MMUT

methylmalonyl-CoA mutase

Basic information

Region (hg38): 6:49430359-49463253

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

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 (743 variants)
• Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency (344 variants)
• Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency (103 variants)
• Methylmalonic acidemia (64 variants)
• not specified (35 variants)
• METHYLMALONIC ACIDURIA, mut(0) TYPE (11 variants)
• Inborn genetic diseases (8 variants)
• MMUT-related condition (5 variants)
• Abnormality of metabolism/homeostasis (3 variants)
• METHYLMALONIC ACIDURIA, mut(-) TYPE (2 variants)
• Neonatal encephalopathy (1 variants)
• See cases (1 variants)
• Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins (1 variants)
• Peroxisome biogenesis disorder 8A (Zellweger);Peroxisome biogenesis disorder 8B (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	174	3	179
missense	59	71	151	6	3	290
nonsense	43	27				70
start loss	1					1
frameshift	58	18	1			77
inframe indel	2	3	3			8
splice donor/acceptor (+/-2bp)	17	14	1			32
splice region	1	2	8	31	1	43
non coding	2	1	30	81	23	137
Total	182	134	188	261	29

Highest pathogenic variant AF is 0.000197

Variants in MMUT

This is a list of pathogenic ClinVar variants found in the MMUT region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-49430402-C-T		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Benign (Jan 13, 2018)
6-49430409-G-A		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 13, 2018)
6-49430476-A-G		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 13, 2018)
6-49430514-G-T		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 13, 2018)
6-49430544-A-G		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 13, 2018)
6-49430546-A-G		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 13, 2018)
6-49430620-G-GT		Methylmalonic acidemia	Likely benign (Jun 14, 2016)
6-49430684-A-T		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 13, 2018)
6-49430742-C-T		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 13, 2018)
6-49430953-T-C		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 13, 2018)
6-49431037-A-G		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 12, 2018)
6-49431092-A-T		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 12, 2018)
6-49431101-G-A		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 13, 2018)
6-49431148-T-C		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Benign (Jan 13, 2018)
6-49431170-T-C		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 12, 2018)
6-49431262-C-T		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 13, 2018)
6-49431263-G-A		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 13, 2018)
6-49431283-T-C		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Apr 27, 2017)
6-49431447-C-T		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 13, 2018)
6-49431450-T-C		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Conflicting classifications of pathogenicity (Jun 20, 2021)
6-49431471-T-G		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 13, 2018)
6-49431526-AT-A		Methylmalonic acidemia	Benign/Likely benign (Aug 10, 2019)
6-49431526-A-AT			Benign (Nov 05, 2019)
6-49431528-T-A		Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	Uncertain significance (Jan 12, 2018)
6-49431566-T-G		Methylmalonic acidemia	Uncertain significance (Jun 14, 2016)

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
1.71e-22	0.00272	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

Haploinsufficiency Scores

• pHI: 0.113
• hipred: N
• hipred_score: 0.466
• ghis: 0.525

Essentials

• essential_gene_gene_trap: N

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