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Aliases for MMAA Gene

Aliases for MMAA Gene

  • Methylmalonic Aciduria (Cobalamin Deficiency) CblA Type 2 3 5
  • Methylmalonic Aciduria (Cobalamin Deficiency) Type A 2
  • Methylmalonic Aciduria Type A Protein, Mitochondrial 3
  • Mutant Adenosylcobalamin 3
  • EC 3.6.-.- 4
  • CblA 3

External Ids for MMAA Gene

Previous GeneCards Identifiers for MMAA Gene

  • GC04P146932
  • GC04P147026
  • GC04P147137
  • GC04P147118
  • GC04P146898
  • GC04P146759
  • GC04P146540
  • GC04P142270

Summaries for MMAA Gene

Entrez Gene Summary for MMAA Gene

  • 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]

GeneCards Summary for MMAA Gene

MMAA (Methylmalonic Aciduria (Cobalamin Deficiency) CblA Type) is a Protein Coding gene. Diseases associated with MMAA include Methylmalonic Aciduria, Cbla Type and Methylmalonic Aciduria, Cblb Type. Among its related pathways are Defective MMAA causes methylmalonic aciduria type cblA and Diseases of metabolism. Gene Ontology (GO) annotations related to this gene include GTP binding and hydrolase activity.

UniProtKB/Swiss-Prot for MMAA Gene

  • GTPase, binds and hydrolyzes GTP (PubMed:28497574, PubMed:20876572). Involved in intracellular vitamin B12 metabolism, mediates the transport of cobalamin (Cbl) into mitochondria for the final steps of adenosylcobalamin (AdoCbl) synthesis. Functions as a G-protein chaperone that assists AdoCbl cofactor delivery from MMAB to the methylmalonyl-CoA mutase (MUT) and reactivation of the enzyme during catalysis (PubMed:28497574, PubMed:20876572).

Gene Wiki entry for MMAA Gene

Additional gene information for MMAA Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MMAA Gene

Genomics for MMAA Gene

GeneHancer (GH) Regulatory Elements for MMAA Gene

Promoters and enhancers for MMAA Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04I145617 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 569.6 +1.2 1192 3.6 MLX ZFP64 ARID4B SIN3A DMAP1 ZNF2 ZBTB7B YY1 POLR2B ZNF766 MMAA ENSG00000248356 NCOA4P3
GH04I145679 Promoter/Enhancer 1.3 EPDnew Ensembl ENCODE 18.7 +61.9 61933 2 FOXA2 ZNF189 OSR2 HIC1 SP1 ZSCAN21 JUND ZNF366 GLIS1 ZNF629 C4orf51 MMAA ENSG00000248356 GC04M145759
GH04I145728 Promoter/Enhancer 2.1 FANTOM5 Ensembl ENCODE dbSUPER 4.3 +114.8 114827 8.4 PKNOX1 FOXA2 IRF4 YY1 GLIS2 FOS RUNX3 SP3 RXRA SP5 MMAA GC04M145759 C4orf51
GH04I145175 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 2.4 -438.7 -438749 7.7 HDGF PKNOX1 SMAD1 ARNT ARID4B SIN3A FEZF1 DMAP1 IRF4 YY1 OTUD4 LOC105377463 ANAPC10 ABCE1 MMAA
GH04I145544 Enhancer 1 Ensembl ENCODE dbSUPER 4.5 -72.5 -72462 3.4 JUN CEBPB EP300 SP1 ZFHX2 PRDM6 JUND POLR2A FOS FOSL2 MMAA SMAD1-AS1 LOC285422 SMAD1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around MMAA on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MMAA gene promoter:

Genomic Locations for MMAA Gene

Genomic Locations for MMAA Gene
chr4:145,618,263-145,660,035
(GRCh38/hg38)
Size:
41,773 bases
Orientation:
Plus strand
chr4:146,539,415-146,581,187
(GRCh37/hg19)

Genomic View for MMAA Gene

Genes around MMAA on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MMAA Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MMAA Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MMAA Gene

Proteins for MMAA Gene

  • Protein details for MMAA Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8IVH4-MMAA_HUMAN
    Recommended name:
    Methylmalonic aciduria type A protein, mitochondrial
    Protein Accession:
    Q8IVH4
    Secondary Accessions:
    • B3KX40
    • Q495G7

    Protein attributes for MMAA Gene

    Size:
    418 amino acids
    Molecular mass:
    46538 Da
    Quaternary structure:
    • Homodimer (PubMed:20876572). Interacts with MUT (the apoenzyme form); the interaction is GTP dependent (PubMed:20876572, PubMed:28497574).

    Three dimensional structures from OCA and Proteopedia for MMAA Gene

neXtProt entry for MMAA Gene

Post-translational modifications for MMAA Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for MMAA Gene

No data available for DME Specific Peptides for MMAA Gene

Domains & Families for MMAA Gene

Gene Families for MMAA Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins

Protein Domains for MMAA Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for MMAA Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q8IVH4

UniProtKB/Swiss-Prot:

MMAA_HUMAN :
  • Belongs to the SIMIBI class G3E GTPase family. ArgK/MeaB subfamily.
Family:
  • Belongs to the SIMIBI class G3E GTPase family. ArgK/MeaB subfamily.
genes like me logo Genes that share domains with MMAA: view

Function for MMAA Gene

Molecular function for MMAA Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=42 uM for GTP {ECO:0000269 PubMed:28497574}; KM=330 uM for GTP {ECO:0000269 PubMed:20876572}; KM=74 uM for GTP (in presence of MUT) {ECO:0000269 PubMed:20876572}; Note=kcat is 0.201 min(-1) for GTP hydrolysis (PubMed:28497574). kcat is 0.03 min(-1) for GTP hydrolysis (PubMed:20876572). {ECO:0000269 PubMed:20876572, ECO:0000269 PubMed:28497574};
UniProtKB/Swiss-Prot CatalyticActivity:
GTP + H(2)O = GDP + phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation:
GTPase activity is stimulated by MUT.
UniProtKB/Swiss-Prot Function:
GTPase, binds and hydrolyzes GTP (PubMed:28497574, PubMed:20876572). Involved in intracellular vitamin B12 metabolism, mediates the transport of cobalamin (Cbl) into mitochondria for the final steps of adenosylcobalamin (AdoCbl) synthesis. Functions as a G-protein chaperone that assists AdoCbl cofactor delivery from MMAB to the methylmalonyl-CoA mutase (MUT) and reactivation of the enzyme during catalysis (PubMed:28497574, PubMed:20876572).

Enzyme Numbers (IUBMB) for MMAA Gene

Phenotypes From GWAS Catalog for MMAA Gene

Gene Ontology (GO) - Molecular Function for MMAA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003924 GTPase activity IMP,IEA 28497574
GO:0005515 protein binding IPI 20876572
GO:0005525 GTP binding IEA,IDA 20876572
GO:0016787 hydrolase activity IEA --
GO:0042802 identical protein binding IDA 20876572
genes like me logo Genes that share ontologies with MMAA: view
genes like me logo Genes that share phenotypes with MMAA: view

Human Phenotype Ontology for MMAA Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

Clone Products

  • Addgene plasmids for MMAA

No data available for Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for MMAA Gene

Localization for MMAA Gene

Subcellular locations from UniProtKB/Swiss-Prot for MMAA Gene

Mitochondrion.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MMAA gene
Compartment Confidence
mitochondrion 5
cytosol 3
nucleus 2
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for MMAA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IEA --
GO:0005759 mitochondrial matrix TAS --
genes like me logo Genes that share ontologies with MMAA: view

Pathways & Interactions for MMAA Gene

genes like me logo Genes that share pathways with MMAA: view

UniProtKB/Swiss-Prot Q8IVH4-MMAA_HUMAN

  • Pathway: Cofactor biosynthesis; adenosylcobalamin biosynthesis.

Gene Ontology (GO) - Biological Process for MMAA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0009235 cobalamin metabolic process TAS 28497574
GO:0009236 cobalamin biosynthetic process IEA --
GO:0019626 short-chain fatty acid catabolic process TAS --
genes like me logo Genes that share ontologies with MMAA: view

No data available for SIGNOR curated interactions for MMAA Gene

Drugs & Compounds for MMAA Gene

(5) Drugs for MMAA Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Hydroxocobalamin Approved Pharma Target, other/unknown 337
Cyanocobalamin Approved Nutra Target, cofactor 337
Cobamamide Approved Pharma 0
Cobalamin Nutra 337
genes like me logo Genes that share compounds with MMAA: view

Transcripts for MMAA Gene

Unigene Clusters for MMAA Gene

Methylmalonic aciduria (cobalamin deficiency) cblA type:
Representative Sequences:

Clone Products

  • Addgene plasmids for MMAA

Alternative Splicing Database (ASD) splice patterns (SP) for MMAA Gene

ExUns: 1 ^ 2a · 2b · 2c ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b
SP1:
SP2: -
SP3:

Relevant External Links for MMAA Gene

GeneLoc Exon Structure for
MMAA
ECgene alternative splicing isoforms for
MMAA

Expression for MMAA Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MMAA Gene

mRNA differential expression in normal tissues according to GTEx for MMAA Gene

This gene is overexpressed in Liver (x4.6).

Protein differential expression in normal tissues from HIPED for MMAA Gene

This gene is overexpressed in Heart (25.2) and Gallbladder (8.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for MMAA Gene



Protein tissue co-expression partners for MMAA Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of MMAA Gene:

MMAA

SOURCE GeneReport for Unigene cluster for MMAA Gene:

Hs.452864

mRNA Expression by UniProt/SwissProt for MMAA Gene:

Q8IVH4-MMAA_HUMAN
Tissue specificity: Widely expressed. Highest expression is observed in liver and skeletal muscle.

Evidence on tissue expression from TISSUES for MMAA Gene

  • Nervous system(4.5)
  • Liver(4.4)
  • Blood(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for MMAA Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • lymphatic
  • nervous
  • respiratory
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • head
Thorax:
  • esophagus
  • lung
Abdomen:
  • liver
  • stomach
General:
  • blood
  • bone marrow
  • coagulation system
  • red blood cell
  • white blood cell
genes like me logo Genes that share expression patterns with MMAA: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for MMAA Gene

Orthologs for MMAA Gene

This gene was present in the common ancestor of animals.

Orthologs for MMAA Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MMAA 33 34
  • 99.76 (n)
dog
(Canis familiaris)
Mammalia MMAA 33 34
  • 91.99 (n)
cow
(Bos Taurus)
Mammalia MMAA 33 34
  • 89.61 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia MMAA 34
  • 83 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Mmaa 33 16 34
  • 82.23 (n)
rat
(Rattus norvegicus)
Mammalia Mmaa 33
  • 80.96 (n)
oppossum
(Monodelphis domestica)
Mammalia MMAA 34
  • 79 (a)
OneToOne
chicken
(Gallus gallus)
Aves MMAA 33 34
  • 74.75 (n)
lizard
(Anolis carolinensis)
Reptilia MMAA 34
  • 73 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia mmaa 33
  • 72.6 (n)
Str.18824 33
zebrafish
(Danio rerio)
Actinopterygii mmaa 33 34
  • 63.36 (n)
Dr.9506 33
worm
(Caenorhabditis elegans)
Secernentea mmaa-1 33 34
  • 54.71 (n)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.722 33
Species where no ortholog for MMAA was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MMAA Gene

ENSEMBL:
Gene Tree for MMAA (if available)
TreeFam:
Gene Tree for MMAA (if available)

Paralogs for MMAA Gene

No data available for Paralogs for MMAA Gene

Variants for MMAA Gene

Sequence variations from dbSNP and Humsavar for MMAA Gene

SNP ID Clin Chr 04 pos Variation AA Info Type
rs1029096863 pathogenic, Methylmalonic aciduria cblA type 145,646,009(+) C/T coding_sequence_variant, stop_gained
rs1030045984 uncertain-significance, Methylmalonic acidemia 145,655,501(+) G/A 3_prime_UTR_variant
rs104893846 pathogenic, Methylmalonic aciduria cblA type 145,639,422(+) C/T 5_prime_UTR_variant, coding_sequence_variant, stop_gained
rs104893849 pathogenic, Methylmalonic aciduria cblA type, Methylmalonic aciduria type cblA (MMAA) [MIM:251100] 145,646,043(+) A/G coding_sequence_variant, missense_variant
rs104893851 pathogenic, Methylmalonic aciduria cblA type, not provided 145,639,572(+) C/T 5_prime_UTR_variant, coding_sequence_variant, stop_gained

Structural Variations from Database of Genomic Variants (DGV) for MMAA Gene

Variant ID Type Subtype PubMed ID
nsv830105 CNV loss 17160897

Variation tolerance for MMAA Gene

Residual Variation Intolerance Score: 14.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.80; 66.90% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MMAA Gene

Human Gene Mutation Database (HGMD)
MMAA
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MMAA

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MMAA Gene

Disorders for MMAA Gene

MalaCards: The human disease database

(7) MalaCards diseases for MMAA Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
methylmalonic aciduria, cbla type
  • methylmalonic acidemia, cbla type
methylmalonic aciduria, cblb type
  • methylmalonic acidemia, cblb type
vitamin b12-responsive methylmalonic acidemia
  • adenosylcobalamin deficiency
transcobalamin ii deficiency
  • tc ii deficiency
organic acidemia
  • organic acid metabolism disorder
- elite association - COSMIC cancer census association via MalaCards
Search MMAA in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

MMAA_HUMAN
  • Methylmalonic aciduria type cblA (MMAA) [MIM:251100]: A disorder of methylmalonate and cobalamin metabolism due to defective synthesis of adenosylcobalamin. {ECO:0000269 PubMed:12438653, ECO:0000269 PubMed:15308131, ECO:0000269 PubMed:15523652, ECO:0000269 PubMed:17957493, ECO:0000269 PubMed:20876572, ECO:0000269 PubMed:23026888, ECO:0000269 PubMed:28497574}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for MMAA

genes like me logo Genes that share disorders with MMAA: view

No data available for Genatlas for MMAA Gene

Publications for MMAA Gene

  1. Mutations in the MMAA gene in patients with the cblA disorder of vitamin B12 metabolism. (PMID: 15523652) Lerner-Ellis JP … Rosenblatt DS (Human mutation 2004) 3 4 22 25 58
  2. Identification of the gene responsible for the cblA complementation group of vitamin B12-responsive methylmalonic acidemia based on analysis of prokaryotic gene arrangements. (PMID: 12438653) Dobson CM … Gravel RA (Proceedings of the National Academy of Sciences of the United States of America 2002) 2 3 4 22 58
  3. Methylmalonic acidaemia: examination of genotype and biochemical data in 32 patients belonging to mut, cblA or cblB complementation group. (PMID: 17957493) Merinero B … Ugarte M (Journal of inherited metabolic disease 2008) 3 4 22 58
  4. Protein destabilization and loss of protein-protein interaction are fundamental mechanisms in cblA-type methylmalonic aciduria. (PMID: 28497574) Plessl T … Froese DS (Human mutation 2017) 3 4 58
  5. High resolution melting analysis of the MMAA gene in patients with cblA and in those with undiagnosed methylmalonic aciduria. (PMID: 23026888) Dempsey-Nunez L … Rosenblatt DS (Molecular genetics and metabolism 2012) 3 4 58

Products for MMAA Gene

  • Addgene plasmids for MMAA

Sources for MMAA Gene

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