecipitation, western blot, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
      protein-protein
      Interacting group
      Assay
      References
      anti tag coimmunoprecipitation, anti tag western blot, western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
      colocalization, fluorescence microscopy, inferred by author, anti bait coimmunoprecipitation, anti tag western blot
      two hybrid, pull down, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot
      pull down, anti tag western blot, colocalization, fluorescence microscopy, inferred by author, anti tag coimmunoprecipitation, western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      affinity technology, enzymatic reaction, ultraviolet-visible spectroscopy, inferred by author, anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, colocalization, fluorescence microscopy, bead aggregation assay
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      pull down, anti tag western blot, anti tag coimmunoprecipitation, western blot, proximity ligation assay, fluorescence microscopy
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot, enzymatic study, autoradiography
      pull down, anti tag western blot, two hybrid
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
      two hybrid, pull down, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
      anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      protein-protein
      Interacting group
      Assay
      References
      enzymatic study, autoradiography
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      enzymatic study, autoradiography, anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, anti tag western blot, enzymatic study, autoradiography
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      pull down, anti tag western blot
      protein-protein
      Interacting group
      Assay
      References
      mass spectrometry studies of complexes, anti tag coimmunoprecipitation, western blot, bimolecular fluorescence complementation, fluorescence microscopy, pull down, anti tag western blot, enzymatic study, autoradiography, molecular weight estimation by staining, two hybrid, fluorescent resonance energy transfer, protein complementation assay
      anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting, proximity ligation assay, fluorescence microscopy
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot, western blot
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      enzymatic study, autoradiography
      anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, western blot, anti tag western blot
      anti tag coimmunoprecipitation, western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot, two hybrid
      anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, western blot
      pull down, western blot, enzymatic study, autoradiography
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, peptide massfingerprinting
      enzymatic study, western blot, pull down, anti tag western blot
      anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot, mass spectrometry studies of complexes, pull down, molecular weight estimation by staining
      anti tag coimmunoprecipitation, peptide massfingerprinting
      anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
      tandem affinity purification, molecular sieving, molecular weight estimation by staining, two hybrid, anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting, pull down, western blot, bimolecular fluorescence complementation, fluorescence microscopy, x-ray crystallography, anti bait coimmunoprecipitation, autoradiography, mass spectrometry studies of complexes, enzymatic study, protein cross-linking with a bifunctional reagent, molecular weight, coimmunoprecipitation
      anti tag coimmunoprecipitation, peptide massfingerprinting
      experimental knowledge based, anti tag coimmunoprecipitation, anti tag western blot, pull down, western blot
      anti tag coimmunoprecipitation, anti tag western blot
      anti tag coimmunoprecipitation, anti tag western blot, peptide massfingerprinting
      protein kinase assay, anti tag western blot
      anti tag coimmunoprecipitation, western blot, enzymatic study, autoradiography, anti tag western blot
      anti tag coimmunoprecipitation, anti tag western blot
      enzymatic study, western blot, anti tag coimmunoprecipitation, anti tag western blot, autoradiography
      anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot
      protein-protein
      Interacting group
      Assay
      References
      anti tag coimmunoprecipitation, anti tag western blot, enzymatic study, western blot
      protein kinase assay, anti tag western blot
      anti tag coimmunoprecipitation, anti tag western blot, enzymatic study, western blot
      Alleles Reported to Model Human Disease (Disease Ontology) (34 alleles)
      Models Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Interaction
      References
      Models Based on Experimental Evidence ( 7 )
      Modifiers Based on Experimental Evidence ( 3 )
      Models Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Interaction
      References
      Models Based on Experimental Evidence ( 5 )
      Modifiers Based on Experimental Evidence ( 11 )
      Allele
      Disease
      Interaction
      References
      model of  carcinoma
      model of  cancer
      is ameliorated by Rox8EY02351
      model of  carcinoma
      is exacerbated by ykiUAS.cHa
      is ameliorated by Atg1UAS.cSa
      exacerbates  carcinoma
      Models Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 3 )
      Models Based on Experimental Evidence ( 7 )
      Modifiers Based on Experimental Evidence ( 4 )
      Alleles Representing Disease-Implicated Variants
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Related mammalian, viral, bacterial, or synthetic transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      loss of function allele
      ethyl methanesulfonate
      loss of function allele
      CRISPR/Cas9
      loss of function allele
      CRISPR/Cas9
      loss of function allele
      CRISPR/Cas9
      loss of function allele
      spontaneous
      amorphic allele - genetic evidence
      Delta2-3 transposase
      loss of function allele
      Delta2-3 transposase
      loss of function allele
      ethyl methanesulfonate
      loss of function allele
      ethyl methanesulfonate
      loss of function allele
      X ray
      loss of function allele
      ethyl methanesulfonate
      loss of function allele
      ethyl methanesulfonate
      loss of function allele
      ethyl methanesulfonate
      loss of function allele
      loss of function allele
      CRISPR/Cas9
      loss of function allele
      X ray
      loss of function allele
      ethyl methanesulfonate
      loss of function allele
      X ray
      References (3)