Pathology

 germline mutation in

• cryptogenic cirrhosis (MIM.215600)

 genic variants in

• risk factor for hepatic cirrhosis
• risk factor for chronic pancreatitis
• inflammatory bowel disease (IBDs) (Crohn disease or ulcerative colitis)

 KRT8 (and KRT18) proteins hyperphosphorylation

• site-specific keratin phosphorylation in liver disease is a progression marker when increased and a likely regression marker when decreased (#15368451#)
• KRT8 (and KRT18) phosphorylation plays a significant and site-specific role in regulating keratin filament organization, association with binding proteins, and modulation of cell cycle progression. (#15368451#)

References

 Owens DW, Lane EB. Keratin mutations and intestinal pathology. J Pathol. 2004 Nov;204(4):377-85. PMID: #15495267#

 Buning C, Halangk J, Dignass A, Ockenga J, Deindl P, Nickel R, Genschel J, Landt O, Lochs H, Schmidt H, Witt H. Keratin 8 Y54H and G62C mutations are not associated with inflammatory bowel disease. Dig Liver Dis. 2004 Jun;36(6):388-91. PMID: #15248378#

 Zatloukal K, Stumptner C, Fuchsbichler A, Fickert P, Lackner C, Trauner M, Denk H. The keratin cytoskeleton in liver diseases. J Pathol. 2004 Nov;204(4):367-76. PMID: #15495250#

 Owens DW, Wilson NJ, Hill AJ, Rugg EL, Porter RM, Hutcheson AM, Quinlan RA, van Heel D, Parkes M, Jewell DP, Campbell SS, Ghosh S, Satsangi J, Lane EB. Human keratin 8 mutations that disturb filament assembly observed in inflammatory bowel disease patients. J Cell Sci. 2004 Apr 15;117(Pt 10):1989-99. PMID: #15090596#

 Ku NO, Gish R, Wright TL, Omary MB. Keratin 8 mutations in patients with cryptogenic liver disease. N Engl J Med. 2001 May 24;344(21):1580-7. PMID: #11372009#

 Cavestro GM, Frulloni L, Nouvenne A, Neri TM, Calore B, Ferri B, Bovo P, Okolicsanyi L, Di Mario F, Cavallini G. Association of keratin 8 gene mutation with chronic pancreatitis. Dig Liver Dis. 2003 Jun;35(6):416-20. PMID: #12868678#

 Drenth JP, Verlaan M. Genetic aspects of chronic pancreatitis, and the exploration of an association with keratin 8/18. Dig Liver Dis. 2003 Jun;35(6):386-8. PMID: #12868673#