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

    Gene ID: 166785, updated on 14-Nov-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (145619385..145660033)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (148935202..148975850)
    RS_2024_09 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 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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    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
    		Compare labs

    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

    • 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 membrane scission GTPase motor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    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 HTP PubMed 
    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_2024_08

    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

    Gene LinkOut

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

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