EIF2B1

eukaryotic translation initiation factor 2B subunit alpha

Basic information

Region (hg38): 12:123620406-123633766

Previous symbols: [ "EIF2B" ]

Links

ENSG00000111361 ∙ NCBI:1967 ∙ OMIM:606686 ∙ HGNC:3257 ∙ Uniprot:Q14232 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukoencephalopathy with vanishing white matter 1	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; 18263758; 20301435
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 EIF2B1 gene.

• not_provided (223 variants)
• Inborn_genetic_diseases (29 variants)
• Vanishing_white_matter_disease (26 variants)
• Leukoencephalopathy_with_vanishing_white_matter_1 (15 variants)
• not_specified (6 variants)
• EIF2B1-related_disorder (1 variants)
• Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EIF2B1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001414.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	84	1	88
missense	4	2	64	2		72
nonsense	5	1				6
start loss						0
frameshift	12	4	1			17
splice donor/acceptor (+/-2bp)		7				7
Total	21	14	68	86	1

Highest pathogenic variant AF is 0.00016726967

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EIF2B1	protein_coding	protein_coding	ENST00000424014	9	13361

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000761	0.926	125673	0	75	125748	0.000298

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.38	114	164	0.696	0.00000983	1974
Missense in Polyphen		38	58.661	0.64779		694
Synonymous	-0.614	71	64.7	1.10	0.00000436	607
Loss of Function	1.64	9	16.1	0.560	8.84e-7	198

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000317	0.000316
Middle Eastern	0.000218	0.000217
South Asian	0.00101	0.00101
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:15776425}. 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: 0.125

Intolerance Scores

• loftool: 0.364
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.42

Haploinsufficiency Scores

• pHI: 0.435
• hipred: Y
• hipred_score: 0.625
• ghis: 0.672

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.993

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Eif2b1

Gene ontology

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