MAN2B1

mannosidase alpha class 2B member 1, the group of Mannosidases alpha class 2

Basic information

Region (hg38): 19:12643831-12666742

Previous symbols: [ "MANB" ]

Links

ENSG00000104774

∙ NCBI:4125 ∙ OMIM:609458 ∙ HGNC:6826 ∙ Uniprot:O00754 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

alpha-mannosidosis (Definitive), mode of inheritance: AR
alpha-mannosidosis (Definitive), mode of inheritance: AR
alpha-mannosidosis (Strong), mode of inheritance: AR
alpha-mannosidosis (Strong), mode of inheritance: AR
alpha-mannosidosis (Strong), mode of inheritance: AR
alpha-mannosidosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mannosidosis, alpha B, lysosomal	AR	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical	Manifestations can include immunodeficiency, and prophylactic vaccines and early and aggressive treatment of infections can be beneficial; Some individuals may manifest with early-onest hearing impairment, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Enzyme replacement therapy has been described as beneficial	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic; Ophthalmologic	4358183; 995502; 724292; 6860058; 4082921; 1472354; 8357013; 7702090; 9158146; 9758606; 11014473; 15534274; 18651971; 20301570; 22161967; 29716835; 29859105; 31241255; 32331969; 33317989

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAN2B1 gene.

Deficiency_of_alpha-mannosidase (1711 variants)
not_provided (149 variants)
Inborn_genetic_diseases (119 variants)
not_specified (42 variants)
MAN2B1-related_disorder (29 variants)
Intellectual_disability (5 variants)
Mannosidosis,_alpha-,_types_I_and_II (3 variants)
Methylmalonic_aciduria_due_to_methylmalonyl-CoA_mutase_deficiency (1 variants)
Craniosynostosis_syndrome (1 variants)
Myoepithelial_tumor (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAN2B1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000528.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	23 clinvar	505 clinvar	8 clinvar	537
missense		40 clinvar	408 clinvar	34 clinvar	5 clinvar	487
nonsense	33 clinvar	55 clinvar	1 clinvar			89
start loss			6			6
frameshift	65 clinvar	78 clinvar	4 clinvar			147
splice donor/acceptor (+/-2bp)	11 clinvar	63 clinvar	4 clinvar			78
Total	109	237	446	539	13

Highest pathogenic variant AF is 0.00017161458

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAN2B1	protein_coding	protein_coding	ENST00000456935	24	20232

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.79e-22	0.230	125637	0	111	125748	0.000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.15	557	639	0.872	0.0000449	6509
Missense in Polyphen		199	249.61	0.79724		2653
Synonymous	-0.153	280	277	1.01	0.0000205	2072
Loss of Function	1.75	41	55.0	0.745	0.00000268	568

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00122	0.00119
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00130	0.00129
European (Non-Finnish)	0.000461	0.000457
Middle Eastern	0.0000544	0.0000544
South Asian	0.000262	0.000261
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover. Cleaves all known types of alpha-mannosidic linkages.;
Disease: DISEASE: Mannosidosis, alpha B, lysosomal (MANSA) [MIM:248500]: A lysosomal storage disease characterized by accumulation of unbranched oligosaccharide chains. This accumulation is expressed histologically as cytoplasmic vacuolation predominantly in the CNS and parenchymatous organs. Depending on the clinical findings at the age of onset, a severe infantile (type I) and a mild juvenile (type II) form of alpha-mannosidosis are recognized. There is considerable variation in the clinical expression with mental retardation, recurrent infections, impaired hearing and Hurler- like skeletal changes being the most consistent abnormalities. {ECO:0000269|PubMed:12718372, ECO:0000269|PubMed:15712269, ECO:0000269|PubMed:22161967, ECO:0000269|PubMed:9158146, ECO:0000269|PubMed:9758606, ECO:0000269|PubMed:9915946}. 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;er associated degradation (erad) pathway;Lysosomal oligosaccharide catabolism;Metabolism of carbohydrates;Innate Immune System;Immune System;Metabolism (Consensus)

Recessive Scores

pRec: 0.224

Intolerance Scores

loftool: 0.190
rvis_EVS: 0.12
rvis_percentile_EVS: 62.23

Haploinsufficiency Scores

pHI: 0.0604
hipred: N
hipred_score: 0.274
ghis: 0.532

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.292

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Man2b1
Phenotype: vision/eye phenotype; hearing/vestibular/ear 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); digestive/alimentary phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); hematopoietic system phenotype; growth/size/body region phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype;

Gene ontology

Biological process: mannose metabolic process;cellular protein modification process;protein deglycosylation;oligosaccharide catabolic process;neutrophil degranulation
Cellular component: extracellular region;extracellular space;vacuolar membrane;azurophil granule lumen;lysosomal lumen;extracellular exosome
Molecular function: alpha-mannosidase activity;carbohydrate binding;metal ion binding