ETV6: A Candidate Gene for Predisposition to “Blend Pedigrees”? A Case Report from the NEXT-Famly Clinical Trial

Table 3

Main hotspot mutations in the ETV6 gene and their impact on the protein.

Mutation	Domain	Effect
P214L	Central regulatory domain	(i) Repression of DNA binding by the ETS domain; (ii) Defective proplatelet formation and megakaryocyte maturation; (iii) Alteration of proplatelet spreading; (iv) Down regulation of several cytoskeletal proteins; (v) ETV6 delocalization
N385Vfs	ETS	(i) Reduction in repressive activity; (ii) Targeted proteins downregulation
Y401N	ETS	(i) Impaired interaction with corepressor; (ii) Defective proplatelet formation and megakaryocyte maturation
R369W/R369Q	ETS	(i) Reduction in repressive activity; (ii) Targeted protein downregulation; (iii) ETV6 delocalization

ETS = highly conserved C-teminal DNA-binding domain.