{"entity": "publication", "iuid": "026e176cc2744047a1ae797684e42264", "timestamp": "2026-09-23T18:38:30.494Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/026e176cc2744047a1ae797684e42264.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/026e176cc2744047a1ae797684e42264"}}, "title": "A missense mutation converts the Na+,K+-ATPase into an ion channel and causes therapy-resistant epilepsy.", "authors": [{"family": "Ygberg", "given": "Sofia", "initials": "S", "orcid": "0000-0002-3854-2716", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0b032359f6bf48be84cbb595142d9382.json"}}, {"family": "Akkuratov", "given": "Evgeny E", "initials": "EE", "orcid": "0000-0002-2552-9512", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/abd9e4662bb543eebb0451af868bc319.json"}}, {"family": "Howard", "given": "Rebecca J", "initials": "RJ", "orcid": "0000-0003-2049-3378", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ce04593b5b24aaa8978fda1447dd0bf.json"}}, {"family": "Taylan", "given": "Fulya", "initials": "F", "orcid": "0000-0002-2907-0235", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fc9bc4b87d0f43b9a0528e936921e5ae.json"}}, {"family": "Jans", "given": "Daniel C", "initials": "DC", "orcid": "0000-0002-6356-9742", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9ff40f8719c944e6b0ff27ded3b05a27.json"}}, {"family": "Mahato", "given": "Dhani R", "initials": "DR"}, {"family": "Katz", "given": "Adriana", "initials": "A"}, {"family": "Kinoshita", "given": "Paula F", "initials": "PF"}, {"family": "Portal", "given": "Benjamin", "initials": "B"}, {"family": "Nennesmo", "given": "Inger", "initials": "I"}, {"family": "Lindskog", "given": "Maria", "initials": "M", "orcid": "0000-0001-9484-1983", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/de1f718eadcd41b7b3d5834bf34886b1.json"}}, {"family": "Karlish", "given": "Steven J D", "initials": "SJD"}, {"family": "Andersson", "given": "Magnus", "initials": "M"}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d28fb4cc61f4033b2ac525fed3d6b94.json"}}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/04321d9fb805493db538489927a42c8f.json"}}, {"family": "Aperia", "given": "Anita", "initials": "A"}], "type": "case reports", "published": "2021-12-00", "journal": {"title": "J Biol Chem", "issn": "1083-351X", "volume": "297", "issue": "6", "pages": "101355", "issn-l": "0021-9258"}, "abstract": "The ion pump Na+,K+-ATPase is a critical determinant of neuronal excitability; however, its role in the etiology of diseases of the central nervous system (CNS) is largely unknown. We describe here the molecular phenotype of a Trp931Arg mutation of the Na+,K+-ATPase catalytic \u03b11 subunit in an infant diagnosed with therapy-resistant lethal epilepsy. In addition to the pathological CNS phenotype, we also detected renal wasting of Mg2+. We found that membrane expression of the mutant \u03b11 protein was low, and ion pumping activity was lost. Arginine insertion into membrane proteins can generate water-filled pores in the plasma membrane, and our molecular dynamic (MD) simulations of the principle states of Na+,K+-ATPase transport demonstrated massive water inflow into mutant \u03b11 and destabilization of the ion-binding sites. MD simulations also indicated that a water pathway was created between the mutant arginine residue and the cytoplasm, and analysis of oocytes expressing mutant \u03b11 detected a nonspecific cation current. Finally, neurons expressing mutant \u03b11 were observed to be depolarized compared with neurons expressing wild-type protein, compatible with a lowered threshold for epileptic seizures. The results imply that Na+,K+-ATPase should be considered a neuronal locus minoris resistentia in diseases associated with epilepsy and with loss of plasma membrane integrity.", "doi": "10.1016/j.jbc.2021.101355", "pmid": "34717959", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8637647"}, {"db": "pii", "key": "S0021-9258(21)01161-3"}], "notes": [], "created": "2026-09-23T10:14:51.669Z", "modified": "2026-09-23T14:51:35.637Z"}