EIF2B4

Chr 2AR

eukaryotic translation initiation factor 2B subunit delta

Also known as: EIF-2B, EIF2B, EIF2Bdelta, VWM4

NCBI Gene: 8890 ENSG00000115211 UniProt: Q9UI10 OMIM: 606687

The protein functions as the delta subunit of eukaryotic initiation factor 2B (EIF2B), a GTP exchange factor essential for protein synthesis. Mutations cause leukoencephalopathy with vanishing white matter, sometimes accompanied by ovarian failure, through an autosomal recessive inheritance pattern. The high constraint scores (pLI 0.96, LOEUF 0.33) support that pathogenicity occurs predominantly through loss-of-function mechanisms affecting protein synthesis regulation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Eukaryotic initiation factor 2B (EIF2B), which is necessary for protein synthesis, is a GTP exchange factor composed of five different subunits. The protein encoded by this gene is the fourth, or delta, subunit. Defects in this gene are a cause of leukoencephalopathy with vanishing white matter (VWM) and ovarioleukodystrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Leukoencephalopathy with vanishing white matter 4, with or without ovarian failureMIM #620314

Clinical highlights

Gene-disease validity (ClinGen)

leukoencephalopathy with vanishing white matter 4 · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.33

LOEUF· LoF intol.

LOF

Mechanism· G2P

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GeneReview available — EIF2B4