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    MMACHC metabolism of cobalamin associated C [ Homo sapiens (human) ]

    Gene ID: 25974, updated on 27-Nov-2024

    Summary

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    Official Symbol
    MMACHCprovided by HGNC
    Official Full Name
    metabolism of cobalamin associated Cprovided by HGNC
    Primary source
    HGNC:HGNC:24525
    See related
    Ensembl:ENSG00000132763 MIM:609831; AllianceGenome:HGNC:24525
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    cblC
    Summary
    The exact function of the protein encoded by this gene is not known, however, its C-terminal region shows similarity to TonB, a bacterial protein involved in energy transduction for cobalamin (vitamin B12) uptake. Hence, it is postulated that this protein may have a role in the binding and intracellular trafficking of cobalamin. Mutations in this gene are associated with methylmalonic aciduria and homocystinuria type cblC. [provided by RefSeq, Oct 2009]
    Expression
    Ubiquitous expression in thyroid (RPKM 13.1), kidney (RPKM 10.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MMACHC in Genome Data Viewer
    Location:
    1p34.1
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (45500300..45513382)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (45372667..45385751)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (45965972..45979054)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene testis associated actin remodelling kinase 2 Neighboring gene peptidylprolyl isomerase A pseudogene 36 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:45909108-45909337 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 829 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 970 Neighboring gene Sharpr-MPRA regulatory region 45 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:45965685-45966217 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 972 Neighboring gene CCDC163 homolog Neighboring gene ReSE screen-validated silencer GRCh37_chr1:45986750-45986912 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 973 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:45992726-45993234 Neighboring gene peroxiredoxin 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:46003942-46004442 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:46004443-46004943 Neighboring gene high mobility group box 1 pseudogene 48 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 974 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 975 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 831 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 976 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 977 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 978 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 979 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:46021723-46022469 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:46022470-46023215 Neighboring gene aldo-keto reductase family 1 member A1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Report - Report on the heterozygosis mutations of c.567dupT, p.(Ile190Tyrfs*13) of MMACHC gene in 1 Child patient with methylmalonic academia. Liu K, et al. Pak J Pharm Sci, 2016 May. PMID 27383490
    2. Epigenetic modification of the gene for the vitamin B(12) chaperone MMACHC can result in increased tumorigenicity and methionine dependence. Loewy AD, et al. Mol Genet Metab, 2009 Apr. PMID 19200761
    3. Spectrum of mutations in MMACHC, allelic expression, and evidence for genotype-phenotype correlations. Lerner-Ellis JP, et al. Hum Mutat, 2009 Jul. PMID 19370762
    4. Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product. Hannibal L, et al. Mol Genet Metab, 2009 Aug. PMID 19447654, Free PMC Article
    5. Genetic and cellular studies of oxidative stress in methylmalonic aciduria (MMA) cobalamin deficiency type C (cblC) with homocystinuria (MMACHC). Richard E, et al. Hum Mutat, 2009 Nov. PMID 19760748

    See all (74) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The MMACHC variant c.158T>C: Mild clinical and biochemical phenotypes and marked hydroxocobalamin response in cblC patients.
      Title: The MMACHC variant c.158T>C: Mild clinical and biochemical phenotypes and marked hydroxocobalamin response in cblC patients.
    2. Clinical and electroencephalogram characteristics of methylmalonic acidemia with MMACHC and MUT gene mutations.
      Title: Clinical and electroencephalogram characteristics of methylmalonic acidemia with MMACHC and MUT gene mutations.
    3. [Analysis of clinical phenotypes and MMACHC gene variants in 65 children with Methylmalonic acidemia and homocysteinemia].
      Title: [Analysis of clinical phenotypes and MMACHC gene variants in 65 children with Methylmalonic acidemia and homocysteinemia].
    4. [Factors affecting phenotypes in the patients with MMACHC gene c.609G>A homozygous variant cblC type methylmalonic acidemia combined with homocysteinuria].
      Title: [Factors affecting phenotypes in the patients with MMACHC gene c.609G>A homozygous variant cblC type methylmalonic acidemia combined with homocysteinuria].
    5. Investigation on a MMACHC mutant from cblC disease: The c.394C>T variant.
      Title: Investigation on a MMACHC mutant from cblC disease: The c.394C>T variant.
    6. Epimutations in both the TESK2 and MMACHC promoters in the Epi-cblC inherited disorder of intracellular metabolism of vitamin B12.
      Title: Epimutations in both the TESK2 and MMACHC promoters in the Epi-cblC inherited disorder of intracellular metabolism of vitamin B(12).
    7. Intracellular processing of vitamin B12 by MMACHC (CblC).
      Title: Intracellular processing of vitamin B(12) by MMACHC (CblC).
    8. Epimutation of MMACHC compound to a genetic mutation in cblC cases.
      Title: Epimutation of MMACHC compound to a genetic mutation in cblC cases.
    9. Clinical features and outcomes of patients with cblC type methylmalonic acidemia carrying gene c.609G>A mutation.
      Title: Clinical features and outcomes of patients with cblC type methylmalonic acidemia carrying gene c.609G>A mutation.
    10. A high frequency and geographical distribution of MMACHC R132* mutation in children with cobalamin C defect.
      Title: A high frequency and geographical distribution of MMACHC R132* mutation in children with cobalamin C defect.
    Submit: New GeneRIF Correction See all GeneRIFs (57)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Cobalamin C disease
    MedGen: C1848561 OMIM: 277400 GeneReviews: Disorders of Intracellular Cobalamin Metabolism
    		Compare labs

    EBI GWAS Catalog

    Description
    Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ25671, DKFZp564I122

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables FAD binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables FAD binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cobalamin binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables cyanocobalamin reductase (cyanide-eliminating) (NADP+) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables cyanocobalamin reductase (cyanide-eliminating) (NADP+) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables cyanocobalamin reductase (cyanide-eliminating) (NADP+) activity TAS
    Traceable Author Statement
    more info
    		  
    enables demethylase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables demethylase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables glutathione binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables oxidoreductase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transferase activity, transferring alkyl or aryl (other than methyl) groups EXP
    Inferred from Experiment
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cobalamin metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cobalamin metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cobalamin metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cobalamin metabolic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in demethylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in glutathione metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    cyanocobalamin reductase / alkylcobalamin dealkylase
    Names
    alkylcobalamin:glutathione S-alkyltransferase
    cyanocobalamin reductase (cyanide-eliminating)
    methylmalonic aciduria (cobalamin deficiency) cblC type, with homocystinuria
    methylmalonic aciduria and homocystinuria type C protein
    NP_001317469.1
    NP_056321.2

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_013378.2 RefSeqGene

      Range
      5002..18084
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001330540.2 → NP_001317469.1  cyanocobalamin reductase / alkylcobalamin dealkylase isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice junction compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.
      Source sequence(s)
      AL451136
      Consensus CDS
      CCDS81315.1
      UniProtKB/TrEMBL
      A0A0C4DGU2
      Related
      ENSP00000478859.1, ENST00000616135.1
      Conserved Domains (1) summary
      pfam16690
      Location:1 → 177
      MMACHC; Methylmalonic aciduria and homocystinuria type C family

    2. NM_015506.3 → NP_056321.2  cyanocobalamin reductase / alkylcobalamin dealkylase isoform 1

      See identical proteins and their annotated locations for NP_056321.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AK098537, AL451136, BM980565, BU632364, BU839693
      Consensus CDS
      CCDS41324.1
      UniProtKB/Swiss-Prot
      Q5T157, Q9BRQ7, Q9Y4U1
      Related
      ENSP00000383840.4, ENST00000401061.9
      Conserved Domains (1) summary
      pfam16690
      Location:20 → 234
      MMACHC; Methylmalonic aciduria and homocystinuria type C family

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      45500300..45513382
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      45372667..45385751
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y4U1.3 GenPept UniProtKB/Swiss-Prot:Q9Y4U1

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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