FB2026_03 , released September 17, 2026
Human Disease Model Report: intellectual disability, BRWD-related
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General Information
Name
intellectual disability, BRWD-related
FlyBase ID
FBhh0001168
Disease Ontology Term
Parent Disease
OMIM
Overview

Two of the three bromodomain- and WD repeat domain-containing genes in human, PHIP and BRWD3, are implicated in forms of syndromic intellectual disability (see MIM:617991, MIM:300659). The third related gene in human is BRWD1. The functions of these genes are not well characterized; several are known to localize to the nucleus and are thought to play a role in transcriptional regulation. There is a single orthologous gene in Drosophila, Dmel\BRWD3, for which loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

None of the human genes (PHIP, BRWD3, BRWD1) has been introduced into flies.

Animals homozygous for amorphic mutations of Dmel\BRWD3 typically die during the pupal stage. In mutant clones in the eye, photoreceptor neurons fail to complete differentiation. Knockdown in classes of neurons, effected by RNAi, results in reduced dendritic branching of the targeted cells. It is postulated that BRWD3 plays a role in transcriptional regulation by controlling the levels of chromatin-associated H3.3 (in flies, Dmel\His3.3A and Dmel\His3.3B). Additional interacting genes have been described; see below and in the Dmel\BRWD3 gene report.

[updated Jan. 2020 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: intellectual disability, BRWD-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype

(FlyBase Curators, 2013-)

Intellectual disability can be subdivided into syndromic forms, characterized by cognitive impairment accompanied by dysmorphic features, malformations or neurological abnormalities, and nonsyndromic forms, characterized by cognitive impairment without additional features (Basel-Vanagaite, 2008; DOI: 10.1002/9780470015902.a0021454).

Intellectual disability is characterized by impairments in intellectual functioning and adaptive behavior; symptoms must be present before a child becomes 18 years old (http://medical-dictionary.thefreedictionary.com/mental+retardation; 2016.01.19).

Genetics
Cellular phenotype and pathology
Molecular information

PHIP is a probable regulator of the insulin and insulin-like growth factor signaling pathways. [Gene Cards, PHIP; 2020.01.22]

BRWD1 and BRWD3 play roles in the regulation of cell morphology and cytoskeletal organization and are required in the control of cell shape; may be involved in chromatin remodeling. [Gene Cards, BRWD1, BRWD3; 2020.01.22]

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 (3 human to 1 Drosophila).

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

    Many to one (3 human to 1 Drosophila).

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Gene Snapshot
      BRWD3 (BRWD3) encodes a member of the Bromodomain and WD repeat_containing protein (BRWD) family. It regulates ecdysone and JAK-STAT signaling pathways and contributes to eye development, cell death and phagocytosis. [Date last reviewed: 2019-03-07]
      Molecular function (GO)
        Cellular component (GO)
        Gene Groups / Pathways
        Comments on ortholog(s)

        Moderate- to high-scoring ortholog of human PHIP, BRWD3 and BRWD1 (1 Drosophila to 3 human). Dmel\BRWD3 shares 34-37% identity and 48-55% 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
        Other Genes Used: Viral, Bacterial, Synthetic (0)
          Summary of Physical Interactions (8 groups)
          protein-protein
          Interacting group
          Assay
          References
          experimental knowledge based
          experimental knowledge based
          enzymatic study, anti tag western blot, pull down, two hybrid
          anti tag coimmunoprecipitation, anti tag western blot
          pull down, molecular weight estimation by staining
          pull down, anti tag western blot
          experimental knowledge based
          anti tag coimmunoprecipitation, anti tag western blot
          Alleles Reported to Model Human Disease (Disease Ontology) (0 alleles)
          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
          amorphic allele - genetic evidence
          P-element activity
          References (3)