ArticleHuman molecular genetics2019
A neurodevelopmental disorder caused by mutations in the VPS51 subunit of the GARP and EARP complexes.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Genetic aetiology of global developmental delay and intellectual disability in Africa: a scoping review.Frontiers in genetics · 2026Pooled it
- Golgi CATCHR complexes function as organizing hubs for vesicle tethering and fusion.bioRxiv : the preprint server for biology · 2026Article
- Article
- EIPR1 variants cause a neurodevelopmental disorder with endolysosomal and dense core vesicle defects.Brain : a journal of neurology · 2026Article
- GARP Complex in Golgi Physiology.Sub-cellular biochemistry · 2026Review
- Genetic Insights in Hindbrain Abnormalities Through Network Analysis Expose Key Biological Pathways in Hindbrain Development.Cerebellum (London, England) · 2025Article
- A global genetic interaction map of a human cell reveals conserved principles of genetic networks.bioRxiv : the preprint server for biology · 2025Article
- From Gene to Pathways: Understanding Novel Vps51 Variant and Its Cellular Consequences.International journal of molecular sciences · 2025Article
- Biallelic Loss-of-Function Variant inInternational journal of molecular sciences · 2025Article
- Proximity-dependent biotinylation reveals an interaction between ubiquitin-specific peptidase 46 and centrosome-related proteins.FEBS open bio · 2025Article
- Pontocerebellar hypoplasia: a review from 1912 to 2022.Brain communications · 2025Review
- ARMH3 is an ARL5 effector that promotes PI4KB-catalyzed PI4P synthesis at the trans-Golgi network.Nature communications · 2024Article
- Acute GARP depletion disrupts vesicle transport, leading to severe defects in sorting, secretion, and O-glycosylation.bioRxiv : the preprint server for biology · 2024Article
- Article
- Clinical and biochemical footprints of congenital disorders of glycosylation: Proposed nosology.Molecular genetics and metabolism · 2024Review
- [A case report and literature review of pontocerebellar hypoplasia type 13 combined with abnormal liver function caused by VPS51 gene variation].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Review
- Broadening the phenotype and genotype spectrum of novel mutations in pontocerebellar hypoplasia with a comprehensive molecular literature review.BMC medical genomics · 2024Article
- Exploring the pathological mechanisms underlying Cohen syndrome.Frontiers in neuroscience · 2024Review
- FAM91A1-TBC1D23 complex structure reveals human genetic variations susceptible for PCH.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Functional Evidence ofInternational journal of molecular sciences · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Golgi-associated retrograde protein (GARP) and endosome-associated recycling protein (EARP) are related heterotetrameric complexes that associate with the cytosolic face of the trans-Golgi network and recycling endosomes, respectively. At these locations, GARP and EARP function to promote the fusion of endosome-derived transport carriers with their corresponding compartments. GARP and EARP share three subunits, VPS51, VPS52 and VPS53, and each has an additional complex-specific subunit, VPS54 or VPS50, respectively. The role of these complexes in human physiology, however, remains poorly understood. By exome sequencing, we have identified compound heterozygous mutations in the gene encoding the shared GARP/EARP subunit VPS51 in a 6-year-old patient with severe global developmental delay, microcephaly, hypotonia, epilepsy, cortical vision impairment, pontocerebellar abnormalities, failure to thrive, liver dysfunction, lower extremity edema and dysmorphic features. The mutation in one allele causes a frameshift that produces a longer but highly unstable protein that is degraded by the proteasome. In contrast, the other mutant allele produces a protein with a single amino acid substitution that is stable but assembles less efficiently with the other GARP/EARP subunits. Consequently, skin fibroblasts from the patient have reduced levels of fully assembled GARP and EARP complexes. Likely because of this deficiency, the patient's fibroblasts display altered distribution of the cation-independent mannose 6-phosphate receptor, which normally sorts acid hydrolases to lysosomes. Furthermore, a fraction of the patient's fibroblasts exhibits swelling of lysosomes. These findings thus identify a novel genetic locus for a neurodevelopmental disorder and highlight the critical importance of GARP/EARP function in cellular and organismal physiology.
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