Ask about this productRelated genes to: LOH12CR1 antibody
- Gene:
- BORCS5 NIH gene
- Name:
- BLOC-1 related complex subunit 5
- Previous symbol:
- LOH12CR1
- Synonyms:
- LOH1CR12
- Chromosome:
- 12p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2002-01-08
- Date modifiied:
- 2016-10-05
Related products to: LOH12CR1 antibody
Related articles to: LOH12CR1 antibody
- BORCS5 encodes a subunit of the BLOC-One-Related Complex (BORC), which is known to promote anterograde movement and fusion of lysosomes. We identified 16 individuals from nine families with bi-allelic BORCS5 variants, revealing a spectrum of neurodevelopmental and neurodegenerative phenotypes. Carriers of homozygous protein-truncating variants (PTVs), resulting in complete loss of BORCS5, presented with prenatally lethal arthrogryposis multiplex congenita, brain malformations, and neuropathological evidence of neuroaxonal dystrophy. Individuals with missense or splice-site variants presented differently, with microcephaly, developmental epileptic encephalopathy, optic atrophy, spasticity, and progressive movement disorders. In this group, brain MRI showed diffuse hypomyelination, corpus callosum abnormalities, as well as progressive global cerebral atrophy, consistent with neurodegeneration. Borcs5 knockout in zebrafish exhibited microcephaly, motor deficits, and increased seizure susceptibility, mirroring the patients' clinical presentation. At the cellular level, only BORCS5 PTVs, but not missense variants, led to perinuclear lysosomal clustering and impaired lysosomal axonal trafficking in induced pluripotential stem cell-derived forebrain neurons. However, both PTVs and missense variants were associated with reduced lysosomal proteolysis and activity of lysosomal hydrolases glucocerebrosidase and cathepsin B, indicating lysosomal dysfunction. Our study reveals a role for BORCS5 in modulation of lysosomal function, in addition to its known role in lysosome movement and fusion, possibly underlying the diverse clinical manifestations in individuals with BORCS5-related disorders. - Source: PubMed
Publication date: 2026/04/21
Mencacci Niccolò EMinakaki GeorgiaMaroofian RezaDe Pace RaffaellaPaimboeuf AdelineBranco Fonseca TiagoAbramova TatianaShannon PatrickChitayat DavidMagrinelli FrancescaPeng Wesley JChatterjee DiptamanEldessouky Sara HBaptista JuliaMarton TamasVogt JulieOrtigoza-Escobar Juan DarioMartorell LoretoGómez-Chiari MartaWentzensen Ingrid MKamsteeg Erik-JanZaki Maha SScardamaglia AnnaritaZifarelli GiovanniAl-Hassnan Zuhair NasserMiller ElkaShinar ShiriMatsa Lova SAppikonda Sri Hari ChandanOtaify Ghada AAl-Thihli KhalidAl-Maawali AlmundherSchwake MichaelSeverino MariasavinaHoulden HenryPatten Shunmoogum ABonifacino Juan SBhatia Kailash PKrainc Dimitri - BORC and BLOC-1 are multisubunit complexes that regulate endolysosomal trafficking. Although they are presumed to be distinct, their paralogous origins and shared subunits suggest the potential for higher-order assembly. Here, we reveal the conserved octameric architecture of BORC formed by two intertwined tetramers and present the structure of C. elegans BORC. Through cross-linking mass spectrometry of endogenous complexes, we validate this model for human BORC and demonstrate that the integrity of the complex, which is essential for lysosomal transport, relies on specific interfacial residues. We also clarify the disruptive nature of disease-causing mutations and propose that the formation and function of BORC are likely regulated by specific cues. These cues might include the phosphorylation of Snapin and a pH-sensitive histidine residue in BORCS5. Additionally, we present direct biochemical and structural evidence of BORC-BLOC-1 hybrid complexes. Finally, we link a specific hybrid complex to the regulation of transferrin receptor recycling via interaction with the EARP complex. Our work challenges the paradigm of BORC and BLOC-1 as separate entities, establishing a model of dynamic complex formation wherein modular assembly creates functional specialization to meet diverse cellular demands. - Source: PubMed
Publication date: 2026/01/20
de Araujo Mariana E GJ Amann SaschaStasyk TarasSchleiffer AlexanderRauch EvaFlümann PaulaSinger Isabel IKremser LeopoldDostal VojtechLaopanupong ThanidaObojes NikolausWallnöfer Moritz HGradl Flora SKurzbauer RobertKrebiehl CarolineKofler SamuelGrishkovskaya IrinaVogel Georg FHess Michael WSarg BettinaClausen TimHaselbach DavidHuber Lukas A - Neuroaxonal dystrophy (NAD) with osteopetrosis syndrome (OMIM # 600329) was first reported in a consanguineous Moroccan Jewish family. However, to date, no genetic variant has been linked to this disease. We report on sibs, born to consanguineous Pakistani parents identified prenatally with cerebral ventriculomegaly and agenesis of the corpus callosum, and autopsies done on both showed similar abnormalities, including facial dysmorphism, osteopetrosis, and neuropathologic findings consistent with NAD. Trio exome sequencing identified a homozygous c.283 C>T; p.(Arg95Ter) variant in exon 3 of the BORCS5 gene (NM_058169.4) in each of the couple's fetuses, and each of the parents was heterozygous for this variant. Interestingly, one of the affected fetuses was also homozygous for a biallelic missense VUS variant in SCYL2 (NM_017988.5) c.902G>A; p. Arg301His, heterozygous in parents. However, the autopsy findings on the two sibs were identical, raising the possibility that this SCYL2 homozygote variant did not contribute to the phenotype. - Source: PubMed
Publication date: 2025/07/07
Fisher YaelGreenberg OrliShannon PatrickStaines AndreaMcGivern BobbiNapier Melanie PatriciaChitayat David - encodes a subunit of the BLOC-one-related complex (BORC), which is known to mediate the kinesin-dependent anterograde movement of lysosomes. Using whole-exome sequencing, we identified 12 cases from seven families carrying bi-allelic variants, including four loss-of-function and two missense variants. Carriers of homozygous loss-of-function variants presented with prenatally lethal arthrogryposis multiplex congenita, brain malformations, and neuropathological evidence of diffuse neuroaxonal dystrophy. Individuals with missense variants presented differently, with microcephaly, developmental epileptic encephalopathy, intellectual disability, optic atrophy, spasticity, and progressive movement disorders. In this group, brain MRI showed diffuse hypomyelination and progressive global cerebral atrophy, consistent with neurodegeneration. knockout in zebrafish exhibited microcephaly, motor deficits, and seizures, mirroring the patients' clinical presentation. At the cellular level, BORCS5 loss-of-function but not missense variants, resulted in lower protein expression and impaired BORC assembly, paralleled by perinuclear lysosomal clustering. However, both loss-of-function and missense BORCS5 variants were associated with reduced total lysosomal proteolysis, reduced activity of the lysosomal hydrolases glucocerebrosidase and cathepsin B, and presence of multilamellar bodies, indicating lysosomal dysfunction. Our study reveals a novel role for BORCS5 in the regulation of lysosomal function, in addition to its known role in the anterograde movement of lysosomes, possibly underlying the diverse clinical manifestations in individuals with BORCS5-related disorders. - Source: PubMed
Publication date: 2025/05/07
Mencacci Niccolò EMinakaki GeorgiaMaroofian RezaDe Pace RaffaellaPaimboeuf AdelineShannon PatrickChitayat DavidMagrinelli FrancescaPeng Wesley JChatterjee DiptamanEldessouky Sara HBaptista JuliaMarton TamasVogt JulieOrtigoza-Escobar Juan DarioMartorell LoretoGómez-Chiari MartaWentzensen Ingrid MKamsteeg Erik-JanZaki Maha SScardamaglia AnnaritaZifarelli GiovanniAl-Hassnan Zuhair NasserMiller ElkaShinar ShiriMatsa Lova SAppikonda Sri Hari ChandanSchwake MichaelSeverino MariasavinaHoulden HenryPatten Shunmoogum ABonifacino Juan SBhatia Kailash PKrainc Dimitri - The purpose of this study was to systematically analyze the population genetic structure and genetic diversity among wild, local and commercial populations using whole-genome sequencing data from 416 individuals of 22 duck breeds in China and to further explore genetic pathways and candidate genes associated with importantly economic traits. - Source: PubMed
Publication date: 2024/11/28
Huang ZhirongZhang LiyunLuo MaojunZhang XumengHuang YunmaoTian YunboWu ZhongpingLi Xiujin