MMAB

metabolism of cobalamin associated B, the group of Cilia and flagella associated

Basic information

Region (hg38): 12:109553714-109573580

Links

ENSG00000139428 ∙ NCBI:326625 ∙ OMIM:607568 ∙ HGNC:19331 ∙ Uniprot:Q96EY8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• methylmalonic aciduria, cblB type (Definitive), mode of inheritance: AR
• methylmalonic aciduria, cblB type (Definitive), mode of inheritance: AR
• methylmalonic aciduria, cblB type (Strong), mode of inheritance: AR
• methylmalonic aciduria, cblB type (Supportive), mode of inheritance: AR
• methylmalonic aciduria, cblB type (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Methylmalonic acidemia, cblB type	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; Neurologic; Ophthalmologic	7213387; 12471062; 16410054; 20301409; 20301503; 20556797; 21416195; 24813872

ClinVar

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

• Methylmalonic aciduria, cblB type (379 variants)
• not provided (71 variants)
• Methylmalonic acidemia (39 variants)
• not specified (27 variants)
• Inborn genetic diseases (15 variants)
• Hyperimmunoglobulin D with periodic fever (5 variants)
• Mevalonic aciduria (5 variants)
• MMAB-related condition (2 variants)
• Glycogen storage disease due to glucose-6-phosphatase deficiency type IA (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MMAB 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	93	1	96
missense	4	7	54	5	3	73
nonsense	9	5	1			15
start loss	3	1				4
frameshift	9	9				18
inframe indel		2	3			5
splice donor/acceptor (+/-2bp)	4	11				15
splice region			2	22	1	25
non coding			76	37	50	163
Total	29	35	136	135	54

Highest pathogenic variant AF is 0.0000347

Variants in MMAB

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

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

Position	Type	Phenotype	Significance	ClinVar
12-109553732-C-T		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 12, 2018)
12-109553733-G-A		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 13, 2018)
12-109553763-T-C		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 13, 2018)
12-109553768-C-T		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 12, 2018)
12-109553850-G-T		Methylmalonic aciduria, cblB type	Benign (Jan 12, 2018)
12-109553876-T-A		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 12, 2018)
12-109553880-C-T		Methylmalonic aciduria, cblB type	Benign (Jan 13, 2018)
12-109553886-C-T		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 13, 2018)
12-109553954-G-A		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 12, 2018)
12-109553985-A-C		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 12, 2018)
12-109554001-A-G		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 13, 2018)
12-109554009-T-C		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 13, 2018)
12-109554078-G-A		Methylmalonic acidemia	Uncertain significance (Jun 14, 2016)
12-109554114-C-T		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 12, 2018)
12-109554115-G-A		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 13, 2018)
12-109554138-G-A		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 12, 2018)
12-109554193-A-G		Methylmalonic aciduria, cblB type	Benign (Jan 12, 2018)
12-109554245-C-T		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 13, 2018)
12-109554288-C-T		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 12, 2018)
12-109554289-G-A		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 12, 2018)
12-109554292-C-G		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 12, 2018)
12-109554327-C-G		Methylmalonic aciduria, cblB type	Benign (Jan 12, 2018)
12-109554344-C-G		Methylmalonic aciduria, cblB type	Benign (Jan 12, 2018)
12-109554349-C-G		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 13, 2018)
12-109554392-T-C		Methylmalonic aciduria, cblB type	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MMAB	protein_coding	protein_coding	ENST00000545712	9	20138

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00413	0.964	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.109	152	148	1.03	0.00000948	1588
Missense in Polyphen		41	46.261	0.88628		504
Synonymous	-0.454	71	66.3	1.07	0.00000490	501
Loss of Function	1.88	6	13.4	0.447	5.86e-7	170

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000406	0.000331
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000152	0.000141
Middle Eastern	0.00	0.00
South Asian	0.000393	0.000359
Other	0.000691	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adenosyltransferase involved in intracellular vitamin B12 metabolism. Generates adenosylcobalamin (AdoCbl) and directly delivers the cofactor to MUT in a transfer taht is stimulated by ATP-binding to MMAB and gated by MMAA. {ECO:0000305|PubMed:28497574}.
• Pathway: Porphyrin and chlorophyll metabolism - Homo sapiens (human);Vitamin B12 Metabolism;Cobalamin (Cbl, vitamin B12) transport and metabolism;Metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors (Consensus)

Recessive Scores

• pRec: 0.223

Intolerance Scores

• loftool: 0.271
• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.41

Haploinsufficiency Scores

• pHI: 0.203
• hipred: N
• hipred_score: 0.187
• ghis: 0.473

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.862

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mmab

Gene ontology

• Biological process: cobalamin metabolic process;cobalamin biosynthetic process
• Cellular component: mitochondrial matrix
• Molecular function: protein binding;ATP binding;cob(I)yrinic acid a,c-diamide adenosyltransferase activity;cobalamin binding