ArticleHuman mutation2014
Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency.
Article in Human mutation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- Clinical, phenotypic and genetic landscape of case reports with genetically proven inherited disorders of vitamin BCell reports. Medicine · 2022Pooled it
- Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision.Journal of inherited metabolic disease · 2021Guideline
- Untargeted metabolomics reveals distinct metabolic profiles in MUT-type methylmalonic acidemia.Molecular and cellular pediatrics · 2026Article
- Newborn screening for methylmalonic acidemia: insights from a retrospective analysis in Hefei, China.Orphanet journal of rare diseases · 2026Article
- Article
- Isolated methylmalonic acidemia in Mexico: Genotypic spectrum, report of two novel MMUT variants and a possible synergistic heterozygosity effect.Molecular genetics and metabolism reports · 2024Article
- Clinical and electroencephalogram characteristics of methylmalonic acidemia with MMACHC and MUT gene mutations.BMC pediatrics · 2024Article
- Biomarkers to predict disease progression and therapeutic response in isolated methylmalonic acidemia.Journal of inherited metabolic disease · 2023Review
- Association between host genetics of sheep and the rumen microbial composition.Tropical animal health and production · 2022Article
- Utilization of cobalamin is ubiquitous in early-branching fungal phyla.Genome biology and evolution · 2021Article
- Naturally occurring cobalamin (BBiochimie · 2021Article
- Investigating the structural impacts of a novel missense variant identified with whole exome sequencing in an Egyptian patient with propionic acidemia.Molecular genetics and metabolism reports · 2020Article
- Pre-implantation genetic diagnosis in an Iranian family with a novel mutation in MUT gene.BMC medical genetics · 2020Article
- Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency.Biochimica et biophysica acta. Molecular basis of disease · 2019Article
- Mutation analysis of genes related to methylmalonic acidemia: identification of eight novel mutations.Molecular biology reports · 2019Article
- Systemic Messenger RNA Therapy as a Treatment for Methylmalonic Acidemia.Cell reports · 2017Article
- Eight novel MUT loss-of-function missense mutations in Chinese patients with isolated methylmalonic academia.World journal of pediatrics : WJP · 2017Article
- Novel Mouse Models of Methylmalonic Aciduria Recapitulate Phenotypic Traits with a Genetic Dosage Effect.The Journal of biological chemistry · 2016Article
- From structural biology to designing therapy for inborn errors of metabolism.Journal of inherited metabolic disease · 2016Review
- Neutralizing Antibodies Against Adeno-Associated Viral Capsids in Patients with mut Methylmalonic Acidemia.Human gene therapy · 2016Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Methylmalonyl-CoA mutase (MUT) is an essential enzyme in propionate catabolism that requires adenosylcobalamin as a cofactor. Almost 250 inherited mutations in the MUT gene are known to cause the devastating disorder methylmalonic aciduria; however, the mechanism of dysfunction of these mutations, more than half of which are missense changes, has not been thoroughly investigated. Here, we examined 23 patient missense mutations covering a spectrum of exonic/structural regions, clinical phenotypes, and ethnic populations in order to determine their influence on protein stability, using two recombinant expression systems and a thermostability assay, and enzymatic function by measuring MUT activity and affinity for its cofactor and substrate. Our data stratify MUT missense mutations into categories of biochemical defects, including (1) reduced protein level due to misfolding, (2) increased thermolability, (3) impaired enzyme activity, and (4) reduced cofactor response in substrate turnover. We further demonstrate the stabilization of wild-type and thermolabile mutants by chemical chaperones in vitro and in bacterial cells. This in-depth mutation study illustrates the tools available for MUT enzyme characterization, guides future categorization of further missense mutations, and supports the development of alternative, chaperone-based therapy for patients not responding to current treatment.
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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.