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): 3:184314494-184335358

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

Links

ENSG00000114867 ∙ NCBI:1981 ∙ OMIM:600495 ∙ HGNC:3296 ∙ Uniprot:Q04637 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Parkinson disease 18	AD	Neurologic	Response to levodopa has been described, though the evidence for causation is mixed	Neurologic	21907011; 23408866; 25227500; 25368108

ClinVar

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

• Inborn genetic diseases (46 variants)
• not provided (42 variants)
• not specified (10 variants)
• Parkinson disease 18, autosomal dominant, susceptibility to (10 variants)
• EIF4G1-related condition (2 variants)

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				9	2	11
missense			52	2	3	57
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding					21	21
Total	0	0	53	11	26

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)
3-184315620-A-T			Benign (Jun 18, 2021)
3-184315838-A-C		EIF4G1-related disorder	Likely benign (Oct 31, 2019)
3-184316135-G-C		not specified	Uncertain significance (Dec 27, 2023)
3-184316175-C-A		not specified	Uncertain significance (Oct 06, 2023)
3-184316552-GT-G			Benign (Jun 21, 2021)
3-184317341-C-T			Likely benign (Jul 15, 2018)
3-184317345-C-T		not specified	Uncertain significance (Sep 27, 2021)
3-184317349-C-T		EIF4G1-related disorder	Uncertain significance (Dec 19, 2023)
3-184317427-C-T		not specified	Uncertain significance (Feb 10, 2023)
3-184317492-G-C		not specified	Uncertain significance (Dec 07, 2021)
3-184317604-T-A			Benign (Jun 20, 2021)
3-184317660-G-A			Benign (Jun 21, 2021)
3-184317739-C-G		not specified	Uncertain significance (Jul 20, 2021)
3-184319426-GGT-G			Benign (Jun 19, 2021)
3-184319447-GTGTGTGTGTGTGTGTGTGTT-G			Benign (Jun 19, 2021)
3-184319449-GTGTGTGTGTGTGTGTGTT-G			Benign (Jun 19, 2021)
3-184319451-GTGTGTGTGTGTGTGTT-G			Benign (Jun 19, 2021)
3-184319739-G-T		EIF4G1-related disorder	Uncertain significance (Jan 17, 2023)
3-184319745-A-G		not specified	Benign (-)
3-184319759-G-T		not specified	Uncertain significance (Jun 16, 2023)
3-184319800-C-T		Parkinson disease 18, autosomal dominant, susceptibility to	Uncertain significance (Jan 07, 2022)
3-184319928-T-G			Benign (Jun 21, 2021)
3-184320972-G-A		not specified	Uncertain significance (Aug 08, 2022)
3-184321086-A-T			Benign (Jun 18, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EIF4G1	protein_coding	protein_coding	ENST00000424196	32	20864

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	8.43e-13	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.22	727	916	0.793	0.0000619	10353
Missense in Polyphen		204	347.35	0.5873		3914
Synonymous	-2.54	413	352	1.17	0.0000221	3337
Loss of Function	8.33	2	84.7	0.0236	0.00000577	931

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000293	0.0000293
Ashkenazi Jewish	0.000597	0.000595
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000624	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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