EIF2S3

eukaryotic translation initiation factor 2 subunit gamma

Basic information

Region (hg38): X:24054945-24078810

Previous symbols: [ "EIF2G" ]

Links

ENSG00000130741 ∙ NCBI:1968 ∙ OMIM:300161 ∙ HGNC:3267 ∙ Uniprot:P41091 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• diabetes mellitus (Strong), mode of inheritance: XL
• MEHMO syndrome (Strong), mode of inheritance: XL
• MEHMO syndrome (Supportive), mode of inheritance: XL
• MEHMO syndrome (Definitive), mode of inheritance: AD
• MEHMO syndrome (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
MEHMO syndrome	XL	Endocrine	Awareness of endocrine manifestations, including growth hormone deficiency and hypogonadism, may allow early recognition and treatment	Craniofacial; Endocrine; Musculoskeletal; Neurologic	23063529; 27333055; 28055140

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EIF2S3 gene.

• not provided (32 variants)
• MEHMO syndrome (11 variants)
• Inborn genetic diseases (8 variants)
• not specified (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EIF2S3 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			1	8	4	13
missense		3	20			23
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			3	4		7
non coding			1			1
Total	0	4	22	8	4

Variants in EIF2S3

This is a list of pathogenic ClinVar variants found in the EIF2S3 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-24054973-C-G			Uncertain significance (Aug 18, 2017)
X-24054974-G-T			Uncertain significance (Jan 01, 2019)
X-24054995-T-C			Likely benign (Dec 01, 2022)
X-24054996-C-T		not specified	Likely benign (Oct 01, 2022)
X-24055016-G-C			Likely benign (Apr 01, 2023)
X-24055033-C-T		MEHMO syndrome	Uncertain significance (Nov 02, 2023)
X-24055644-C-T		not specified • MEHMO syndrome	Benign (Aug 09, 2021)
X-24055651-A-G		EIF2S3-related disorder	Uncertain significance (Feb 06, 2024)
X-24055668-A-G		not specified	Benign (Apr 04, 2018)
X-24055686-T-C		not specified • EIF2S3-related disorder	Benign/Likely benign (Jan 30, 2024)
X-24057415-C-G			Uncertain significance (May 15, 2017)
X-24057417-A-G		not specified	Likely benign (Jan 18, 2024)
X-24057426-A-G			Uncertain significance (Mar 16, 2022)
X-24057627-T-G		Inborn genetic diseases	Uncertain significance (Jan 19, 2022)
X-24057645-G-A		Inborn genetic diseases	Uncertain significance (Jan 05, 2018)
X-24057651-C-A		not specified	Uncertain significance (Jul 06, 2017)
X-24057652-C-G			Uncertain significance (Jan 01, 2024)
X-24057657-T-G		Inborn genetic diseases	Uncertain significance (May 11, 2022)
X-24057660-C-T			Uncertain significance (Jul 01, 2018)
X-24057677-T-C			Likely benign (Nov 01, 2020)
X-24057695-T-A		MEHMO syndrome	Uncertain significance (Dec 12, 2016)
X-24057745-A-G		not specified	Likely benign (-)
X-24057750-G-A			Uncertain significance (Oct 16, 2020)
X-24057757-G-A			Likely benign (Aug 01, 2022)
X-24060121-T-C			Likely benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EIF2S3	protein_coding	protein_coding	ENST00000253039	12	23256

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.964	0.0361	125716	0	21	125737	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.61	42	177	0.237	0.0000130	3052
Missense in Polyphen		0	44.217	0		855
Synonymous	-0.130	63	61.7	1.02	0.00000462	944
Loss of Function	3.32	1	14.7	0.0678	0.00000100	295

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000406	0.000327
Ashkenazi Jewish	0.000139	0.0000992
East Asian	0.00	0.00
Finnish	0.000193	0.000139
European (Non-Finnish)	0.000126	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000236	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: As a subunit of eukaryotic initiation factor 2 (eIF2), involved in the early steps of protein synthesis. In the presence of GTP, eIF2 forms a ternary complex with initiator tRNA Met-tRNAi and then recruits the 40S ribosomal complex, a step that determines the rate of protein translation. This step is followed by mRNA binding to form the 43S pre-initiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex. In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF2B (By similarity). Along with its paralog on chromosome Y, may contribute to spermatogenesis up to the round spermatid stage (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q9Z0N1}.
• Pathway: RNA transport - Homo sapiens (human);Translation Factors;double stranded rna induced gene expression;skeletal muscle hypertrophy is regulated via akt-mtor pathway;Formation of the ternary complex, and subsequently, the 43S complex;Translation initiation complex formation;Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S;Recycling of eIF2:GDP;Eukaryotic Translation Initiation;Translation;Metabolism of proteins;Transport of small molecules;regulation of eif2;ABC-family proteins mediated transport;eukaryotic protein translation;Ribosomal scanning and start codon recognition;L13a-mediated translational silencing of Ceruloplasmin expression;GTP hydrolysis and joining of the 60S ribosomal subunit;Cap-dependent Translation Initiation (Consensus)

Recessive Scores

• pRec: 0.218

Intolerance Scores

• loftool: 0.117
• rvis_EVS: 0.13
• rvis_percentile_EVS: 62.74

Haploinsufficiency Scores

• pHI: 0.862
• hipred: Y
• hipred_score: 0.598

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Eif2s3x

Zebrafish Information Network

• Gene name: eif2s3
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: necrotic

Gene ontology

• Biological process: formation of translation preinitiation complex;translational initiation;transmembrane transport
• Cellular component: nucleus;cytoplasm;cytosol;eukaryotic translation initiation factor 2 complex;extracellular exosome
• Molecular function: translation initiation factor activity;GTPase activity;protein binding;GTP binding;translation factor activity, RNA binding;cadherin binding