EIF2B3

eukaryotic translation initiation factor 2B subunit gamma

Basic information

Region (hg38): 1:44850521-44986722

Links

ENSG00000070785 ∙ NCBI:8891 ∙ OMIM:606273 ∙ HGNC:3259 ∙ Uniprot:Q9NR50 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• leukoencephalopathy with vanishing white matter (Strong), mode of inheritance: AR
• ovarioleukodystrophy (Supportive), mode of inheritance: AR
• leukoencephalopathy with vanishing white matter 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukoencephalopathy with vanishing white matter 3	AR	Obstetric	Individuals with Ovarioleukodystrophy may suffer from premature ovarian failure, and measures to allow reproduction (eg,through egg preservation) may be desired	Endocrine; Neurologic; Obstetric	11704758; 11835386; 15136673; 18263758; 19158808; 20301435; 21484434; 22312164; 23115207
The evidence is unclear, but it is possible that certain circumstances may aggravate the condition and accelerate neurological decline, including head trauma (children may benefit from wearing helmets), contact sports, and stressful situations (including high body temperature, and prophylactic measures and rapid treatment related to infections may be beneficial)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EIF2B3 gene.

• not provided (153 variants)
• Vanishing white matter disease (53 variants)
• not specified (18 variants)
• Inborn genetic diseases (12 variants)
• Leukoencephalopathy with vanishing white matter 3 (4 variants)
• Leukoencephalopathy with vanishing white matter 1 (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EIF2B3 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			4	32	1	37
missense	1	5	72	5	1	84
nonsense						0
start loss			1			1
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			5	5		10
non coding			10	22	17	49
Total	1	6	87	59	19

Highest pathogenic variant AF is 0.0000460

Variants in EIF2B3

This is a list of pathogenic ClinVar variants found in the EIF2B3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-44850550-A-G		Vanishing white matter disease	Likely benign (Jan 13, 2018)
1-44850669-C-T		Vanishing white matter disease	Uncertain significance (Jan 12, 2018)
1-44850685-G-A		Vanishing white matter disease	Uncertain significance (Jan 12, 2018)
1-44850750-G-C		Vanishing white matter disease	Uncertain significance (Jan 13, 2018)
1-44850896-G-A		Vanishing white matter disease	Uncertain significance (Jan 12, 2018)
1-44850957-C-T			Likely benign (Jan 29, 2024)
1-44850965-G-A			Uncertain significance (Dec 02, 2021)
1-44850978-C-A			Likely benign (Sep 18, 2023)
1-44850981-G-A			Likely benign (Jun 21, 2023)
1-44850990-A-G			Likely benign (Sep 27, 2023)
1-44850991-T-C		Vanishing white matter disease	Uncertain significance (Jan 13, 2018)
1-44851018-GA-G			Benign (Oct 29, 2023)
1-44851021-A-G			Likely benign (May 24, 2023)
1-44857686-G-T			Likely benign (Sep 27, 2023)
1-44857687-AT-A			Likely benign (Sep 27, 2023)
1-44857688-T-C			Likely benign (Aug 08, 2023)
1-44857692-A-C			Likely benign (Jan 11, 2023)
1-44857695-C-G			Likely benign (Jul 13, 2023)
1-44857721-T-C			Uncertain significance (Dec 19, 2021)
1-44857723-G-A		Vanishing white matter disease	Uncertain significance (Jan 12, 2018)
1-44857729-T-C			Likely benign (Sep 12, 2023)
1-44857733-A-G		Vanishing white matter disease • See cases • Leukoencephalopathy with vanishing white matter 1	Uncertain significance (Apr 22, 2024)
1-44857736-A-C		Vanishing white matter disease	Uncertain significance (Apr 27, 2017)
1-44857750-G-A			Likely benign (Jul 16, 2023)
1-44857757-C-A			Uncertain significance (Aug 30, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EIF2B3	protein_coding	protein_coding	ENST00000360403	11	135833

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.567	0.433	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.04	198	244	0.812	0.0000129	2952
Missense in Polyphen		20	31.108	0.64293		383
Synonymous	1.41	68	84.5	0.805	0.00000412	867
Loss of Function	3.63	5	24.3	0.206	0.00000127	302

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP.
• Disease: DISEASE: Leukodystrophy with vanishing white matter (VWM) [MIM:603896]: A leukodystrophy that occurs mainly in children. Neurological signs include progressive cerebellar ataxia, spasticity, inconstant optic atrophy and relatively preserved mental abilities. The disease is chronic-progressive with, in most individuals, additional episodes of rapid deterioration following febrile infections or minor head trauma. While childhood onset is the most common form of the disorder, some severe forms are apparent at birth. A severe, early-onset form seen among the Cree and Chippewayan populations of Quebec and Manitoba is called Cree leukoencephalopathy. Milder forms may not become evident until adolescence or adulthood. Some females with milder forms of the disease who survive to adolescence exhibit ovarian dysfunction. This variant of the disorder is called ovarioleukodystrophy. {ECO:0000269|PubMed:11835386, ECO:0000269|PubMed:19158808, ECO:0000269|PubMed:21484434}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: RNA transport - Homo sapiens (human);Translation Factors;Recycling of eIF2:GDP;Eukaryotic Translation Initiation;Translation;Metabolism of proteins;Cap-dependent Translation Initiation (Consensus)

Recessive Scores

• pRec: 0.168

Intolerance Scores

• loftool: 0.122
• rvis_EVS: -0.12
• rvis_percentile_EVS: 45.13

Haploinsufficiency Scores

• pHI: 0.526
• hipred: Y
• hipred_score: 0.696
• ghis: 0.572

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.923

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Eif2b3
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype

Gene ontology

• Biological process: translational initiation;response to heat;response to glucose;oligodendrocyte development;hippocampus development;response to peptide hormone;T cell receptor signaling pathway
• Cellular component: cytoplasm;cytosol;eukaryotic translation initiation factor 2B complex
• Molecular function: translation initiation factor activity;guanyl-nucleotide exchange factor activity;protein binding;translation factor activity, RNA binding;nucleotidyltransferase activity