GeneBe

MMUT

methylmalonyl-CoA mutase

Basic information

Region (hg38): 6:49430360-49463253

Previous symbols: [ "MUT" ]

Links

ENSG00000146085 ∙ NCBI:4594 ∙ OMIM:609058 ∙ HGNC:7526 ∙ Uniprot:P22033 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency (Definitive), mode of inheritance: AR
  • vitamin B12-unresponsive methylmalonic acidemia type mut- (Supportive), mode of inheritance: AR
  • vitamin B12-unresponsive methylmalonic acidemia type mut0 (Supportive), mode of inheritance: AR
  • methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency (Strong), mode of inheritance: AR
  • methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Methylmalonic acidemia due to methylmalonyl-CoA mutase deficiencyARBiochemicalLong-term dietary (high-calorie diet low in propiogenic amino acid precursors with carnitine supplementation) and medical management (eg, IM hydroxocobalamin, antibiotics to decrease propionate production) is indicated; Fasting and high-protein consumption should be avoided; In the emergent setting, prompt recognition and appropriate metabolic care may be beneficial to decrease morbidity and mortality; Antioxidants for optic nerve atrophy may be beneficial; Liver/kidney transplant has been described in methylmalonic acidemiaBiochemical; Hematologic; Cardiovascular; Neurologic; Ophthalmologic6132336; 1977311; 1970180; 1968706; 1346616; 1351030; 7681251; 15643616; 12948746; 16451139; 18563634; 20301409; 22614770; 22695176

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MMUT gene.

  • not_provided (855 variants)
  • Methylmalonic_aciduria_due_to_methylmalonyl-CoA_mutase_deficiency (343 variants)
  • Methylmalonic_aciduria_due_to_complete_methylmalonyl-CoA_mutase_deficiency (145 variants)
  • not_specified (126 variants)
  • Methylmalonic_acidemia (76 variants)
  • MMUT-related_disorder (25 variants)
  • METHYLMALONIC_ACIDURIA,_mut(0)_TYPE (14 variants)
  • Abnormality_of_metabolism/homeostasis (3 variants)
  • METHYLMALONIC_ACIDURIA,_mut(-)_TYPE (3 variants)
  • Methylmalonic_aciduria (2 variants)
  • Neonatal_encephalopathy (1 variants)
  • Peroxisome_biogenesis_disorder_8B (1 variants)
  • Peroxisome_biogenesis_disorder_8A_(Zellweger) (1 variants)
  • See_cases (1 variants)
  • Acute_infantile_liver_failure_due_to_synthesis_defect_of_mtDNA-encoded_proteins (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MMUT gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000255.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
8
clinvar
232
clinvar
3
clinvar
 243
missense
62
clinvar
114
clinvar
251
clinvar
12
clinvar
1
clinvar
 440
nonsense
54
clinvar
26
clinvar
 80
start loss
1
 1
frameshift
72
clinvar
27
clinvar
3
clinvar
 102
splice donor/acceptor (+/-2bp)
20
clinvar
20
clinvar
1
clinvar
 41
Total 209 187 263 244 4

Highest pathogenic variant AF is 0.000208783

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
MMUTprotein_codingprotein_codingENST00000274813 1232832
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.71e-220.0027212557001781257480.000708
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.2294014140.9680.00002124896
Missense in Polyphen169194.830.86742234
Synonymous0.01181321320.9990.000006281484
Loss of Function0.4023537.70.9290.00000228415

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.002100.00210
Ashkenazi Jewish0.001490.00149
East Asian0.001360.00136
Finnish0.00004660.0000462
European (Non-Finnish)0.0004760.000440
Middle Eastern0.001360.00136
South Asian0.001080.00108
Other0.0006520.000652

dbNSFP

Source: dbNSFP

Function
FUNCTION: Involved in the degradation of several amino acids, odd- chain fatty acids and cholesterol via propionyl-CoA to the tricarboxylic acid cycle. MCM has different functions in other species.;
Disease
DISEASE: Methylmalonic aciduria type mut (MMAM) [MIM:251000]: An often fatal disorder of organic acid metabolism. Common clinical features include lethargy, vomiting, failure to thrive, hypotonia, neurological deficit and early death. Two forms of the disease are distinguished by the presence (mut-) or absence (mut0) of residual enzyme activity. Mut0 patients have more severe neurological manifestations of the disease than do MUT- patients. MMAM is unresponsive to vitamin B12 therapy. {ECO:0000269|PubMed:10923046, ECO:0000269|PubMed:11350191, ECO:0000269|PubMed:1346616, ECO:0000269|PubMed:1351030, ECO:0000269|PubMed:15643616, ECO:0000269|PubMed:15781192, ECO:0000269|PubMed:16281286, ECO:0000269|PubMed:1670635, ECO:0000269|PubMed:17113806, ECO:0000269|PubMed:17957493, ECO:0000269|PubMed:19588269, ECO:0000269|PubMed:1977311, ECO:0000269|PubMed:1980486, ECO:0000269|PubMed:22727635, ECO:0000269|PubMed:25125334, ECO:0000269|PubMed:26615597, ECO:0000269|PubMed:27167370, ECO:0000269|PubMed:28101778, ECO:0000269|PubMed:7909321, ECO:0000269|PubMed:7912889, ECO:0000269|PubMed:9285782, ECO:0000269|PubMed:9452100, ECO:0000269|PubMed:9554742}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.691

Intolerance Scores

loftool
rvis_EVS
0.2
rvis_percentile_EVS
67.36

Haploinsufficiency Scores

pHI
0.113
hipred
N
hipred_score
0.466
ghis
0.525

Essentials

essential_gene_CRISPR
essential_gene_CRISPR2
essential_gene_gene_trap
N
gene_indispensability_pred
gene_indispensability_score

Mouse Genome Informatics

Gene name
Mut
Phenotype
digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype;