EIF4G1

eukaryotic translation initiation factor 4 gamma 1, the group of Small nucleolar RNA protein coding host genes|MIF4G domain containing proteins

Basic information

Region (hg38): 3:184314495-184335358

Previous symbols: [ "EIF4G", "EIF4F" ]

Links

ENSG00000114867NCBI:1981OMIM:600495HGNC:3296Uniprot:Q04637AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Parkinson disease 18, autosomal dominant, susceptibility to (Moderate), mode of inheritance: AD
  • Parkinson disease 18, autosomal dominant, susceptibility to (Disputed Evidence), mode of inheritance: Unknown
  • Parkinson disease 18, autosomal dominant, susceptibility to (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Parkinson disease 18ADNeurologicResponse to levodopa has been described, though the evidence for causation is mixedNeurologic21907011; 23408866; 25227500; 25368108

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EIF4G1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EIF4G1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
13
clinvar
3
clinvar
16
missense
70
clinvar
4
clinvar
4
clinvar
78
nonsense
0
start loss
1
clinvar
1
frameshift
0
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
0
splice region
1
2
3
non coding
21
clinvar
21
Total 0 0 71 18 28

Variants in EIF4G1

This is a list of pathogenic ClinVar variants found in the EIF4G1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
3-184315558-T-A Benign (Jun 20, 2021)1258758
3-184315620-A-T Benign (Jun 18, 2021)1225346
3-184315838-A-C EIF4G1-related disorder Likely benign (Oct 31, 2019)3049318
3-184316135-G-C not specified Uncertain significance (Dec 27, 2023)3088037
3-184316175-C-A not specified Uncertain significance (Oct 06, 2023)3088028
3-184316552-GT-G Benign (Jun 21, 2021)1243147
3-184317341-C-T Likely benign (Jul 15, 2018)760817
3-184317345-C-T not specified Uncertain significance (Sep 27, 2021)2249054
3-184317349-C-T EIF4G1-related disorder Uncertain significance (Dec 19, 2023)3032152
3-184317427-C-T not specified Uncertain significance (Feb 10, 2023)2482862
3-184317492-G-C not specified Uncertain significance (Dec 07, 2021)2265702
3-184317604-T-A Benign (Jun 20, 2021)1227934
3-184317660-G-A Benign (Jun 21, 2021)1251295
3-184317739-C-G not specified Uncertain significance (Jul 20, 2021)2238850
3-184319426-GGT-G Benign (Jun 19, 2021)1183465
3-184319447-GTGTGTGTGTGTGTGTGTGTT-G Benign (Jun 19, 2021)1244682
3-184319449-GTGTGTGTGTGTGTGTGTT-G Benign (Jun 19, 2021)1280193
3-184319451-GTGTGTGTGTGTGTGTT-G Benign (Jun 19, 2021)1283267
3-184319739-G-T EIF4G1-related disorder Uncertain significance (Jan 17, 2023)2629995
3-184319745-A-G not specified Benign (-)1174883
3-184319759-G-T not specified Uncertain significance (Jun 16, 2023)2603896
3-184319800-C-T Parkinson disease 18, autosomal dominant, susceptibility to Uncertain significance (Jan 07, 2022)1334462
3-184319928-T-G Benign (Jun 21, 2021)1243000
3-184320972-G-A not specified Uncertain significance (Aug 08, 2022)2306200
3-184320988-G-C EIF4G1-related disorder Uncertain significance (Aug 23, 2024)3349241

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
EIF4G1protein_codingprotein_codingENST00000424196 3220864
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.008.43e-131257330151257480.0000596
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.227279160.7930.000061910353
Missense in Polyphen204347.350.58733914
Synonymous-2.544133521.170.00002213337
Loss of Function8.33284.70.02360.00000577931

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00002930.0000293
Ashkenazi Jewish0.0005970.000595
East Asian0.000.00
Finnish0.00004620.0000462
European (Non-Finnish)0.00006240.0000615
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome.;
Disease
DISEASE: Parkinson disease 18 (PARK18) [MIM:614251]: An autosomal dominant, late-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. {ECO:0000269|PubMed:21907011}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Viral myocarditis - Homo sapiens (human);RNA transport - Homo sapiens (human);Translation Factors;Signal Transduction;mtor signaling pathway;regulation of eif-4e and p70s6 kinase;skeletal muscle hypertrophy is regulated via akt-mtor pathway;internal ribosome entry pathway;Translation initiation complex formation;Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S;Cytokine Signaling in Immune system;Eukaryotic Translation Initiation;Translation;Metabolism of proteins;mTORC1-mediated signalling;AUF1 (hnRNP D0) binds and destabilizes mRNA;mTOR signalling;Metabolism of RNA;Immune System;insulin Mam;Nonsense-Mediated Decay (NMD);EGFR1;Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC);eukaryotic protein translation;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);Ribosomal scanning and start codon recognition;L13a-mediated translational silencing of Ceruloplasmin expression;Regulation of mRNA stability by proteins that bind AU-rich elements;GTP hydrolysis and joining of the 60S ribosomal subunit;Cap-dependent Translation Initiation;Deadenylation of mRNA;Deadenylation-dependent mRNA decay;Validated targets of C-MYC transcriptional activation;ISG15 antiviral mechanism;Antiviral mechanism by IFN-stimulated genes;Interferon Signaling;insulin (Consensus)

Recessive Scores

pRec
0.171

Intolerance Scores

loftool
0.135
rvis_EVS
-1.27
rvis_percentile_EVS
5.21

Haploinsufficiency Scores

pHI
0.880
hipred
Y
hipred_score
0.783
ghis
0.601

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.864

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Eif4g1
Phenotype
normal phenotype;

Gene ontology

Biological process
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;behavioral fear response;cap-dependent translational initiation;translation;translational initiation;regulation of translational initiation;mitochondrion organization;positive regulation of cell population proliferation;negative regulation of autophagy;negative regulation of peptidyl-threonine phosphorylation;positive regulation of cell death;viral process;positive regulation of cell growth;cellular response to nutrient levels;positive regulation of cellular protein metabolic process;developmental process;positive regulation of peptidyl-serine phosphorylation;cellular macromolecule biosynthetic process;regulation of mRNA stability;positive regulation of neuron differentiation;regulation of gene silencing by miRNA;regulation of cellular response to stress;energy homeostasis;positive regulation of G1/S transition of mitotic cell cycle;negative regulation of neuron death;positive regulation of eukaryotic translation initiation factor 4F complex assembly;regulation of presynapse assembly;positive regulation of mRNA cap binding;positive regulation of miRNA mediated inhibition of translation;regulation of polysome binding
Cellular component
nucleus;cytoplasm;cytosol;polysome;membrane;eukaryotic translation initiation factor 4F complex;cytosolic small ribosomal subunit
Molecular function
RNA binding;mRNA binding;translation initiation factor activity;protein binding;ATP binding;translation factor activity, RNA binding;eukaryotic initiation factor 4E binding;translation initiation factor binding;protein-containing complex scaffold activity;identical protein binding