MMACHC

Chr 1

metabolism of cobalamin associated C

Also known as: cblC

NCBI Gene: 25974ENSG00000132763UniProt: Q9Y4U1

The exact function of the protein encoded by this gene is not known, however, its C-terminal region shows similarity to TonB, a bacterial protein involved in energy transduction for cobalamin (vitamin B12) uptake. Hence, it is postulated that this protein may have a role in the binding and intracellular trafficking of cobalamin. Mutations in this gene are associated with methylmalonic aciduria and homocystinuria type cblC. [provided by RefSeq, Oct 2009]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMethylmalonic aciduria and homocystinuria, cblC type

Clinical highlights

Gene-disease validity (ClinGen)
methylmalonic aciduria and homocystinuria type cblC · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
54
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
1.75
LOEUF
LOF
Mechanism· G2P
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GeneReview available — MMACHC
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
1.75LOEUF
pLI 0.000
Z-score -0.76
OE 1.21 (0.84–1.75)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-1.08Z-score
OE missense 1.23 (1.10–1.38)
213 obs / 173.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?1.21 (0.84–1.75)
0≤0.351.4
Missense OE?1.23 (1.10–1.38)
0≤0.61.4
Synonymous OE?1.26
0≤1.21.6
LoF obs/exp: 18 / 14.8Missense obs/exp: 213 / 173.2Syn Z: -1.65

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MMACHC · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients