{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chapman KA"],"funding":["National Institute of Neurological Disorders and Stroke","NIMH NIH HHS","NINDS NIH HHS","National Institute of Mental Health","National Institutes of Health","University of Arizona"],"pagination":["2381-2401"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12440709"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["112(10)"],"pubmed_abstract":["Transmembrane protein 184B (TMEM184B) is an endosomal 7-pass transmembrane protein with evolutionarily conserved roles in synaptic structure and axon degeneration. We report six pediatric cases who have de novo heterozygous variants in TMEM184B; five individuals harbor a rare missense variant, and one individual has an mRNA splice site change. This cohort is unified by overlapping neurodevelopmental deficits including developmental delay, corpus callosum hypoplasia, seizures, and/or microcephaly. TMEM184B is predicted to contain a pore domain wherein four of five human disease-associated missense variants cluster. Structural modeling suggests that all missense variants alter TMEM184B protein stability. To understand the contribution of TMEM184B to neural development in vivo, we knocked dow"],"journal":["American journal of human genetics"],"pubmed_title":["Pathogenic variants in TMEM184B cause a neurodevelopmental syndrome associated with alteration of metabolic signaling."],"pmcid":["PMC12440709"],"funding_grant_id":["R01 MH106826","R01 NS105680"],"pubmed_authors":["Muss C","Powell AT","Keren B","Sofocleous C","Chapman KA","Pond KW","Fryssira H","Correia SP","Accogli A","Berger SI","Davis EE","Kellaris G","Traeger-Synodinos J","Stodberg T","Tsoutsou E","Sciruicchio V","Kodiparthi SV","Marinakis NM","Salpietro V","Striano P","Heron D","Sirimulla S","Bhattacharya MRC","White HG","Ullah F","Yahiku ZA","Khan S"],"additional_accession":[]},"is_claimable":false,"name":"Pathogenic variants in TMEM184B cause a neurodevelopmental syndrome associated with alteration of metabolic signaling.","description":"Transmembrane protein 184B (TMEM184B) is an endosomal 7-pass transmembrane protein with evolutionarily conserved roles in synaptic structure and axon degeneration. We report six pediatric cases who have de novo heterozygous variants in TMEM184B; five individuals harbor a rare missense variant, and one individual has an mRNA splice site change. This cohort is unified by overlapping neurodevelopmental deficits including developmental delay, corpus callosum hypoplasia, seizures, and/or microcephaly. TMEM184B is predicted to contain a pore domain wherein four of five human disease-associated missense variants cluster. Structural modeling suggests that all missense variants alter TMEM184B protein stability. To understand the contribution of TMEM184B to neural development in vivo, we knocked dow","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-06-04T11:00:33.08Z","creation":"2026-05-08T03:10:51.717Z"},"accession":"S-EPMC12440709","cross_references":{"pubmed":["40885185"],"doi":["10.1016/j.ajhg.2025.08.004"]}}