Fibrocystin
Mammalian protein
From Wikipedia, the free encyclopedia
Fibrocystin is a large, receptor-like protein that in humans is encoded by the PKHD1 gene. It is thought to be involved in the tubulogenesis and/or maintenance of duct-lumen architecture of epithelium.[5] FPC associates with the primary cilia of epithelial cells and co-localizes with the Pkd2 gene product polycystin-2 (PC2), suggesting that these two proteins may function in a common molecular pathway.[6]
Pathology
Mutations of its encoding gene (chromosomal locus 6p12.2) can cause autosomal recessive polycystic kidney disease (ARPKD). PKHD1 gene codes for fibrocystin. Fibrocystin is found in the epithelial cell of both the renal tubule and the bile ducts. A mutation in PKHD1 (can be autosomal recessive pattern or spontaneous mutations) leading to a deficiency in fibrocystin causes characteristic polycystic dilation of both structures.
PKHD1 is a relatively large gene, comprising dozens of exons and introns, and multiple alternatively spliced isoforms.[7] ARPKD has been shown to be caused numerous reports of biallelic truncating mutations, including missense mutations - elucidating that the disease may stem from the absence of PKHD1 or, alternatively, it's abnormal structure. Morover, several report have shown that non-coding deep-intronic variant can introduce a pathogenic pseudoexon (an intronic sequence that is being mistakenly recognised as an exon by the cell's splicing mechanism) into the coding sequence - resulting in a premature stop codon and total loss of th protein.[8] While these cases are rare and sporadic relative to the identification of "straight forward" coding mutations in PKHD1, the can be a major cause of morbidity in specific isolated population, such as Israeli Bedouins.
