EIF2B4

eukaryotic translation initiation factor 2B subunit delta

Basic information

Region (hg38): 2:27364352-27370338

Links

ENSG00000115211OMIM:606687HGNC:3260Uniprot:Q9UI10AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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
  • leukoencephalopathy with vanishing white matter 4 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Leukoencephalopathy with vanishing white matter 4ARObstetricIndividuals 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; 15776425; 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 EIF2B4 gene.

  • not_provided (383 variants)
  • Vanishing_white_matter_disease (53 variants)
  • Inborn_genetic_diseases (51 variants)
  • Leukoencephalopathy_with_vanishing_white_matter_4 (16 variants)
  • not_specified (13 variants)
  • EIF2B4-related_disorder (7 variants)
  • Leukoencephalopathy_with_vanishing_white_matter_1 (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EIF2B4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001034116.2. 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
148
clinvar
3
clinvar
153
missense
6
clinvar
14
clinvar
113
clinvar
6
clinvar
1
clinvar
140
nonsense
5
clinvar
1
clinvar
6
start loss
0
frameshift
8
clinvar
2
clinvar
1
clinvar
11
splice donor/acceptor (+/-2bp)
2
clinvar
7
clinvar
9
Total 21 23 117 154 4

Highest pathogenic variant AF is 0.0000762119

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
EIF2B4protein_codingprotein_codingENST00000451130 126135
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9610.03881257310171257480.0000676
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.7982572960.8690.00001883428
Missense in Polyphen75109.240.686581333
Synonymous-1.351331151.160.000005961173
Loss of Function4.18427.80.1440.00000165321

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002680.000268
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00004390.0000439
Middle Eastern0.000.00
South Asian0.0001630.000163
Other0.000.00

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:12707859, 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
0.132

Intolerance Scores

loftool
0.0313
rvis_EVS
-0.76
rvis_percentile_EVS
13.45

Haploinsufficiency Scores

pHI
0.715
hipred
Y
hipred_score
0.706
ghis
0.570

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.902

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Eif2b4
Phenotype
nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype;

Gene ontology

Biological process
ovarian follicle development;translational initiation;regulation of translation;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;translation initiation factor binding