Pathogenic variants in <i>TMEM184B</i> cause a neurodevelopmental syndrome associated with alteration of metabolic signaling.

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

SUBMITTER: Chapman KA 

PROVIDER: S-EPMC11245063 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature