MMAB

Chr 12AR

metabolism of cobalamin associated B

Also known as: ATR, CFAP23, cblB, cob

NCBI Gene: 326625ENSG00000139428UniProt: Q96EY8OMIM: 607568

The MMAB protein catalyzes the final step in converting vitamin B12 into adenosylcobalamin, a coenzyme required for methylmalonyl-CoA mutase function. Mutations cause vitamin B12-responsive methylmalonic aciduria (cblB type), inherited in an autosomal recessive pattern. The pathogenic mechanism involves loss of function, disrupting the conversion process and leading to methylmalonic acid accumulation.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.881 OMIM phenotype
Clinical Summary— MMAB
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Gene-Disease Validity (ClinGen)
methylmalonic aciduria, cblB type · 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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ClinVar Variants
78 unique Pathogenic / Likely Pathogenic· 85 VUS of 400 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — MMAB
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.88LOEUF
pLI 0.004
Z-score 1.88
OE 0.45 (0.24–0.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.11Z-score
OE missense 1.03 (0.90–1.17)
152 obs / 148.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.45 (0.24–0.88)
0≤0.351.4
Missense OE1.03 (0.90–1.17)
0≤0.61.4
Synonymous OE1.07
0≤1.21.6
LoF obs/exp: 6 / 13.4Missense obs/exp: 152 / 148.3Syn Z: -0.45
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMMAB-related methylmalonic aciduriaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7033th %ile
GOF
0.5562th %ile
LOF
0.3067th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic37
VUS85
Likely Benign197
Benign28
Conflicting11
41
Pathogenic
37
Likely Pathogenic
85
VUS
197
Likely Benign
28
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
31
5
5
0
41
Likely Pathogenic
24
11
2
0
37
VUS
1
50
34
0
85
Likely Benign
0
2
84
111
197
Benign
0
0
28
0
28
Conflicting
—11
Total5668153111399

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MMAB · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Comparison of Antibodies to Detect Uroplakin in Urothelial Carcinomas
Kristoffersen HL et al.·Appl Immunohistochem Mol Morphol
2022
Circulating long non-coding RNAs NKILA, NEAT1, MALAT1, and MIAT expression and their association in type 2 diabetes mellitus
Alfaifi M et al.·BMJ Open Diabetes Res Care
2021
Single cell sequencing revealed the mechanism of PD-1 resistance affected by the expression profile of peripheral blood immune cells in ESCC
Deng T et al.·Front Immunol
2022Functional
Construction of a risk prediction model using m6A RNA methylation regulators in prostate cancer: comprehensive bioinformatic analysis and histological validation
Quan Y et al.·Cancer Cell Int
2022Functional
Risk factors of previously undiagnosed and known untreated hypertension among patients with Type-2 diabetes mellitus
Adnan M et al.·Pak J Med Sci
2023Cohort
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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