NPFFR2 gene compound heterozygous variants associated with preeclampsia identified by whole-exome sequencing

•Compound heterozygous variants of NPFFR2 were identified in preeclampsia family considered to be potentially pathogenic variants associated with preeclampsia.•Due to the compound heterozygous variants of NPFFR2, more bonds are generated between amino acids and spatial adjacent amino acids, which may lead to more stable active conformation of protein.•The increasing NPFFR2 protein in placenta is released to maternal peripheral blood through maternal-fetal circulation.•Our results provide new insights into the underlying mechanisms of preeclampsia induced by NPFFR2 specificity variants.