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

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 22.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
ENST00000274813.4	ENSP00000274813.3	12	yes	-
ENST00000878060.1	ENSP00000548119.1	12	-	-
ENST00000878061.1	ENSP00000548120.1	11	-	-
ENST00000878062.1	ENSP00000548121.1	12	-	-

Phenotypes

GenCC

Source: genCC

• methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency (Definitive), mode of inheritance: AR
• methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency (Strong), 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 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Methylmalonic acidemia due to methylmalonyl-CoA mutase deficiency	AR	Biochemical	Long-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 acidemia	Biochemical; Hematologic; Cardiovascular; Neurologic; Ophthalmologic	6132336; 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 (872 variants)
• Methylmalonic_aciduria_due_to_methylmalonyl-CoA_mutase_deficiency (351 variants)
• not_specified (151 variants)
• Methylmalonic_aciduria_due_to_complete_methylmalonyl-CoA_mutase_deficiency (145 variants)
• Methylmalonic_acidemia (82 variants)
• MMUT-related_disorder (25 variants)
• METHYLMALONIC_ACIDURIA,_mut(0)_TYPE (14 variants)
• Likely_inborn_error_of_metabolism (3 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	237	3	248
missense	64	119	269	11	1	464
nonsense	56	26				82
start loss	1					1
frameshift	73	28	3			104
splice donor/acceptor (+/-2bp)	20	22	5			47
Total	214	195	285	248	4

Highest pathogenic variant AF is 0.000208783

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MMUT	protein_coding	protein_coding	ENST00000274813	12	32832

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125570	0	178	125748	0.000708

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.229	401	414	0.968	0.0000212	4896
Missense in Polyphen		169	194.83	0.8674		2234
Synonymous	0.0118	132	132	0.999	0.00000628	1484
Loss of Function	0.402	35	37.7	0.929	0.00000228	415

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00210	0.00210
Ashkenazi Jewish	0.00149	0.00149
East Asian	0.00136	0.00136
Finnish	0.0000466	0.0000462
European (Non-Finnish)	0.000476	0.000440
Middle Eastern	0.00136	0.00136
South Asian	0.00108	0.00108
Other	0.000652	0.000652

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

• rvis_EVS: 0.2
• rvis_percentile_EVS: 67.36

Essentials

• essential_gene_gene_trap: N