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MIM.177060 19p13.2-p13.1

Monday 6 October 2003

The protein product of the PRKCSH gene is reported as hepatocystin and predicted it to be localized to the endoplasmic reticulum. MIM.177060. Locus:19p13.2-p13.1


PRKCSH encodes a previously described human protein termed "protein kinase C substrate 80K-H" or "noncatalytic beta-subunit of glucosidase II." This protein is highly conserved, is expressed in all tissues tested, and contains a leader sequence, an LDLa domain, two EF-hand domains, and a conserved C-terminal HDEL sequence. Its function may be dependent on calcium binding, and its putative actions include the regulation of N-glycosylation of proteins and signal transduction via fibroblast growth-factor receptor.


- mutations in autosomal dominant polycystic liver disease (ADPLD) (12529853)

  • ADPLD is a rare disorder that is characterized by the progressive development of fluid-filled biliary epithelial cysts in the liver.
  • Positional cloning has identified two genes that are mutated in ADPLD, PRKCSH and SEC63, which encode the beta-subunit of glucosidase II and Sec63, respectively.
  • Both proteins are components of the molecular machinery involved in the translocation, folding and quality control of newly synthesized glycoproteins in the endoplasmic reticulum.
  • Most mutations are truncating and probably lead to a complete loss of the corresponding proteins and the defective processing of a key regulator of biliary cell growth.
  • In light of the focal nature of liver cysts in ADPLD, the apparent loss-of-function mutations in PRKCSH, and the two-hit mechanism operational in dominant polycystic kidney disease, ADPLD may also occur by a two-hit mechanism.


- Drenth JP, Martina JA, van de Kerkhof R, Bonifacino JS, Jansen JB. Polycystic liver disease is a disorder of cotranslational protein processing. Trends Mol Med. 2005 Jan;11(1):37-42. PMID: 15649821

- Drenth JP, Martina JA, Te Morsche RH, Jansen JB, Bonifacino JS. Molecular characterization of hepatocystin, the protein that is defective in autosomal dominant polycystic liver disease. Gastroenterology. 2004 Jun;126(7):1819-27. PMID: 15188177

- Drenth JP, Tahvanainen E, te Morsche RH, Tahvanainen P, Kaariainen H, Hockerstedt K, van de Kamp JM, Breuning MH, Jansen JB. Abnormal hepatocystin caused by truncating PRKCSH mutations leads to autosomal dominant polycystic liver disease. Hepatology. 2004 Apr;39(4):924-31. PMID: 15057895

- Drenth JP, te Morsche RH, Smink R, Bonifacino JS, Jansen JB. Germline mutations in PRKCSH are associated with autosomal dominant polycystic liver disease. Nat Genet. 2003 Mar;33(3):345-7. PMID: 12577059