biostudies-literatureUnknownAguilan JTNICHD NIH HHSNIMH NIH HHSNCI NIH HHSNIH HHS<h4>Background</h4>Jansen de Vries Syndrome (JdVS) is a rare neurodevelopmental disorder (NDD) caused by gain-of-function (GOF) truncating mutations in <i>PPM1D</i> exons 5 or 6. PPM1D is a serine/threonine phosphatase that plays an important role in the DNA damage response (DDR) by negatively regulating TP53 (P53). JdVS-associated mutations lead to the formation of a truncated PPM1D protein that retains catalytic activity and has a GOF effect because of reduced degradation. Somatic <i>PPM1D</i> exons 5 and 6 truncating mutations are well-established factors in a number of cancers, due to excessive dephosphorylation and reduced function of P53 and other substrates involved in DDR. Children with JdVS have a variety of neurodevelopmental, psychiatric, and physical problems. In addition, a smbioRxiv : the preprint server for biology2023.07.08.548192https://www.ebi.ac.uk/biostudies/studies/S-EPMC10350077biostudies-literatureProteomics and phosphoproteomics profiling in glutamatergic neurons and microglia in an iPSC model of Jansen de Vries Syndrome.PMC10350077R21 MH131740P30 CA013330S10 OD030286P30 HD071593S10 OD026833Aguilan JTBaykara RNSidoli SBarnes JLachman HMZhang JPedrosa EDolstra HfalseProteomics and phosphoproteomics profiling in glutamatergic neurons and microglia in an iPSC model of Jansen de Vries Syndrome.<h4>Background</h4>Jansen de Vries Syndrome (JdVS) is a rare neurodevelopmental disorder (NDD) caused by gain-of-function (GOF) truncating mutations in <i>PPM1D</i> exons 5 or 6. PPM1D is a serine/threonine phosphatase that plays an important role in the DNA damage response (DDR) by negatively regulating TP53 (P53). JdVS-associated mutations lead to the formation of a truncated PPM1D protein that retains catalytic activity and has a GOF effect because of reduced degradation. Somatic <i>PPM1D</i> exons 5 and 6 truncating mutations are well-established factors in a number of cancers, due to excessive dephosphorylation and reduced function of P53 and other substrates involved in DDR. Children with JdVS have a variety of neurodevelopmental, psychiatric, and physical problems. In addition, a sm2023-01-01T00:00:00Z2023 Jul2026-05-25T03:08:41.06Z2026-05-25T03:07:32.572ZS-EPMC103500773746146310.1101/2023.07.08.548192