MMADHC

Chr 2AR

metabolism of cobalamin associated D

Also known as: C2orf25, CL25022, HMAD, MACD, MAHCD, cblD

This gene encodes a mitochondrial protein that regulates cobalamin (vitamin B12) metabolism and trafficking, specifically controlling the biosynthesis and proportion of two essential coenzymes, methylcobalamin and adenosylcobalamin. Mutations cause methylmalonic aciduria and homocystinuria cblD type, an autosomal recessive disorder of cobalamin metabolism that can present with megaloblastic anemia and affects both amino acid and organic acid metabolism. The gene shows low constraint against loss-of-function variants (pLI 0.00002, LOEUF 0.994), which is consistent with its autosomal recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.993 OMIM phenotypes
Clinical SummaryMMADHC
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Gene-Disease Validity (ClinGen)
inborn disorder of cobalamin metabolism and transport · 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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.99LOEUF
pLI 0.000
Z-score 1.59
OE 0.59 (0.360.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.41Z-score
OE missense 1.09 (0.961.24)
168 obs / 153.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.59 (0.360.99)
00.351.4
Missense OE1.09 (0.961.24)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 10 / 17.1Missense obs/exp: 168 / 153.6Syn Z: -0.25

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MMADHC · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC