ArticleBlood2022
Heterozygous variants of CLPB are a cause of severe congenital neutropenia.
Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Autosomal dominant gain-of-function mutations in LCP1 cause a syndromic neutropenia and immunodeficiency.Genes & diseases · 2027Article
- HAX1 drives assembly and activation of the mitochondrial intermembrane space chaperone CLPB.bioRxiv : the preprint server for biology · 2026Article
- CLPB deficiency-associated congenital neutropenia: A rare case report and literature review.Medicine · 2026Review
- Neuronal mitochondrial disaggregase CLPB ameliorates Huntington's disease pathology in mice.Theranostics · 2026Article
- CircPAFAH1B2 induces chondrocytes mitochondrial dysfunction and promotes cartilage degeneration through binding molecular chaperone ClpB.Journal of advanced research · 2025Article
- Quality control at the powerhouse: mitochondrial proteostasis dysfunction and disease.Biochemical Society transactions · 2025Article
- Computational Insights into the Polypharmacological Landscape of BCR-ABL Inhibitors: Emphasis on Imatinib and Nilotinib.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Expanding the phenotypic and genetic landscape of congenital neutropenia through whole-exome and genome sequencing.HemaSphere · 2025Article
- CLPB Deficiency, a Mitochondrial Chaperonopathy With Neutropenia and Neurological Presentation.Journal of inherited metabolic disease · 2025Review
- Dependence of mitochondrial calcium signalling and dynamics on the disaggregase, CLPB.Nature communications · 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
- The genetic landscape of congenital neutropenia in Poland: summary of the nationwide screening campaign.Frontiers in immunology · 2025Article
- Inherited Predispositions to Myeloid Neoplasms: Pathogenesis and Clinical Implications.Annual review of pathology · 2025Review
- Design principles to tailor Hsp104 therapeutics.Cell reports · 2024Article
- Design principles to tailor Hsp104 therapeutics.bioRxiv : the preprint server for biology · 2024Article
- The metabolic basis of inherited neutropenias.British journal of haematology · 2024Review
- Idasanutlin and navitoclax induce synergistic apoptotic cell death in T-cell acute lymphoblastic leukemia.Leukemia · 2023Article
- Structural basis of impaired disaggregase function in the oxidation-sensitive SKD3 mutant causing 3-methylglutaconic aciduria.Nature communications · 2023Article
- Article
- Deciphering the mechanism and function of Hsp100 unfoldases from protein structure.Biochemical Society transactions · 2022Article
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14 authors at 5 institutions in 2 countries.
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Abstract
Severe congenital neutropenia is an inborn disorder of granulopoiesis. Approximately one third of cases do not have a known genetic cause. Exome sequencing of 104 persons with congenital neutropenia identified heterozygous missense variants of CLPB (caseinolytic peptidase B) in 5 severe congenital neutropenia cases, with 5 more cases identified through additional sequencing efforts or clinical sequencing. CLPB encodes an adenosine triphosphatase that is implicated in protein folding and mitochondrial function. Prior studies showed that biallelic mutations of CLPB are associated with a syndrome of 3-methylglutaconic aciduria, cataracts, neurologic disease, and variable neutropenia. However, 3-methylglutaconic aciduria was not observed and, other than neutropenia, these clinical features were uncommon in our series. Moreover, the CLPB variants are distinct, consisting of heterozygous variants that cluster near the adenosine triphosphate-binding pocket. Both genetic loss of CLPB and expression of CLPB variants result in impaired granulocytic differentiation of human hematopoietic progenitor cells and increased apoptosis. These CLPB variants associate with wild-type CLPB and inhibit its adenosine triphosphatase and disaggregase activity in a dominant-negative fashion. Finally, expression of CLPB variants is associated with impaired mitochondrial function but does not render cells more sensitive to endoplasmic reticulum stress. Together, these data show that heterozygous CLPB variants are a new and relatively common cause of congenital neutropenia and should be considered in the evaluation of patients with congenital neutropenia.
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