EIF2AK4 was first reported in relation to autosomal recessive pulmonary veno-occlusive disease (PVOD) in 2014 (Eyries et al., PMID:24292273). More than 22 distinct variants (e.g. missense, in-frame indel, nonsense, frameshift, etc) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level genetic data and protein expression in lung.
Summary of case-level data: 43.4 points (max. 12 points) variants in this gene have been reported in more than 21 probands (PMIDs: 24292273, 24135949, 25512148, 28972005, and others). Summary of experimental evidence: 0.5 points.
The evidence supporting this gene-disease relationship has been replicated over more than 5 years. In summary, EIF2AK4 is definitively associated with autosomal recessive pulmonary veno-occlusive disease/capillary haemangiomatosis (PVOD/PCH) which is frequently misdiagnosed as pulmonary arterial hypertension. This classification was approved by the ClinGen PH Gene Curation Expert Panel on August 30, 2022 (SOP v9).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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