FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: diabetes mellitus type 2, susceptibility to, HHEX-related
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General Information
Name
diabetes mellitus type 2, susceptibility to, HHEX-related
FlyBase ID
FBhh0000172
Disease Ontology Term
Parent Disease
OMIM
Overview

This report describes diabetes mellitus, noninsulin-dependent, HHEX-related. The human gene HHEX, a homeobox-containing transcription factor, is located within a region associated with noninsulin-dependent diabetes mellitus in several studies. There is a single fly ortholog, Dmel\HHEX, for which RNAi-targeting constructs have been generated.

The human HHEX gene has not been introduced into flies.

Using various GAL4 drivers, animals carrying RNAi constructs targeted against Dmel\HHEX have been characterized. Ubiquitous knockdown results in intolerance of high levels of dietary sucrose and failure to pupariate. Tissue-specific knockdown results in metabolic defects and enhanced lethality; fat-body-specific loss of Dmel\HHEX led to increased hemolymph glucose and reduced insulin sensitivity.

[updated Feb. 2016 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: diabetes mellitus, noninsulin-dependent (type 2) (fly models overview)
Symptoms and phenotype

Diabetes mellitus, type 2, also called non-insulin-dependent diabetes mellitus, occurs when cells become resistant to the effects of insulin, thus disrupting the body's ability to metabolize glucose and to properly control the amount of sugar in the blood. [from Genetics Home Reference, Diabetes; 2016.02.02]

(FlyBase Curators, 2013-)

Over time, high blood glucose can lead to serious problems such as cataracts and/or retinopathy, impaired kidney function, diabetic neuropathy, and macrovascular complications (heart attack, stroke, peripheral vascular disease). [from endocrineweb; http://www.endocrineweb.com/conditions/type-2-diabetes/type-2-diabetes-complications]

(FlyBase Curators, 2013-)
Specific Disease Summary: diabetes mellitus type 2, susceptibility to, HHEX-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype

See general description of diabetes mellitus, noninsulin-dependent (FBhh0000153).

(FlyBase Curators, 2013-)
Genetics

HHEX is associated with type II diabetes mellitus and insulin response in a large number of GWAS studies (see GWAS Catalog, below in 'External links').

(FlyBase Curators, 2013-)

Variants within or near the HHEX gene have been identified as diabetes susceptibility loci. [from MIM:125853; 2016.02.04]

(OMIM, 2013-)
Cellular phenotype and pathology
Molecular information

The HHEX protein acts as a transcriptional repressor that plays a role in establishing anterior identity and may play a role in hematopoietic differentiation. [from UniProt:Q03014; 2016.02.04]

(FlyBase Curators, 2013-)

HHEX is a hematopoietically expressed homeobox gene; it is also found in some nonhematopoietic tissues, including liver. [from MIM:604420; 2016.02.04]

(OMIM, 2013-)
External links
Disease synonyms
diabetes mellitus, noninsulin-dependent, HHEX-related
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    Symbol / Name
    HHEX; hematopoietically expressed homeobox
    D. melanogaster ortholog (based on DIOPT)
    Dmel\HHEX
    (DIOPT, 2013-)
    Comments on ortholog(s)

    One to one: 1 human to 1 Drosophila.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Dmel\HHEX
      Gene Snapshot
      Hematopoietically expressed homeobox (HHEX) encodes a transcription factor involved in response to sucrose. [Date last reviewed: 2019-07-11]
      Molecular function (GO)
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      Ortholog of human gene HHEX (1 Drosophila to 1 human). Dmel\HHEX shares 30% identity and 38% similarity with the human gene.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      H. sapiens (Human)
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (7 groups)
        HHEX
        protein-protein
        Interacting group
        Assay
        References
        HHEX - abd-A
        bimolecular fluorescence complementation, fluorescence microscopy
        (Bischof et al., 2018)
        HHEX - B-H2
        two hybrid array
        (Shokri et al., 2019)
        HHEX - esc
        two hybrid array
        (Shokri et al., 2019)
        HHEX - Hr78
        two hybrid array
        (Shokri et al., 2019)
        HHEX - MESR4
        two hybrid array
        (Shokri et al., 2019)
        HHEX - Rel
        two hybrid array
        (Shokri et al., 2019)
        HHEX - Ubx
        bimolecular fluorescence complementation, fluorescence microscopy
        (Bischof et al., 2018)
        Alleles Reported to Model Human Disease (Disease Ontology) (1 alleles)
        HHEX
        Models Based on Experimental Evidence ( 1 )
        Allele
        Disease
        Evidence
        References
        HHEXGD4293
        model of  candidiasis
        CEA
        (Glittenberg et al., 2022)
        model of  type 2 diabetes mellitus
        CEA
        (Pendse et al., 2013)
        Modifiers Based on Experimental Evidence ( 0 )
        Allele
        Disease
        Interaction
        References
        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
        HHEXGD4293
        P{GD4293}
        w1118; P{GD4293}v15721
        HHEXKK107506
        P{KK107506}
        P{KK107506}VIE-260B
        HHEXHMJ22210
        P{TRiP.HMJ22210}
        y1 v1; P{TRiP.HMJ22210}attP40/CyO
        HHEXHMC05113
        P{TRiP.HMC05113}
        y1 sc* v1 sev21; P{TRiP.HMC05113}attP40
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        References (10)