MAN2B1

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

Basic information

Region (hg38): 19:12646510-12666742

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; 31241255; 33317989

ClinVar

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

• Deficiency of alpha-mannosidase (1330 variants)
• not provided (137 variants)
• Inborn genetic diseases (54 variants)
• not specified (32 variants)
• Intellectual disability (4 variants)
• MAN2B1-related condition (2 variants)
• Craniosynostosis syndrome;Intellectual disability (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.

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			12	379	7	398
missense	3	14	311	13	10	351
nonsense	26	46				72
start loss			6			6
frameshift	51	60	2			113
inframe indel			7			7
splice donor/acceptor (+/-2bp)	8	48	3			59
splice region	1	3	21	91	3	119
non coding			8	168	30	206
Total	88	168	349	560	47

Highest pathogenic variant AF is 0.000311

Variants in MAN2B1

This is a list of pathogenic ClinVar variants found in the MAN2B1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-12646515-G-C		Deficiency of alpha-mannosidase	Uncertain significance (Jan 13, 2018)
19-12646520-A-C		Deficiency of alpha-mannosidase	Uncertain significance (Jan 13, 2018)
19-12646529-G-A		Deficiency of alpha-mannosidase	Uncertain significance (Jan 13, 2018)
19-12646578-C-T		Deficiency of alpha-mannosidase	Likely benign (May 01, 2023)
19-12646579-G-A		Deficiency of alpha-mannosidase	Uncertain significance (Jan 15, 2018)
19-12646623-A-G		Deficiency of alpha-mannosidase	Likely benign (May 19, 2023)
19-12646626-A-G		Deficiency of alpha-mannosidase	Likely benign (Feb 27, 2023)
19-12646632-C-T		Deficiency of alpha-mannosidase	Likely benign (Apr 10, 2023)
19-12646641-T-C		Deficiency of alpha-mannosidase	Likely benign (Dec 14, 2023)
19-12646643-G-A		Deficiency of alpha-mannosidase	Uncertain significance (Mar 03, 2023)
19-12646647-T-C		Deficiency of alpha-mannosidase	Likely benign (Jun 23, 2023)
19-12646650-G-T		Deficiency of alpha-mannosidase	Conflicting classifications of pathogenicity (Jun 09, 2023)
19-12646652-C-T		Inborn genetic diseases • Deficiency of alpha-mannosidase	Uncertain significance (Oct 17, 2022)
19-12646654-A-G		Deficiency of alpha-mannosidase	Uncertain significance (Feb 18, 2022)
19-12646656-G-A		Deficiency of alpha-mannosidase	Likely benign (Jun 14, 2023)
19-12646657-A-G		Deficiency of alpha-mannosidase	Likely pathogenic (Aug 01, 2023)
19-12646662-G-A		Deficiency of alpha-mannosidase	Likely benign (Jul 27, 2019)
19-12646663-C-T		Deficiency of alpha-mannosidase	Benign (Jan 31, 2024)
19-12646664-G-A		Deficiency of alpha-mannosidase	Uncertain significance (Aug 16, 2022)
19-12646665-G-A		Deficiency of alpha-mannosidase	Conflicting classifications of pathogenicity (Jul 29, 2023)
19-12646674-G-A		Deficiency of alpha-mannosidase	Likely benign (Feb 16, 2023)
19-12646678-T-TC		not specified	Uncertain significance (Jan 04, 2023)
19-12646682-G-A		Deficiency of alpha-mannosidase	Likely benign (Mar 23, 2023)
19-12646683-C-T		Deficiency of alpha-mannosidase	Conflicting classifications of pathogenicity (Jan 25, 2024)
19-12646685-TG-T		Deficiency of alpha-mannosidase	Pathogenic (-)

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