MMADHC

Chr 2

metabolism of cobalamin associated D

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

NCBI Gene: 27249ENSG00000168288UniProt: Q9H3L0

This gene encodes a mitochondrial protein that is involved in an early step of vitamin B12 metabolism. Vitamin B12 (cobalamin) is essential for normal development and survival in humans. Mutations in this gene cause methylmalonic aciduria and homocystinuria type cblD (MMADHC), a disorder of cobalamin metabolism that is characterized by decreased levels of the coenzymes adenosylcobalamin and methylcobalamin. Pseudogenes have been identified on chromosomes 11 and X.[provided by RefSeq, Nov 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMethylmalonic aciduria and homocystinuria, cblD type
UniProtHomocystinuria-megaloblastic anemia, cblD type
UniProtMethylmalonic aciduria, cblD type

Clinical highlights

Gene-disease validity (ClinGen)
inborn disorder of cobalamin metabolism and transport · 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.
0
Active trials
10
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.99
LOEUF
LOF
Mechanism· G2P
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GeneReview available — MMADHC
Authoritative clinical overview · Recommended first read
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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?
0.99LOEUF
pLI 0.000
Z-score 1.59
OE 0.59 (0.36–0.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-0.41Z-score
OE missense 1.09 (0.96–1.24)
168 obs / 153.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.59 (0.36–0.99)
0≤0.351.4
Missense OE?1.09 (0.96–1.24)
0≤0.61.4
Synonymous OE?1.04
0≤1.21.6
LoF obs/exp: 10 / 17.1Missense obs/exp: 168 / 153.6Syn Z: -0.25

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

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