{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang W"],"funding":["Target ALS","The Conrad Prebys Foundation"],"pagination":["e187199"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12016931"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(8)"],"pubmed_abstract":["Mitogen-activated protein kinase 8 interacting protein 3 (MAPK8IP3) gene encoding a protein called JIP3 is an adaption protein of the kinesin-1 complex known to play a role in axonal transport of cargo. Mutations in the gene have been linked to severe neurodevelopmental disorders, resulting in developmental delay, intellectual disability, ataxia, tremor, autism, seizures, and visual impairment. A patient who has a missense mutation in the MAPK8IP3 gene (c. 1714 C>T, Arg578Cys) (R578C) manifests dystonia, gross motor delay, and developmental delay. Here, we showed that the mutation was a toxic gain-of-function mutation that altered the interactome of JIP3; disrupted axonal transport of late endosomes; increased signaling via c-Jun N-terminal kinase, resulting in apoptosis; and disrupted dop"],"journal":["JCI insight"],"pubmed_title":["A toxic gain-of-function variant in MAPK8IP3 provides insights into JIP3 cellular roles."],"pmcid":["PMC12016931"],"funding_grant_id":["465","TT-2024-C1-L1"],"pubmed_authors":["Zhang W","Chung WK","Mittal S","Thomas R","Foroughishafiei A","Crooke ST","Skourti-Stathaki K","Nunes Bastos R"],"additional_accession":[]},"is_claimable":false,"name":"A toxic gain-of-function variant in MAPK8IP3 provides insights into JIP3 cellular roles.","description":"Mitogen-activated protein kinase 8 interacting protein 3 (MAPK8IP3) gene encoding a protein called JIP3 is an adaption protein of the kinesin-1 complex known to play a role in axonal transport of cargo. Mutations in the gene have been linked to severe neurodevelopmental disorders, resulting in developmental delay, intellectual disability, ataxia, tremor, autism, seizures, and visual impairment. A patient who has a missense mutation in the MAPK8IP3 gene (c. 1714 C>T, Arg578Cys) (R578C) manifests dystonia, gross motor delay, and developmental delay. Here, we showed that the mutation was a toxic gain-of-function mutation that altered the interactome of JIP3; disrupted axonal transport of late endosomes; increased signaling via c-Jun N-terminal kinase, resulting in apoptosis; and disrupted dop","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Apr","modification":"2026-06-03T04:52:52.52Z","creation":"2026-05-28T03:06:54.739Z"},"accession":"S-EPMC12016931","cross_references":{"pubmed":["40111412"],"doi":["10.1172/jci.insight.187199"]}}