Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase

MAN1B1 encodes endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase, an enzyme involved in glycoprotein quality control. It functions by trimming alpha-1,2-linked mannose residues from misfolded glycoproteins to facilitate their recognition and degradation, primarily converting Man(9)GlcNAc(2) to Man(8)GlcNAc(2) (UniProt: Q9UKM7). MAN1B1 operates within the endoplasmic reticulum quality control compartment and is associated with Rafiq syndrome, an autosomal recessive neurodevelopmental disorder characterized by intellectual disability, motor impairment, and distinctive craniofacial features (UniProt: Q9UKM7).

In Alzheimer's Disease, MAN1B1 protein levels are significantly reduced in post-mortem AD brain tissue compared to age-matched controls. Analysis of human post-mortem AD brain samples using TMT-labeled proteomics across subcellular fractions identified a mean log2 fold-change of −0.72 (Chaparral AD proteomics). This downregulation suggests potential dysregulation of ER-mediated protein quality control mechanisms in AD pathology, though the functional significance of this change requires further investigation.