PKD1 - polycystic kidney disease 1 (autosomal dominant)

Human Kidney Gene DataBase

Name

polycystic kidney disease 1 (autosomal dominant)

Symbol

PKD1

Aliases

PBP

Gene Product

polycystin 1 precursor

Category

Deletion in Kidney Cystic Disease
LOH in Kidney Cystic Disease
Mutation in End-Stage Renal Disease
Mutation in Kidney Cystic Disease
Polymorphism in Kidney Cystic Disease

UniGene

Hs.75813

Reference Sequence

mRNA: NM_000296

Protein: NP_000287

OMIM and SNP

OMIM: 601313

SNP: NCBI SNP

Locus

LocusLink: 5310

Chromosome: 16

Cytoband: 16p13.3

UCSC Genome Map

Eesembl Genome Map

Summary

This gene encodes a member of the polycystin protein family. Expression of this gene has been linked to the Beta-catenin/TCF pathway. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains, and a cytoplasmic C-tail. The encoded protein may undergo cleavage at a G protein coupled receptor proteolytic site in a process that requires the receptor for egg jelly domain. This protein may function as an integral membrane protein involved in cell-cell/matrix interactions and may modulate intracellular calcium homoeostasis and other signal-transduction pathways. The encoded protein plays a role in renal tubular development. Interactions of this protein with polycystin 2 produce cation-permeable currents. Mutations in this gene have been associated with autosomal dominant polycystic kidney disease. An alternative splice variant has been described but its biological nature has not been determined. Six pseudogenes have been described and are closely linked in a known duplicated region on chromosome 16p.

Gene Ontology

cellular component: integral to plasma membrane
molecular function: sugar binding
biological process: calcium-independent cell-matrix adhesion
biological process: neuropeptide signaling pathway
biological process: heterophilic cell adhesion
biological process: homophilic cell adhesion
biological process: morphogenesis

Expression

EST (275 ESTs, 148 libraries)
Tissue	Breadth ?	CPM ?
blood
bone
brain
cartilage
cerebellum
cervix
colon
ear
embryo
eye
germ cell
head and neck
heart
kidney
lung
lymph node
mammary gland
muscle
nervous
oral cavity
ovary
pancreas
pineal gland
placenta
prostate
skin
spleen
stomach
testis
thymus
uncharacterized tissue
uterus
whole body

SAGE (16728439 tags, 320 libraries)
Tissue	Breadth ?	CPM ?
blood
brain
cerebellum
cervix
colon
eye
foreskin
heart
kidney
liver
lung
mammary gland
mesothelial tissue
muscle
nervous
ovary
pancreas
prostate
skin
stomach
uncharacterized tissue
vascular

Evidence

Deletion in Kidney Cystic Disease

Tsuchiya K, Komeda M, Takahashi M, Yamashita N, Cigira M, Suzuki T, Suzuki K, Nihei H, Mochizuki T, Tsuchiya K, Komeda M, Takahashi M, Yamashita N, Cigira M, Suzuki T, Suzuki K, Nihei H, Mochizuki T, Tsuchiya K, Komeda M, Takahashi M, Yamashita N, Cigira M, Suzuki T, Suzuki K, Nihei H, Mochizuki T Mutational analysis within the 3' region of the PKD1 gene in Japanesefamilies. Mutat Res 2001 Dec;458(3-4):77-84.
Bouba I, Koptides M, Mean R, Costi CE, Demetriou K, Georgiou I, Pierides A, Siamopoulos K, Deltas CC, Bouba I, Koptides M, Mean R, Costi CE, Demetriou K, Georgiou I, Pierides A, Siamopoulos K, Deltas CC, Bouba I, Koptides M, Mean R, Costi CE, Demetriou K, Georgiou I, Pierides A, Siamopoulos K, Deltas CC, Bouba I, Koptides M, Mean R, Costi CE, Demetriou K, Georgiou I, Pierides A, Siamopoulos K, Deltas CC Novel PKD1 deletions and missense variants in a cohort of Hellenicpolycystic kidney disease families. Eur J Hum Genet 2001 Sep;9(9):677-84.
Longa L, Scolari F, Brusco A, Carbonara C, Polidoro S, Valzorio B, Riegler P, Migone N, Maiorca R A large TSC2 and PKD1 gene deletion is associated with renal andextrarenal signs of autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 1997 Sep;12(9):1900-7.
Brook-Carter PT, Peral B, Ward CJ, Thompson P, Hughes J, Maheshwar MM, Nellist M, Gamble V, Harris PC, Sampson JR Deletion of the TSC2 and PKD1 genes associated with severe infantilepolycystic kidney disease--a contiguous gene syndrome. Nat Genet 1994 Dec;8(4):328-32.
Ariyurek Y, Leeuwen IL, Spruit L, Ravine D, Breuning MH, Peters DJ, Ariyurek Y, Leeuwen IL, Spruit L, Ravine D, Breuning MH, Peters DJ Large deletions in the polycystic kidney disease 1 (PKD1) gene. Hum Mutat 2004 Jan;23(1):99.

LOH in Kidney Cystic Disease

Badenas C, Torra R, Perez-Oller L, Mallolas J, Talbot-Wright R, Torregrosa V, Darnell A Loss of heterozygosity in renal and hepatic epithelial cystic cells fromADPKD1 patients. Eur J Hum Genet 2000 Jul;8(7):487-92.
Brasier JL, Henske EP, Brasier JL, Henske EP Loss of the polycystic kidney disease (PKD1) region of chromosome 16p13 inrenal cyst cells supports a loss-of-function model for cyst pathogenesis. J Clin Invest 1997 Jan 15;99(2):194-9.

Mutation in End-Stage Renal Disease

Rossetti S, Burton S, Strmecki L, Pond GR, San Millan JL, Zerres K, Barratt TM, Ozen S, Torres VE, Bergstralh EJ, Winearls CG, Harris PC, Rossetti S, Burton S, Strmecki L, Pond GR, San Millan JL, Zerres K, Barratt TM, Ozen S, Torres VE, Bergstralh EJ, Winearls CG, Harris PC The position of the polycystic kidney disease 1 (PKD1) gene mutationcorrelates with the severity of renal disease. J Am Soc Nephrol 2002 May;13(5):1230-7.

Mutation in Kidney Cystic Disease

Rossetti S, Chauveau D, Walker D, Saggar-Malik A, Winearls CG, Torres VE, Harris PC, Rossetti S, Chauveau D, Walker D, Saggar-Malik A, Winearls CG, Torres VE, Harris PC A complete mutation screen of the ADPKD genes by DHPLC. Kidney Int 2002 May;61(5):1588-99.
Ding L, Zhang S, Qiu W, Xiao C, Wu S, Zhang G, Cheng L, Zhang S, Ding L, Zhang S, Qiu W, Xiao C, Wu S, Zhang G, Cheng L, Zhang S Novel mutations of PKD1 gene in Chinese patients with autosomal dominantpolycystic kidney disease. Nephrol Dial Transplant 2002 Jan;17(1):75-80.
Tsuchiya K, Komeda M, Takahashi M, Yamashita N, Cigira M, Suzuki T, Suzuki K, Nihei H, Mochizuki T, Tsuchiya K, Komeda M, Takahashi M, Yamashita N, Cigira M, Suzuki T, Suzuki K, Nihei H, Mochizuki T, Tsuchiya K, Komeda M, Takahashi M, Yamashita N, Cigira M, Suzuki T, Suzuki K, Nihei H, Mochizuki T Mutational analysis within the 3' region of the PKD1 gene in Japanesefamilies. Mutat Res 2001 Dec;458(3-4):77-84.
Perrichot RA, Mercier B, de Parscau L, Simon PM, Cledes J, Ferec C Inheritance of a stable mutation in a family with early-onset disease. Nephron 2001 Apr;87(4):340-5.
Afzal AR, Florencio RN, Taylor R, Patton MA, Saggar-Malik A, Jeffery S, Afzal AR, Florencio RN, Taylor R, Patton MA, Saggar-Malik A, Jeffery S Novel mutations in the duplicated region of the polycystic kidney disease1 (PKD1) gene provides supporting evidence for gene conversion. Genet Test 2000;4(4):365-70.
Pei Y, Paterson AD, Wang KR, He N, Hefferton D, Watnick T, Germino GG, Parfrey P, Somlo S, St George-Hyslop P Bilineal disease and trans-heterozygotes in autosomal dominant polycystickidney disease. Am J Hum Genet 2001 Feb;68(2):355-63. Epub 2001 Jan 10.
Aguiari G, Savelli S, Garbo M, Bozza A, Augello G, Penolazzi L, De Paoli Vitali E, La Torre C, Cappelli G, Piva R, del Senno L, Aguiari G, Savelli S, Garbo M, Bozza A, Augello G, Penolazzi L, De Paoli Vitali E, La Torre C, Cappelli G, Piva R, del Senno L Novel splicing and missense mutations in autosomal dominant polycystickidney disease 1 (PKD1) gene: expression of mutated genes. Hum Mutat 2000 Nov;16(5):444-5.
Phakdeekitcharoen B, Watnick TJ, Ahn C, Whang DY, Burkhart B, Germino GG Thirteen novel mutations of the replicated region of PKD1 in an Asianpopulation. Kidney Int 2000 Oct;58(4):1400-12.
Inoue S, Inoue K, Utsunomiya M, Nozaki J, Yamada Y, Iwasa T, Mori E, Yoshinaga T, Koizumi A, Inoue S, Inoue K, Utsunomiya M, Nozaki J, Yamada Y, Iwasa T, Mori E, Yoshinaga T, Koizumi A Mutation analysis in PKD1 of Japanese autosomal dominant polycystic kidneydisease patients. Hum Mutat 2002 Jun;19(6):622-8.
McCluskey M, Schiavello T, Hunter M, Hantke J, Angelicheva D, Bogdanova N, Markoff A, Thomas M, Dworniczak B, Horst J, Kalaydjieva L, McCluskey M, Schiavello T, Hunter M, Hantke J, Angelicheva D, Bogdanova N, Markoff A, Thomas M, Dworniczak B, Horst J, Kalaydjieva L Mutation detection in the duplicated region of the polycystic kidneydisease 1 (PKD1) gene in PKD1-linked Australian families. Hum Mutat 2002 Mar;19(3):240-50.
Mizoguchi M, Tamura T, Yamaki A, Higashihara E, Shimizu Y, Mizoguchi M, Tamura T, Yamaki A, Higashihara E, Shimizu Y Mutations of the PKD1 gene among Japanese autosomal dominant polycystickidney disease patients, including one heterozygous mutation identified inmembers of the same family. J Hum Genet 2001;46(9):511-7.
Rossetti S, Strmecki L, Gamble V, Burton S, Sneddon V, Peral B, Roy S, Bakkaloglu A, Komel R, Winearls CG, Harris PC Mutation analysis of the entire PKD1 gene: genetic and diagnosticimplications. Am J Hum Genet 2001 Jan;68(1):46-63. Epub 2000 Dec 12.
Perrichot RA, Mercier B, Simon PM, Whebe B, Cledes J, Ferec C DGGE screening of PKD1 gene reveals novel mutations in a large cohort of146 unrelated patients. Hum Genet 1999 Sep;105(3):231-9.
Bogdanova N, McCluskey M, Sikmann K, Markoff A, Todorov V, Dimitrakov D, Schiavello T, Thomas M, Kalaydjieva L, Dworniczak B, Horst J, Bogdanova N, McCluskey M, Sikmann K, Markoff A, Todorov V, Dimitrakov D, Schiavello T, Thomas M, Kalaydjieva L, Dworniczak B, Horst J Screening the 3' region of the polycystic kidney disease 1 (PKD1) gene in41 Bulgarian and Australian kindreds reveals a prevalence of proteintruncating mutations. Hum Mutat 2000;16(2):166-74.
Koptides M, Mean R, Demetriou K, Constantinides R, Pierides A, Harris PC, Deltas CC Screening of the PKD1 duplicated region reveals multiple single nucleotidepolymorphisms and a de novo mutation in Hellenic polycystic kidney diseasefamilies. Hum Mutat 2000 Aug;16(2):176.
Perrichot R, Mercier B, Quere I, Carre A, Simon P, Whebe B, Cledes J, Ferec C Novel mutations in the duplicated region of PKD1 gene. Eur J Hum Genet 2000 May;8(5):353-9.
Kim UK, Jin DK, Ahn C, Shin JH, Lee KB, Kim SH, Chae JJ, Hwang DY, Lee JG, Namkoong Y, Lee CC, Kim UK, Jin DK, Ahn C, Shin JH, Lee KB, Kim SH, Chae JJ, Hwang DY, Lee JG, Namkoong Y, Lee CC Novel mutations of the PKD1 gene in Korean patients with autosomaldominant polycystic kidney disease. Mutat Res 2000 Feb;432(1-2):39-45.
Koptides M, Mean R, Demetriou K, Pierides A, Deltas CC Genetic evidence for a trans-heterozygous model for cystogenesis inautosomal dominant polycystic kidney disease. Hum Mol Genet 2000 Feb 12;9(3):447-52.
Afzal AR, Hand M, Ternes-Pereira E, Saggar-Malik A, Taylor R, Jeffery S, Afzal AR, Hand M, Ternes-Pereira E, Saggar-Malik A, Taylor R, Jeffery S Novel mutations in the 3 region of the polycystic kidney disease 1 (PKD1)gene. Hum Genet 1999 Dec;105(6):648-53.
Thongnoppakhun A, Rungroj N, Wilairat P, Vareesangthip K, Sirinavin C, Yenchitsomanus PT, Thongnoppakhun A, Rungroj N, Wilairat P, Vareesangthip K, Sirinavin C, Yenchitsomanus PT, Thongnoppakhun A, Rungroj N, Wilairat P, Vareesangthip K, Sirinavin C, Yenchitsomanus PT A novel splice-acceptor site mutation (IVS13-2A>T) of polycystic kidneydisease 1 (PKD1) gene resulting in an RNA processing defect with a74-nucleotide deletion in exon 14 of the mRNA transcript. Hum Mutat 2000 Jan;15(1):115.
Thomas R, McConnell R, Whittacker J, Kirkpatrick P, Bradley J, Sandford R Identification of mutations in the repeated part of the autosomal dominantpolycystic kidney disease type 1 gene, PKD1, by long-range PCR. Am J Hum Genet 1999 Jul;65(1):39-49.
Koptides M, Constantinides R, Kyriakides G, Hadjigavriel M, Patsalis PC, Pierides A, Deltas CC Loss of heterozygosity in polycystic kidney disease with a missensemutation in the repeated region of PKD1. Hum Genet 1998 Dec;103(6):709-17.
Daniells C, Maheshwar M, Lazarou L, Davies F, Coles G, Ravine D, Daniells C, Maheshwar M, Lazarou L, Davies F, Coles G, Ravine D Novel and recurrent mutations in the PKD1 (polycystic kidney disease)gene. Hum Genet 1998 Feb;102(2):216-20.
Roelfsema JH, Spruit L, Saris JJ, Chang P, Pirson Y, van Ommen GJ, Peters DJ, Breuning MH, Roelfsema JH, Spruit L, Saris JJ, Chang P, Pirson Y, van Ommen GJ, Peters DJ, Breuning MH Mutation detection in the repeated part of the PKD1 gene. Am J Hum Genet 1997 Nov;61(5):1044-52.
Torra R, Badenas C, Darnell A, Bru C, Escorsell A, Estivill X, Torra R, Badenas C, Darnell A, Bru C, Escorsell A, Estivill X Autosomal dominant polycystic kidney disease with anticipation andCaroli's disease associated with a PKD1 mutation. Rapid communication. Kidney Int 1997 Jul;52(1):33-8.
Rossetti S, Bresin E, Restagno G, Carbonara A, Corra S, De Prisco O, Pignatti PF, Turco AE Autosomal dominant polycystic kidney disease (ADPKD) in an Italian familycarrying a novel nonsense mutation and two missense changes in exons 44and 45 of the PKD1 Gene. Am J Med Genet 1996 Oct 16;65(2):155-9.
Neophytou P, Constantinides R, Lazarou A, Pierides A, Deltas CC, Neophytou P, Constantinides R, Lazarou A, Pierides A, Deltas CC, Neophytou P, Constantinides R, Lazarou A, Pierides A, Deltas CC Detection of a novel nonsense mutation and an intragenic polymorphism inthe PKD1 gene of a Cypriot family with autosomal dominant polycystickidney disease. Hum Genet 1996 Oct;98(4):437-42.
Peral B, Ong AC, San Millan JL, Gamble V, Rees L, Harris PC A stable, nonsense mutation associated with a case of infantile onsetpolycystic kidney disease 1 (PKD1). Hum Mol Genet 1996 Apr;5(4):539-42.
Peral B, San Millan JL, Ong AC, Gamble V, Ward CJ, Strong C, Harris PC Screening the 3' region of the polycystic kidney disease 1 (PKD1) genereveals six novel mutations. Am J Hum Genet 1996 Jan;58(1):86-96.
Turco AE, Rossetti S, Bresin E, Corra S, Gammaro L, Maschio G, Pignatti PF A novel nonsense mutation in the PKD1 gene (C3817T) is associated withautosomal dominant polycystic kidney disease (ADPKD) in a largethree-generation Italian family. Hum Mol Genet 1995 Aug;4(8):1331-5.
Coto E, Aguado S, Alvarez J, Menendez Diaz MJ, Lopez-Larrea C Genetic and clinical studies in autosomal dominant polycystic kidneydisease type 1 (ADPKD1). J Med Genet 1992 Apr;29(4):243-6.
Parfrey PS, Bear JC, Morgan J, Cramer BC, McManamon PJ, Gault MH, Churchill DN, Singh M, Hewitt R, Somlo S, et al. The diagnosis and prognosis of autosomal dominant polycystic kidneydisease. N Engl J Med 1990 Oct 18;323(16):1085-90.

Polymorphism in Kidney Cystic Disease

Baboolal K, Ravine D, Daniels J, Williams N, Holmans P, Coles GA, Williams JD, Baboolal K, Ravine D, Daniels J, Williams N, Holmans P, Coles GA, Williams JD Association of the angiotensin I converting enzyme gene deletionpolymorphism with early onset of ESRF in PKD1 adult polycystic kidneydisease. Kidney Int 1997 Sep;52(3):607-13.

Other key publications related to this gene