Component

Human MMACHC gene

Human MMACHC gene

4 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Fibroblasts from three cblC patients had little or no conversion of cobalt-57-labeled propylcobalamin into adenosylcobalamin and methylcobalamin, whereas control skin fibroblasts converted the probe.

    Human MMACHC gene → Propylcobalamin source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    evidence_location
    Abstract; indexed Methods: Assessment of dealkylation; Discussion
    experimental_model
    Human control and cblC patient fibroblast labeling
    exposure
    0.125 nM cobalt-57 propylcobalamin for 48 hours
    limitations
    Propylcobalamin is a synthetic C3 probe; patients and genotypes differ and this comparison does not quantify every natural vitamer response.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    A synthetic B12 probe exposed the processing defect in patient cells.
    primary_references
    [hannibal-2009-cell-processing] Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product (2009). https://pubmed.ncbi.nlm.nih.gov/19447654/ DOI: 10.1016/j.ymgme.2009.04.005
    tissue_or_cell_type
    Skin fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 809–821

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human control and cblC patient fibroblast labeling · source_derived_draft · unverified_draft

    ### b12-cblc-propyl-probe Fibroblasts from three cblC patients had little or no conversion of cobalt-57-labeled propylcobalamin into adenosylcobalamin and methylcobalamin, whereas control skin fibroblasts converted the probe. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A synthetic B12 probe exposed the processing defect in patient cells. organism: Homo sapiens tissue_or_cell_type: Skin fibroblasts experimental_model: Human control and cblC patient fibroblast labeling limitations: Propylcobalamin is a synthetic C3 probe; patients and genotypes differ and this comparison does not quantify every natural vitamer response. exposure: 0.125 nM cobalt-57 propylcobalamin for 48 hours cross_nutrient: false evidence_location: Abstract; indexed Methods: Assessment of dealkylation; Discussion [hannibal-2009-cell-processing] Processing of alkylcobalamins in mammalian cells: A role for the MMACHC (cblC) gene product (2009). https://pubmed.ncbi.nlm.nih.gov/19447654/ DOI: 10.1016/j.ymgme.2009.04.005
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. In CHU-12122 epi-cblC fibroblasts, the promoter-hypermethylated paternal MMACHC allele was transcriptionally silent; only the maternal coding-mutant allele was detected in transcripts.

    MMACHC promoter CpG methylation → MMACHC gene transcription source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    evidence_location
    Results: Figures 1, 4–6; Methods: PRDX1 silencing
    experimental_model
    Allele-specific human epi-cblC expression and bisulfite analysis
    exposure
    Paternal secondary epimutation plus maternal c.270_271insA coding variant
    limitations
    Family-specific compound genetic/epigenetic machinery defect; not a nutritional methylation intervention.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    The intact B12-processing allele was switched off by the inherited epigenetic defect.
    primary_references
    [gueant-2018-epi-cblc] A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients (2018). https://pubmed.ncbi.nlm.nih.gov/29302025/ DOI: 10.1038/s41467-017-02306-5
    tissue_or_cell_type
    CHU-12122 fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 921–933

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Allele-specific human epi-cblC expression and bisulfite analysis · source_derived_draft · unverified_draft

    ### b12-mmachc-epi-silencing In CHU-12122 epi-cblC fibroblasts, the promoter-hypermethylated paternal MMACHC allele was transcriptionally silent; only the maternal coding-mutant allele was detected in transcripts. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The intact B12-processing allele was switched off by the inherited epigenetic defect. organism: Homo sapiens tissue_or_cell_type: CHU-12122 fibroblasts experimental_model: Allele-specific human epi-cblC expression and bisulfite analysis limitations: Family-specific compound genetic/epigenetic machinery defect; not a nutritional methylation intervention. exposure: Paternal secondary epimutation plus maternal c.270_271insA coding variant cross_nutrient: false evidence_location: Results: Figures 1, 4–6; Methods: PRDX1 silencing [gueant-2018-epi-cblc] A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients (2018). https://pubmed.ncbi.nlm.nih.gov/29302025/ DOI: 10.1038/s41467-017-02306-5
    Complete structured claim and evidence

  2. PRDX1 splice-acceptor variants c.515-1G>T or c.515-2A>T were linked to exon-6/termination-signal skipping and antisense readthrough across MMACHC in epi-cblC fibroblasts.

    Human PRDX1 gene → PRDX1 readthrough antisense RNA across MMACHC source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    evidence_location
    Results: Figures 1, 4–6; Methods: PRDX1 silencing
    experimental_model
    Human epi-cblC fibroblast RNA-seq and RT-PCR
    exposure
    Inherited PRDX1 splice variants
    limitations
    Specific cis-acting alleles; does not imply ordinary PRDX1 antioxidant activity suppresses B12 processing.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    A neighboring gene’s splice defect made transcription run through the B12-processing gene.
    primary_references
    [gueant-2018-epi-cblc] A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients (2018). https://pubmed.ncbi.nlm.nih.gov/29302025/ DOI: 10.1038/s41467-017-02306-5
    tissue_or_cell_type
    Patient skin fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 907–919

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human epi-cblC fibroblast RNA-seq and RT-PCR · source_derived_draft · unverified_draft

    ### b12-prdx1-readthrough PRDX1 splice-acceptor variants c.515-1G>T or c.515-2A>T were linked to exon-6/termination-signal skipping and antisense readthrough across MMACHC in epi-cblC fibroblasts. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A neighboring gene’s splice defect made transcription run through the B12-processing gene. organism: Homo sapiens tissue_or_cell_type: Patient skin fibroblasts experimental_model: Human epi-cblC fibroblast RNA-seq and RT-PCR limitations: Specific cis-acting alleles; does not imply ordinary PRDX1 antioxidant activity suppresses B12 processing. exposure: Inherited PRDX1 splice variants cross_nutrient: false evidence_location: Results: Figures 1, 4–6; Methods: PRDX1 silencing [gueant-2018-epi-cblc] A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients (2018). https://pubmed.ncbi.nlm.nih.gov/29302025/ DOI: 10.1038/s41467-017-02306-5
    Complete structured claim and evidence

  3. PRDX1-targeting siRNA restored detectable MMACHC expression in WG3838 epi-cblC fibroblasts, unlike control siRNA.

    Human PRDX1 gene → MMACHC gene transcription source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    evidence_location
    Results: Figures 1, 4–6; Methods: PRDX1 silencing
    experimental_model
    Human WG3838 fibroblast siRNA and quantitative RT-PCR
    exposure
    PRDX1-targeting versus control siRNA
    limitations
    Expression rescue is not demonstrated clinical treatment or proof of complete metabolic correction; MeWo-LC1 methylation endpoint is a different experiment.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Reducing the abnormal neighboring transcript allowed the processing gene to be expressed again.
    primary_references
    [gueant-2018-epi-cblc] A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients (2018). https://pubmed.ncbi.nlm.nih.gov/29302025/ DOI: 10.1038/s41467-017-02306-5
    tissue_or_cell_type
    Patient fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 935–947

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human WG3838 fibroblast siRNA and quantitative RT-PCR · source_derived_draft · unverified_draft

    ### b12-prdx1-sirna-restores-mmachc PRDX1-targeting siRNA restored detectable MMACHC expression in WG3838 epi-cblC fibroblasts, unlike control siRNA. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing the abnormal neighboring transcript allowed the processing gene to be expressed again. organism: Homo sapiens tissue_or_cell_type: Patient fibroblasts experimental_model: Human WG3838 fibroblast siRNA and quantitative RT-PCR limitations: Expression rescue is not demonstrated clinical treatment or proof of complete metabolic correction; MeWo-LC1 methylation endpoint is a different experiment. exposure: PRDX1-targeting versus control siRNA cross_nutrient: false evidence_location: Results: Figures 1, 4–6; Methods: PRDX1 silencing [gueant-2018-epi-cblc] A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients (2018). https://pubmed.ncbi.nlm.nih.gov/29302025/ DOI: 10.1038/s41467-017-02306-5
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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