ArticleFEBS open bio2019
Endoplasmic reticulum quality control of LDLR variants associated with familial hypercholesterolemia.
Article in FEBS open bio, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 51 citations in OpenAlex.
- Evaluation of the cellular impact of missense variants in low-density lipoprotein receptor-related protein 6 (LRP6) associated with cardiovascular diseases in HeLa and HEK293T cell lines.Frontiers in cell and developmental biology · 2026Article
- Identification of a Novel VLDLR Variant in the First Report of CAMRQ1 From Africa: Expanding the Spectrum of Cerebellar Ataxia Syndromes.Human mutation · 2026Article
- Pathways and Molecular Mechanisms Governing LDL Receptor Regulation.Circulation research · 2025Review
- Synergistic effects of mutation and glycosylation on disease progression.Frontiers in molecular biosciences · 2025Review
- Hartnup disease-causing SLC6A19 mutations lead to B0AT1 aberrant trafficking and ACE2 mis-localisation implicating the endoplasmic reticulum protein quality control.Frontiers in cell and developmental biology · 2025Article
- Pathogenicity of the LDLR c.97C>T (p.Gln33Ter) Mutation in Familial Hypercholesterolemia.Molecular genetics & genomic medicine · 2024Article
- The double whammy of ER-retention and dominant-negative effects in numerous autosomal dominant diseases: significance in disease mechanisms and therapy.Journal of biomedical science · 2024Review
- LDLR c.415G > A causes familial hypercholesterolemia by weakening LDLR binding to LDL.Lipids in health and disease · 2024Article
- Post-translational regulation of the low-density lipoprotein receptor provides new targets for cholesterol regulation.Biochemical Society transactions · 2024Article
- A familial missense variant in the Alzheimer's disease gene SORL1 impairs its maturation and endosomal sorting.Acta neuropathologica · 2024Article
- Cellular and functional evaluation of LDLR missense variants reported in hypercholesterolemic patients demonstrates their hypomorphic impacts on trafficking and LDL internalization.Frontiers in cell and developmental biology · 2024Article
- A familial missense variant in the Alzheimer's Disease genebioRxiv : the preprint server for biology · 2023Article
- In vitro assessment of the pathogenicity of the LDLR c.2160delC variant in familial hypercholesterolemia.Lipids in health and disease · 2023Article
- GRP78/BiP alleviates oxLDL-induced hepatotoxicity in familial hypercholesterolemia caused by missense variants of LDLR in a HepG2 cellular model.Lipids in health and disease · 2023Article
- Characterization of ACE2 naturally occurring missense variants: impact on subcellular localization and trafficking.Human genomics · 2022Article
- Relationship between Brain Metabolic Disorders and Cognitive Impairment: LDL Receptor Defect.International journal of molecular sciences · 2022Review
- Review
- PDI Family Members as Guides for Client Folding and Assembly.International journal of molecular sciences · 2020Review
- Transmembrane Polar Relay Drives the Allosteric Regulation for ABCG5/G8 Sterol Transporter.International journal of molecular sciences · 2020Article
- Endoplasmic Reticulum Associated Protein Degradation (ERAD) in the Pathology of Diseases Related to TGFβ Signaling Pathway: Future Therapeutic Perspectives.Frontiers in molecular biosciences · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss-of-function mutations in the low-density lipoprotein receptor (LDLR) gene can cause familial hypercholesterolemia (FH), but detailed functional evidence for pathogenicity is limited to a few reported mutations. Here, we investigated the cellular pathogenic mechanisms of three mutations in LDLR causing FH, which are structurally identical to pathogenic mutations in the very low-density lipoprotein receptor (VLDLR). Similar to the VLDLR mutants, LDLR mutants D482H and C667F were found to be localized to the ER, while D445E, which is a conserved amino acid change, did not affect the trafficking of the receptor to the plasma membrane, as confirmed by the N-glycosylation profile. Although the ER-retained mutant proteins were soluble, induction of ER stress was observed as indicated by spliced X-box binding protein-1 (XBP-1) mRNA levels. The mutants were found to associate with ER quality control components, and their stability was enhanced by inhibitors of proteasome. Our results contribute to the growing list of transport-deficient class II LDLR variants leading to FH and provide evidence for the involvement of endoplasmic reticulum-associated degradation in their stability.
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