ArticleThe Journal of clinical investigation2024
Biallelic Cys141Tyr variant of SEL1L is associated with neurodevelopmental disorders, agammaglobulinemia, and premature death.
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 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- 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
- Cholesterol synthases suppress metastasis and stemness through PDIA4/ACLY or SYVN1/SCD1 axis in advanced colorectal cancer.Communications biology · 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
- 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
- Endoplasmic reticulum (ER) protein degradation by ER-associated degradation and ER-phagy.Trends in cell biology · 2025Review
- SEL1L-HRD1-mediated ERAD in mammals.Nature cell biology · 2025Review
- Structural insights into the human HRD1 ubiquitin ligase complex.Nature communications · 2025Article
- Impact of immunodeficiencies on immunity induced by SARS-CoV-2 infection, mRNA BNT162b2 vaccination, and their combination in children and young adults.Frontiers in immunology · 2025Article
- Diversity and structural-functional insights of alpha-solenoid proteins.Protein science : a publication of the Protein Society · 2024Review
- Genome-wide screens identify SEL1L as an intracellular rheostat controlling collagen turnover.Nature communications · 2024Article
- Hypomorphic human SEL1L and HRD1 variants uncouple multilayered ER-associated degradation machinery.The Journal of clinical investigation · 2024Article
- Hypomorphic variants of SEL1L-HRD1 ER-associated degradation are associated with neurodevelopmental disorders.The Journal of clinical investigation · 2024Article
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Authors and funding
19 authors at 8 institutions in 5 countries.
Funding
Abstract
Suppressor of lin-12-like-HMG-CoA reductase degradation 1 (SEL1L-HRD1) ER-associated degradation (ERAD) plays a critical role in many physiological processes in mice, including immunity, water homeostasis, and energy metabolism; however, its relevance and importance in humans remain unclear, as no disease variant has been identified. Here, we report a biallelic SEL1L variant (p. Cys141Tyr) in 5 patients from a consanguineous Slovakian family. These patients presented with not only ERAD-associated neurodevelopmental disorders with onset in infancy (ENDI) syndromes, but infantile-onset agammaglobulinemia with no mature B cells, resulting in frequent infections and early death. This variant disrupted the formation of a disulfide bond in the luminal fibronectin II domain of SEL1L, largely abolishing the function of the SEL1L-HRD1 ERAD complex in part via proteasomal-mediated self destruction by HRD1. This study reports a disease entity termed ENDI-agammaglobulinemia (ENDI-A) syndrome and establishes an inverse correlation between SEL1L-HRD1 ERAD functionality and disease severity in humans.
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Registered trials
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.