{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bilches Medinas D"],"funding":["U.S. Department of Defense","Office of Naval Research Global","Fondo Nacional de Desarrollo Científico y Tecnológico","European Commission","Air Force Office of Scientific Research","Muscular Dystrophy Association","Michael J. Fox Foundation for Parkinson&apos;s Research"],"pagination":["e105531"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8762563"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["41(2)"],"pubmed_abstract":["Recessive gene mutations underlie many developmental disorders and often lead to disabling neurological problems. Here, we report identification of a homozygous c.170G>A (p.Cys57Tyr or C57Y) mutation in the gene coding for protein disulfide isomerase A3 (PDIA3, also known as ERp57), an enzyme that catalyzes formation of disulfide bonds in the endoplasmic reticulum, to be associated with syndromic intellectual disability. Experiments in zebrafish embryos show that PDIA3<sup>C57Y</sup> expression is pathogenic and causes developmental defects such as axonal disorganization as well as skeletal abnormalities. Expression of PDIA3<sup>C57Y</sup> in the mouse hippocampus results in impaired synaptic plasticity and memory consolidation. Proteomic and functional analyses reveal that PDIA3<sup>C57Y<"],"journal":["The EMBO journal"],"pubmed_title":["Mutation in protein disulfide isomerase A3 causes neurodevelopmental defects by disturbing endoplasmic reticulum proteostasis."],"pmcid":["PMC8762563"],"funding_grant_id":["W81XWH2110960","1161524","9277","FA9550‐16‐1‐0384","11180825","1200459","1191538","N62909‐16‐1‐2003","575897","R&amp;D MSCA‐RISE 734749","1140549","1180419","11140430"],"pubmed_authors":["Pina R","Uyan O","Afzal M","Woehlbier U","Saaranen MJ","Bilches Medinas D","Concha ML","Cabral-Miranda F","Borgonovo J","Pulgar E","Morales B","Bodaleo F","Rozas P","Urra H","Contreras D","Reardon C","Yıldız-Bolukbası E","Mumtaz S","Rozas C","Quiroz G","Malik S","Hetz C","Wright MT","Ruddock LW","Plate L","Diaz R","Gonzalez-Billault C","Tolun A","Valenzuela V","Sena-Esteves M","Brown RH"],"additional_accession":[]},"is_claimable":false,"name":"Mutation in protein disulfide isomerase A3 causes neurodevelopmental defects by disturbing endoplasmic reticulum proteostasis.","description":"Recessive gene mutations underlie many developmental disorders and often lead to disabling neurological problems. Here, we report identification of a homozygous c.170G>A (p.Cys57Tyr or C57Y) mutation in the gene coding for protein disulfide isomerase A3 (PDIA3, also known as ERp57), an enzyme that catalyzes formation of disulfide bonds in the endoplasmic reticulum, to be associated with syndromic intellectual disability. Experiments in zebrafish embryos show that PDIA3<sup>C57Y</sup> expression is pathogenic and causes developmental defects such as axonal disorganization as well as skeletal abnormalities. Expression of PDIA3<sup>C57Y</sup> in the mouse hippocampus results in impaired synaptic plasticity and memory consolidation. Proteomic and functional analyses reveal that PDIA3<sup>C57Y<","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2026-07-16T04:10:00.992Z","creation":"2025-04-07T03:18:05.469Z"},"accession":"S-EPMC8762563","cross_references":{"pubmed":["34904718"],"doi":["10.15252/embj.2020105531"]}}