Disorders of Intracellular Cobalamin Metabolism: genes and variants
Disorders of Intracellular Cobalamin Metabolism is linked to 2 analyzed proteins (MMACHC and MMADHC). 1 DNA variants are known to cause it; 25 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Disorders of Intracellular Cobalamin Metabolism
MMACHC: Cyanocobalamin reductase / alkylcobalamin dealkylase
It processes intracellular cobalamin so that vitamin B12 can be converted into the active cofactors needed for methionine synthase and methylmalonyl-CoA mutase. Biallelic loss causes cblC disease, with combined methylmalonic acidemia and homocystinuria and highly variable neurologic and systemic manifestations.
1 disease-causing and 16 uncertain variants in MMACHC are linked to Disorders of Intracellular Cobalamin Metabolism.
MMADHC: Cobalamin trafficking protein CblD
It directs intracellular cobalamin toward the methylcobalamin and adenosylcobalamin pathways needed for methionine and methylmalonyl-CoA metabolism. Biallelic pathogenic variants cause cblD disease, producing isolated or combined methylmalonic acidemia and homocystinuria.
0 disease-causing and 9 uncertain variants in MMADHC are linked to Disorders of Intracellular Cobalamin Metabolism.
Known disease-causing variants in Disorders of Intracellular Cobalamin Metabolism
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| MMACHC G147A | 147 | Disease-causing (★★) |
Same protein, different disease
- Cobalamin C disease is also caused by MMACHC variants; they fall mostly in different places as the Disorders of Intracellular Cobalamin Metabolism variants (40 disease-causing).
Diseases related to Disorders of Intracellular Cobalamin Metabolism
- Cobalamin C disease, also linked to MMACHC and MMADHC
- Methylmalonic aciduria and homocystinuria type cblD, also linked to MMADHC
Frequently asked questions
Which genes are linked to Disorders of Intracellular Cobalamin Metabolism?
In CATVariant, Disorders of Intracellular Cobalamin Metabolism is linked to 2 analyzed proteins: MMACHC (Cyanocobalamin reductase / alkylcobalamin dealkylase) and MMADHC (Cobalamin trafficking protein CblD).
How many genetic variants are linked to Disorders of Intracellular Cobalamin Metabolism?
34 variants: 1 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 25 are of uncertain significance or have conflicting reports.
Which uncertain variants in Disorders of Intracellular Cobalamin Metabolism look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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