vitamin B12-unresponsive methylmalonic acidemia type mut-

Summary

vitamin B12-unresponsive methylmalonic acidemia type mut- (MONDO:0019267) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 29

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		450	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

29 HPO clinical features (Orphanet curated; top 29 by frequency):

HPO ID	Term	Frequency
HP:0001254	Lethargy	Very frequent (80-99%)
HP:0001259	Coma	Very frequent (80-99%)
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0001944	Dehydration	Very frequent (80-99%)
HP:0001987	Hyperammonemia	Very frequent (80-99%)
HP:0002039	Anorexia	Very frequent (80-99%)
HP:0002098	Respiratory distress	Very frequent (80-99%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001332	Dystonia	Frequent (30-79%)
HP:0001744	Splenomegaly	Frequent (30-79%)
HP:0002017	Nausea and vomiting	Frequent (30-79%)
HP:0002721	Immunodeficiency	Frequent (30-79%)
HP:0011968	Feeding difficulties	Frequent (30-79%)
HP:0000083	Renal insufficiency	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001266	Choreoathetosis	Occasional (5-29%)
HP:0001297	Stroke	Occasional (5-29%)
HP:0001638	Cardiomyopathy	Occasional (5-29%)
HP:0001733	Pancreatitis	Occasional (5-29%)
HP:0001873	Thrombocytopenia	Occasional (5-29%)
HP:0001875	Decreased total neutrophil count	Occasional (5-29%)
HP:0001903	Anemia	Occasional (5-29%)
HP:0002027	Abdominal pain	Occasional (5-29%)
HP:0002240	Hepatomegaly	Occasional (5-29%)
HP:0100022	Abnormality of movement	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	vitamin B12-unresponsive methylmalonic acidemia type mut-
Mondo ID	MONDO:0019267
Orphanet	79312
SNOMED CT	237946002
UMLS	C0342719
MedGen	575192
GARD	0016714
Is cancer (heuristic)	no

Also known as: partial deficiency of methylmalonyl-CoA mutase · vitamin B12-unresponsive methylmalonic aciduria type mut-

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of amino acid and other organic acid metabolism › inborn disorder of amino acid metabolism › inborn organic aciduria › methylmalonic acidemia › methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency › vitamin B12-unresponsive methylmalonic acidemia type mut-

Related subtypes (1): vitamin B12-unresponsive methylmalonic acidemia type mut0

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
MMUT	Definitive	Autosomal recessive	methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MMUT	Orphanet:289916	Vitamin B12-unresponsive methylmalonic acidemia type mut0
MMUT	Orphanet:79312	Vitamin B12-unresponsive methylmalonic acidemia type mut-

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MMUT	HGNC:7526	ENSG00000146085	P22033	Methylmalonyl-CoA mutase, mitochondrial	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MMUT	Methylmalonyl-CoA mutase, mitochondrial	Catalyzes the reversible isomerization of methylmalonyl-CoA (MMCoA) (generated from branched-chain amino acid metabolism and degradation of dietary odd chain fatty acids and cholesterol) to succinyl-CoA (3-carboxypropionyl-CoA), a key inte…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MMUT	Enzyme (other)	yes	5.4.99.2	MMCoA_mutase_a_cat, MeMalonylCoA_mutase_a/b_cat, Cobalamin-bd

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
choroid plexus epithelium	1
nephron tubule	1
oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MMUT	296	ubiquitous	marker	choroid plexus epithelium, oocyte, nephron tubule

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MMUT	3,709

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MMUT	P22033	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective MMAA causes MMA, cblA type	1	5710.0×	7e-04	MMUT
Defective MUT causes MMAM	1	5710.0×	7e-04	MMUT
Diseases of mitochondrial beta oxidation	1	5710.0×	7e-04	MMUT
Diseases of propionyl-CoA catabolism	1	5710.0×	7e-04	MMUT
Propionyl-CoA catabolism	1	2284.0×	0.001	MMUT
Cobalamin (Cbl) metabolism	1	1268.9×	0.002	MMUT
Defects in cobalamin (B12) metabolism	1	815.7×	0.003	MMUT
Cobalamin (Cbl, vitamin B12) transport and metabolism	1	634.4×	0.003	MMUT
Defects in vitamin and cofactor metabolism	1	601.0×	0.003	MMUT
Mitochondrial Fatty Acid Beta-Oxidation	1	380.7×	0.004	MMUT
Metabolism of water-soluble vitamins and cofactors	1	181.3×	0.009	MMUT
Fatty acid metabolism	1	131.3×	0.011	MMUT
Metabolism of vitamins and cofactors	1	116.5×	0.011	MMUT
Diseases of metabolism	1	80.4×	0.015	MMUT
Metabolism of lipids	1	31.6×	0.036	MMUT
Disease	1	13.1×	0.081	MMUT
Metabolism	1	11.6×	0.086	MMUT

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete propionate metabolic process, methylmalonyl pathway	1	16852.0×	3e-04	MMUT
succinyl-CoA biosynthetic process	1	8426.0×	3e-04	MMUT
homocysteine metabolic process	1	1872.4×	9e-04	MMUT
positive regulation of GTPase activity	1	276.3×	0.005	MMUT
post-embryonic development	1	205.5×	0.005	MMUT

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MMUT	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MMUT	5.4.99.2	methylmalonyl-CoA mutase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	MMUT
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MMUT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.