ArticleThe Journal of clinical investigation2024
Hypomorphic variants of SEL1L-HRD1 ER-associated degradation are associated with neurodevelopmental disorders.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The trial behind it
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Who cites it
28 citing papers in PubMed, 32 citations in OpenAlex.
- Comparative analysis of Cdc48-dependent proteolysis at the ER, mitochondria and chloroplasts.Nature communications · 2026Review
- Functional rescue of a disease-linked ERAD pathway mutation via alternative splicing.The EMBO journal · 2026Article
- Neuronal SEL1L-HRD1 ER-associated degradation is essential for motor function and survival in mice.The Journal of clinical investigation · 2026Article
- A molecular switch in NAC prevents mitochondrial protein mistargeting by SRP.Nature communications · 2026Article
- SEL1L-HRD1 ERAD-autophagy interplay maintains mitochondrial homeostasis in brown adipocytes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- SEL1L-HRD1 ER-associated degradation facilitates prohormone convertase 2 maturation and glucagon production in islet α cells.Nature communications · 2026Article
- Functional integrity of the SEL1L-HRD1 complex is critical for endoplasmic reticulum-associated degradation and organismal viability.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Structural basis and pathological implications of the dimeric OS9-SEL1L-HRD1 ERAD Core Complex.Nature communications · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Targeting MAN1B1 potently enhances bladder cancer antitumor immunity via deglycosylation of CD47.Cancer communications (London, England) · 2025Article
- Disturbances of endoplasmic reticulum proteostasis in neurodevelopmental disorders.Biochemical Society transactions · 2025Review
- SEL1L-HRD1-mediated ERAD in mammals.Nature cell biology · 2025Review
- Endoplasmic reticulum (ER) protein degradation by ER-associated degradation and ER-phagy.Trends in cell biology · 2025Review
- Sex-related differences and associated transcriptional signatures in the brain ventricular system and cerebrospinal fluid development in full-term neonates.Biology of sex differences · 2025Article
- Purkinje cell-specific deficiency in SEL1L-hrd1 endoplasmic reticulum-associated degradation causes progressive cerebellar ataxia in mice.JCI insight · 2024Article
- Purkinje cell-specific deficiency in SEL1L-hrd1 endoplasmic reticulum-associated degradation causes progressive cerebellar ataxia in mice.JCI insight · 2024Article
- Purkinje cell-specific deficiency in SEL1L-hrd1 endoplasmic reticulum-associated degradation causes progressive cerebellar ataxia in mice.JCI insight · 2024Article
- Regulation of hepatic inclusions and fibrinogen biogenesis by SEL1L-HRD1 ERAD.Nature communications · 2024Article
- Regulation of hepatic inclusions and fibrinogen biogenesis by SEL1L-HRD1 ERAD.Nature communications · 2024Article
- Regulation of leptin signaling and diet-induced obesity by SEL1L-HRD1 ER-associated degradation in POMC expressing neurons.Nature communications · 2024Article
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 6 countries.
Funding
Abstract
Recent studies using cell type-specific knockout mouse models have improved our understanding of the pathophysiological relevance of suppressor of lin-12-like-HMG-CoA reductase degradation 1 (SEL1L-HRD1) endoplasmic reticulum-associated (ER-associated) degradation (ERAD); however, its importance in humans remains unclear, as no disease variant has been identified. Here, we report the identification of 3 biallelic missense variants of SEL1L and HRD1 (or SYVN1) in 6 children from 3 independent families presenting with developmental delay, intellectual disability, microcephaly, facial dysmorphisms, hypotonia, and/or ataxia. These SEL1L (p.Gly585Asp, p.Met528Arg) and HRD1 (p.Pro398Leu) variants were hypomorphic and impaired ERAD function at distinct steps of ERAD, including substrate recruitment (SEL1L p.Gly585Asp), SEL1L-HRD1 complex formation (SEL1L p.Met528Arg), and HRD1 activity (HRD1 p.Pro398Leu). Our study not only provides insights into the structure-function relationship of SEL1L-HRD1 ERAD, but also establishes the importance of SEL1L-HRD1 ERAD in humans.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.