U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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

Gene ID: 4125, updated on 3-Apr-2024

Summary

Go to the top of the page Help
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
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
Location:
19p13.13
Exon count:
24
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (12646512..12666742, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (12771019..12791240, complement)
105.20220307 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

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • Project title: 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

Go to the top of the pageHelp

Related articles in PubMed

  1. Hearing impairment as an early sign of alpha-mannosidosis in children with a mild phenotype: Report of seven new cases. Lehalle D, et al. Am J Med Genet A, 2019 Sep. PMID 31241255
  2. 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
  3. 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
  4. 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
  5. 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

See all (72) 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

Go to the top of the page Help

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
Compare labs

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

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

Go to the top of the page Help

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

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

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

Go to the top of the page Help
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)

Go to the top of the page Help

NEW Try the new Transcript table

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, ENST00000221363.8
    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_2023_10

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

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Medical
Molecular Biology Databases
Research Materials
Tools
Miscellaneous