FB2026_03 , released September 17, 2026
Human Disease Model Report: intellectual disability, autosomal dominant 55, with seizures
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General Information
Name
intellectual disability, autosomal dominant 55, with seizures
FlyBase ID
FBhh0001609
Disease Ontology Term
Parent Disease
OMIM
INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 55, WITH SEIZURES; MRD55
Overview

This report describes intellectual disability, autosomal dominant 55, with seizures, a subtype of autosomal dominant intellectual disability. The human gene implicated is NUS1, which encodes . NUS1 is also associated with Parkinson disease (postulated), NUS1-related (FBhh0000997). There is one high-scoring fly ortholog, Dmel\Tango14, for which multiple genetic reagents, including a loss of function allele, RNAi-targeting constructs, alleles caused by insertional mutagenesis, and alleles representing human disease-implicated variants have been generated. See the 'Disease-Implicated Variants' table below.

Human NUS1 has not been introduced into flies.

Pan-neuronal RNAi knockdown of Dmel\Tango14 resulted in a bang-sensitive seizure phenotype. A similar phenotype was observed in flies bearing a knock-in allele of Dmel\Tango14 bearing a human disease-implicated variant. Both also exhibited an upregulation the unfolded protein response signaling genes Xbp1 and Hsc70-3.

[updated June 2024 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: intellectual disability, autosomal dominant
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 disability, autosomal dominant 55, with seizures
OMIM report

[INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 55, WITH SEIZURES; MRD55](https://omim.org/entry/617831)

Human gene(s) implicated

[NUS1 DEHYDRODOLICHYL DIPHOSPHATE SYNTHASE SUBUNIT; NUS1](https://omim.org/entry/610463)

Symptoms and phenotype

Patients present with developmental delay or impaired intellectual development, seizures, and ataxia (Yu, et al, 2021, pubmed:33731878). [from MIM:617831; 2024.11.20]

(OMIM, 2013-)
Genetics

Autosomal dominant intellectual disability 55 with seizures (MRD55) is caused by heterozygous mutation in the NUS1 gene on chromosome 6q22. [from MIM:617831; 2024.11.20]

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

The NUS1 gene encodes a membrane protein that is a subunit of cis-prenyltransferase (cis-PTase) and is involved in the synthesis of dolichol, which is necessary for protein glycosylation (summary by Park et al., 2014, pubmed:25066056). [from MIM:610463; 2024.11.20]

(OMIM, 2013-)

GRM1 encodes a metabotropic glutamate receptor that functions by activating phospholipase C. [provided by RefSeq, May 2013]

(FlyBase Curators, 2013-)
External links
Disease synonyms
intellectual developmental disorder, autosomal dominant 55, with seizures
Lennox-Gastaut Syndrome
MRD55
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    Symbol / Name
    NUS1; NUS1 dehydrodolichyl diphosphate synthase subunit
    D. melanogaster ortholog (based on DIOPT)
    Dmel\Tango14
    (DIOPT, 2013-)
    Comments on ortholog(s)

    One to one (1 human to 1 Drosophila); NUS1 has one high-scoring Drosophila ortholog, Tango14.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Dmel\Tango14
      Gene Snapshot
      Transport and Golgi organization 14 (Tango14) encodes a subunit of the dehydrodolichyl diphosphate synthase complex that catalyzes the condensation of multiple copies of isopentenyl diphosphate to produce di-trans,poly-cis-polyprenyl diphosphatefarnesyl pyrophosphate in the first step of the biosynthesis of dolichyl phosphate. [Date last reviewed: 2025-08-21]
      Molecular function (GO)
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      High-scoring ortholog of human NUS1 (1 Drosophila to 1 human).

      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 (0 groups)
        Alleles Reported to Model Human Disease (Disease Ontology) (5 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
        Tango14RNAi.UAS.cSa
        P{UAS-Tango14.RNAi.S}
        Tango14GD481
        P{GD481}
        w1118; P{GD481}v42499
        Tango14KK107564
        P{KK107564}
        P{KK107564}VIE-260B
        Tango14JF01144
        P{TRiP.JF01144}
        y1 v1; P{TRiP.JF01144}attP2
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        Tango14CRISPR
        loss of function allele
        CRISPR/Cas9
        Tango14W276C
        CRISPR/Cas9
        References (4)