Functional validation of EIF2AK4 (GCN2) missense variants associated with pulmonary arterial hypertension.

ABSTRACT: Pulmonary arterial hypertension (PAH) is a disorder with a large genetic component. Biallelic mutations of EIF2AK4, which encodes the kinase GCN2, are causal in two ultra-rare subtypes of PAH, pulmonary veno-occlusive disease and pulmonary capillary haemangiomatosis. EIF2AK4 variants of unknown significance have also been identified in patients with classical PAH, though their relationship to disease remains unclear. To provide patients with diagnostic information and enable family testing, the functional consequences of such rare variants must be determined, but existing computational methods are imperfect. We applied a suite of bioinformatic and experimental approaches to sixteen EIF2AK4 variants that had been identified in patients. By experimentally testing the functional integrity of

SUBMITTER: Emanuelli G 

PROVIDER: S-EPMC11336063 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature