ArticleHuman molecular genetics2014
CLYBL is a polymorphic human enzyme with malate synthase and β-methylmalate synthase activity.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
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- Humanized Extracellular Vesicles for Efficient RNA Delivery.bioRxiv : the preprint server for biology · 2025Article
- CLYBL averts vitamin BNature chemical biology · 2025Article
- Acetylation suppresses breast cancer progression by sustaining CLYBL stability.Journal of translational medicine · 2025Article
- Bottom-up approach to deciphering the targets of the ubiquitin-proteasome system in porcine sperm capacitation.Scientific reports · 2024Article
- Genome-wide association analysis of fleece traits in Northwest Xizang white cashmere goat.Frontiers in veterinary science · 2024Article
- Glyoxylate protects against cyanide toxicity through metabolic modulation.Scientific reports · 2022Article
- Thioesterase enzyme families: Functions, structures, and mechanisms.Protein science : a publication of the Protein Society · 2022Article
- Genomic basis of evolutionary adaptation in a warm-blooded fish.Innovation (Cambridge (Mass.)) · 2022Article
- The immunometabolite itaconate inhibits heme synthesis and remodels cellular metabolism in erythroid precursors.Blood advances · 2021Article
- Multiple metabolic changes mediate the response of Caenorhabditis elegans to the complex I inhibitor rotenone.Toxicology · 2021Article
- MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations.Nucleic acids research · 2021Article
- Biomarker discovery in attention deficit hyperactivity disorder: RNA sequencing of whole blood in discordant twin and case-controlled cohorts.BMC medical genomics · 2020Article
- The SDHB Arg230His mutation causing familial paraganglioma alters glycolysis in a newDisease models & mechanisms · 2020Article
- Itaconate: A Metabolite Regulates Inflammation Response and Oxidative Stress.Oxidative medicine and cellular longevity · 2020Review
- CitE Enzymes Are Essential forFrontiers in cellular and infection microbiology · 2018Article
- Identification of specific metabolic pathways as druggable targets regulating the sensitivity to cyanide poisoning.PloS one · 2018Article
- An update on vitamin B12-related gene polymorphisms and B12 status.Genes & nutrition · 2018Review
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
Abstract
CLYBL is a human mitochondrial enzyme of unknown function that is found in multiple eukaryotic taxa and conserved to bacteria. The protein is expressed in the mitochondria of all mammalian organs, with highest expression in brown fat and kidney. Approximately 5% of all humans harbor a premature stop polymorphism in CLYBL that has been associated with reduced levels of circulating vitamin B12. Using comparative genomics, we now show that CLYBL is strongly co-expressed with and co-evolved specifically with other components of the mitochondrial B12 pathway. We confirm that the premature stop polymorphism in CLYBL leads to a loss of protein expression. To elucidate the molecular function of CLYBL, we used comparative operon analysis, structural modeling and enzyme kinetics. We report that CLYBL encodes a malate/β-methylmalate synthase, converting glyoxylate and acetyl-CoA to malate, or glyoxylate and propionyl-CoA to β-methylmalate. Malate synthases are best known for their established role in the glyoxylate shunt of plants and lower organisms and are traditionally described as not occurring in humans. The broader role of a malate/β-methylmalate synthase in human physiology and its mechanistic link to vitamin B12 metabolism remain unknown.
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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.