RasGRP2 Structure, Function and Genetic Variants in Platelet Pathophysiology

Int J Mol Sci. 2020 Feb 6;21(3):1075. doi: 10.3390/ijms21031075.

Abstract

RasGRP2 is calcium and diacylglycerol-regulated guanine nucleotide exchange factor I that activates Rap1, which is an essential signaling-knot in "inside-out" αIIbβ3 integrin activation in platelets. Inherited platelet function disorder caused by variants of RASGRP2 represents a new congenital bleeding disorder referred to as platelet-type bleeding disorder-18 (BDPLT18). We review here the structure of RasGRP2 and its functions in the pathophysiology of platelets and of the other cellular types that express it. We will also examine the different pathogenic variants reported so far as well as strategies for the diagnosis and management of patients with BDPLT18.

Keywords: RasGRP2; inherited platelet disorder; platelet.

Publication types

  • Review

MeSH terms

  • Blood Platelet Disorders / congenital
  • Blood Platelet Disorders / genetics*
  • Blood Platelets / pathology*
  • Child, Preschool
  • Female
  • Guanine Nucleotide Exchange Factors / genetics*
  • Guanine Nucleotide Exchange Factors / metabolism
  • Hemorrhage / congenital
  • Hemorrhage / genetics*
  • Humans
  • Infant
  • Male
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Shelterin Complex
  • Signal Transduction / genetics
  • Telomere-Binding Proteins / metabolism

Substances

  • Guanine Nucleotide Exchange Factors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • RASGRP2 protein, human
  • Shelterin Complex
  • TERF2IP protein, human
  • Telomere-Binding Proteins