Human Disease Model Report: intellectual disability, autosomal recessive 46

General Information

Name

intellectual disability, autosomal recessive 46

FlyBase ID

FBhh0000248

Disease Ontology Term

autosomal recessive intellectual developmental disorder 46

Parent Disease

intellectual disability, autosomal recessive

OMIM

INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 46; MRT46

Overview

This report describes intellectual disability, autosomal recessive 46; an alternative designation of this disease is 'mental retardation, autosomal recessive 46' (MRT46). The human gene implicated in this disease is NDST1, which catalyzes both the N-deacetylation and the N-sulfation of heparan sulfate glycosaminoglycans; it is a transmembrane protein that resides in the Golgi apparatus. There is a single fly ortholog, sfl, for which loss-of-function alleles, RNAi-targeting constructs and an allele caused by insertional mutagenesis have been generated. Dmel\sfl is also orthologous to human genes NDST2, NDST3, AND NDST4. The NDST1 gene has also been implicated in a recent GWAS study with non-obstructive azoospermia (FBhh0000239).

The NDST1 gene has not been introduced into flies.

In Drosophila, systemic knockdown of sfl typically results in lethality during the pupal stage. Assessments of larval phenotypes reveal locomotor defects and abnormalities in synaptic physiology and morphology. Genetic interactions of Dmel\sfl have been characterized; see the gene report for sfl.

[updated Apr. 2016 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: intellectual disability, autosomal recessive

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 recessive 46

OMIM report

[INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 46; MRT46](https://omim.org/entry/616116)

Human gene(s) implicated

[N-DEACETYLASE/N-SULFOTRANSFERASE 1; NDST1](https://omim.org/entry/600853)

Symptoms and phenotype

Patients from a small number of families have been characterized. All had delayed psychomotor development apparent from infancy or early childhood with delayed or absent expressive speech; most patients had hypotonia; some had therapy-responsive seizures. [from MIM:616116]

(OMIM, 2013-)

Genetics

Autosomal recessive mental retardation 46 (MRT46) is caused by homozygous mutation in the NDST1 gene, exhibiting an autosomal-recessive mode of inheritance. [from MIM:616116]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

NDST1 is a member of the heparan sulfate/heparin GlcNAc N-deacetylase/N-sulfotransferase family, involved in the biosynthesis of heparan sulfate proteoglycans. The NDST1 enzyme is a type II transmembrane protein that resides in the Golgi apparatus. [from Gene Cards, NDST1; 2016.04.07]

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): NDST1
Gene Cards: NDST1
MedlinePlus (gene): NDST1
MARRVEL (human gene): NDST1
NCBI MedGen: Mental retardation, autosomal recessive 46 (MRT46)
NCBI (Entrez) gene: NDST1; N-deacetylase and N-sulfotransferase 1

Disease synonyms

intellectual disability, autosomal recessive 46

mental retardation, autosomal recessive 46

MRT46

Related Diseases

Related human health report(s)

autism spectrum disorder, susceptibility to (postulated), NDST-related

Related Specific Diseases

OMIM phenotypic series

Intellectual developmental disorder, autosomal recessive

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[MRT2](https://omim.org/entry/607417)

[CRBN](https://omim.org/entry/609262)

intellectual disability, autosomal recessive 2

[MRT3](https://omim.org/entry/608443)

[CC2D1A](https://omim.org/entry/610055)

intellectual disability, autosomal recessive 3

[MRT5](https://omim.org/entry/611091)

[NSUN2](https://omim.org/entry/610916)

intellectual disability, autosomal recessive 5

[MRT37](https://omim.org/entry/615493)

[ANK3](https://omim.org/entry/600465)

intellectual disability, autosomal recessive 37

[MRT46](https://omim.org/entry/616116)

[NDST1](https://omim.org/entry/600853)

intellectual disability, autosomal recessive 46

[MRT56](https://omim.org/entry/617125)

[ZC3H14](https://omim.org/entry/613279)

intellectual disability, autosomal recessive 56

[MRT65](https://omim.org/entry/618109)

[KDM5B](https://omim.org/entry/605393)

intellectual disability, autosomal recessive 65

[MRT71](https://omim.org/entry/618504)

[ALKBH8](https://omim.org/entry/613306)

intellectual disability, autosomal recessive 71

[MRT82](https://omim.org/entry/620779)

[NSUN6](https://omim.org/entry/617199)

intellectual disability, syndromic, autosomal recessive 82

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

NDST1; N-deacetylase and N-sulfotransferase 1

D. melanogaster ortholog (based on DIOPT)

Dmel\sfl

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 4 human to 1 Drosophila; additional high-scoring human orthologous genes are NDST2, NDST3, and NDST4; one low-scoring ortholog also exists.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\sfl

Gene Snapshot

sulfateless sfl encodes a heparan sulfate-glucosamine N-sulfotransferase that catalyzes both the N-deacetylation and the N-sulfation of N-acetyl-glucosamine (GlcNAc) of the heparan sulfate glycosaminoglycan chain. It is involved in the first step in heparan sulfate modification and is required for subsequent sulfotransferase reactions at the 2-O position of iduronate or glucuronate, and the 6-O-position of glucosamine. [Date last reviewed: 2024-12-19]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Ortholog of human genes NDST1, NDST2, NDST3, AND NDST4 (1 Drosophila to 4 human). Dmel\sfl shares 53-55% identity and 70-71% 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 (7 groups)

sfl

RNA-protein

Interacting group

Assay

References

sfl - eIF3a

anti tag coimmunoprecipitation, nucleic acid uv cross-linking assay, reverse transcription pcr, quantitative reverse transcription pcr

(Song et al., 2022)

sfl - eIF3b

anti tag coimmunoprecipitation, nucleic acid uv cross-linking assay, quantitative reverse transcription pcr, reverse transcription pcr

(Song et al., 2022)

sfl - eIF3d1

anti tag coimmunoprecipitation, nucleic acid uv cross-linking assay, reverse transcription pcr, quantitative reverse transcription pcr

(Song et al., 2022)

sfl - eIF3i

anti tag coimmunoprecipitation, nucleic acid uv cross-linking assay, quantitative reverse transcription pcr

(Song et al., 2022)

sfl - eIF3j

anti tag coimmunoprecipitation, nucleic acid uv cross-linking assay, reverse transcription pcr, quantitative reverse transcription pcr

(Song et al., 2022)

sfl - eIF3k

anti tag coimmunoprecipitation, nucleic acid uv cross-linking assay, quantitative reverse transcription pcr, reverse transcription pcr

(Song et al., 2022)

sfl - RpS23

anti tag coimmunoprecipitation, nucleic acid uv cross-linking assay, quantitative reverse transcription pcr

(Song et al., 2022)

Alleles Reported to Model Human Disease (Disease Ontology) (5 alleles)

sfl

Models Based on Experimental Evidence ( 4 )

Allele

Disease

Evidence

References

sfl^HMS00543

model of germ cell cancer

CEA

(Levings and Nakato, 2018)

sfl^GD2336

model of intellectual disability

CEA

(Reuter et al., 2014)

sfl^{RNAi.UAS.THFC}

model of azoospermia

CEA

(Yu et al., 2015)

sfl^GLC01656

model of autism spectrum disorder

CEA

(Hope et al., 2019)

Modifiers Based on Experimental Evidence ( 3 )

Allele

Disease

Interaction

References

sfl^HMS00543

ameliorates Alzheimer's disease

modeled by Psn^541.UAS

(Reynolds-Peterson et al., 2020)

modeled by Psn^RNAi.UAS.3

(Schultheis et al., 2024)

model of germ cell cancer

is exacerbated by Egfr^f2

(Levings and Nakato, 2018)

sfl^9B4

ameliorates Parkinson's disease 2

modeled by park^Δ21, park¹

(Reynolds-Peterson et al., 2020)

sfl^GD2336

exacerbates neonatal diabetes mellitus

modeled by Hsap\INS^C96Y.UAS

(He et al., 2014)

exacerbates mucopolysaccharidosis type IIIA

modeled by Sgsh^GD1578

(Webber et al., 2018)

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

sfl^{siRNA.UAS.circ-1}

P{UAS-sfl.siRNA.circ-1}

sfl^{siRNA.UAS.circ-2}

P{UAS-sfl.siRNA.circ-2}

sfl^{siRNA.UAS.circ-3}

P{UAS-sfl.siRNA.circ-3}

w¹¹¹⁸; P{GD2336}v5070

sfl^HMS00543

P{TRiP.HMS00543}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00543}attP2

sfl^GLC01656

P{TRiP.GLC01656}

y¹ v¹; P{TRiP.GLC01656}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

sfl^9B4

References (5)

Report Sections

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