VPS33B Gene

The VPS33B gene (VPS33B stands for Vacuolar Protein Sorting-Associated Protein 33B) is a protein-coding gene , located on chromosome 15q26.1.

Vesicle-mediated protein sorting plays an important role in the partitioning of intracellular molecules to different organelles. Genetic studies in yeast have identified more than 40 genes involved in vacuolar protein sorting (VPS). Appears to be involved in sorting specific cargoes from the trans-Golgi network into alpha-granule-directed multivesicular bodies (MVBs).

The encoded protein may play a role in vesicle-mediated protein transport to lysosomal compartments and in membrane docking/fusion reactions of late endosomes/lysosomes. It is required for the proper transport and targeting of the collagen-modifying enzyme lysylhydroxylase 3 (LH3) to intracellular collagen (Gruber R et al. 2017)

Mediates phagolysosome fusion in macrophages. Presumably involved in endosome maturation with the participation of VIPAS39. In epithelial cells, the VPS33B:VIPAS39 complex may play a role in the apical recycling pathway and in the maintenance of apical-basolateral polarity (Bach H et al. 2008). Appears to be involved in sorting specific cargoes from the trans-Golgi network to alpha-granular multivesicular bodies (MVBs), thereby promoting MVBs maturation in megakaryocytes.

Diseases associated with VPS33B include

• Arthrogryposis, renal dysfunction and cholestasis
• Progressive familial intrahepatic cholestasis
• ARKID syndrome (biallelic mutations in VPS33B)

1. Alter S et al. (2018) Novel VPS33B mutation in a patient with autosomal recessive keratoderma-ichthyosis-deafness syndrome. Am J Med Genet A 176:2862-2866
2. Bach H et al. (2008) Mycobacterium tuberculosis virulence is mediated by PtpA dephosphorylation of human vacuolar protein sorting 33B. Cell Host Microbe. 2008 May 15;3(5):316-22.
3. Chai M et al. (2018) Identification of genes and signaling pathways associated with arthrogryposis-renal dysfunction-cholestasis syndrome using weighted correlation network analysis. Int J Mol Med 42:2238-2246.
4. Gruber R et al. (2017) Autosomal Recessive Keratoderma-Ichthyosis-Deafness (ARKID) Syndrome Is Caused by VPS33B Mutations Affecting Rab Protein Interaction and Collagen Modification. J Invest Dermatol 137:845-854.
5. Huang DG et al. (2017) Clinical features and VPS33B mutations in a family affected by arthrogryposis, renal dysfunction, and cholestasis syndrome. Zhongguo Dang Dai Er Ke Za Zhi 19:1077-1082.
6. Ilhan O et al. (2016) Arthrogryposis-renal tubular dysfunction-cholestasis syndrome: a cause of neonatal cholestasis. Case report. Arch Argent Pediatr 114:e9-12.
7. Moon AT et al. (2017) A Novel VPS33B Mutation in a Patient with Arthrogryposis-Renal Dysfunction-Cholestasis Syndrome. Pediatr Dermatol 34:e171-e173.