FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: intellectual developmental disorder, X-linked, syndromic, Pilorge type
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General Information
Name
intellectual developmental disorder, X-linked, syndromic, Pilorge type
FlyBase ID
FBhh0001445
Disease Ontology Term
Parent Disease
OMIM
INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, PILORGE TYPE; MRXSP
Overview

This report describes intellectual developmental disorder, X-linked, syndromic, Pilorge type (MRXSP); MRXSP exhibits dominant inheritance in females. The human gene implicated in this disorder, GLRA2, encodes a subunit of ligand-gated glycine receptors. A variant of GLRA2 was initially characterized as part of a large-scale assessment of genes implicated in susceptibility to autism; additional variants of GLRA2 were identified among patients with neurodevelopmental disorders beyond autism. The Drosophila gene GluClα is orthologous to GLRA2, as well as to GLRA1, GLRA3, and GLRA4. Multiple genetic reagents have been generated for GluClα including RNAi-targeting constructs, a targeted CRISPR knockout construct, and alleles caused by insertional mutagenesis.

UAS constructs of the human Hsap\GLRA2 gene have been introduced into flies, including wild-type and variants implicated in disease. See the 'Disease-Implicated Variants' table below. Assessment in flies has been used to identify loss-of-function vs. gain-of-function variants.

[updated May 2022 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: intellectual disability, X-linked, syndromic
Symptoms and phenotype

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).

(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).

(FlyBase Curators, 2013-)
Specific Disease Summary: intellectual developmental disorder, X-linked, syndromic, Pilorge type
OMIM report

[INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC, PILORGE TYPE; MRXSP](https://omim.org/entry/301076)

Human gene(s) implicated

[GLYCINE RECEPTOR, ALPHA-2 SUBUNIT; GLRA2](https://omim.org/entry/305990)

Symptoms and phenotype

The Pilorge type of X-linked syndromic intellectual developmental disorder (MRXSP) is characterized by global developmental delay with variably impaired intellectual development, speech delay, and behavioral abnormalities, including autism spectrum disorder (ASD). More variable features include motor incoordination, seizures, and ocular abnormalities (summary by Marcogliese et al., 2022; pubmed:35294868). [from MIM:301076; 2022.05.17]

(OMIM, 2013-)
Genetics

Pilorge type of X-linked syndromic intellectual developmental disorder (MRXSP) is caused by heterozygous or hemizygous mutation in the GLRA2 gene. [from MIM:301076; 2022.05.17]

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

The glycine receptor consists of two subunits, alpha and beta, and acts as a pentamer. The protein encoded by GLRA2 is an alpha subunit. Glycine receptors are ligand-gated chloride channels responsible for mediating the inhibitory effects of glycine, playing a role in the down-regulation of neuronal excitability. [Gene Cards, GLRA2; 2022.03.28]

(FlyBase Curators, 2013-)
External links
Disease synonyms
MRXSP
neurodevelopmental disorder with developmental delay, intellectual disability, autism, and epilepsy, GLRA2-related
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
Symbol / Name
GLRA2; glycine receptor alpha 2
D. melanogaster ortholog (based on DIOPT)
Dmel\GluClα
(DIOPT, 2013-)
Comments on ortholog(s)

Many to one: 4 human genes to 1 Drosophila gene; multiple related genes in both species.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Dmel\GluClα
    Gene Snapshot
    Contributions welcome
    Molecular function (GO)
    Cellular component (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    High-scoring ortholog of human GLRA1, GLRA2, GLRA3, GLRA4 (1 Drosophila to 4 human; multiple related genes in both species).

    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 (1 groups)
      GluClα
      protein-protein
      Interacting group
      Assay
      References
      GluClα - mmd
      anti tag coimmunoprecipitation, western blot, pull down, Identification by mass spectrometry
      (Sanfilippo et al., 2024)
      Alleles Reported to Model Human Disease (Disease Ontology) (4 alleles)
      Hsap\GLRA2
      Models Based on Experimental Evidence ( 3 )
      Modifiers Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Interaction
      References
      GluClα
      Models Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Evidence
      References
      GluClαglc1
      model of  Kohlschutter-Tonz syndrome
      CEA with Indy302
      (Jeong et al., 2021)
      Modifiers Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Interaction
      References
      Alleles Representing Disease-Implicated Variants
      Genetic Tools, Stocks and Reagents
      References (7)