MAN2B1

Chr 19AR

mannosidase alpha class 2B member 1

Also known as: LAMAN, MANB

NCBI Gene: 4125 ENSG00000104774 UniProt: O00754 OMIM: 609458

The encoded enzyme hydrolyzes terminal alpha-D-mannose residues in oligosaccharides during lysosomal degradation of N-linked glycoproteins. Mutations cause alpha-mannosidosis types I and II, a lysosomal storage disorder with autosomal recessive inheritance that affects multiple organ systems including the nervous system, skeleton, and immune system. This gene shows very low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mannosidosis, alpha-, types I and IIMIM #248500

Clinical highlights

Gene-disease validity (ClinGen)

alpha-mannosidosis · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.97

LOEUF

LOF

Mechanism· G2P

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GeneReview available — MAN2B1