SVEP1

The SVEP1 protein enables integrin binding and is required for embryonic lymphatic vascular development, including lymphatic endothelial cell migration and formation of lymphovenous contact sites, while also regulating vascular smooth muscle contraction and platelet activation. Mutations cause autosomal recessive primary lymphedema with additional features including cutis laxa, cardiac septal defects, and intellectual disability. The high pLI score (0.9999) and low LOEUF score (0.254) indicate the gene is highly intolerant to loss-of-function variants, suggesting pathogenicity results from loss of protein function.