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MMAA metabolism of cobalamin associated A [ Homo sapiens (human) ]

Gene ID: 166785, updated on 3-Apr-2024

Summary

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Official Symbol
MMAAprovided by HGNC
Official Full Name
metabolism of cobalamin associated Aprovided by HGNC
Primary source
HGNC:HGNC:18871
See related
Ensembl:ENSG00000151611 MIM:607481; AllianceGenome:HGNC:18871
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
cblA
Summary
The protein encoded by this gene is involved in the translocation of cobalamin into the mitochondrion, where it is used in the final steps of adenosylcobalamin synthesis. Adenosylcobalamin is a coenzyme required for the activity of methylmalonyl-CoA mutase. Defects in this gene are a cause of methylmalonic aciduria. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in liver (RPKM 3.7), kidney (RPKM 2.7) and 25 other tissues See more
Orthologs
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Genomic context

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See MMAA in Genome Data Viewer
Location:
4q31.21
Exon count:
8
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (145619385..145660033)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (148935202..148975850)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (146540537..146581185)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC285422 Neighboring gene long intergenic non-protein coding RNA 2491 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15731 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15732 Neighboring gene nuclear receptor coactivator 4 pseudogene 3 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:146608063-146608617 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr4:146619735-146620662 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:146620663-146621589 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:146624094-146624783 Neighboring gene NANOG hESC enhancer GRCh37_chr4:146625046-146625631 Neighboring gene chromosome 4 open reading frame 51 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21965 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21966 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15733 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:146655149-146655948 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:146655949-146656746 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:146683575-146684076 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:146684077-146684576 Neighboring gene zinc finger protein 827 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21967 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr4:146729136-146730335 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21969 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:146746417-146746985 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:146753533-146754304 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:146756877-146757401 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:146757402-146757925 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:146758974-146759498 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:146759499-146760022 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:146799791-146800383 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21970 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15734 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21971 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:146853271-146853772 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15735 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15736 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15737 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21972 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr4:146875811-146877010 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15738 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21973 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21974 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr4:146975373-146976572 Neighboring gene uncharacterized LOC105377468 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21976

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. Mild clinical features of isolated methylmalonic acidemia associated with a novel variant in the MMAA gene in two Chinese siblings. Lin Y, et al. BMC Med Genet, 2018 Jul 11. PMID 29996803, Free PMC Article
  2. Identification of a novel deletion in the MMAA gene in two Iranian siblings with vitamin B12-responsive methylmalonic acidemia. Keyfi F, et al. Cell Mol Biol Lett, 2016. PMID 28536607, Free PMC Article
  3. High resolution melting analysis of the MMAA gene in patients with cblA and in those with undiagnosed methylmalonic aciduria. Dempsey-Nunez L, et al. Mol Genet Metab, 2012 Nov. PMID 23026888
  4. Spondylocostal dysostosis associated with methylmalonic aciduria. Honjo RS, et al. Genet Test Mol Biomarkers, 2009 Apr. PMID 19371216
  5. Mutation analysis of the MMAA and MMAB genes in Japanese patients with vitamin B(12)-responsive methylmalonic acidemia: identification of a prevalent MMAA mutation. Yang X, et al. Mol Genet Metab, 2004 Aug. PMID 15308131

See all (25) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The two siblings were associated with the MMAA c.365T>C variant.
    Title: Mild clinical features of isolated methylmalonic acidemia associated with a novel variant in the MMAA gene in two Chinese siblings.
  2. localization of hMMAA and its colocalization with hMCM in human
    Title: Human MMAA induces the release of inactive cofactor and restores methylmalonyl-CoA mutase activity through their complex formation.
  3. A novel deletion in the MMAA gene in two Iranian siblings with vitamin B12-responsive methylmalonic academia was identified. The deletion in exon 4 of the MMAA gene (c.674 delA) is a pathogenic allele via a nucleotide frame shift resulting in a stop codon and termination of protein synthesis 38 nucleotides (12 amino acids) downstream of the deletion.
    Title: Identification of a novel deletion in the MMAA gene in two Iranian siblings with vitamin B12-responsive methylmalonic acidemia.
  4. Ten novel mutational MMAA variants have been identified in patients with methylmalonic aciduria.
    Title: High resolution melting analysis of the MMAA gene in patients with cblA and in those with undiagnosed methylmalonic aciduria.
  5. MMAA acts as a chaperone of human MCM protein.
    Title: Protection and reactivation of human methylmalonyl-CoA mutase by MMAA protein.
  6. Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation.
    Title: Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation.
  7. Spondylocostal dysostosis associated with MMAA is presented in a young boy.
    Title: Spondylocostal dysostosis associated with methylmalonic aciduria.
  8. Methylmalonic acidaemia: examination of genotype and biochemical data in 32 patients belonging to mut, cblA or cblB complementation group.
    Title: Methylmalonic acidaemia: examination of genotype and biochemical data in 32 patients belonging to mut, cblA or cblB complementation group.
  9. Long-term outcome in methylmalonic acidurias is influenced by the underlying genetic defects in MCM/MMAA/MMAB.
    Title: Long-term outcome in methylmalonic acidurias is influenced by the underlying defect (mut0, mut-, cblA, cblB).
  10. DNA from 37 cblA patients was analyzed for deleterious mutations in the MMAA gene by DNA sequencing of exons and flanking sequences
    Title: Mutations in the MMAA gene in patients with the cblA disorder of vitamin B12 metabolism.
Submit: New GeneRIF Correction See all GeneRIFs (12)

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
Methylmalonic aciduria, cblA type
MedGen: C1855109 OMIM: 251100 GeneReviews: Isolated Methylmalonic Acidemia
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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

  • MGC120010, MGC120011, MGC120012, MGC120013

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables GTP binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables GTPase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables GTPase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables GTPase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables identical protein binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in cobalamin metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cobalamin metabolic process TAS
Traceable Author Statement
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 
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
methylmalonic aciduria type A protein, mitochondrial
Names
methylmalonic aciduria (cobalamin deficiency) cblA type
mutant adenosylcobalamin

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_007536.2 RefSeqGene

    Range
    25344..65992
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1301

mRNA and Protein(s)

  1. NM_001375644.1 → NP_001362573.1  methylmalonic aciduria type A protein, mitochondrial precursor

    Status: REVIEWED

    Source sequence(s)
    AC093864
    Consensus CDS
    CCDS3766.1
    UniProtKB/Swiss-Prot
    B3KX40, Q495G7, Q8IVH4
    UniProtKB/TrEMBL
    Q495G5
    Related
    ENSP00000497046.1, ENST00000648388.1
    Conserved Domains (1) summary
    PRK09435
    Location:86 → 418
    PRK09435; methylmalonyl Co-A mutase-associated GTPase MeaB

  2. NM_172250.3 → NP_758454.1  methylmalonic aciduria type A protein, mitochondrial precursor

    See identical proteins and their annotated locations for NP_758454.1

    Status: REVIEWED

    Source sequence(s)
    AC093864, AK126662
    Consensus CDS
    CCDS3766.1
    UniProtKB/Swiss-Prot
    B3KX40, Q495G7, Q8IVH4
    UniProtKB/TrEMBL
    Q495G5
    Related
    ENSP00000497008.1, ENST00000649156.2
    Conserved Domains (1) summary
    PRK09435
    Location:86 → 418
    PRK09435; methylmalonyl Co-A mutase-associated GTPase MeaB

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_000004.12 Reference GRCh38.p14 Primary Assembly

    Range
    145619385..145660033
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011531684.4 → XP_011529986.1  methylmalonic aciduria type A protein, mitochondrial isoform X1

    See identical proteins and their annotated locations for XP_011529986.1

    UniProtKB/Swiss-Prot
    B3KX40, Q495G7, Q8IVH4
    UniProtKB/TrEMBL
    Q495G5
    Conserved Domains (1) summary
    PRK09435
    Location:86 → 418
    PRK09435; methylmalonyl Co-A mutase-associated GTPase MeaB

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    148935202..148975850
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054349101.1 → XP_054205076.1  methylmalonic aciduria type A protein, mitochondrial isoform X1

    UniProtKB/Swiss-Prot
    B3KX40, Q495G7, Q8IVH4
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8IVH4.1 GenPept UniProtKB/Swiss-Prot:Q8IVH4

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