Human Gene MMADHC (uc002txc.3)
  Description: Homo sapiens methylmalonic aciduria (cobalamin deficiency) cblD type, with homocystinuria (MMADHC), nuclear gene encoding mitochondrial protein, mRNA.
RefSeq Summary (NM_015702): 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].
Transcript (Including UTRs)
   Position: hg19 chr2:150,426,147-150,444,330 Size: 18,184 Total Exon Count: 8 Strand: -
Coding Region
   Position: hg19 chr2:150,426,488-150,443,611 Size: 17,124 Coding Exon Count: 7 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviews
Model InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:150,426,147-150,444,330)mRNA (may differ from genome)Protein (296 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: MMAD_HUMAN
DESCRIPTION: RecName: Full=Methylmalonic aciduria and homocystinuria type D protein, mitochondrial; Flags: Precursor;
FUNCTION: Involved in cobalamin metabolism.
SUBCELLULAR LOCATION: Mitochondrion (Potential).
TISSUE SPECIFICITY: Widely expressed at high levels.
DISEASE: Defects in MMADHC are the cause of methylmalonic aciduria and homocystinuria type cblD (MMAHCD) [MIM:277410]. A 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).
SEQUENCE CAUTION: Sequence=AAG43124.1; Type=Frameshift; Positions=171, 178, 185, 188, 200;
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MMADHC";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): MMADHC
CDC HuGE Published Literature: MMADHC
Positive Disease Associations: Alcoholism , Erythrocyte Count , Menopause , Prostatic Neoplasms , Sleep
Related Studies:
  1. Alcoholism
    Andrew C Heath et al. Biological psychiatry 2011, A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications., Biological psychiatry. [PubMed 21529783]
    We conclude that 1) meta-analyses of consumption data may contribute usefully to gene discovery; 2) translation of human alcoholism GWAS results to drug discovery or clinically useful prediction of risk will be challenging; and 3) through accumulation across studies, GWAS data may become valuable for improved genetic risk differentiation in research in biological psychiatry (e.g., prospective high-risk or resilience studies).
  2. Erythrocyte Count
    , , . [PubMed 0]
  3. Menopause
    Lisette Stolk et al. Nature genetics 2009, Loci at chromosomes 13, 19 and 20 influence age at natural menopause., Nature genetics. [PubMed 19448619]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: MMADHC
Diseases sorted by gene-association score: methylmalonic aciduria and homocystinuria, cbld type* (1570), methylmalonic acidemia with homocystinuria type cbld* (700), mmadhc-related methylmalonic acidemia* (100), homocystinuria (51), transcobalamin ii deficiency (6), megaloblastic anemia (6), methylmalonic acidemia (5), vitamin metabolic disorder (5), organic acidemia (5)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 52.92 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 1394.73 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -73.30205-0.358 Picture PostScript Text
3' UTR -67.10341-0.197 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR019362 - MMADHC

Pfam Domains:
PF10229 - Methylmalonic aciduria and homocystinuria type D protein

ModBase Predicted Comparative 3D Structure on Q9H3L0
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene DetailsGene Details Gene DetailsGene Details 
Gene SorterGene Sorter Gene SorterGene Sorter 
 RGDEnsemblFlyBaseWormBase 
 Protein SequenceProtein SequenceProtein SequenceProtein Sequence 
 AlignmentAlignmentAlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding

Biological Process:
GO:0009108 coenzyme biosynthetic process
GO:0009235 cobalamin metabolic process

Cellular Component:
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005829 cytosol


-  Descriptions from all associated GenBank mRNAs
  KJ898680 - Synthetic construct Homo sapiens clone ccsbBroadEn_08074 MMADHC gene, encodes complete protein.
KR709430 - Synthetic construct Homo sapiens clone CCSBHm_00002106 MMADHC (MMADHC) mRNA, encodes complete protein.
KR709431 - Synthetic construct Homo sapiens clone CCSBHm_00002108 MMADHC (MMADHC) mRNA, encodes complete protein.
KR709432 - Synthetic construct Homo sapiens clone CCSBHm_00002109 MMADHC (MMADHC) mRNA, encodes complete protein.
KR709433 - Synthetic construct Homo sapiens clone CCSBHm_00002111 MMADHC (MMADHC) mRNA, encodes complete protein.
AF131802 - Homo sapiens clone 25022 mRNA sequence, complete cds.
LP895410 - Sequence 274 from Patent EP3253886.
BC023995 - Homo sapiens methylmalonic aciduria (cobalamin deficiency) cblD type, with homocystinuria, mRNA (cDNA clone MGC:24534 IMAGE:4103877), complete cds.
AF161510 - Homo sapiens HSPC161 mRNA, complete cds.
BC000932 - Homo sapiens methylmalonic aciduria (cobalamin deficiency) cblD type, with homocystinuria, mRNA (cDNA clone MGC:4901 IMAGE:3446713), complete cds.
AF060224 - Homo sapiens clone 010b06 My011 protein mRNA, complete cds.
BC022859 - Homo sapiens methylmalonic aciduria (cobalamin deficiency) cblD type, with homocystinuria, mRNA (cDNA clone MGC:22822 IMAGE:3826071), complete cds.
BC010894 - Homo sapiens methylmalonic aciduria (cobalamin deficiency) cblD type, with homocystinuria, mRNA (cDNA clone MGC:13355 IMAGE:4246499), complete cds.
AK310001 - Homo sapiens cDNA, FLJ17043.
AK313284 - Homo sapiens cDNA, FLJ93796.
JD020257 - Sequence 1281 from Patent EP1572962.
JD024098 - Sequence 5122 from Patent EP1572962.
JD033676 - Sequence 14700 from Patent EP1572962.
JD022647 - Sequence 3671 from Patent EP1572962.
JD034699 - Sequence 15723 from Patent EP1572962.
JD024149 - Sequence 5173 from Patent EP1572962.
JD023897 - Sequence 4921 from Patent EP1572962.
JD029171 - Sequence 10195 from Patent EP1572962.
JD019372 - Sequence 396 from Patent EP1572962.
JD035407 - Sequence 16431 from Patent EP1572962.
JD024510 - Sequence 5534 from Patent EP1572962.
JD023802 - Sequence 4826 from Patent EP1572962.
JD030691 - Sequence 11715 from Patent EP1572962.
JD033890 - Sequence 14914 from Patent EP1572962.
JD200387 - Sequence 181411 from Patent EP1572962.
JD318717 - Sequence 299741 from Patent EP1572962.
JD538600 - Sequence 519624 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q9H3L0 (Reactome details) participates in the following event(s):

R-HSA-3149494 MMACHC:cob(II)alamin binds MMADHC
R-HSA-196741 Cobalamin (Cbl, vitamin B12) transport and metabolism
R-HSA-196849 Metabolism of water-soluble vitamins and cofactors
R-HSA-3359473 Defective MMADHC causes methylmalonic aciduria and homocystinuria type cblD
R-HSA-196854 Metabolism of vitamins and cofactors
R-HSA-3296469 Defects in cobalamin (B12) metabolism
R-HSA-1430728 Metabolism
R-HSA-3296482 Defects in vitamin and cofactor metabolism
R-HSA-5668914 Diseases of metabolism
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: B2R895, C2orf25, CL25022, D3DP91, HSPC161, MMAD_HUMAN, My011, NM_015702, NP_056517, O95891, Q9H3L0
UCSC ID: uc002txc.3
RefSeq Accession: NM_015702
Protein: Q9H3L0 (aka MMAD_HUMAN)
CCDS: CCDS2189.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene MMADHC:
cbl (Disorders of Intracellular Cobalamin Metabolism)
dystonia-ov (Hereditary Dystonia Overview)
mma (Isolated Methylmalonic Acidemia)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_015702.2
exon count: 8CDS single in 3' UTR: no RNA size: 1466
ORF size: 891CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1934.00frame shift in genome: no % Coverage: 98.02
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.