EIF2AK4 (eIF-2-alpha kinase GCN2) variants and mutations

EIF2AK4 (also known as eIF-2-alpha kinase GCN2) is a human protein-coding gene encoding an eIF-2-alpha kinase GCN2 protein. It senses amino-acid deprivation and other stresses and reduces global translation through phosphorylation of eIF2alpha. Biallelic loss-of-function variants are a major cause of pulmonary capillary hemangiomatosis and pulmonary veno-occlusive disease. This analysis covers 1,801 EIF2AK4 variants and mutations. Of these, 77% have computational variant effect predictions. Disease context includes Pulmonary capillary hemangiomatosis, pulmonary venoocclusive disease 2, and heritable pulmonary arterial hypertension. Example EIF2AK4 variants include A2V, A2T, and A2S.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable EIF2AK4 variants

Examples include A2V, A2T, A2S, A2A, G3R, G3A, G3W, G4A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.