Protein tyrosine phosphatase variants in human hereditary disorders and disease susceptibilities

• Protein tyrosine phosphatase enzymes play key roles in cellular signal transduction.
• We discuss the group of PTP genes that is mutated in human hereditary diseases.
• Many SNPs in PTP genes are associated with predisposition to human diseases.
• Findings illustrate the necessity to tightly regulate phosphotyrosine signaling.
• Treatment options await increased knowledge on the regulation of PTP signaling.

Reversible tyrosine phosphorylation of proteins is a key regulatory mechanism to steer normal development and physiological functioning of multicellular organisms. Phosphotyrosine dephosphorylation is exerted by members of the super-family of protein tyrosine phosphatase (PTP) enzymes and many play such essential roles that a wide variety of hereditary disorders and disease susceptibilities in man are caused by PTP alleles. More than two decades of PTP research has resulted in a collection of PTP genetic variants with corresponding consequences at the molecular, cellular and physiological level. Here we present a comprehensive overview of these PTP gene variants that have been linked to disease states in man. Although the findings have direct bearing for disease diagnostics and for research on disease etiology, more work is necessary to translate this into therapies that alleviate the burden of these hereditary disorders and disease susceptibilities in man.