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
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";
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).
Menopause Lisette Stolk et al. Nature genetics 2009, Loci at chromosomes 13, 19 and 20 influence age at natural menopause., Nature genetics.
[PubMed 19448619]
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.
Pfam Domains: PF10229 - Methylmalonic aciduria and homocystinuria type D protein
ModBase Predicted Comparative 3D Structure on Q9H3L0
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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.
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