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

Gene ID: 25974, updated on 5-Mar-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
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Genomic context

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Location:
1p34.1
Exon count:
4
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (45500300..45513382)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (45372667..45385751)
105.20220307 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. [Factors affecting phenotypes in the patients with MMACHC gene c.609G>A homozygous variant cblC type methylmalonic acidemia combined with homocysteinuria]. He R, et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2022 Jun 10. PMID 35773756
  2. Investigation on a MMACHC mutant from cblC disease: The c.394C>T variant. Passantino R, et al. Biochim Biophys Acta Proteins Proteom, 2022 Jun 1. PMID 35618206
  3. Intracellular processing of vitamin B(12) by MMACHC (CblC). Hannibal L, et al. Vitam Horm, 2022. PMID 35337623
  4. Clinical features and outcomes of patients with cblC type methylmalonic acidemia carrying gene c.609G>A mutation. Yu Y, et al. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2021 Aug 25. PMID 34704411, Free PMC Article
  5. Epimutation of MMACHC compound to a genetic mutation in cblC cases. Zhang X, et al. Mol Genet Genomic Med, 2021 Jun. PMID 33982424, Free PMC Article

See all (69) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. [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].
  3. [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].
  4. 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.
  5. 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).
  6. Intracellular processing of vitamin B12 by MMACHC (CblC).
    Title: Intracellular processing of vitamin B(12) by MMACHC (CblC).
  7. Epimutation of MMACHC compound to a genetic mutation in cblC cases.
    Title: Epimutation of MMACHC compound to a genetic mutation in cblC cases.
  8. 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.
  9. 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.
  10. Analysis of fibroblasts from patients with cblC and cblG genetic defects of cobalamin metabolism reveals global dysregulation of alternative splicing.
    Title: Analysis of fibroblasts from patients with cblC and cblG genetic defects of cobalamin metabolism reveals global dysregulation of alternative splicing.
Submit: New GeneRIF Correction See all GeneRIFs (56)

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
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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)

Genotypes

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) activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables cyanocobalamin reductase (cyanide-eliminating) activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables cyanocobalamin reductase (cyanide-eliminating) 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 EXP
Inferred from Experiment
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 IEA
Inferred from Electronic Annotation
more info
  
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_2023_10

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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