MMACHC

Chr 1AR

metabolism of cobalamin associated C

The protein encoded by MMACHC is involved in the binding and intracellular trafficking of cobalamin (vitamin B12), with its C-terminal region showing similarity to bacterial proteins involved in cobalamin uptake. Mutations cause methylmalonic aciduria and homocystinuria, cblC type, inherited in an autosomal recessive pattern. The pathogenic mechanism involves defective cobalamin processing leading to impaired methylmalonyl-CoA mutase and methionine synthase function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.751 OMIM phenotype
Clinical SummaryMMACHC
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Gene-Disease Validity (ClinGen)
methylmalonic aciduria and homocystinuria type cblC · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.75LOEUF
pLI 0.000
Z-score -0.76
OE 1.21 (0.841.75)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.08Z-score
OE missense 1.23 (1.101.38)
213 obs / 173.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.21 (0.841.75)
00.351.4
Missense OE1.23 (1.101.38)
00.61.4
Synonymous OE1.26
01.21.6
LoF obs/exp: 18 / 14.8Missense obs/exp: 213 / 173.2Syn Z: -1.65

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗