Seroatlas · Human Serome Atlas

MMADHC

Cobalamin trafficking protein CblD

Also known as: C2orf25, cblD, CL25022, MMAD_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
Q9H3L0
Gene
MMADHC
Ensembl
ENSG00000168288
Chromosome
2
Canonical length
296 aa
Protein class
Disease related genes, Human disease related genes, Predicted intracellular proteins

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

296 residues, UniProt reviewed canonical sequence.

>Q9H3L0|MMADHC
     1  MANVLCNRAR LVSYLPGFCS LVKRVVNPKA FSTAGSSGSD ESHVAAAPPD ICSRTVWPDE
    61  TMGPFGPQDQ RFQLPGNIGF DCHLNGTASQ KKSLVHKTLP DVLAEPLSSE RHEFVMAQYV
   121  NEFQGNDAPV EQEINSAETY FESARVECAI QTCPELLRKD FESLFPEVAN GKLMILTVTQ
   181  KTKNDMTVWS EEVEIEREVL LEKFINGAKE ICYALRAEGY WADFIDPSSG LAFFGPYTNN
   241  TLFETDERYR HLGFSVDDLG CCKVIRHSLW GTHVVVGSIF TNATPDSHIM KKLSGN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MMADHC can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Intracellular
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.41
Highest tissue expression
198 nTPM

Expression across tissuesHPA

Tissue

  • skeletal muscle: 198 nTPM
  • liver: 182 nTPM
  • tongue: 175 nTPM
  • bone marrow: 136 nTPM
  • heart muscle: 107 nTPM
  • kidney: 91 nTPM

Single-cell type

  • esophageal apical cells: 440 nCPM
  • late primary spermatocytes: 366 nCPM
  • syncytiotrophoblasts: 289 nCPM
  • parietal cells: 230 nCPM
  • extravillous trophoblasts: 225 nCPM
  • esophageal suprabasal cells: 220 nCPM

Immune cell

  • basophil: 184 nTPM
  • neutrophil: 151 nTPM
  • eosinophil: 130 nTPM
  • T-reg: 124 nTPM
  • NK-cell: 120 nTPM
  • total PBMC: 120 nTPM

Brain region

  • choroid plexus: 41 nTPM
  • white matter: 36 nTPM
  • cerebellum: 34 nTPM
  • spinal cord: 34 nTPM
  • hypothalamus: 32 nTPM
  • cerebral cortex: 32 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MMADHC.

Disease | AllUniProt

Conditions MMADHC is implicated in, by any mechanism.

  • Methylmalonic aciduria and homocystinuria, cblD type (MAHCD) MIM:277410
  • Homocystinuria-megaloblastic anemia, cblD type (HMAD) MIM:620952
  • Methylmalonic aciduria, cblD type (MACD) MIM:620953

Disease | GeneticClinVar

70 pathogenic / likely-pathogenic of 412 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Methylmalonic aciduria and homocystinuria type cblD
  • Cobalamin C disease
  • Homocystinuria-megaloblastic anemia cblD type
  • Isolated methylmalonic aciduria cblD type
  • See cases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.99
gnomAD pLI
0
gnomAD missense Z
-0.41
DepMap mean gene effect
-0.09
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

  • Methylmalonic aciduria and homocystinuria type D protein
  • Methylmalonic aciduria and homocystinuria type D protein

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads MMADHC as an antibody target. Whether an autoantibody or antibody against MMADHC could matter depends on whether native MMADHC is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

MMADHC is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label MMADHC as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/MMADHC. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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