EIF2B2

eukaryotic translation initiation factor 2B subunit beta

Basic information

Region (hg38): 14:75002921-75012366

Links

ENSG00000119718

∙ NCBI:8892 ∙ OMIM:606454 ∙ HGNC:3258 ∙ Uniprot:P49770 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

leukoencephalopathy with vanishing white matter (Definitive), mode of inheritance: AR
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
leukoencephalopathy with vanishing white matter (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukoencephalopathy with vanishing white matter 2	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; 14566705; 15054402; 18263758; 19625339; 21484434; 22285377; 20301435; 22678813; 22729508
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 EIF2B2 gene.

not_provided (241 variants)
Inborn_genetic_diseases (40 variants)
Vanishing_white_matter_disease (38 variants)
Leukoencephalopathy_with_vanishing_white_matter_2 (19 variants)
EIF2B2-related_disorder (6 variants)
not_specified (5 variants)
Abnormality_of_the_nervous_system (2 variants)
Leukoencephalopathy_with_vanishing_white_matter_1 (2 variants)
Premature_ovarian_insufficiency (2 variants)
See_cases (2 variants)
Osteogenesis_imperfecta (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EIF2B2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014239.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	89 clinvar	1 clinvar	92
missense	3 clinvar	10 clinvar	85 clinvar	3 clinvar	2 clinvar	103
nonsense	3 clinvar	3 clinvar				6
start loss		2	1			3
frameshift	12 clinvar	4 clinvar				16
splice donor/acceptor (+/-2bp)		5 clinvar				5
Total	18	24	88	92	3

Highest pathogenic variant AF is 0.00048819947

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EIF2B2	protein_coding	protein_coding	ENST00000266126	8	6679

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.08e-10	0.0706	125686	0	62	125748	0.000247

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.03	149	189	0.789	0.00000959	2302
Missense in Polyphen		29	53.132	0.54581		684
Synonymous	-0.129	76	74.6	1.02	0.00000403	709
Loss of Function	0.0416	15	15.2	0.988	8.32e-7	176

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000289	0.000289
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000264	0.000264
Middle Eastern	0.000109	0.000109
South Asian	0.000457	0.000457
Other	0.000163	0.000163

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:11704758, ECO:0000269|PubMed:12707859, ECO:0000269|PubMed:15776425, ECO:0000269|PubMed:21484434, ECO:0000269|PubMed:22285377, ECO:0000269|PubMed:22729508}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: RNA transport - Homo sapiens (human);Translation Factors;Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling;Recycling of eIF2:GDP;Eukaryotic Translation Initiation;Translation;Metabolism of proteins;Cap-dependent Translation Initiation (Consensus)

Recessive Scores

pRec: 0.178

Intolerance Scores

loftool: 0.317
rvis_EVS: -0.27
rvis_percentile_EVS: 34.32

Haploinsufficiency Scores

pHI: 0.223
hipred: Y
hipred_score: 0.751
ghis: 0.593

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.829

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Eif2b2
Phenotype: hematopoietic system phenotype;

Gene ontology

Biological process: ovarian follicle development;translational initiation;regulation of translational initiation;central nervous system development;response to heat;response to glucose;oligodendrocyte development;myelination;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;ATP binding;GTP binding