ArticleThe Journal of clinical investigation2021
C2orf69 mutations disrupt mitochondrial function and cause a multisystem human disorder with recurring autoinflammation.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Smoking Status and Type 2 Diabetes, and Cardiovascular Disease: A Comprehensive Analysis of Shared Genetic Etiology and Causal Relationship.Frontiers in endocrinology · 2022Pooled it
- Article
- A rare autoinflammatory syndrome associated with a C2orf69 frameshift mutation: a case report.Immunologic research · 2025Article
- Identification and validation of oxidative stress-related diagnostic markers for recurrent pregnancy loss: insights from machine learning and molecular analysis.Molecular diversity · 2025Article
- α/β Hydrolases: Toward Unraveling Entangled Classification.Proteins · 2025Article
- DNA methylation age acceleration contributes to the development and prediction of non-alcoholic fatty liver disease.GeroScience · 2024Article
- Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee.Journal of clinical immunology · 2022Article
- The use of virtual tools in narrowing the impact of health disparities in neurology.Frontiers in pediatrics · 2022Article
- Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy.American journal of human genetics · 2021Article
Corrections and comments
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Authors and funding
34 authors at 17 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUNDDeciphering the function of the many genes previously classified as uncharacterized open reading frame (ORF) would complete our understanding of a cell's function and its pathophysiology.METHODSWhole-exome sequencing, yeast 2-hybrid and transcriptome analyses, and molecular characterization were performed in this study to uncover the function of the C2orf69 gene.RESULTSWe identified loss-of-function mutations in the uncharacterized C2orf69 gene in 8 individuals with brain abnormalities involving hypomyelination and microcephaly, liver dysfunction, and recurrent autoinflammation. C2orf69 contains an N-terminal signal peptide that is required and sufficient for mitochondrial localization. Consistent with mitochondrial dysfunction, the patients showed signs of respiratory chain defects, and a CRISPR/Cas9-KO cell model of C2orf69 had similar respiratory chain defects. Patient-derived cells revealed alterations in immunological signaling pathways. Deposits of periodic acid-Schiff-positive (PAS-positive) material in tissues from affected individuals, together with decreased glycogen branching enzyme 1 (GBE1) activity, indicated an additional impact of C2orf69 on glycogen metabolism.CONCLUSIONSOur study identifies C2orf69 as an important regulator of human mitochondrial function and suggests that this gene has additional influence on other metabolic pathways.
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