PKHD1
PKHD1 ( . Engl . Abbreviation for polycystic kidney and hepatic disease 1 = "polycystic kidney and liver disease 1") is a gene that both in humans and other mammals - species , the genome is included. PKHD1 is one of the largest human genes known to date.
function
The PKHD1 gene codes for the transmembrane protein fibrocystin . Fibrocystin is found in the basal body of the primary cilia . In the apical domain of polarized epithelial cells , it appears to play an important role in the formation of the tubules and / or the maintenance of the architecture of the lumen of the collecting duct in the kidney . Mutations in PKHD1 can autosomal - recessive inherited and then to autosomal recessive polycystic kidney disease (ARPKD) - often along with a congenital liver fibrosis - lead. ARPKD is the most severe form of cystic kidney and often occurs in early childhood.
genetics
The PKHD1 gene is located in humans on chromosome 6 gene locus p21.2-p12. It is about 469 kb and contains at least 86 exons , which encode a protein (fibrocystin) with 4074 amino acids . The exons are transcribed into a variety of different proteins by alternative splicing . The longest open reading frame is 12,222 base pairs with 67 exons.
Mutations
The PKHD1 gene is characterized by a very high diversity, so there are very many different alleles within the population. In 2005, 263 different PKHD1 mutations were identified, which were found in 639 mutated alleles. The mutations are found throughout the gene, but they are not evenly distributed across the gene.
Individual evidence
- ↑ PKHD1 (Polycystic Kidney and Hepatic Disease 1) ( Memento of the original dated November 2, 2005 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. Aachen University Hospital, accessed on September 19, 2008
- ↑ LF Onuchic et al: PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats. In: Am J Hum Genet 52, 2002, pp. 1305-1317 PMID 11898128
- ↑ a b C. J. Ward et al .: Cellular and subcellular localization of the ARPKD protein; fibrocystin is expressed on primary cilia. In: Human Molecular Genetics , 12, 2003, pp. 2703-2710. PMID 12925574
- ↑ C. Bergmann et al.: Algorithm for efficient PKHD1 mutation screening in autosomal recessive polycystic kidney disease (ARPKD). In: Hum Mutat 25, 2005, pp. 225-231. PMID 15706593
