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Aliases for MMACHC Gene

Aliases for MMACHC Gene

  • Methylmalonic Aciduria (Cobalamin Deficiency) CblC Type, With Homocystinuria 2 3 5
  • Cyanocobalamin Reductase (Cyanide-Eliminating) 3 4
  • CblC 3 4
  • Methylmalonic Aciduria And Homocystinuria Type C Protein 3
  • EC 1.16.1.- 4

External Ids for MMACHC Gene

Previous GeneCards Identifiers for MMACHC Gene

  • GC01P045636
  • GC01P045733
  • GC01P045965
  • GC01P044077

Summaries for MMACHC Gene

Entrez Gene Summary for MMACHC Gene

  • 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]

GeneCards Summary for MMACHC Gene

MMACHC (Methylmalonic Aciduria (Cobalamin Deficiency) CblC Type, With Homocystinuria) is a Protein Coding gene. Diseases associated with MMACHC include Methylmalonic Aciduria And Homocystinuria, Cblc Type and Methylmalonic Acidemia With Homocystinuria. Among its related pathways are Diseases of metabolism and Vitamin digestion and absorption. GO annotations related to this gene include cobalamin binding.

UniProtKB/Swiss-Prot for MMACHC Gene

  • Catalyzes the reductive dealkylation of cyanocobalamin to cob(II)alamin, using FAD or FMN as cofactor and NADPH as cosubstrate (PubMed:19700356, PubMed:21697092, PubMed:22642810). Can also catalyze the glutathione-dependent reductive demethylation of methylcobalamin, and, with much lower efficiency, the glutathione-dependent reductive demethylation of adenosylcobalamin (PubMed:19801555, PubMed:22642810, PubMed:25809485). Under anaerobic conditions cob(I)alamin is the first product; it is highly reactive and is converted to aquocob(II)alamin in the presence of oxygen (PubMed:19801555). Binds cyanocobalamin, adenosylcobalamin, methylcobalamin and other, related vitamin B12 derivatives (PubMed:21071249).

Gene Wiki entry for MMACHC Gene

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

Genomics for MMACHC Gene

Regulatory Elements for MMACHC Gene

Enhancers for MMACHC Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH01G045334 1.4 Ensembl ENCODE 15.6 -161.8 -161780 7.9 MLX CREB3L1 AGO1 DMAP1 FEZF1 YY1 ZNF143 SP3 NFYC MEF2D PRDX1 MMACHC CCDC163 TESK2 MUTYH UROD TOE1 HPDL
GH01G045348 0.9 Ensembl ENCODE 15.2 -151.0 -150973 1.9 MAFG CEBPB RAD21 ATF2 NR2F2 ZNF316 MAFF GATA2 FOS PRDX1 MMACHC TESK2 PIR46302 ENSG00000236872
GH01G045409 1.6 FANTOM5 Ensembl ENCODE 5.6 -88.8 -88762 3.8 FEZF1 ZNF2 ZNF121 ZNF766 GATA2 ELK1 FOS KLF7 TSHZ1 ZNF662 TOE1 ZSWIM5 PTCH2 PRDX1 RPS8 TESK2 LURAP1 RPL7AP16 RPS15AP10 HMGB1P48
GH01G045541 1.7 FANTOM5 Ensembl ENCODE 4.7 +43.8 43798 4.9 HDGF PKNOX1 MLX ZFP64 WRNIP1 ARID4B DMAP1 ZNF48 YY1 ELK1 CCDC163 PRDX1 IPP AKR1A1 MMACHC TESK2 GPBP1L1 TOE1 GC01P045551 HMGB1P48
GH01G045325 1.2 Ensembl ENCODE 5.7 -171.7 -171733 4.7 HDGF PKNOX1 AGO1 YY1 ETS1 ZNF121 FOS REST MAFF PBX2 CCDC163 TOE1 MMACHC HPDL
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around MMACHC on UCSC Golden Path with GeneCards custom track

Promoters for MMACHC Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000005858 147 1601 HDGF PKNOX1 FOXA2 CREB3L1 ARNT WRNIP1 ARID4B SIN3A DMAP1 ZNF2

Genomic Location for MMACHC Gene

Chromosome:
1
Start:
45,500,053 bp from pter
End:
45,513,382 bp from pter
Size:
13,330 bases
Orientation:
Plus strand

Genomic View for MMACHC Gene

Genes around MMACHC on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for MMACHC Gene

Proteins for MMACHC Gene

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

    Protein Symbol:
    Q9Y4U1-MMAC_HUMAN
    Recommended name:
    Methylmalonic aciduria and homocystinuria type C protein
    Protein Accession:
    Q9Y4U1
    Secondary Accessions:
    • Q5T157
    • Q9BRQ7

    Protein attributes for MMACHC Gene

    Size:
    282 amino acids
    Molecular mass:
    31728 Da
    Cofactor:
    Name=FAD; Xref=ChEBI:CHEBI:57692; Name=FMN; Xref=ChEBI:CHEBI:58210;
    Quaternary structure:
    • Monomer in the absence of bound substrate (PubMed:21697092, PubMed:22642810). Homodimer; dimerization is triggered by binding to FMN or adenosylcobalamin (PubMed:22642810). Heterodimer with MMADHC (PubMed:21071249, PubMed:23415655, PubMed:26483544).
    SequenceCaution:
    • Sequence=AAH06122.3; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for MMACHC Gene

neXtProt entry for MMACHC Gene

Post-translational modifications for MMACHC Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for MMACHC Gene

No data available for DME Specific Peptides for MMACHC Gene

Domains & Families for MMACHC Gene

Protein Domains for MMACHC Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for MMACHC Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9Y4U1

UniProtKB/Swiss-Prot:

MMAC_HUMAN :
  • Belongs to the MMACHC family.
Family:
  • Belongs to the MMACHC family.
genes like me logo Genes that share domains with MMACHC: view

No data available for Gene Families for MMACHC Gene

Function for MMACHC Gene

Molecular function for MMACHC Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=27.7 uM for glutathione {ECO:0000269 PubMed:19801555};
UniProtKB/Swiss-Prot Function:
Catalyzes the reductive dealkylation of cyanocobalamin to cob(II)alamin, using FAD or FMN as cofactor and NADPH as cosubstrate (PubMed:19700356, PubMed:21697092, PubMed:22642810). Can also catalyze the glutathione-dependent reductive demethylation of methylcobalamin, and, with much lower efficiency, the glutathione-dependent reductive demethylation of adenosylcobalamin (PubMed:19801555, PubMed:22642810, PubMed:25809485). Under anaerobic conditions cob(I)alamin is the first product; it is highly reactive and is converted to aquocob(II)alamin in the presence of oxygen (PubMed:19801555). Binds cyanocobalamin, adenosylcobalamin, methylcobalamin and other, related vitamin B12 derivatives (PubMed:21071249).

Enzyme Numbers (IUBMB) for MMACHC Gene

Gene Ontology (GO) - Molecular Function for MMACHC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 23415655
GO:0016491 oxidoreductase activity TAS --
GO:0031419 cobalamin binding IEA --
GO:0032451 demethylase activity IDA 19801555
GO:0033787 cyanocobalamin reductase (cyanide-eliminating) activity TAS --
genes like me logo Genes that share ontologies with MMACHC: view
genes like me logo Genes that share phenotypes with MMACHC: view

Human Phenotype Ontology for MMACHC Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for MMACHC Gene

MGI Knock Outs for MMACHC:

Animal Model Products

CRISPR Products

miRNA for MMACHC Gene

miRTarBase miRNAs that target MMACHC

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Transcription Factor Targets and HOMER Transcription for MMACHC Gene

Localization for MMACHC Gene

Subcellular locations from UniProtKB/Swiss-Prot for MMACHC Gene

Cytoplasm.

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 MMACHC gene
Compartment Confidence
cytosol 5
mitochondrion 3
nucleus 3
plasma membrane 2
golgi apparatus 2
lysosome 1

Gene Ontology (GO) - Cellular Components for MMACHC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA,IEA 23270877
GO:0005739 mitochondrion IEA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with MMACHC: view

Pathways & Interactions for MMACHC Gene

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

UniProtKB/Swiss-Prot Q9Y4U1-MMAC_HUMAN

  • Pathway: Cofactor biosynthesis; adenosylcobalamin biosynthesis.

Gene Ontology (GO) - Biological Process for MMACHC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006749 glutathione metabolic process IDA 19801555
GO:0009235 cobalamin metabolic process TAS --
GO:0009236 cobalamin biosynthetic process IEA --
GO:0055114 oxidation-reduction process IDA,IEA 19801555
GO:0070988 demethylation IDA 19801555
genes like me logo Genes that share ontologies with MMACHC: view

No data available for SIGNOR curated interactions for MMACHC Gene

Drugs & Compounds for MMACHC Gene

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Hydroxocobalamin Approved Pharma Target, other/unknown 258
Cyanocobalamin Approved Nutra Target, cofactor 259
Cobalamin Nutra 259
Cobalt Pharma 167
genes like me logo Genes that share compounds with MMACHC: view

Transcripts for MMACHC Gene

mRNA/cDNA for MMACHC Gene

Unigene Clusters for MMACHC Gene

Methylmalonic aciduria (cobalamin deficiency) cblC type, with homocystinuria:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

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

No ASD Table

Relevant External Links for MMACHC Gene

GeneLoc Exon Structure for
MMACHC
ECgene alternative splicing isoforms for
MMACHC

Expression for MMACHC Gene

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

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

This gene is overexpressed in Liver (x4.8).

Protein differential expression in normal tissues from HIPED for MMACHC Gene

This gene is overexpressed in Gallbladder (40.8) and Testis (28.2).

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



Protein tissue co-expression partners for MMACHC Gene

NURSA nuclear receptor signaling pathways regulating expression of MMACHC Gene:

MMACHC

SOURCE GeneReport for Unigene cluster for MMACHC Gene:

Hs.13024

mRNA Expression by UniProt/SwissProt for MMACHC Gene:

Q9Y4U1-MMAC_HUMAN
Tissue specificity: Widely expressed. Expressed at higher level in fetal liver. Also expressed in spleen, lymph node, thymus and bone marrow. Weakly or not expressed in peripheral blood leukocytes.

Evidence on tissue expression from TISSUES for MMACHC Gene

  • Liver(4.3)
  • Nervous system(4.3)
  • Lung(4)

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

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Organs:
Head and neck:
  • brain
  • cerebellum
  • cerebrospinal fluid
  • cheek
  • chin
  • cranial nerve
  • ear
  • eye
  • face
  • forehead
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • meninges
  • mouth
  • neck
  • nose
  • outer ear
  • skull
Thorax:
  • chest wall
  • clavicle
  • heart
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • kidney
  • pancreas
Pelvis:
  • pelvis
  • ureter
  • urinary bladder
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • coagulation system
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
  • spinal column
  • spinal cord
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with MMACHC: view

Primer Products

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

Orthologs for MMACHC Gene

This gene was present in the common ancestor of animals.

Orthologs for MMACHC Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MMACHC 34 35
  • 99.41 (n)
cow
(Bos Taurus)
Mammalia MMACHC 34 35
  • 88.45 (n)
dog
(Canis familiaris)
Mammalia -- 35
  • 88 (a)
OneToMany
MMACHC 34
  • 86.36 (n)
-- 35
  • 85 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Mmachc 34
  • 83.69 (n)
mouse
(Mus musculus)
Mammalia Mmachc 34 16 35
  • 82.56 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 35
  • 72 (a)
OneToMany
-- 35
  • 72 (a)
OneToMany
oppossum
(Monodelphis domestica)
Mammalia MMACHC 35
  • 71 (a)
OneToOne
chicken
(Gallus gallus)
Aves MMACHC 34 35
  • 63.55 (n)
lizard
(Anolis carolinensis)
Reptilia MMACHC 35
  • 56 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia mmachc 34
  • 58.85 (n)
Str.14656 34
zebrafish
(Danio rerio)
Actinopterygii mmachc 34 35
  • 58.87 (n)
wufc29d04 34
worm
(Caenorhabditis elegans)
Secernentea cblc-1 34 35
  • 48.67 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 44 (a)
OneToOne
Species where no ortholog for MMACHC 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 MMACHC Gene

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

Paralogs for MMACHC Gene

Pseudogenes.org Pseudogenes for MMACHC Gene

genes like me logo Genes that share paralogs with MMACHC: view

No data available for Paralogs for MMACHC Gene

Variants for MMACHC Gene

Sequence variations from dbSNP and Humsavar for MMACHC Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type
rs121918240 Pathogenic, Methylmalonic aciduria and homocystinuria type cblC (MMAHCC) [MIM:277400] 45,508,282(+) GATCC(C/T)GGCCC reference, missense
rs121918243 Pathogenic, Methylmalonic aciduria and homocystinuria type cblC (MMAHCC) [MIM:277400] 45,508,848(+) CATCC(A/G)AGGGG reference, missense
rs140522266 Pathogenic, Methylmalonic aciduria and homocystinuria type cblC (MMAHCC) [MIM:277400], Methylmalonic aciduria and homocystinuria type cblC (MMAHCC) [MIM:277400] 45,508,806(+) ATCAG(A/C/G)TGTGT reference, missense
rs200895671 Methylmalonic aciduria and homocystinuria type cblC (MMAHCC) [MIM:277400] 45,508,931(+) CTGAC(A/C/T)GTATC reference, missense
rs372670428 Methylmalonic aciduria and homocystinuria type cblC (MMAHCC) [MIM:277400] 45,508,323(+) ACTAC(C/T)ACCAA reference, missense

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

Variant ID Type Subtype PubMed ID
esv3893512 CNV gain 25118596
nsv829726 CNV loss 17160897

Variation tolerance for MMACHC Gene

Residual Variation Intolerance Score: 94.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.57; 65.07% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for MMACHC Gene

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

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

Disorders for MMACHC Gene

MalaCards: The human disease database

(11) MalaCards diseases for MMACHC Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
methylmalonic aciduria and homocystinuria, cblc type
  • methylmalonic aciduria and homocystinuria type cblc
methylmalonic acidemia with homocystinuria
  • methylmalonic acidemia and homocystinemia
macular dystrophy, concentric annular
  • maculopathy, bull's eye
homocystinuria
  • cbs deficiency
methylmalonic acidemia
  • methylmalonic acidemia, cbla type
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

MMAC_HUMAN
  • Methylmalonic aciduria and homocystinuria type cblC (MMAHCC) [MIM:277400]: A disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Affected individuals may have developmental, hematologic, neurologic, metabolic, ophthalmologic, and dermatologic clinical findings. Although considered a disease of infancy or childhood, some individuals develop symptoms in adulthood. {ECO:0000269 PubMed:16311595, ECO:0000269 PubMed:19700356, ECO:0000269 PubMed:20219402, ECO:0000269 PubMed:22642810, ECO:0000269 PubMed:25809485}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for MMACHC

Genetic Association Database (GAD)
MMACHC
Human Genome Epidemiology (HuGE) Navigator
MMACHC
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
MMACHC
genes like me logo Genes that share disorders with MMACHC: view

No data available for Genatlas for MMACHC Gene

Publications for MMACHC Gene

  1. Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type. (PMID: 16311595) Lerner-Ellis J.P. … Rosenblatt D.S. (Nat. Genet. 2006) 2 3 4 22 25 64
  2. Mechanism of vitamin B12-responsiveness in cblC methylmalonic aciduria with homocystinuria. (PMID: 19700356) Froese D.S. … Gravel R.A. (Mol. Genet. Metab. 2009) 2 3 4 22 64
  3. A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins. (PMID: 19801555) Kim J. … Banerjee R. (J. Biol. Chem. 2009) 2 3 4 64
  4. Spectrum of mutations in MMACHC, allelic expression, and evidence for genotype-phenotype correlations. (PMID: 19370762) Lerner-Ellis J.P. … Fowler B. (Hum. Mutat. 2009) 3 22 46 64
  5. Late-onset cobalamin-C disorder: a challenging diagnosis. (PMID: 17431913) Ben-Omran T.I. … Feigenbaum A. (Am. J. Med. Genet. A 2007) 3 22 25 64

Products for MMACHC Gene

Sources for MMACHC Gene

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