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    MAN2B1 mannosidase alpha class 2B member 1 [ Homo sapiens (human) ]

    Gene ID: 4125, updated on 2-Nov-2024

    Summary

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    Official Symbol
    MAN2B1provided by HGNC
    Official Full Name
    mannosidase alpha class 2B member 1provided by HGNC
    Primary source
    HGNC:HGNC:6826
    See related
    Ensembl:ENSG00000104774 MIM:609458; AllianceGenome:HGNC:6826
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MANB; LAMAN
    Summary
    This gene encodes an enzyme that hydrolyzes terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides. Its activity is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover and it is member of family 38 of glycosyl hydrolases. The full length protein is processed in two steps. First, a 49 aa leader sequence is cleaved off and the remainder of the protein is processed into 3 peptides of 70 kDa, 42 kDa (D) and 13/15 kDa (E). Next, the 70 kDa peptide is further processed into three peptides (A, B and C). The A, B and C peptides are disulfide-linked. Defects in this gene have been associated with lysosomal alpha-mannosidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]
    Expression
    Ubiquitous expression in spleen (RPKM 48.9), appendix (RPKM 36.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MAN2B1 in Genome Data Viewer
    Location:
    19p13.13
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (12646512..12666742, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (12771019..12791240, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (12757326..12777556, complement)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene zinc finger protein 791 Neighboring gene uncharacterized LOC105372279 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:12750843-12751363 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr19:12754106-12755305 Neighboring gene ribosomal protein L10 pseudogene 16 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14063 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10155 Neighboring gene MPRA-validated peak3365 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:12775226-12776174 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:12776175-12777122 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10156 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14069 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14070 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:12781177-12781850 Neighboring gene CRISPRi-FlowFISH-validated DHPS regulatory element Neighboring gene WD repeat domain 83 opposite strand Neighboring gene WD repeat domain 83 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14071 Neighboring gene deoxyhypusine synthase Neighboring gene CRISPRi-FlowFISH-validated WDR83OS regulatory elements

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Characterization of human liver alpha-D-mannosidase purified by affinity chromatography. Phillips NC, et al. Biochem J, 1976 Mar 1. PMID 821469, Free PMC Article
    2. Molecular diagnosis of a Chinese pedigree with α-mannosidosis and identification of a novel missense mutation. Wu X, et al. J Pediatr Endocrinol Metab, 2014 May. PMID 24353136
    3. Traffic of human α-mannosidase in plant cells suggests the presence of a new endoplasmic reticulum-to-vacuole pathway without involving the Golgi complex. De Marchis F, et al. Plant Physiol, 2013 Apr. PMID 23449646, Free PMC Article
    4. Lysosomal storage disease in the brain: mutations of the β-mannosidase gene identified in autosomal dominant nystagmus. Yu P, et al. Genet Med, 2015 Dec. PMID 25741867
    5. Alpha-mannosidosis: correlation between phenotype, genotype and mutant MAN2B1 subcellular localisation. Borgwardt L, et al. Orphanet J Rare Dis, 2015 Jun 6. PMID 26048034, Free PMC Article

    See all (76) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. A diagnosis can be established by measuring the activity of lysosomal alpha-mannosidase in leucocytes and screening for abnormal urinary excretion of mannose-rich oligosaccharides. Genetic confirmation is obtained with the identification of MAN2B1 mutations.
      Title: Hearing impairment as an early sign of alpha-mannosidosis in children with a mild phenotype: Report of seven new cases.
    2. A novel heterozygous mutation (c.2013G>A; p.R638H) of MANBA was identified in patients with autosomal-dominant nystagmus. An additional mutation (c.2346T>A; p.L749H) in MANBA was found by screening patients with sporadic nystagmus.
      Title: Lysosomal storage disease in the brain: mutations of the β-mannosidase gene identified in autosomal dominant nystagmus.
    3. Our results indicate a correlation between the MAN2B1 genotypes and the cognitive function, upper limb coordination, balance, FVC% and the storage of oligosaccharides in CSF.
      Title: Alpha-mannosidosis: correlation between phenotype, genotype and mutant MAN2B1 subcellular localisation.
    4. The results showed that the alpha-mannosidosis patient has compound heterozygous mutations in the MAN2B1 gene
      Title: Molecular diagnosis of a Chinese pedigree with α-mannosidosis and identification of a novel missense mutation.
    5. MAN2B1 is targeted to the vacuole without passing through the Golgi complex.
      Title: Traffic of human α-mannosidase in plant cells suggests the presence of a new endoplasmic reticulum-to-vacuole pathway without involving the Golgi complex.
    6. A single nucleotide polymorphism in MAN2B, rs228614, is associated with risk for multiple sclerosis.
      Title: MANBA, CXCR5, SOX8, RPS6KB1 and ZBTB46 are genetic risk loci for multiple sclerosis.
    7. Observational study of gene-disease association. (HuGE Navigator)
      Title: Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study.
    8. Expressed MAN2B1 and MAN2B2 in Drosophila S2 cells and functionally characterized them. MAN2B1 and MAN2B2 were significantly inhibited by the class II alpha-mannosidase inhibitors, swainsonine and mannostatin A.
      Title: Human lysosomal alpha-mannosidases exhibit different inhibition and metal binding properties.
    9. 5 new mutations were found in the MAN2B1 gene: c.157G>T, c.562C>T, c.599A>T, c.293dupA, c.2402G>A (p.E53X, p.R188X, p.H200L, p.Y99VfsX61, p.G801D). p.H200L could involve the catalytic mechanism. p.G801D would affect correct folding.
      Title: Identification and characterization of five novel MAN2B1 mutations in Italian patients with alpha-mannosidosis.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Deficiency of alpha-mannosidase
    MedGen: C0024748 OMIM: 248500 GeneReviews: Alpha-Mannosidosis
    		not available

    EBI GWAS Catalog

    Description
    Genome-wide study of percent emphysema on computed tomography in the general population. The Multi-Ethnic Study of Atherosclerosis Lung/SNP Health Association Resource Study.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Specific alterations of the N-linked carbohydrates on HIV-1 gp120 and gp41 by glucosidases and mannosidase inhibitors can enhance mannose-binding lectin (MBL)-mediated neutralization of virus by strengthening the interaction of HIV-1 with MBL PubMed
    env HIV-1 gp120 N-linked oligosaccharides are processed by manosidase I and II in the Golgi complex PubMed
    Envelope surface glycoprotein gp160, precursor env Oligosaccharide side-chains of HIV-1 gp160 are processed by glycosidase I and II, mannosidase I and II, acetylglucosaminyl transferase I and II, and fucosyl, galactosyl and sialyl transferases in both the endoplasmic reticulum and golgi apparatus PubMed
    Envelope transmembrane glycoprotein gp41 env Mannose-containing, N-linked oligosaccharide side-chains of HIV-1 gp41 are involved in the initial stage of infection by HIV-1; glycosylation inhibitors block virus-cell and cell-cell fusion and release of the virions PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables alpha-mannosidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables carbohydrate binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in learning or memory IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mannose metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in oligosaccharide catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein deglycosylation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in protein modification process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in azurophil granule lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    located_in lysosomal lumen TAS
    Traceable Author Statement
    more info
    		  
    is_active_in lysosome IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    lysosomal alpha-mannosidase
    Names
    lysosomal acid alpha-mannosidase
    mannosidase alpha-B
    mannosidase, alpha B, lysosomal
    NP_000519.2
    NP_001166969.1
    XP_005259970.1
    XP_047294797.1
    XP_054177008.1
    XP_054177009.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008318.1 RefSeqGene

      Range
      5036..25266
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000528.4 → NP_000519.2  lysosomal alpha-mannosidase isoform 1 precursor

      See identical proteins and their annotated locations for NP_000519.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      BC000736, DB237901
      Consensus CDS
      CCDS32919.1
      UniProtKB/Swiss-Prot
      G5E928, O00754, O15330, Q16680, Q93094, Q9BW13
      UniProtKB/TrEMBL
      A8K6A7
      Related
      ENSP00000395473.2, ENST00000456935.7
      Conserved Domains (4) summary
      PLN02701
      Location:63 → 1000
      PLN02701; alpha-mannosidase
      cd10810
      Location:63 → 341
      GH38N_AMII_LAM_like; N-terminal catalytic domain of lysosomal alpha-mannosidase and similar proteins; glycoside hydrolase family 38 (GH38)
      smart00872
      Location:387 → 465
      Alpha-mann_mid; Alpha mannosidase, middle domain
      pfam07748
      Location:510 → 1000
      Glyco_hydro_38C; Glycosyl hydrolases family 38 C-terminal domain

    2. NM_001173498.2 → NP_001166969.1  lysosomal alpha-mannosidase isoform 2 precursor

      See identical proteins and their annotated locations for NP_001166969.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks a CAG copy at an splice site in the CDS, as compared to variant 1. The resulting isoform (2) lacks an internal Q, as compared to isoform 1.
      Source sequence(s)
      AK291572, BM982008, DB237901, U05572
      Consensus CDS
      CCDS54224.1
      UniProtKB/TrEMBL
      A8K6A7
      Related
      ENSP00000221363.4, ENST00000221363.9
      Conserved Domains (4) summary
      PLN02701
      Location:63 → 999
      PLN02701; alpha-mannosidase
      cd10810
      Location:63 → 341
      GH38N_AMII_LAM_like; N-terminal catalytic domain of lysosomal alpha-mannosidase and similar proteins; glycoside hydrolase family 38 (GH38)
      smart00872
      Location:386 → 464
      Alpha-mann_mid; Alpha mannosidase, middle domain
      pfam07748
      Location:509 → 999
      Glyco_hydro_38C; Glycosyl hydrolases family 38 C-terminal domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      12646512..12666742 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005259913.3 → XP_005259970.1  lysosomal alpha-mannosidase isoform X1

      UniProtKB/TrEMBL
      A8K6A7
      Conserved Domains (4) summary
      PLN02701
      Location:63 → 1001
      PLN02701; alpha-mannosidase
      cd10810
      Location:63 → 341
      GH38N_AMII_LAM_like; N-terminal catalytic domain of lysosomal alpha-mannosidase and similar proteins; glycoside hydrolase family 38 (GH38)
      smart00872
      Location:388 → 466
      Alpha-mann_mid; Alpha mannosidase, middle domain
      pfam07748
      Location:511 → 1001
      Glyco_hydro_38C; Glycosyl hydrolases family 38 C-terminal domain

    2. XM_047438841.1 → XP_047294797.1  lysosomal alpha-mannosidase isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      12771019..12791240 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054321033.1 → XP_054177008.1  lysosomal alpha-mannosidase isoform X1

    2. XM_054321034.1 → XP_054177009.1  lysosomal alpha-mannosidase isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O00754.3 GenPept UniProtKB/Swiss-Prot:O00754

    Gene LinkOut

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