MANBA

mannosidase beta, the group of Mannosidases type beta

Basic information

Region (hg38): 4:102630770-102760994

Links

ENSG00000109323 ∙ NCBI:4126 ∙ OMIM:609489 ∙ HGNC:6831 ∙ Uniprot:O00462 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• beta-mannosidosis (Definitive), mode of inheritance: AR
• beta-mannosidosis (Strong), mode of inheritance: AR
• beta-mannosidosis (Strong), mode of inheritance: AR
• beta-mannosidosis (Strong), mode of inheritance: AR
• beta-mannosidosis (Supportive), mode of inheritance: AR
• beta-mannosidosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mannosidosis, beta A, lysosomal	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Musculoskeletal; Neurologic	3762648; 2945113; 2079835; 1623631; 1499588; 8285582; 59034; 9384606; 12468273; 16401745; 17420068; 18565776; 19728872; 22369051

ClinVar

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

• Beta-D-mannosidosis (651 variants)
• Inborn_genetic_diseases (94 variants)
• not_provided (81 variants)
• MANBA-related_disorder (21 variants)
• not_specified (11 variants)
• Intellectual_disability (6 variants)
• Meniere_disease (4 variants)
• Hearing_impairment (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MANBA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005908.4. 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	1		1	219	3	224
missense	1	9	220	17	1	248
nonsense	29	13	1			43
start loss			1			1
frameshift	24	12	4			40
splice donor/acceptor (+/-2bp)	3	21				24
Total	58	55	227	236	4

Highest pathogenic variant AF is 0.00035274

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MANBA	protein_coding	protein_coding	ENST00000226578	17	129492

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.31e-18	0.423	125636	0	112	125748	0.000445

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0496	468	471	0.994	0.0000250	5801
Missense in Polyphen		139	155.82	0.89206		1972
Synonymous	0.364	167	173	0.965	0.00000952	1609
Loss of Function	1.75	35	48.1	0.728	0.00000229	552

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000813	0.000811
Ashkenazi Jewish	0.00	0.00
East Asian	0.000273	0.000272
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000608	0.000607
Middle Eastern	0.000273	0.000272
South Asian	0.000359	0.000359
Other	0.000816	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Exoglycosidase that cleaves the single beta-linked mannose residue from the non-reducing end of all N-linked glycoprotein oligosaccharides.
• Disease: DISEASE: Mannosidosis, beta A, lysosomal (MANSB) [MIM:248510]: An autosomal recessive lysosomal storage disease of glycoprotein catabolism. Clinical features are heterogeneous with a wide range of symptoms and age of onset. The disease is associated with a range of neurological involvement, including various degrees of mental retardation in most of the cases, hearing loss and speech impairment, hypotonia, epilepsy and peripheral neuropathy. Affected individuals have a profound reduction in beta A mannosidase activity in plasma, fibroblasts and leukocytes. {ECO:0000269|PubMed:9384606}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Other glycan degradation - Homo sapiens (human);Neutrophil degranulation;Lysosomal oligosaccharide catabolism;Metabolism of carbohydrates;Innate Immune System;Immune System;Metabolism (Consensus)

Recessive Scores

• pRec: 0.331

Intolerance Scores

• loftool: 0.513
• rvis_EVS: -0.62
• rvis_percentile_EVS: 17.47

Haploinsufficiency Scores

• pHI: 0.107
• hipred: N
• hipred_score: 0.289
• ghis: 0.530

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.252

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Manba
• Phenotype: hematopoietic system 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); reproductive system phenotype; liver/biliary system phenotype; immune system phenotype; renal/urinary system 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); endocrine/exocrine gland phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: manba
• Affected structure: pericardium
• Phenotype tag: abnormal
• Phenotype quality: edematous

Gene ontology

• Biological process: cellular protein modification process;glycoprotein catabolic process;oligosaccharide catabolic process;neutrophil degranulation;mannan catabolic process
• Cellular component: lysosome;plasma membrane;azurophil granule membrane;lysosomal lumen;intracellular membrane-bounded organelle
• Molecular function: beta-mannosidase activity;mannose binding