Ptpn11 gene

PTPN11 is the acronym for "protein tyrosine phosphatase non-receptor type 11", also known as "protein tyrosine phosphatase 1D" -PTP-1D-, an enzyme encoded by the PTPN11 gene in humans.

PTPN11 is amember of the protein tyrosine phosphatase (PTP) family that is found in many tissues. This family of enzymes consists of signal molecules that regulate a variety of cellular processes including cell growth, cell differentiation and oncogenic transformations.

Mutations of the PTPN11 gene are responsible for Noonan Syndrome.

They are also found in acute myeloid leukemia. Oncogenic mutations of the PTPN11 gene are also found in acrolentiginous melanoma.

Somatic mutations in the PTPN11 gene have been shown to lead to the phenotype of pakomatosis spiloroesa. At the molecular genetic level, it was shown that the same mutation could be detected in both the pigmentary and vascular hamartomas of this syndrome in the same individual. However, the mutation was not detectable in the blood. It could be shown that the same variants can cause either the pigmentary or the vascular phenotype alone. Apparently, the PTPN11 mutation in the pigmentary lesions leads to an increased tendency to develop malignancy. In vitro modeling of the missense variants confirms an overactivation of the downstream MAPK pathway and a widespread disruption of angiogenesis of human endothelial cells. Importantly, patients with PTPN11 mosaicism theoretically carry the risk of inheriting the variant as a germline RASopathy (Polubothu S et al. 2023).

1. Polubothu S et al. (2019) Phakomatosis pigmentovascularis spilorosea and speckled lentiginous naevus syndrome are caused by mosaic mutations in gene PTPN11. Pediatr Dermatol 36:S7
2. Polubothu S et al. (2023) PTPN11 Mosaicism Causes a Spectrum of Pigmentary and Vascular Neurocutaneous Disorders and Predisposes to Melanoma. J Invest Dermatol 143:1042-1051.e3.