MMAB

更新于：2025-05-07

基本信息

别名

ATP:co(I)rrinoid adenosyltransferase MMAB、cblB、CFAP23

+ [8]

简介

Converts cob(I)alamin to adenosylcobalamin (adenosylcob(III)alamin), a coenzyme for methylmalonyl-CoA mutase, therefore participates in the final step of the vitamin B12 conversion (PubMed:12514191). Generates adenosylcobalamin (AdoCbl) and directly delivers the cofactor to MUT in a transfer that is stimulated by ATP-binding to MMAB and gated by MMAA (Probable).

关联

项与 MMAB 相关的药物

AAV9-MMAB (NIH/NCATS)

靶点

MMAB

作用机制

MMAB modulators

在研机构

National Institutes of Health [+1]

原研机构

National Center for Advancing Translational Sciences [+1]

在研适应症

甲基丙二酸血症

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 MMAB 相关的临床结果

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100 项与 MMAB 相关的转化医学

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0 项与 MMAB 相关的专利（医药）

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项与 MMAB 相关的文献（医药）

2025-07-01·Journal of Affective Disorders

Genetic insights into the role of mitochondria-related genes in mental disorders: An integrative multi-omics analysis

Article

作者: Jia, Xinlei ; Wei, Ya Bin ; Sun, Yaoyao ; Que, Jianyu ; Yu, Lulu ; Cui, Naixue ; Feng, Zhendong ; Zheng, Yi-Ran ; Liu, Jia Jia ; Lu, Yan'e

BACKGROUNDMitochondrial dysfunction has been implicated in the development of mental disorders, yet the underlying mechanisms remain unclear. In this study, we employed summary-data-based Mendelian randomization (SMR) analysis to explore the associations between mitochondrial-related genes and seven common mental disorders across gene expression, DNA methylation, and protein levels.METHODSummary statistics from genome-wide association studies were used for seven mental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, anxiety, bipolar disorder, major depressive disorder, post-traumatic stress disorder, and schizophrenia (SCZ). Instrumental variables associated with 1136 mitochondria-related genes were derived from summary statistics for DNA methylation, gene expression, and protein quantitative trait loci. SMR analyses and colocalization analyses were then conducted across these three biological levels to explore the associations with each of the seven mental disorders.RESULTSWe identified mitochondria-related genes associated with mental disorders with multi-omics evidence: RMDN1 for ADHD, and ACADVL, ETFA, MMAB, and PPA2 for SCZ. Specifically, an increase of one standard deviation in the level of RMDN1 was linked to a 12 % decrease in the risk of developing ADHD (OR = 0.88, 95 % CI: 0.83-0.94). Increased levels of ETFA (OR = 1.79, 95 % CI: 1.24-2.60) and MMAB (OR = 1.10, 95 % CI: 1.05-1.16) were significantly associated with increased risk of SCZ. Conversely, high levels of ACADVL (OR = 0.50, 95 % CI: 0.33-0.77) and PPA2 (OR = 0.68, 95 % CI: 0.55-0.85) were associated with a reduced risk of SCZ.CONCLUSIONSThese findings suggested that dysfunction in mitochondria-related genes may underlie the molecular mechanisms of ADHD and SCZ, providing novel biomarkers for diagnosis and therapeutic interventions.

2025-01-01·Progress in Neuro-Psychopharmacology and Biological Psychiatry

Multi-omics data integration reveals novel genes related to autoimmune hypothyroidism in the brain: A molecular basis for the brain–thyroid axis

Article

作者: Gao, Xiao ; Li, Ningjun ; Liu, Jun ; Cui, Weiwei ; Li, Can ; Yu, Hong ; Li, Zuoxi ; Liu, Xuehuan ; Lian, Xinying

BACKGROUNDThe mechanisms underlying the complex relationship between autoimmune hypothyroidism and neurological disorders remain unclear. We conducted a comprehensive analysis of associations between alternative splicing, transcriptomics, and proteomics data and autoimmune hypothyroidism.METHODSSplicing-wide association studies (SWAS), proteome-wide association studies (PWAS), and transcriptome-wide association studies (TWAS) were used to identify genes and proteins that regulate autoimmune hypothyroidism within the brain axis. We performed TWAS on GTEx V8 thyroid tissue data to identify autoimmune hypothyroidism-associated thyroid axis genes. A FUSION analysis of overlapping genes in the brain and thyroid axes and brain splicing weights was conducted to determine the influence of alternative splicing in the brain on thyroid tissue gene expression.RESULTSSWAS identified 223 alternative splicing events, TWAS identified 270 genes, and PWAS revealed five genes (FDPS, PPIL3, PEX6, MMAB, and ALDH2) encoding proteins associated with autoimmune hypothyroidism. Neuroimaging analyses revealed distinct brain-imaging phenotypes associated with these five genes. TWAS of thyroid tissue identified four genes (FDPS, PPIL3, MMAB, and ALDH2) associated with the brain axis related to thyroid tissue. A FUSION analysis indicated that alternative splicing changes in ALDH2 in brain tissue influenced its expression in thyroid tissue.CONCLUSIONIntegrating brain splicing, proteomic, and transcriptomic data supports the association between specific genes and proteins in the brain and autoimmune hypothyroidism. Additionally, ALDH2 alternative splicing in brain tissue influences its thyroid tissue expression. These findings provide new insights into the molecular basis of autoimmune hypothyroidism, facilitating future pathogenesis research.

2024-12-01·Molecular Genetics and Metabolism Reports

Isolated methylmalonic acidemia in Mexico: Genotypic spectrum, report of two novel MMUT variants and a possible synergistic heterozygosity effect

Article

作者: Ortega-Valdez, Enrique ; Fernández-Hernández, Liliana ; Carrillo-Nieto, Rosa Itzel ; Vela-Amieva, Marcela ; López-Mejía, Lizbeth ; Fernández-Lainez, Cynthia ; Alcántara-Ortigoza, Miguel Ángel ; Guillén-López, Sara ; Ridaura-Sanz, Cecilia ; Rojas-Maruri, Mauricio ; Reyna-Fabián, Miriam ; González-del Angel, Ariadna ; González-Del Angel, Ariadna

Isolated methylmalonic acidemia (iMMA) is a group of monogenic metabolic disorders affecting methylmalonate and cobalamin metabolism. Five iMMA-responsible genes have been described to date: MMUT (MIM *609058), MMAA (MIM *607481, MMAB (MIM *607568), MMADHC (MIM *611935), and MCEE (MIM *608419). Although iMMA is the most common form of organic acidemia reported in Mexico, its genotypic spectrum is still largely unknown. We performed a clinical exome analysis on 42 unrelated Mexican patients with iMMA. MMUT deficiency accounted for 73.8 % of all cases, followed by MMAA (14.2 %), MMAB (7.2 %), and MMADHC (2.4 %) deficiencies. One patient presented MMUT and MMAA double heterozygosity, which should be further experimentally confirmed to prove that synergistic heterozygosity could be another inheritance mechanism in iMMA. The most frequent MMUT genotype involved the Hispanic variant NM_000255.4:c. [322C > T];[322C > T] or p.[Arg108Cys];[Arg108Cys] (14.3 %). Two novel MMUT variants, NM_000255.4:c.589G > A or p.(Ala197Thr) and c.1476C > A or p.(Tyr492*), were identified in a deceased newborn presenting the neonatal-onset severe form of the disease. In silico protein modeling of the p.(Arg108Cys) and novel p.(Ala197Thr) MMUT variants suggested disruption of the substrate-binding and catalytic domains of the protein, respectively. This study expands the current knowledge on the molecular spectrum of iMMA in the Mexican population and reinforces the importance of genetic analysis in guiding clinical management.