EIF2S3 eukaryotic translation initiation factor 2 subunit gamma [Homo sapiens (human)] - Gene

Summary

Official Symbol: EIF2S3provided by HGNC
Official Full Name: eukaryotic translation initiation factor 2 subunit gammaprovided by HGNC
Primary source: HGNC:HGNC:3267
See related: Ensembl:ENSG00000130741 MIM:300161; AllianceGenome:HGNC:3267
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: EIF2; EIF2G; MEHMO; eIF2gX; MRXSBRK; eIF-2gA; EIF2gamma
Summary: The protein encoded by this gene is the largest subunit of a heterotrimeric GTP-binding protein involved in the recruitment of methionyl-tRNA(i) to the 40 S ribosomal subunit. [provided by RefSeq, Jan 2010]
Expression: Ubiquitous expression in ovary (RPKM 61.4), lymph node (RPKM 53.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xp22.11

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (24054956..24078810)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (23639400..23663280)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (24073073..24096927)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Binding of human Cdc123 to eIF2gamma.
Title: Binding of human Cdc123 to eIF2γ.
mRNA analysis revealed a novel pathogenic EIF2S3 variant causing MEHMO syndrome.
Title: mRNA analysis revealed a novel pathogenic EIF2S3 variant causing MEHMO syndrome.
Eukaryotic initiation factor-2, gamma subunit, suppresses proliferation and regulates the cell cycle via the MAPK/ERK signaling pathway in acute myeloid leukemia.
Title: Eukaryotic initiation factor-2, gamma subunit, suppresses proliferation and regulates the cell cycle via the MAPK/ERK signaling pathway in acute myeloid leukemia.
Novel pathogenic EIF2S3 missense variants causing clinically variable MEHMO syndrome with impaired eIF2gamma translational function, and literature review.
Title: Novel pathogenic EIF2S3 missense variants causing clinically variable MEHMO syndrome with impaired eIF2γ translational function, and literature review.
Our data suggest that the p.Pro432Ser mutation impairs eIF2gamma function leading to a relatively mild novel phenotype compared with previous EIF2S3 mutations. Our studies support a critical role for EIF2S3 in human hypothalamo-pituitary development and function, and glucose regulation, expanding the range of phenotypes associated with EIF2S3 mutations beyond classical MEHMO syndrome.
Title: Impaired EIF2S3 function associated with a novel phenotype of X-linked hypopituitarism with glucose dysregulation.
Results suggest that the I259M mutation impairs Met-tRNAiMet binding, causing altered control of protein synthesis that underlies MEHMO syndrome.
Title: MEHMO syndrome mutation EIF2S3-I259M impairs initiator Met-tRNAiMet binding to eukaryotic translation initiation factor eIF2.
We aimed to provide more details on the endocrine phenotype in two previously reported male probands with MEHMO carrying a frame-shift mutation (I465fs) in the EIF2S3 gene
Title: Neonatal hypoglycemia, early-onset diabetes and hypopituitarism due to the mutation in EIF2S3 gene causing MEHMO syndrome.
Data suggest that more severe EIF2S3 mutations cause the full MEHMO phenotype, while less deleterious mutations cause a milder form of the syndrome with only a subset of the symptoms.
Title: EIF2S3 Mutations Associated with Severe X-Linked Intellectual Disability Syndrome MEHMO.
Our data confirm that EIF2S3 mutation is implicated in a rare, but recognizable, form of syndromic intellectual disability.
Title: Two novel EIF2S3 mutations associated with syndromic intellectual disability with severe microcephaly, growth retardation, and epilepsy.
The human X-chromosomal neurological disorder characterized by intellectual disability and microcephaly is caused by a missense mutation in eIF2gamma (encoded by EIF2S3), the core subunit of the heterotrimeric eIF2 complex.
Title: eIF2γ mutation that disrupts eIF2 complex integrity links intellectual disability to impaired translation initiation.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
MEHMO syndrome MedGen: C1846278 OMIM: 300148 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Rev	rev	HIV-1 Rev interacting protein, eukaryotic translation initiation factor 2, subunit 3 (EIF2S3), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa. The interaction of Rev with EIF2S3 is increased by RRE	PubMed
Tat	tat	Expression of HIV-1 Tat upregulates the abundance of eukaryotic translation initiation factor 2, subunit 3 gamma (EIF2S3) in the nucleoli of Jurkat T-cells	PubMed
	tat	HIV-1 Tat competes with eukaryotic initiation factor 2, a well characterized substrate of PKR, for phosphorylation by activated PKR	PubMed
	tat	Eukaryotic translation initiation factor 2 (eIF2) recognizes and binds the TAR secondary structure in HIV-1 RNA, suggesting a role in Tat transactivation of the viral LTR promoter	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

EIF2S3 (e-PCR)
- UniSTS:498180

A009Y29 (e-PCR)
- UniSTS:60188

EIF2S3_1860 (e-PCR)
- UniSTS:462889

D8S2279 (e-PCR)
- UniSTS:473907

G32988 (e-PCR)
- UniSTS:117565

RH17627 (e-PCR)
- UniSTS:32858

D17S1239 (e-PCR)
- UniSTS:149852

D12S1830 (e-PCR)
- UniSTS:19063

L29953 (e-PCR)
- UniSTS:52164

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables GTP binding	IEA Inferred from Electronic Annotation more info
enables GTPase activity	TAS Traceable Author Statement more info	PubMed
enables cadherin binding	HDA more info	PubMed
enables membrane scission GTPase motor activity	IEA Inferred from Electronic Annotation more info
enables methionyl-initiator methionine tRNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to tRNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables translation factor activity, RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables translation initiation factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables translation initiation factor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in cytoplasmic translational initiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in formation of translation preinitiation complex	IBA Inferred from Biological aspect of Ancestor more info
involved_in translational initiation	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
part_of eukaryotic translation initiation factor 2 complex	IBA Inferred from Biological aspect of Ancestor more info
part_of eukaryotic translation initiation factor 2 complex	IDA Inferred from Direct Assay more info	PubMed
part_of eukaryotic translation initiation factor 2 complex	IPI Inferred from Physical Interaction more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
NOT located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: eukaryotic translation initiation factor 2 subunit 3

Names: eIF-2-gamma X; eIF-2gX; eIF2-gamma X; eukaryotic translation initiation factor 2 subunit gamma X; eukaryotic translation initiation factor 2, subunit 3 gamma, 52kDa; eukaryotic translation initiation factor 2G; mental retardation, epileptic seizures, hypogonadism and -genitalism, microcephaly and obesity syndrome

NP_001406.1

EC 3.6.5.3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.