EIF2B2

eukaryotic translation initiation factor 2B subunit beta

Basic information

Region (hg38): 14:75002921-75012366

Links

ENSG00000119718NCBI:8892OMIM:606454HGNC:3258Uniprot:P49770AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Leukoencephalopathy with vanishing white matter 2ARObstetricIndividuals with Ovarioleukodystrophy may suffer from premature ovarian failure, and measures to allow reproduction (eg,through egg preservation) may be desiredEndocrine; Neurologic; Obstetric11704758; 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.

EffectPLPVUSLBBSum
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 0.000488199

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
EIF2B2protein_codingprotein_codingENST00000266126 86679
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
2.08e-100.07061256860621257480.000247
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.031491890.7890.000009592302
Missense in Polyphen2953.1320.54581684
Synonymous-0.1297674.61.020.00000403709
Loss of Function0.04161515.20.9888.32e-7176

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002890.000289
Ashkenazi Jewish0.0002980.000298
East Asian0.0001090.000109
Finnish0.00009240.0000924
European (Non-Finnish)0.0002640.000264
Middle Eastern0.0001090.000109
South Asian0.0004570.000457
Other0.0001630.000163

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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