Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome

Nat Genet. 2004 Apr;36(4):400-4. doi: 10.1038/ng1325. Epub 2004 Mar 28.


ARC syndrome (OMIM 208085) is an autosomal recessive multisystem disorder characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with bile duct hypoplasia and low gamma glutamyl transpeptidase (gGT) activity. Platelet dysfunction is common. Affected infants do not thrive and usually die in the first year of life. To elucidate the molecular basis of ARC, we mapped the disease to a 7-cM interval on 15q26.1 and then identified germline mutations in the gene VPS33B in 14 kindreds with ARC. VPS33B encodes a homolog of the class C yeast vacuolar protein sorting gene, Vps33, that contains a Sec1-like domain important in the regulation of vesicle-to-target SNARE complex formation and subsequent membrane fusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthrogryposis / genetics*
  • Blotting, Western
  • Cell Line
  • Cholestasis / genetics*
  • Chromosomes, Human, Pair 15
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Humans
  • Kidney Diseases / genetics*
  • Male
  • Membrane Fusion / genetics
  • Membrane Fusion / physiology*
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Membrane Proteins / physiology*
  • Mutation*
  • Plasmids
  • Proteins / chemistry
  • Proteins / genetics*
  • SNARE Proteins
  • Syndrome
  • Vesicular Transport Proteins*


  • Membrane Proteins
  • Proteins
  • SNARE Proteins
  • VPS33B protein, human
  • Vesicular Transport Proteins