FIGURE 3.

Variants of EIF2AK4 associated with pulmonary vascular disease. Schematic representation of the general control nondepressible (GCN)2 protein and its domains; boxes correspond to the 39 exons in EIF2AK4. Domains are highlighted: RWD (RING-finger proteins, WD repeat-containing proteins, yeast DEAD-like helicase), pseudokinase, eukaryotic initiation factor (eIF)2α kinase, histidyl-tRNA synthetase-like and carboxy-terminal domain (CTD). Predicted pathogenic variants are shown as lollipops: above the protein are likely pathogenic variants associated with pulmonary arterial hypertension (PAH), below are likely pathogenic variants associated with pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary haemangiomatosis (PCH). The lollipop length indicates the approximate number of such alleles reported in the literate allowing for incomplete reporting. Note, c.3344C>T (p.P1115L) in exon 23 in at the histidyl-tRNA synthetase-like domain has been reported in five families affected by PAH or PVOD (#). Potentially, 48 alleles have been described, but this may be confounded by overlaps between published reports.