Human Disease Model Report: intellectual disability, autosomal recessive 56

General Information

Name

intellectual disability, autosomal recessive 56

FlyBase ID

FBhh0000602

Disease Ontology Term

autosomal recessive intellectual developmental disorder 56

Parent Disease

intellectual disability, autosomal recessive

OMIM

INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 56; MRT56

Overview

This report describes intellectual disability, autosomal recessive 56; an alternative designation of this disease is 'mental retardation, autosomal recessive 56 '(MRT56). The human gene implicated in this disease is ZC3H14, which encodes a zinc finger poly(A)-binding protein that participates in regulation of mRNA stability, nuclear export, and translation. There is a single Drosophila ortholog, Nab2, for which amorphic alleles caused by small deletions, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

UAS constructs of the wild-type (tagged) human Hsap\ZC3H14 gene have been introduced into flies. Heterologous rescue (functional complementation) has been demonstrated: human ZC3H14 can functionally substitute for Nab2 in when expressed in neurons, rescuing defects in development and locomotion that are present in Nab2 null flies.

Most animals that are homozygous for a null mutation of Nab2 die during the pupal stage or as pharate adults; a small percentage eclose as adults. Surviving adults display several visible phenotypes, as well as impaired locomotor behavior, anatomical abnormalities in brain structures, and a shorter lifespan. Embryos lacking germline Nab2 function die early in embryogenesis. Genetic interactions have been described for Dmel\Nab2; see the Nab2 gene report.

[updated Sep. 2017 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 56

OMIM report

[INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 56; MRT56](https://omim.org/entry/617125)

Human gene(s) implicated

[ZINC FINGER CCCH DOMAIN-CONTAINING PROTEIN 14: ZC3H14](https://omim.org/entry/613279)

Symptoms and phenotype

MRT56 is a nonsyndromic intellectual disability. [from MIM:617125; 2017.09.07]

(OMIM, 2013-)

Genetics

Autosomal recessive mental retardation-56 (MRT56) is caused by homozygous mutation in the ZC3H14 gene. [from MIM:617125; 2017.09.07]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

Homozygous Nab2-null mutant flies exhibit extended poly(A) tails compared to wild-type.

(FlyBase Curators, 2013-)

ZC3H14 belongs to a family of poly(A)-binding proteins that influence gene expression by regulating mRNA stability, nuclear export, and translation (Kelly et al., 2007; pubmed:17630287). [from MIM:613279; 2017.09.07]

(OMIM, 2013-)

External links

Gene2Function (human gene): ZC3H14
Gene Cards: ZC3H14
MedlinePlus (gene): ZC3H14
MARRVEL (human gene): ZC3H14
NCBI MedGen: Mental retardation, autosomal recessive 56 (MRT56)
NCBI (Entrez) gene: ZC3H14; zinc finger CCCH-type containing 14

Disease synonyms

autosomal recessive, nonsyndromic intellectual disability

intellectual disability, autosomal recessive 56

intellectual disability disease locus on chromosome 14q31.3

mental retardation, autosomal recessive 56

MRT56

Related Diseases

Related human health report(s)

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

Hsap\ZC3H14

Human gene (HGNC)

Symbol / Name

ZC3H14; zinc finger CCCH-type containing 14

D. melanogaster ortholog (based on DIOPT)

Dmel\Nab2

(DIOPT, 2013-)

Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\Nab2

Gene Snapshot

Nuclear polyadenosine RNA-binding 2 (Nab2) encodes a zinc-finger polyadenosine RNA binding protein that is expressed widely in many cell types but required specifically within the developing nervous system for proper behavior and axonogenesis. The product of Nab2 in supports in neurons short term memory and development of the brain mushroom bodies. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Moderate-to-high-scoring ortholog of human gene ZC3H14 (1 Drosophila to 1 human); Dmel\Nab2 shares 24% identity and 36% similarity with the human gene.

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 (4 groups)

Nab2

protein-protein

Interacting group

Assay

References

Nab2 - Atx2

anti tag coimmunoprecipitation, western blot

(Rounds et al., 2022)

Nab2 - Fmr1

anti tag coimmunoprecipitation, western blot

(Rounds et al., 2022, Bienkowski et al., 2017)

RNA-protein

Interacting group

Assay

References

Nab2 - CaMKII

anti tag coimmunoprecipitation, quantitative reverse transcription pcr

(Bienkowski et al., 2017)

Nab2 - Sxl

anti tag coimmunoprecipitation, quantitative reverse transcription pcr

(Jalloh et al., 2023)

Alleles Reported to Model Human Disease (Disease Ontology) (3 alleles)

Nab2

Models Based on Experimental Evidence ( 3 )

Allele

Disease

Evidence

References

Nab2^EP3716

model of autosomal recessive intellectual developmental disorder

CEA

(Rounds et al., 2022, Bienkowski et al., 2017)

Nab2^ex3

model of autosomal recessive intellectual developmental disorder

CEA

(Corgiat et al., 2022, Rounds et al., 2022, Bienkowski et al., 2017)

model of autosomal recessive intellectual developmental disorder 56

CEC

(Pak et al., 2011)

Nab2^GD11745

model of intellectual disability

CEA

(Kelly et al., 2016)

model of autosomal recessive intellectual developmental disorder 56

CEC

(Pak et al., 2011)

model of autosomal recessive intellectual developmental disorder

CEA

(Bienkowski et al., 2017)

Modifiers Based on Experimental Evidence ( 3 )

Allele

Disease

Interaction

References

Nab2^EP3716

model of autosomal recessive intellectual developmental disorder

is ameliorated by Fmr1^Δ113M

(Bienkowski et al., 2017)

is ameliorated by Fmr1^Δ50M

(Bienkowski et al., 2017)

is ameliorated by Pabp2^EP2264

(Bienkowski et al., 2017)

is ameliorated by Fmr1^GL00075

(Bienkowski et al., 2017)

is ameliorated by Gαo^KO

(Rounds et al., 2022)

is ameliorated by sm¹

(Rounds et al., 2022)

is ameliorated by HmgZ^KG01188

(Rounds et al., 2022)

is ameliorated by stai^KO

(Rounds et al., 2022)

is exacerbated by drk^e0A

(Rounds et al., 2022)

is ameliorated by Bsg^k13638

(Rounds et al., 2022)

is ameliorated by mtd⁴

(Rounds et al., 2022)

is ameliorated by Arpc2^KG04658

(Rounds et al., 2022)

is ameliorated by Atx2^DG08112

(Rounds et al., 2022)

is ameliorated by Atx2^X1

(Rounds et al., 2022)

exacerbates fragile X syndrome

modeled by Fmr1^UAS.cWa

(Bienkowski et al., 2017)

Nab2^ex3

model of autosomal recessive intellectual developmental disorder

is ameliorated by Appl^d

(Corgiat et al., 2022)

is ameliorated by Vang^stbm-6

(Corgiat et al., 2022)

is ameliorated by dsh¹

(Corgiat et al., 2022)

is exacerbated by Fmr1^Δ113M

(Bienkowski et al., 2017)

is exacerbated by Fmr1^Δ50M

(Bienkowski et al., 2017)

is ameliorated by Atx2^X1

(Rounds et al., 2022)

is ameliorated by Atx2^DG08112

(Rounds et al., 2022)

model of autosomal recessive intellectual developmental disorder 56

is exacerbated by Pabp2⁵⁵

(Pak et al., 2011)

is ameliorated by Pabp2^EP2264

(Pak et al., 2011)

is exacerbated by hrg¹⁰

(Pak et al., 2011)

ameliorates fragile X syndrome

modeled by Fmr1^Δ50M

(Bienkowski et al., 2017)

modeled by Fmr1^Δ113M

(Bienkowski et al., 2017)

Nab2^GD11745

model of autosomal recessive intellectual developmental disorder

is exacerbated by Fmr1^Δ113M

(Bienkowski et al., 2017)

is exacerbated by Fmr1^UAS.cWa

(Bienkowski et al., 2017)

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

Hsap\ZC3H14^UAS.Tag:HA

PBac{UAS-hZC3H14.HA}

y¹ w^*; PBac{UAS-hZC3H14.HA}VK00037/SM6a

Hsap\ZC3H14^{Iso1.UAS.Tag:FLAG}

P{UAS-FLAG-ZC3H14.1}

Hsap\ZC3H14^{Iso4.UAS.Tag:FLAG}

P{UAS-FLAG-ZC3H14.4}

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

Nab2^GD11745

P{GD11745}

w¹¹¹⁸; P{GD11745}v27487

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01925}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Nab2^EP3716

P-element activity

w¹¹¹⁸; P{EP}Nab2^EP3716/TM6B, Tb¹

Nab2^ex1