This gene encodes a mitochondrial protein that is involved in an early step of vitamin B12 metabolism. Vitamin B12 (cobalamin) is essential for normal development and survival in humans. Mutations in this gene cause methylmalonic aciduria and homocystinuria type cblD (MMADHC), a disorder of cobalamin metabolism that is characterized by decreased levels of the coenzymes adenosyl... See more...

Aliases for MMADHC Gene

Aliases for MMADHC Gene

  • Metabolism Of Cobalamin Associated D 2 3 5
  • CL25022 2 3 4
  • CblD 2 3 4
  • Methylmalonic Aciduria (Cobalamin Deficiency) CblD Type, With Homocystinuria 2 3
  • Methylmalonic Aciduria And Homocystinuria Type D Protein, Mitochondrial 3 4
  • Cobalamin Trafficking Protein CblD 3 4
  • C2orf25 3 4
  • Methylmalonic Aciduria And Homocystinuria, CblD Type 2
  • Chromosome 2 Open Reading Frame 25 2
  • Protein C2orf25, Mitochondrial 3
  • MMADHC 5

External Ids for MMADHC Gene

Previous HGNC Symbols for MMADHC Gene

  • C2orf25

Previous GeneCards Identifiers for MMADHC Gene

  • GC02M150135
  • GC02M150426
  • GC02M142325

Summaries for MMADHC Gene

Entrez Gene Summary for MMADHC Gene

  • This gene encodes a mitochondrial protein that is involved in an early step of vitamin B12 metabolism. Vitamin B12 (cobalamin) is essential for normal development and survival in humans. Mutations in this gene cause methylmalonic aciduria and homocystinuria type cblD (MMADHC), a disorder of cobalamin metabolism that is characterized by decreased levels of the coenzymes adenosylcobalamin and methylcobalamin. Pseudogenes have been identified on chromosomes 11 and X.[provided by RefSeq, Nov 2008]

GeneCards Summary for MMADHC Gene

MMADHC (Metabolism Of Cobalamin Associated D) is a Protein Coding gene. Diseases associated with MMADHC include Methylmalonic Aciduria And Homocystinuria, Cbld Type and Methylmalonic Acidemia Without Homocystinuria. Among its related pathways are Metabolism of water-soluble vitamins and cofactors and Cobalamin (Cbl, vitamin B12) transport and metabolism.

UniProtKB/Swiss-Prot Summary for MMADHC Gene

  • Involved in cobalamin metabolism and trafficking (PubMed:18385497, PubMed:23415655, PubMed:24722857, PubMed:26364851). Plays a role in regulating the biosynthesis and the proportion of two coenzymes, methylcob(III)alamin (MeCbl) and 5'-deoxyadenosylcobalamin (AdoCbl) (PubMed:18385497,PubMed:23415655, PubMed:24722857). Promotes oxidation of cob(II)alamin bound to MMACHC (PubMed:26364851). 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:27771510).

Gene Wiki entry for MMADHC Gene

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

Genomics for MMADHC Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for MMADHC 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
GH02J149585 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 250.7 +1.0 978 3.6 ZNF207 ZNF600 MYC SSRP1 ZNF580 ZNF592 KLF9 POLR2A CEBPA YY1 MMADHC MMADHC-DT lnc-RND3-7 HSALNG0019536 LYPD6
GH02J149566 Enhancer 0.3 Ensembl 11.4 +20.9 20877 0.2 POLR2A MMADHC HSALNG0019536 MMADHC-DT LYPD6
GH02J149617 Enhancer 0.3 Ensembl 11 -29.6 -29623 1.2 JUND MMADHC HSALNG0019539 RF00026-561 RNU6-601P MMADHC-DT RND3
GH02J149536 Enhancer 0.5 Ensembl 4.9 +50.8 50778 0.8 PRDM6 ZNF398 SP7 ZNF629 OSR2 MZF1 ZBTB17 HSALNG0019534 MMADHC HSALNG0019535 LYPD6
GH02J149563 Enhancer 0.2 Ensembl 11.6 +24.0 23977 0.8 HSALNG0019536 MMADHC MMADHC-DT LYPD6 HSALNG0019534
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

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

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

Top Transcription factor binding sites by QIAGEN in the MMADHC gene promoter:
  • AML1a
  • IRF-2
  • MyoD
  • Pax-2
  • Pax-2a
  • Pax-2b
  • STAT5A

Genomic Locations for MMADHC Gene

Latest Assembly
chr2:149,569,637-149,587,778
(GRCh38/hg38)
Size:
18,142 bases
Orientation:
Minus strand

Previous Assembly
chr2:150,426,151-150,444,289
(GRCh37/hg19 by Entrez Gene)
Size:
18,139 bases
Orientation:
Minus strand

chr2:150,426,148-150,444,330
(GRCh37/hg19 by Ensembl)
Size:
18,183 bases
Orientation:
Minus strand

Genomic View for MMADHC Gene

Genes around MMADHC on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for MMADHC Gene

Proteins for MMADHC Gene

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

    Protein Symbol:
    Q9H3L0-MMAD_HUMAN
    Recommended name:
    Cobalamin trafficking protein CblD
    Protein Accession:
    Q9H3L0
    Secondary Accessions:
    • B2R895
    • D3DP91
    • O95891

    Protein attributes for MMADHC Gene

    Size:
    296 amino acids
    Molecular mass:
    32940 Da
    Quaternary structure:
    • Heterodimer with MMACHC. Forms a multiprotein complex with MMACHC, MTR and MTRR (PubMed:27771510).
    SequenceCaution:
    • Sequence=AAG43124.1; Type=Frameshift; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for MMADHC Gene

neXtProt entry for MMADHC Gene

Post-translational modifications for MMADHC Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for MMADHC Gene

No data available for DME Specific Peptides for MMADHC Gene

Domains & Families for MMADHC Gene

Gene Families for MMADHC Gene

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

Protein Domains for MMADHC Gene

InterPro:

Suggested Antigen Peptide Sequences for MMADHC Gene

GenScript: Design optimal peptide antigens:
  • Methylmalonic aciduria and homocystinuria type D protein, mitochondrial (MMAD_HUMAN)
genes like me logo Genes that share domains with MMADHC: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for MMADHC Gene

Function for MMADHC Gene

Molecular function for MMADHC Gene

UniProtKB/Swiss-Prot Function:
Involved in cobalamin metabolism and trafficking (PubMed:18385497, PubMed:23415655, PubMed:24722857, PubMed:26364851). Plays a role in regulating the biosynthesis and the proportion of two coenzymes, methylcob(III)alamin (MeCbl) and 5'-deoxyadenosylcobalamin (AdoCbl) (PubMed:18385497,PubMed:23415655, PubMed:24722857). Promotes oxidation of cob(II)alamin bound to MMACHC (PubMed:26364851). 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:27771510).

Phenotypes From GWAS Catalog for MMADHC Gene

Gene Ontology (GO) - Molecular Function for MMADHC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 23415655
genes like me logo Genes that share ontologies with MMADHC: view
genes like me logo Genes that share phenotypes with MMADHC: view

Human Phenotype Ontology for MMADHC Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Inhibitory RNAs for research

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

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for MMADHC Gene

Localization for MMADHC Gene

Subcellular locations from UniProtKB/Swiss-Prot for MMADHC Gene

Cytoplasm. 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 MMADHC gene
Compartment Confidence
mitochondrion 5
cytosol 4
lysosome 2
plasma membrane 1
extracellular 1
nucleus 1

Gene Ontology (GO) - Cellular Components for MMADHC Gene

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

No data available for Subcellular locations from the Human Protein Atlas (HPA) for MMADHC Gene

Pathways & Interactions for MMADHC Gene

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

Gene Ontology (GO) - Biological Process for MMADHC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0009235 cobalamin metabolic process IEA,TAS --
genes like me logo Genes that share ontologies with MMADHC: view

No data available for SIGNOR curated interactions for MMADHC Gene

Drugs & Compounds for MMADHC Gene

No Compound Related Data Available

Transcripts for MMADHC Gene

mRNA/cDNA for MMADHC Gene

1 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
4 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 MMADHC

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

ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b · 5c ^ 6 ^ 7a · 7b ^ 8 ^ 9a · 9b
SP1: - - -
SP2:
SP3: - -
SP4: - -
SP5: -
SP6: - -

Relevant External Links for MMADHC Gene

GeneLoc Exon Structure for
MMADHC

Expression for MMADHC Gene

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MMADHC Gene

This gene is overexpressed in Bone (17.1), Tlymphocyte (16.8), Neutrophil (15.2), Pancreas (12.3), and Monocytes (7.3).

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



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MMADHC

SOURCE GeneReport for Unigene cluster for MMADHC Gene:

Hs.5324

mRNA Expression by UniProt/SwissProt for MMADHC Gene:

Q9H3L0-MMAD_HUMAN
Tissue specificity: Widely expressed at high levels.

Evidence on tissue expression from TISSUES for MMADHC Gene

  • Nervous system(4.9)
  • Kidney(4.8)
  • Muscle(4.7)
  • Skin(4.6)
  • Blood(4.5)
  • Intestine(3.1)
  • Liver(2.9)
  • Heart(2.4)
  • Stomach(2.1)
  • Lung(2)

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

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • cardiovascular
  • integumentary
  • nervous
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • eye
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • neck
  • skull
Thorax:
  • chest wall
  • clavicle
  • rib
  • rib cage
  • scapula
  • sternum
Pelvis:
  • pelvis
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
  • red blood cell
  • skin
  • spinal column
  • spinal cord
  • vertebrae
genes like me logo Genes that share expression patterns with MMADHC: view

Primer products for research

No data available for mRNA differential expression in normal tissues and Protein tissue co-expression partners for MMADHC Gene

Orthologs for MMADHC Gene

This gene was present in the common ancestor of animals.

Orthologs for MMADHC Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia MMADHC 29 30
  • 99.66 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia MMADHC 29 30
  • 94.03 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia -- 30
  • 93 (a)
OneToMany
MMADHC 29
  • 92.23 (n)
-- 30
  • 85 (a)
OneToMany
Mouse
(Mus musculus)
Mammalia Mmadhc 29 16 30
  • 89.08 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia MMADHC 30
  • 89 (a)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Mmadhc 29
  • 88.29 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia MMADHC 30
  • 70 (a)
OneToOne
Chicken
(Gallus gallus)
Aves MMADHC 29 30
  • 78.27 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia MMADHC 30
  • 80 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia mmadhc 29
  • 71.9 (n)
Str.15175 29
African clawed frog
(Xenopus laevis)
Amphibia Xl.7731 29
Zebrafish
(Danio rerio)
Actinopterygii mmadhc 30
  • 63 (a)
OneToMany
zgc:92335 29
  • 58.36 (n)
MMADHC (2 of 2) 30
  • 52 (a)
OneToMany
Dr.29137 29
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.380 29
Fruit Fly
(Drosophila melanogaster)
Insecta CG12118 30
  • 21 (a)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea Y76A2B.5 29 30
  • 51.07 (n)
OneToOne
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.6866 30
  • 43 (a)
OneToOne
Species where no ortholog for MMADHC was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • 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)
  • 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 MMADHC Gene

ENSEMBL:
Gene Tree for MMADHC (if available)
TreeFam:
Gene Tree for MMADHC (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MMADHC: view image
Alliance of Genome Resources:
Additional Orthologs for MMADHC

Paralogs for MMADHC Gene

(20) SIMAP similar genes for MMADHC Gene using alignment to 2 proteins:

  • MMAD_HUMAN
  • F8WEC0_HUMAN

Pseudogenes.org Pseudogenes for MMADHC Gene

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

No data available for Paralogs for MMADHC Gene

Variants for MMADHC Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MMADHC Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
1008950 Uncertain Significance: Methylmalonic acidemia with homocystinuria cblD 149,575,705(-) A/G
NM_015702.3(MMADHC):c.609+6T>C
INTRON
1016695 Uncertain Significance: Methylmalonic acidemia with homocystinuria cblD 149,576,501(-) T/G
NM_015702.3(MMADHC):c.414A>C (p.Glu138Asp)
MISSENSE
1031933 Uncertain Significance: Methylmalonic acidemia with homocystinuria cblD 149,576,509(-) T/C
NM_015702.3(MMADHC):c.406A>G (p.Ser136Gly)
MISSENSE
1038306 Uncertain Significance: Methylmalonic acidemia with homocystinuria cblD 149,582,129(-) A/G
NM_015702.3(MMADHC):c.152T>C (p.Ile51Thr)
MISSENSE
203838 Uncertain Significance: Methylmalonic aciduria with homocystinuria cblD type; Methylmalonic acidemia with homocystinuria cblD; Disorders of Intracellular Cobalamin Metabolism 149,582,208(-) C/A
NM_015702.3(MMADHC):c.73G>T (p.Val25Phe)
MISSENSE

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

Variant ID Type Subtype PubMed ID
nsv834409 CNV gain 17160897

Variation tolerance for MMADHC Gene

Residual Variation Intolerance Score: 68.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.74; 57.74% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MMADHC Gene

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

SNP Genotyping and Copy Number Assays for research

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

Disorders for MMADHC Gene

MalaCards: The human disease database

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

Disorder Aliases PubMed IDs
methylmalonic aciduria and homocystinuria, cbld type
  • mahcd
methylmalonic acidemia without homocystinuria
  • methylmalonic aciduria without homocystinuria
homocystinuria
  • cbs deficiency
methylmalonic acidemia with homocystinuria
  • methylmalonic acidemia and homocystinemia
methylmalonic aciduria and homocystinuria, cblc type
  • mahcc
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

MMAD_HUMAN
  • Methylmalonic aciduria and homocystinuria, cblD type (MAHCD) [MIM:277410]: An autosomal recessive disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Clinical features include developmental delay, hyotonia, mental retardation, seizures, megaloblastic anemia. Some patients manifest combined methylmalonic aciduria and homocystinuria (referred to as cblD original), some have only isolated homocystinuria (cblD variant 1), and others have only methylmalonic aciduria (cblD variant 2). {ECO:0000269 PubMed:18385497, ECO:0000269 PubMed:24722857, ECO:0000269 PubMed:26483544}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for MMADHC

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with MMADHC: view

No data available for Genatlas for MMADHC Gene

Publications for MMADHC Gene

  1. Gene identification for the cblD defect of vitamin B12 metabolism. (PMID: 18385497) Coelho D … Fowler B (The New England journal of medicine 2008) 2 3 4 72
  2. Mutation of the MMADHC gene in adult-onset cobalamin D deficiency: A report of 2 potentially treatable cases. (PMID: 28939051) Cancho García E … Esteban Durán E (Neurologia (Barcelona, Spain) 2019) 3 72
  3. Methionine synthase and methionine synthase reductase interact with MMACHC and with MMADHC. (PMID: 27771510) Bassila C … Coelho D (Biochimica et biophysica acta. Molecular basis of disease 2017) 3 4
  4. Structural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking. (PMID: 26483544) Froese DS … Yue WW (The Journal of biological chemistry 2015) 3 4
  5. Structure of Human B12 Trafficking Protein CblD Reveals Molecular Mimicry and Identifies a New Subfamily of Nitro-FMN Reductases. (PMID: 26364851) Yamada K … Koutmos M (The Journal of biological chemistry 2015) 3 4

Products for MMADHC Gene

Sources for MMADHC Gene