ArticleJournal of inherited metabolic disease2015
Bi-allelic CLPB mutations cause cataract, renal cysts, nephrocalcinosis and 3-methylglutaconic aciduria, a novel disorder of mitochondrial protein disaggregation.
Article in Journal of inherited metabolic disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- CLPB deficiency-associated congenital neutropenia: A rare case report and literature review.Medicine · 2026Review
- CLPB Deficiency, a Mitochondrial Chaperonopathy With Neutropenia and Neurological Presentation.Journal of inherited metabolic disease · 2025Review
- Extrarenal manifestations in inherited kidney diseases.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Biophysical and NMR analysis reveals binding affinity between HAX1 and CLPB proteins.Magnetic resonance letters · 2025Article
- Mitochondrial CLPB is a pro-survival factor at the onset of granulocytic differentiation of mouse myeloblastic cells.Apoptosis : an international journal on programmed cell death · 2025Article
- Mitochondrial membrane synthesis, remodelling and cellular trafficking.Journal of inherited metabolic disease · 2025Review
- Comprehensive review of mitochondrial nephropathy-a renal phenotype in mitochondrial disease: causative genes, clinical and pathological features, diagnosis, prognosis, and treatment.Clinical and experimental nephrology · 2025Review
- Review of childhood genetic nephrolithiasis and nephrocalcinosis.Frontiers in genetics · 2024Review
- Dodecamer assembly of a metazoan AAAScience advances · 2023Article
- Structural basis of impaired disaggregase function in the oxidation-sensitive SKD3 mutant causing 3-methylglutaconic aciduria.Nature communications · 2023Article
- Article
- Premature Ovarian Insufficiency in CLPB Deficiency: Transcriptomic, Proteomic and Phenotypic Insights.The Journal of clinical endocrinology and metabolism · 2022Article
- Unique structural features govern the activity of a human mitochondrial AAA+ disaggregase, Skd3.Cell reports · 2022Article
- Review
- Biallelic CLPB mutation associated with isolated neutropenia and 3-MGA-uria.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2022Article
- Human mitochondrial AAA+ ATPase SKD3/CLPB assembles into nucleotide-stabilized dodecamers.Biochemical and biophysical research communications · 2022Article
- Rare coding variants in DNA damage repair genes associated with timing of natural menopause.HGG advances · 2022Article
- Mitochondrial Protein Homeostasis and Cardiomyopathy.International journal of molecular sciences · 2022Review
- Inborn errors of metabolism associated with 3-methylglutaconic aciduria.Clinica chimica acta; international journal of clinical chemistry · 2021Review
- Expression and Purification of Recombinant Skd3 (Human ClpB) Protein and Tobacco Etch Virus (TEV) Protease fromBio-protocol · 2020Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Whole exome sequencing was used to investigate the genetic cause of mitochondrial disease in two siblings with a syndrome of congenital lamellar cataracts associated with nephrocalcinosis, medullary cysts and 3-methylglutaconic aciduria. Autosomal recessive inheritance in a gene encoding a mitochondrially targeted protein was assumed; the only variants which satisfied these criteria were c.1882C>T (p.Arg628Cys) and c.1915G>A (p.Glu639Lys) in the CLPB gene, encoding a heat shock protein/chaperonin responsible for disaggregating mitochondrial and cytosolic proteins. Functional studies, including quantitative PCR (qPCR) and Western blot, support pathogenicity of these mutations. Furthermore, molecular modelling suggests that the mutations disrupt interactions between subunits so that the CLPB hexamer cannot form or is unstable, thus impairing its role as a protein disaggregase. We conclude that accumulation of protein aggregates underlies the development of cataracts and nephrocalcinosis in CLPB deficiency, which is a novel genetic cause of 3-methylglutaconic aciduria. A common mitochondrial cause for 3-methylglutaconic aciduria appears to be disruption of the architecture of the mitochondrial membranes, as in Barth syndrome (tafazzin deficiency), Sengers syndrome (acylglycerol kinase deficiency) and MEGDEL syndrome (impaired remodelling of the mitochondrial membrane lipids because of SERAC1 mutations). We now propose that perturbation of the mitochondrial membranes by abnormal protein aggregates leads to 3-methylglutaconic aciduria in CLPB deficiency.
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