EIF4G1

protein-coding

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

Gene summary

The protein encoded by this gene is a component of the multi-subunit protein complex EIF4F. This complex facilitates the recruitment of mRNA to the ribosome, which is a rate-limiting step during the initiation phase of protein synthesis. The recognition of the mRNA cap and the ATP-dependent unwinding of 5'-terminal secondary structure is catalyzed by factors in this complex. The subunit encoded by this gene is a large scaffolding protein that contains binding sites for other members of the EIF4F complex. A domain at its N-terminus can also interact with the poly(A)-binding protein, which may mediate the circularization of mRNA during translation. Alternative splicing results in multiple transcript variants, some of which are derived from alternative promoter usage. [provided by RefSeq, Aug 2010]

Previous symbols:

EIF4G
EIF4F

MANE transcript

NM_198241.3

Inheritance

ClinVar variants

U:212B:52

Top phenotype

Parkinson disease 18, autosomal dominant, susceptibility to

gnomAD constraint

pLI —, LoF o/e 0.02

Max pathogenic AF

—

Genomic locus

chr3:184,314,495-184,335,358

External References & Databases

Ensembl (ENSG00000114867)

Transcript & Mutation Effects

hg38 • Region Span ~20.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Parkinson disease 18, autosomal dominant, susceptibility toLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0013653

Submitter: Labcorp Genetics (formerly Invitae)

Parkinson disease 18, autosomal dominant, susceptibility toMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0013653

Submitter: Genomics England PanelApp

Parkinson disease 18, autosomal dominant, susceptibility toNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0013653

Submitter: Ambry Genetics

Parkinson disease 18, autosomal dominant, susceptibility toLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013653

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Parkinson disease 18, autosomal dominant, susceptibility toAD

Manifestation: Neurologic

Intervention: Neurologic

Rationale: Response to levodopa has been described, though the evidence for causation is mixed

Refs: 21907011; 23408866; 25227500; 25368108

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EIF4G1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 187

not providedTotal: 54

EIF4G1-related disorderTotal: 38

Parkinson disease 18, autosomal dominant, susceptibility toTotal: 16

Parkinson disease, late-onsetTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_198241.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	33 clinvar	1 clinvar	38
missense			194 clinvar	15 clinvar	3 clinvar	212
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	0	0	212	48	4	264

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 102 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_198241.3	RefSeq	NP_937884.2	31	MANE Select
ENST00000346169.7	Ensembl	ENSP00000316879.5	31	MANE Select
NM_001194946.2	RefSeq	NP_001181875.2	32	Standard
NM_001194947.2	RefSeq	NP_001181876.2	32	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Viral myocarditis - Homo sapiens (human)
RNA transport - Homo sapiens (human)
Translation Factors
Signal Transduction
mtor signaling pathway

Biological Process

nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
behavioral fear response
cap-dependent translational initiation
translation
translational initiation

Molecular Function

RNA binding
mRNA binding
translation initiation factor activity
protein binding
ATP binding

Cellular Component

nucleus
cytoplasm
cytosol
polysome
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000424196
Coding exons: 32
Length: 20864
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125748
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.22	727	916	0.793	0.0000619	10353
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00060	0.00060	rare
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.171

Intolerance Scores

LoFtool: 0.135
RVIS EVS: -1.27
RVIS percentile EVS: 5.21

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.864

Gene Damage Prediction

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