ArticleCell discovery2022
Loss of function of CMPK2 causes mitochondria deficiency and brain calcification.
Article in Cell discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Gene Variants Related to Primary Familial Brain Calcification: Perspectives from Bibliometrics and Meta-Analysis.eNeuro · 2025Pooled it
- Macrophage RSAD2 Couples mtDNA Synthesis With a Self-Amplifying Inflammatory Circuit to Orchestrate Tissue Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Brain calcification-associated JAM2 pathogenic mutations impair JAM2-JAM3 tight junction structure and the blood-brain barrier integrity.Brain pathology (Zurich, Switzerland) · 2026Article
- Article
- Palmitic Acid Promotes Antiviral Innate Immunity via ZDHHC20-Mediated CMPK2 Palmitoylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondrial DNA release contributes to neuropathic pain via a cGAS-STING-IRF3-CMPK2-associated immunometabolic feedback mechanism.Journal of translational medicine · 2026Article
- Tristetraprolin protects against osteoarthritis by restraining chondrocyte mitochondrial DNA release through post-transcriptional regulation.Journal of orthopaedic translation · 2026Article
- A Novel Frameshift Mutation inBiomedicines · 2026Article
- Developmentally endothelial locus-1 facilitates intestinal inflammation resolution by suppressing the Cmpk2-cGAS-STING pathway and promoting reparatory macrophage transition.Journal of advanced research · 2026Article
- A novel SLC20A2 nonsense variant and mechanistic studies of primary brain calcification.PloS one · 2026Article
- Glial Connexin-43 Is a Pathogenic Mechanism Promoting Gut Inflammation in Postoperative Ileus Induced by Gut Surgical Manipulation With Potential Relevance to Humans.Cellular and molecular gastroenterology and hepatology · 2026Article
- Experimental Primary Brain Calcification Model and Its Application to Pathogenesis Mechanism Analysis and Therapeutic Research.Neurology international · 2025Review
- NRIR promotes immune escape in hepatocellular cancer by regulating IFNγ-induced PD-L1 expression.Journal of advanced research · 2025Article
- RRP12 Variants Are Associated With Autosomal Recessive Brain Calcifications.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Biological functions and clinical implications of the CMPK2 across multisystemic diseases.Cell & bioscience · 2025Review
- tsRNA-08614 inhibits glycolysis and histone lactylation by ALDH1A3 to confer oxaliplatin sensitivity in colorectal cancer.Translational oncology · 2025Article
- Article
- Mutation spectrum and clinical features of MYORG in Iranian patients with Primary Familial Brain Calcification (PFBC).Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Computational molecular characterization of a novel SLC20A2 variant associated with primary familial brain calcification.Scientific reports · 2025Article
- CMPK2 promotes microglial activation through the cGAS-STING pathway in the neuroinflammatory mechanism.Scientific reports · 2025Article
Corrections and comments
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Authors and funding
41 authors at 9 institutions in 2 countries.
Funding
Abstract
Brain calcification is a critical aging-associated pathology and can cause multifaceted neurological symptoms. Cerebral phosphate homeostasis dysregulation, blood-brain barrier defects, and immune dysregulation have been implicated as major pathological processes in familial brain calcification (FBC). Here, we analyzed two brain calcification families and identified calcification co-segregated biallelic variants in the CMPK2 gene that disrupt mitochondrial functions. Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from these patients showed impaired mitochondria-associated metabolism pathways. In situ hybridization and single-cell RNA sequencing revealed robust Cmpk2 expression in neurons and vascular endothelial cells (vECs), two cell types with high energy expenditure in the brain. The neurons in Cmpk2-knockout (KO) mice have fewer mitochondrial DNA copies, down-regulated mitochondrial proteins, reduced ATP production, and elevated intracellular inorganic phosphate (Pi) level, recapitulating the mitochondrial dysfunction observed in the PBMCs isolated from the FBC patients. Morphologically, the cristae architecture of the Cmpk2-KO murine neurons was also impaired. Notably, calcification developed in a progressive manner in the homozygous Cmpk2-KO mice thalamus region as well as in the Cmpk2-knock-in mice bearing the patient mutation, thus phenocopying the calcification pathology observed in the patients. Together, our study identifies biallelic variants of CMPK2 as novel genetic factors for FBC; and demonstrates how CMPK2 deficiency alters mitochondrial structures and functions, thereby highlighting the mitochondria dysregulation as a critical pathogenic mechanism underlying brain calcification.
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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.