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 methyl... See more...

Aliases for MMACHC Gene

Aliases for MMACHC Gene

  • Metabolism Of Cobalamin Associated C 2 3 5
  • CblC 2 3 4
  • Methylmalonic Aciduria (Cobalamin Deficiency) CblC Type, With Homocystinuria 2 3
  • Methylmalonic Aciduria And Homocystinuria Type C Protein 3 4
  • Cyanocobalamin Reductase / Alkylcobalamin Dealkylase 3 4
  • Cyanocobalamin Reductase (Cyanide-Eliminating) 3 4
  • Alkylcobalamin:Glutathione S-Alkyltransferase 3 4
  • DKFZP564I122 2
  • EC 2.5.1.151 4
  • EC 1.16.1.6 4
  • MMACHC 5

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 (Metabolism Of Cobalamin Associated C) is a Protein Coding gene. Diseases associated with MMACHC include Methylmalonic Aciduria And Homocystinuria, Cblc Type and Disorders Of Intracellular Cobalamin Metabolism. Among its related pathways are Metabolism of water-soluble vitamins and cofactors and Cobalamin (Cbl, vitamin B12) transport and metabolism. Gene Ontology (GO) annotations related to this gene include cobalamin binding.

UniProtKB/Swiss-Prot Summary for MMACHC Gene

  • Cobalamin (vitamin B12) cytosolic chaperone that catalyzes the reductive decyanation of cyanocob(III)alamin (cyanocobalamin, CNCbl) to yield cob(II)alamin and cyanide, using FAD or FMN as cofactors and NADPH as cosubstrate (PubMed:18779575, PubMed:19700356, PubMed:21697092, PubMed:25809485). Cyanocobalamin constitutes the inactive form of vitamin B12 introduced from the diet, and is converted into the active cofactors methylcobalamin (MeCbl) involved in methionine biosynthesis, and 5'-deoxyadenosylcobalamin (AdoCbl) involved in the TCA cycle (PubMed:19801555). Forms a complex with the lysosomal transporter ABCD4 and its chaperone LMBRD1, to transport cobalamin across the lysosomal membrane into the cytosol (PubMed:25535791). The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR (methionine synthase) which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (PubMed:21071249, PubMed:27771510). Also acts as a glutathione transferase by catalyzing the dealkylation of the alkylcob(III)alamins MeCbl and AdoCbl, using the thiolate of glutathione for nucleophilic displacement to generate cob(I)alamin and the corresponding glutathione thioether (PubMed:19801555, PubMed:21697092, PubMed:22642810, PubMed:25809485). The conversion of incoming MeCbl or AdoCbl into a common intermediate cob(I)alamin is necessary to meet the cellular needs for both cofactors (PubMed:19801555). Cysteine and homocysteine cannot substitute for glutathione in this reaction (PubMed:19801555).

Gene Wiki entry for MMACHC Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MMACHC Gene

Genomics for MMACHC Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for MMACHC Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MMACHC on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MMACHC

Top Transcription factor binding sites by QIAGEN in the MMACHC gene promoter:
  • ARP-1
  • C/EBPbeta
  • CBF(2)
  • E47
  • Msx-1
  • MZF-1
  • NF-Y
  • SRF
  • SRF (504 AA)
  • ZID

Genomic Locations for MMACHC Gene

Latest Assembly
chr1:45,500,229-45,513,382
(GRCh38/hg38)
Size:
13,154 bases
Orientation:
Plus strand

Previous Assembly
chr1:45,965,972-45,979,054
(GRCh37/hg19 by Entrez Gene)
Size:
13,083 bases
Orientation:
Plus strand

chr1:45,965,725-45,976,739
(GRCh37/hg19 by Ensembl)
Size:
11,015 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:
    Cyanocobalamin reductase / alkylcobalamin dealkylase
    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;
    Cofactor:
    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). Interacts with LMBRD1 and ABCD4; the interaction ensures the transport of cobalamin from the lysosome to the cytoplasm (PubMed:25535791). Forms a multiprotein complex with MMADHC, MTR and MTRR; the interaction with MTR could modulate MMACHC-dependent processing of cobalamin (PubMed:27771510). Heterodimer with MMADHC; the interaction might play a role in the regulation of the balance between AdoCbl and MeCbl synthesis (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

Gene Families for MMACHC Gene

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

Protein Domains for MMACHC Gene

InterPro:

Suggested Antigen Peptide Sequences for MMACHC Gene

GenScript: Design optimal peptide antigens:
  • Methylmalonic aciduria and homocystinuria type C protein (MMAC_HUMAN)

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

Function for MMACHC Gene

Molecular function for MMACHC Gene

UniProtKB/Swiss-Prot Function:
Cobalamin (vitamin B12) cytosolic chaperone that catalyzes the reductive decyanation of cyanocob(III)alamin (cyanocobalamin, CNCbl) to yield cob(II)alamin and cyanide, using FAD or FMN as cofactors and NADPH as cosubstrate (PubMed:18779575, PubMed:19700356, PubMed:21697092, PubMed:25809485). Cyanocobalamin constitutes the inactive form of vitamin B12 introduced from the diet, and is converted into the active cofactors methylcobalamin (MeCbl) involved in methionine biosynthesis, and 5'-deoxyadenosylcobalamin (AdoCbl) involved in the TCA cycle (PubMed:19801555). Forms a complex with the lysosomal transporter ABCD4 and its chaperone LMBRD1, to transport cobalamin across the lysosomal membrane into the cytosol (PubMed:25535791). The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR (methionine synthase) which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (PubMed:21071249, PubMed:27771510). Also acts as a glutathione transferase by catalyzing the dealkylation of the alkylcob(III)alamins MeCbl and AdoCbl, using the thiolate of glutathione for nucleophilic displacement to generate cob(I)alamin and the corresponding glutathione thioether (PubMed:19801555, PubMed:21697092, PubMed:22642810, PubMed:25809485). The conversion of incoming MeCbl or AdoCbl into a common intermediate cob(I)alamin is necessary to meet the cellular needs for both cofactors (PubMed:19801555). Cysteine and homocysteine cannot substitute for glutathione in this reaction (PubMed:19801555).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=2 [cyanocobalamin reductase]-cob(II)alamin + 2 hydrogen cyanide + NADP(+) = 2 apo--[cyanocobalamin reductase] + 2 cyanocob(III)alamin + H(+) + NADPH; Xref=Rhea:RHEA:16113, Rhea:RHEA-COMP:14717, Rhea:RHEA-COMP:14718, ChEBI:CHEBI:15378, ChEBI:CHEBI:16304, ChEBI:CHEBI:17439, ChEBI:CHEBI:18407, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:83228; EC=1.16.1.6; Evidence={ECO:0000269|PubMed:18779575, ECO:0000269|PubMed:19700356, ECO:0000269|PubMed:21697092, ECO:0000269|PubMed:25809485};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=an alkylcob(III)alamin + apo--[alkylcobalamin reductase] + glutathione = an S-substituted glutathione + cob(I)alamin--[alkylcobalamin reductase] + H(+); Xref=Rhea:RHEA:40719, Rhea:RHEA-COMP:14730, Rhea:RHEA-COMP:14731, ChEBI:CHEBI:15378, ChEBI:CHEBI:57925, ChEBI:CHEBI:60488, ChEBI:CHEBI:83228, ChEBI:CHEBI:90779, ChEBI:CHEBI:140785; EC=2.5.1.151; Evidence={ECO:0000269|PubMed:19801555, ECO:0000269|PubMed:21697092, ECO:0000269|PubMed:22642810, ECO:0000269|PubMed:25809485};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=apo--[alkylcobalamin reductase] + glutathione + methylcob(III)alamin = cob(I)alamin--[alkylcobalamin reductase] + H(+) + S-methyl glutathione; Xref=Rhea:RHEA:63132, Rhea:RHEA-COMP:14730, Rhea:RHEA-COMP:14731, ChEBI:CHEBI:15378, ChEBI:CHEBI:28115, ChEBI:CHEBI:57925, ChEBI:CHEBI:60488, ChEBI:CHEBI:83228, ChEBI:CHEBI:141467; EC=2.5.1.151; Evidence={ECO:0000269|PubMed:19801555, ECO:0000269|PubMed:22642810, ECO:0000269|PubMed:25809485};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=adenosylcob(III)alamin + apo--[alkylcobalamin reductase] + glutathione = cob(I)alamin--[alkylcobalamin reductase] + H(+) + S-adenosylglutathione; Xref=Rhea:RHEA:63136, Rhea:RHEA-COMP:14730, Rhea:RHEA-COMP:14731, ChEBI:CHEBI:15378, ChEBI:CHEBI:18408, ChEBI:CHEBI:57925, ChEBI:CHEBI:60488, ChEBI:CHEBI:83228, ChEBI:CHEBI:146184; EC=2.5.1.151; Evidence={ECO:0000269|PubMed:19801555};.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=27.7 uM for glutathione {ECO:0000269|PubMed:19801555}; Note=kcat is 11.7 h(-1) for the dealkylation of methylcobalamin (MeCbl) (PubMed:19801555). kcat is 0.006 h(-1) for the dealkylation of 5'-deoxyadenosylcobalamin (AdoCbl) (PubMed:19801555). {ECO:0000269|PubMed:19801555};

Enzyme Numbers (IUBMB) for MMACHC Gene

Phenotypes From GWAS Catalog 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 IEA,TAS --
GO:0016740 transferase activity IEA --
GO:0031419 cobalamin binding IEA --
GO:0032451 demethylase activity IBA,IDA 19801555
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:
  • Mmachc Mmachc<tm1.1(NCOM)Mfgc>

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MMACHC

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, cytosol.

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
nucleus 3
plasma membrane 2
mitochondrion 2
extracellular 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
  • Cytosol (2)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MMACHC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA,IDA 23270877
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 IBA,TAS --
GO:0009236 cobalamin biosynthetic process IEA --
GO:0055114 oxidation-reduction process IEA --
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 463
Cyanocobalamin Approved Nutra Target, cofactor 465
Cobalt Approved, Experimental Pharma 212
Cobalamin Experimental Pharma 465
genes like me logo Genes that share compounds with MMACHC: view

Transcripts for MMACHC Gene

mRNA/cDNA for MMACHC Gene

2 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MMACHC

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

No ASD Table

Relevant External Links for MMACHC Gene

GeneLoc Exon Structure for
MMACHC

Expression for MMACHC Gene

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

  • Lung (Respiratory System)

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

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for 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(4.5)
  • Nervous system(4.4)
  • Lung(4)
  • Kidney(2)

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
Regions:
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 for research

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 29 30
  • 99.41 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia MMACHC 29 30
  • 88.45 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia -- 30
  • 88 (a)
OneToMany
MMACHC 29
  • 86.36 (n)
-- 30
  • 85 (a)
OneToMany
Rat
(Rattus norvegicus)
Mammalia Mmachc 29
  • 83.69 (n)
Mouse
(Mus musculus)
Mammalia Mmachc 29 16 30
  • 82.56 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 72 (a)
OneToMany
-- 30
  • 72 (a)
OneToMany
Oppossum
(Monodelphis domestica)
Mammalia MMACHC 30
  • 71 (a)
OneToOne
Chicken
(Gallus gallus)
Aves MMACHC 29 30
  • 63.55 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia MMACHC 30
  • 56 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia mmachc 29
  • 58.85 (n)
Str.14656 29
Zebrafish
(Danio rerio)
Actinopterygii mmachc 29 30
  • 58.87 (n)
OneToOne
wufc29d04 29
Worm
(Caenorhabditis elegans)
Secernentea cblc-1 29 30
  • 48.67 (n)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 44 (a)
OneToOne
Species where no ortholog for MMACHC was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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 Vase (Ciona intestinalis)
  • 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)
Aminode:
Evolutionary constrained regions (ECRs) for MMACHC: view image
Alliance of Genome Resources:
Additional Orthologs for MMACHC

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, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MMACHC Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
1023220 Uncertain Significance: Cobalamin C disease 45,509,009(+) T/C
NM_015506.3(MMACHC):c.643T>C (p.Tyr215His)
MISSENSE
1035324 Uncertain Significance: Cobalamin C disease 45,509,053(+) A/G
NM_015506.3(MMACHC):c.687A>G (p.Gln229=)
SYNONYMOUS
1047063 Uncertain Significance: Cobalamin C disease 45,507,419(+) G/C
NM_015506.3(MMACHC):c.145G>C (p.Ala49Pro)
MISSENSE_VARIANT,FIVE_PRIME_UTR
834511 Uncertain Significance: Cobalamin C disease 45,508,283(+) GGCCCAGACAGCA/G
NM_015506.3(MMACHC):c.354_365del (p.Gln118_Ala121del)
INFRAME_DELETION
848845 Pathogenic: Cobalamin C disease 45,508,983(+) G/A
NM_015506.3(MMACHC):c.617G>A (p.Arg206Gln)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for MMACHC Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

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)

Additional Variant Information for MMACHC Gene

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

SNP Genotyping and Copy Number Assays for research

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

Disorders for MMACHC Gene

MalaCards: The human disease database

(27) MalaCards diseases for MMACHC Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
methylmalonic aciduria and homocystinuria, cblc type
  • mahcc
disorders of intracellular cobalamin metabolism
methylmalonic acidemia with homocystinuria
  • methylmalonic acidemia and homocystinemia
homocystinuria
  • cbs deficiency
methylmalonic aciduria due to methylmalonyl-coa mutase deficiency
  • methylmalonic acidemia due to methylmalonyl-coa mutase deficiency
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

MMAC_HUMAN
  • Methylmalonic aciduria and homocystinuria, cblC type (MAHCC) [MIM:277400]: An autosomal recessive 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 variants affecting the gene represented in this entry.

Additional Disease Information for MMACHC

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Publications for MMACHC Gene

  1. Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type. (PMID: 16311595) Lerner-Ellis JP … Rosenblatt DS (Nature genetics 2006) 2 3 4 22 25 72
  2. Mechanism of vitamin B12-responsiveness in cblC methylmalonic aciduria with homocystinuria. (PMID: 19700356) Froese DS … Gravel RA (Molecular genetics and metabolism 2009) 2 3 4 22 72
  3. Spectrum of mutations in MMACHC, allelic expression, and evidence for genotype-phenotype correlations. (PMID: 19370762) Lerner-Ellis JP … Fowler B (Human mutation 2009) 3 22 40 72
  4. Late-onset cobalamin-C disorder: a challenging diagnosis. (PMID: 17431913) Ben-Omran TI … Feigenbaum A (American journal of medical genetics. Part A 2007) 3 22 25 72
  5. Structure of MMACHC reveals an arginine-rich pocket and a domain-swapped dimer for its B12 processing function. (PMID: 22642810) Froese DS … Yue WW (Biochemistry 2012) 3 4 72

Products for MMACHC Gene

Sources for MMACHC Gene