Human Disease Model Report: congenital heart defect (postulated), EIF4G3-related

General Information

Name

congenital heart defect (postulated), EIF4G3-related

FlyBase ID

FBhh0001348

Disease Ontology Term

Parent Disease

congenital heart defect

OMIM

Overview

Congenital heart defect (CHD), also described as congenital heart disease, is the most common type of birth defect; it is thought to have a significant genetic component. Candidate genes identified in a large-scale exome sequencing analysis have been assessed in a fly system using cardiac-targeted gene silencing of orthologous fly genes. Experiments using the Drosophila ortholog eIF4G1 support EIF4G3 as a candidate gene in the development of CHD.

In a large-scale exome sequencing analysis in Nigeria, a canonical splice site variant in the EIF4G3 gene was found in a child diagnosed with tetralogy of Fallot.

EIF4G3 encodes a component of the eIF4F protein complex, which is involved in mRNA cap recognition and transport of mRNAs to the ribosome. There are two paralogous genes in both human (EIF4G1 and EIF4G3) and flies (eIF4G1 and eIF4G2). The human EIF4G3 gene has not been introduced into flies.

Ubiquitous knockdown of Dmel\eIF4G1, effected by RNAi, results in lethality. Targeted knockdown of eIF4G1 restricted to the developing heart results in 83% lethality prior to the adult stage. Physical and genetic interactions of Dmel\eIF4G1 have been described; see below and in the eIF4G1 gene report.

[updated May 2021 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: congenital heart defect

Symptoms and phenotype

A congenital heart defect is a problem with the structure of the heart; it is the most common type of birth defect. The defects can involve the walls of the heart, the valves of the heart, and the arteries and veins near the heart. They can disrupt the normal flow of blood through the heart: the blood flow can slow down, go in the wrong direction or to the wrong place, or be blocked completely (https://medlineplus.gov/congenitalheartdefects.html).

(FlyBase Curators, 2013-)

Defects range from simple, which might cause no problems, to complex, which can cause life-threatening complications. The most serious defects are categorized as critical congenital heart defects (CCHD). CCHD is life threatening and requires intervention in infancy; approximately 18 out of 10,000 babies are born with CCHD (https://www.aap.org/en-us/advocacy-and-policy/aap-health-initiatives/PEHDIC/Pages/Newborn-Screening-for-CCHD.aspx).

(FlyBase Curators, 2013-)

Genetic causes of congenital heart disease also account for many of the comorbidities seen with increased frequency in congenital heart disease patients, including neurodevelopmental disability, pulmonary disease, arrhythmia, renal disease, heart failure and an increased incidence of malignancy. (Simmons and Brueckner, 2017; pubmed:28872494).

(FlyBase Curators, 2013-)

A number of well studied syndromes, including DiGeorge syndrome, Williams-Beuren syndrome, Alagille syndrome, Noonan syndrome, and Holt-Oram syndrome, include congenital heart defect (Pierpont et al., 2007; pubmed:17519398).

(FlyBase Curators, 2013-)

Congenital heart defects (CHTD) are among the most common congenital defects, occurring with an incidence of 8/1,000 live births. The etiology of CHTD is complex, with contributions from environmental exposure, chromosomal abnormalities, and gene defects. [from MIM:306955; 2018.11.13]

(OMIM, 2013-)

Specific Disease Summary: congenital heart defect (postulated), EIF4G3-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

The protein encoded by EIF4G3 is thought to be part of the eIF4F protein complex, which is involved in mRNA cap recognition and transport of mRNAs to the ribosome. [Gene Cards, EIF4G3; 2021.05.15]

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): EIF4G3
Gene Cards: EIF4G3
MedlinePlus (gene): EIF4G3
MARRVEL (human gene): EIF4G3
NCBI (Entrez) gene: EIF4G3; eukaryotic translation initiation factor 4 gamma 3
National Organization for Rare Disorders: Tetralogy of Fallot

Disease synonyms

Related Diseases

Related human health report(s)

congenital heart defect

Related Specific Diseases

OMIM phenotypic series

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

EIF4G3; eukaryotic translation initiation factor 4 gamma 3

D. melanogaster ortholog (based on DIOPT)

Dmel\eIF4G1

(DIOPT, 2013-)

Dmel\eIF4G2

(DIOPT, 2013-)

Comments on ortholog(s)

Many to many: 2 human genes to 2 Drosophila genes.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\eIF4G1

Gene Snapshot

eukaryotic translation initiation factor 4G1 (eIF4G1) encodes a protein that contributes to translation and spermatogenesis. [Date last reviewed: 2019-07-11]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

TLNF-CIF

Comments on ortholog(s)

Moderate- to high-scoring ortholog of human EIF4G1 and EIF4G3 (2 Drosophila to 2 human). Dmel\eIF4G1 shares 25-27% identity and 39-41% 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 (23 groups)

eIF4G1

protein-protein

Interacting group

Assay

References

eIF4G1 - Akt

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

eIF4G1 - aub

anti tag coimmunoprecipitation, anti tag western blot

(Ma et al., 2017)

eIF4G1 - Capr

anti bait coimmunoprecipitation, western blot

(Papoulas et al., 2010)

eIF4G1 - eIF4A

two hybrid

(Hernandez et al., 2004)

eIF4G1 - eIF4E1

pull down, molecular weight estimation by staining, anti bait coimmunoprecipitation, western blot, isothermal titration calorimetry, predetermined participant, anti tag coimmunoprecipitation, two hybrid, affinity chromatography technology, autoradiography, anti tag western blot, Identification by mass spectrometry, classical fluorescence spectroscopy, x-ray crystallography, cosedimentation

(Wang et al., 2017, Grüner et al., 2016, Zuberek et al., 2016, Ghosh and Lasko, 2015, Peter et al., 2015, Igreja et al., 2014, Hernández et al., 2013, Hernandez et al., 2012, Iwasaki et al., 2009, Baker and Fuller, 2007, Hernandez et al., 2005, Hernandez et al., 2004, Zappavigna et al., 2004, Hernandez et al., 1998, Zapata et al., 1994)

eIF4G1 - eIF4E3

anti bait coimmunoprecipitation, western blot, two hybrid

(Ghosh and Lasko, 2015, Hernandez et al., 2012, Hernandez et al., 2005)

eIF4G1 - eIF4E4

classical fluorescence spectroscopy, predetermined participant, two hybrid

(Zuberek et al., 2016, Hernandez et al., 2005)

eIF4G1 - eIF4E5

two hybrid, classical fluorescence spectroscopy, predetermined participant

(Zuberek et al., 2016, Hernandez et al., 2005)

eIF4G1 - eIF4E7

two hybrid, classical fluorescence spectroscopy, predetermined participant

(Zuberek et al., 2016, Hernandez et al., 2005)

eIF4G1 - Fmr1

anti bait coimmunoprecipitation, western blot, peptide massfingerprinting

(Papoulas et al., 2010)

eIF4G1 - foxo

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

eIF4G1 - ft

anti tag coimmunoprecipitation, peptide massfingerprinting

(Kwon et al., 2013)

eIF4G1 - gig

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

eIF4G1 - ksr

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

eIF4G1 - Mkrn1

anti tag coimmunoprecipitation, anti tag western blot, Identification by mass spectrometry, anti bait coimmunoprecipitation

(Dold et al., 2020)

eIF4G1 - pAbp

anti bait coimmunoprecipitation, Identification by mass spectrometry, western blot, anti tag coimmunoprecipitation, anti tag western blot

(Wang et al., 2017, Ghosh and Lasko, 2015, Zekri et al., 2009)

eIF4G1 - Pdk1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

eIF4G1 - RagC-D

pull down, anti tag western blot, anti tag coimmunoprecipitation, peptide massfingerprinting

(Tsokanos et al., 2016)

eIF4G1 - rictor

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

eIF4G1 - sima

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

eIF4G1 - sstn

anti tag coimmunoprecipitation, peptide massfingerprinting

(Liu et al., 2015)

eIF4G1 - Tsc1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

RNA-protein

Interacting group

Assay

References

eIF4G1 - nanos

pull down, western blot

(Jeske et al., 2011)

Alleles Reported to Model Human Disease (Disease Ontology) (1 alleles)

eIF4G1

Models Based on Experimental Evidence ( 0 )

Allele

Disease

Evidence

References

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

eIF4G1^HMS00762

ameliorates retinitis pigmentosa 4

modeled by ninaE^P37H.GFP

(Zhao et al., 2023)

exacerbates cancer

modeled by Rbf^HMS03004

(Parkhitko et al., 2021)

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

eIF4G1^HMS06053

P{TRiP.HMS06053}

y¹ v¹; P{TRiP.HMS06053}attP2

eIF4G1^GD7098

P{GD7098}

w¹¹¹⁸; P{GD7098}v17002

eIF4G1^HMS00762

P{TRiP.HMS00762}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00762}attP2

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

References (4)

Report Sections

Open Close