FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: attention deficit hyperactivity disorder, susceptibility to (postulated), VPS4A-related
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General Information
Name
attention deficit hyperactivity disorder, susceptibility to (postulated), VPS4A-related
FlyBase ID
FBhh0000656
Disease Ontology Term
Parent Disease
OMIM
Overview

The human gene VPS4A (Vacuolar Protein Sorting 4 Homolog A) has been identified as involved in reward anticipation and reward processing. Dysfunctional reward processing is implicated in various mental and behavioral disorders, including attention deficit hyperactivity disorder (ADHD) and addictions. VPS4A is associated with the endosomal compartments and is involved in intracellular protein trafficking. It is a member of the AAA ATPase family; in human, there is a closely related paralogous gene, VPS4B. There is a single orthologous gene in Drosophila, Dmel\Vps4, for which loss-of-function alleles, UAS constructs, and RNAi targeting constructs have been generated.

The human VPS4A gene has not been introduced into flies.

Pan-neuronal overexpression of Dmel\Vps4 results in flies with a hypoactive phenotype; flies with pan-neuronal Vps4 knockdown of ~20%, effected by RNAi, show significant hyperactivity. Higher levels of pan-neuronal RNAi-effected knockdown result in larval or pupal lethality. Genetic interactions and a large number of physical interactions have been described for Dmel\Vps4; see below and in the Vps4 gene report.

[updated Nov. 2017 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: attention deficit hyperactivity disorder, susceptibility to
Symptoms and phenotype

Attention-deficit/hyperactivity disorder (ADHD) is a chronic condition that includes a combination of persistent problems, such as difficulty sustaining attention, hyperactivity and impulsive behavior; the condition often continues into adulthood (https://www.mayoclinic.org/diseases-conditions/adhd/symptoms-causes/syc-20350889).

(FlyBase Curators, 2013-)

Meta-regression analyses have estimated the worldwide ADHD/HKD prevalence at between 5.3% and 7.1% in children and adolescents, and at 3.4% (range 1.2-7.3%) in adults (http://adhd-institute.com/burden-of-adhd/epidemiology/).

(FlyBase Curators, 2013-)

ADHD is the most common childhood-onset behavioral disorder, affecting approximately 5 to 10% of children and adolescents (Wolraich et al., 1996; pubmed: 8714320). In this condition, persistent inattention and/or hyperactive-impulsive behavior results in impaired social and/or academic functioning. Boys are affected about 8 times more frequently than girls (Zametkin et al., 1990; pubmed:2233902). [from MIM:143465; 2017.11.21]

(OMIM, 2013-)
Specific Disease Summary: attention deficit hyperactivity disorder, susceptibility to (postulated), VPS4A-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    Symbol / Name
    VPS4A; vacuolar protein sorting 4 homolog A
    D. melanogaster ortholog (based on DIOPT)
    Dmel\Vps4
    (DIOPT, 2013-)
    Comments on ortholog(s)

    Many to one (2 human to 1 Drosophila); the human genes are VPS4A and VPS4B.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Dmel\Vps4
      Gene Snapshot
      Vacuolar protein sorting 4 (Vps4) encodes an AAA family ATPase. It catalyzes the ATP-dependent dissociation of class E VPS proteins from endosomal membranes. It functions in endosomal sorting of cargo into the multivesicular body for lysosomal degradation, abscission during cell division, virus release and nuclear envelope membrane sealing after cell division. [Date last reviewed: 2019-03-21]
      Molecular function (GO)
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      High-scoring ortholog of human VPS4A and VPS4B (1 Drosophila to 2 human); Dmel\Vps4 shares 75-76% identity and 86% similarity with the human genes.

      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 (34 groups)
        Vps4
        protein-protein
        Interacting group
        Assay
        References
        Vps4 - CCT3
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - CCT8
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - CG5854
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - chico
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Chmp1
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - CHMP2B
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Cnx99A
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Cyp12d1-p
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Gfat2
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Glt
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - GluProRS
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Idh3a
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Ist1
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Kap-α3
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Mcad
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - mib2
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Mpcp2
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - ninaA
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Ost1
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Pdk1
        anti tag coimmunoprecipitation, Identification by mass spectrometry
        (Vinayagam et al., 2016)
        Vps4 - Pi3K68D
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Pp2A-29B
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - r
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Rdh1
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - ScsβG
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Sec61α
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Sec63
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - SerRS
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - shrb
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Tapδ
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Vps2
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Vps24
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - Vps60
        experimental knowledge based
        (Guruharsha et al., 2011)
        Vps4 - wal
        experimental knowledge based
        (Guruharsha et al., 2011)
        Alleles Reported to Model Human Disease (Disease Ontology) (1 alleles)
        Vps4
        Models Based on Experimental Evidence ( 1 )
        Allele
        Disease
        Evidence
        References
        Vps4HM04061
        model of  attention deficit hyperactivity disorder
        CEA
        (Jia et al., 2016)
        Modifiers Based on Experimental Evidence ( 1 )
        Allele
        Disease
        Interaction
        References
        Vps4HM04061
        ameliorates  Alzheimer's disease 1
        modeled by Hsap\APPUAS.cUa
        (Zhuang et al., 2023)
        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
        Vps4RNAi.UAS.cUa
        P{UAS-Vps4.RNAi.U}
        Vps4GD12054
        P{GD12054}
        w1118; P{GD12054}v35125
        Vps4KK101722
        P{KK101722}
        P{KK101722}VIE-260B
        Vps4HM04061
        P{TRiP.HM04061}
        y1 v1; P{TRiP.HM04061}attP2
        Vps4NIG.6842R
        P{NIG.6842R}
        P{NIG.6842R}1
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        References (4)