ID PKHD1_HUMAN Reviewed; 4074 AA. AC P08F94; Q5VUA2; Q5VUA3; Q5VWV1; Q86Z26; Q8TCZ9; DT 18-MAY-2010, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 1. DT 27-MAR-2024, entry version 112. DE RecName: Full=Fibrocystin {ECO:0000305}; DE AltName: Full=Polycystic kidney and hepatic disease 1 protein; DE AltName: Full=Polyductin; DE AltName: Full=Tigmin; DE Flags: Precursor; GN Name=PKHD1 {ECO:0000303|PubMed:28375157, ECO:0000312|HGNC:HGNC:9016}; GN Synonyms=FCYT, TIGM1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, VARIANTS PKD4 MET-36; RP VAL-222; TRP-1249; ARG-1407; PHE-1664; MET-1741; ARG-1917; GLY-1995; RP LYS-2331; THR-2957; PHE-3018 AND THR-3553, AND VARIANTS VAL-25; MET-752; RP CYS-760; ARG-852; VAL-1262; MET-2938; TYR-3139; ILE-3960 AND ARG-4048. RC TISSUE=Kidney; RX PubMed=11919560; DOI=10.1038/ng833; RA Ward C.J., Hogan M.C., Rossetti S., Walker D., Sneddon T., Wang X., RA Kubly V., Cunningham J.M., Bacallao R., Ishibashi M., Milliner D.S., RA Torres V.E., Harris P.C.; RT "The gene mutated in autosomal recessive polycystic kidney disease encodes RT a large, receptor-like protein."; RL Nat. Genet. 30:259-269(2002). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), ALTERNATIVE SPLICING, RP VARIANTS PKD4 MET-36; VAL-222; LEU-253; HIS-760; SER-1122; TRP-1624 AND RP THR-2957, AND VARIANTS VAL-1870 AND TYR-3139. RC TISSUE=Kidney; RX PubMed=11898128; DOI=10.1086/340448; RA Onuchic L.F., Furu L., Nagasawa Y., Hou X., Eggermann T., Ren Z., RA Bergmann C., Senderek J., Esquivel E., Zeltner R., Rudnik-Schoeneborn S., RA Mrug M., Sweeney W., Avner E.D., Zerres K., Guay-Woodford L.M., Somlo S., RA Germino G.G.; RT "PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel RT large protein containing multiple immunoglobulin-like-plexin-transcription- RT factor domains and parallel beta-helix 1 repeats."; RL Am. J. Hum. Genet. 70:1305-1317(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT TYR-1204. RC TISSUE=Fetal kidney; RX PubMed=12079288; DOI=10.1006/geno.2002.6802; RA Xiong H., Chen Y., Yi Y., Tsuchiya K., Moeckel G., Cheung J., Liang D., RA Tham K., Xu X., Chen X.-Z., Pei Y., Zhao Z.J., Wu G.; RT "A novel gene encoding a TIG multiple domain protein is a positional RT candidate for autosomal recessive polycystic kidney disease."; RL Genomics 80:96-104(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=14978161; DOI=10.1097/01.asn.0000113793.12558.1d; RA Wang S., Luo Y., Wilson P.D., Witman G.B., Zhou J.; RT "The autosomal recessive polycystic kidney disease protein is localized to RT primary cilia, with concentration in the basal body area."; RL J. Am. Soc. Nephrol. 15:592-602(2004). RN [7] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=15458427; DOI=10.1111/j.1523-1755.2004.00844.x; RA Menezes L.F., Cai Y., Nagasawa Y., Silva A.M., Watkins M.L., Da Silva A.M., RA Somlo S., Guay-Woodford L.M., Germino G.G., Onuchic L.F.; RT "Polyductin, the PKHD1 gene product, comprises isoforms expressed in plasma RT membrane, primary cilium, and cytoplasm."; RL Kidney Int. 66:1345-1355(2004). RN [8] RP MUTAGENESIS OF 3617-LYS-ARG-3618, PROTEOLYTIC PROCESSING, CLEAVAGE SITE, RP SHEDDING, AND SUBCELLULAR LOCATION. RX PubMed=17470460; DOI=10.1093/hmg/ddm039; RA Kaimori J.Y., Nagasawa Y., Menezes L.F., Garcia-Gonzalez M.A., Deng J., RA Imai E., Onuchic L.F., Guay-Woodford L.M., Germino G.G.; RT "Polyductin undergoes notch-like processing and regulated release from RT primary cilia."; RL Hum. Mol. Genet. 16:942-956(2007). RN [9] RP INTERACTION WITH PKD2. RX PubMed=18235088; DOI=10.1681/asn.2007070770; RA Kim I., Fu Y., Hui K., Moeckel G., Mai W., Li C., Liang D., Zhao P., Ma J., RA Chen X.Z., George A.L. Jr., Coffey R.J., Feng Z.P., Wu G.; RT "Fibrocystin/polyductin modulates renal tubular formation by regulating RT polycystin-2 expression and function."; RL J. Am. Soc. Nephrol. 19:455-468(2008). RN [10] RP INTERACTION WITH CAMLG. RX PubMed=16243292; DOI=10.1016/j.bbrc.2005.10.022; RA Nagano J., Kitamura K., Hujer K.M., Ward C.J., Bram R.J., Hopfer U., RA Tomita K., Huang C., Miller R.T.; RT "Fibrocystin interacts with CAML, a protein involved in Ca2+ signaling."; RL Biochem. Biophys. Res. Commun. 338:880-889(2005). RN [11] RP PROTEOLYTIC PROCESSING, AND SUBCELLULAR LOCATION. RX PubMed=16956880; DOI=10.1074/jbc.m606740200; RA Hiesberger T., Gourley E., Erickson A., Koulen P., Ward C.J., Masyuk T.V., RA Larusso N.F., Harris P.C., Igarashi P.; RT "Proteolytic cleavage and nuclear translocation of fibrocystin is regulated RT by intracellular Ca2+ and activation of protein kinase C."; RL J. Biol. Chem. 281:34357-34364(2006). RN [12] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=20554582; DOI=10.1093/hmg/ddq233; RA Zhang J., Wu M., Wang S., Shah J.V., Wilson P.D., Zhou J.; RT "Polycystic kidney disease protein fibrocystin localizes to the mitotic RT spindle and regulates spindle bipolarity."; RL Hum. Mol. Genet. 19:3306-3319(2010). RN [13] RP FUNCTION. RX PubMed=30898581; DOI=10.1016/j.jhep.2019.02.024; RA Tsunoda T., Kakinuma S., Miyoshi M., Kamiya A., Kaneko S., Sato A., RA Tsuchiya J., Nitta S., Kawai-Kitahata F., Murakawa M., Itsui Y., RA Nakagawa M., Azuma S., Sogo T., Komatsu H., Mukouchi R., Inui A., RA Fujisawa T., Nakauchi H., Asahina Y., Watanabe M.; RT "Loss of fibrocystin promotes interleukin-8-dependent proliferation and RT CTGF production of biliary epithelium."; RL J. Hepatol. 71:143-152(2019). RN [14] RP VARIANTS PKD4 MET-36; SER-223; LEU-253; SER-473; PRO-496; CYS-656; ASN-703; RP HIS-760; LEU-805; LYS-997; GLU-1030; SER-1122; SER-1123; TRP-1249; RP ARG-1407; LEU-1486; TRP-1624; PHE-1664; MET-1741; ARG-1917; GLY-1995; RP THR-1998; PRO-2134; LYS-2331; TYR-2761; THR-2957; PHE-3018; VAL-3081; RP VAL-3293; GLY-3471; CYS-3482 AND THR-3553, AND VARIANTS MET-579; SER-830 RP AND TYR-3139. RX PubMed=12506140; DOI=10.1097/01.asn.0000039578.55705.6e; RA Bergmann C., Senderek J., Sedlacek B., Pegiazoglou I., Puglia P., RA Eggermann T., Rudnik-Schoeneborn S., Furu L., Onuchic L.F., De Baca M., RA Germino G.G., Guay-Woodford L., Somlo S., Moser M., Buettner R., Zerres K.; RT "Spectrum of mutations in the gene for autosomal recessive polycystic RT kidney disease (ARPKD/PKHD1)."; RL J. Am. Soc. Nephrol. 14:76-89(2003). RN [15] RP VARIANTS PKD4 MET-36; VAL-326; ASN-387 DEL; PRO-899; SER-1123; ILE-1584; RP ILE-1781; LEU-1789; GLY-1942; ASP-1971; LEU-2032; GLY-2422; PRO-2772; RP CYS-2863; THR-2957; LEU-2983; GLY-3036; TYR-3124; LEU-3167; ASP-3175; RP SER-3175; THR-3177; VAL-3293 AND SER-3783, AND VARIANTS ASP-457; PHE-732; RP CYS-760; PRO-1150; LEU-1283; PHE-1709; VAL-1870; GLY-2615; ALA-2641; RP GLY-2861; LYS-2869; TYR-3139; ILE-3143; ASP-3440; LYS-3551; ARG-3899 AND RP ILE-3960. RX PubMed=12874454; DOI=10.1097/01.asn.0000078805.87038.05; RA Furu L., Onuchic L.F., Gharavi A., Hou X., Esquivel E.L., Nagasawa Y., RA Bergmann C., Senderek J., Avner E., Zerres K., Germino G.G., RA Guay-Woodford L.M., Somlo S.; RT "Milder presentation of recessive polycystic kidney disease requires RT presence of amino acid substitution mutations."; RL J. Am. Soc. Nephrol. 14:2004-2014(2003). RN [16] RP VARIANTS PKD4 VAL-17; MET-36; VAL-222; LEU-739; LEU-757; LEU-805; THR-1389; RP MET-1741; LEU-1833; CYS-1838; ASN-1867; GLY-1942; PHE-2688; THR-2957; RP THR-3177; ARG-3346; VAL-3468; VAL-3502 AND TYR-3622, AND VARIANTS CYS-760; RP SER-830; VAL-1262; PHE-1709; VAL-1870; LYS-2869; TYR-3139; ARG-3505; RP GLN-3529; ARG-3899; ILE-3960 AND ARG-4048. RX PubMed=12846734; DOI=10.1046/j.1523-1755.2003.00111.x; RA Rossetti S., Torra R., Coto E., Consugar M., Kubly V., Malaga S., RA Navarro M., El-Youssef M., Torres V.E., Harris P.C.; RT "A complete mutation screen of PKHD1 in autosomal-recessive polycystic RT kidney disease (ARPKD) pedigrees."; RL Kidney Int. 64:391-403(2003). RN [17] RP REVIEW ON VARIANTS. RX PubMed=15108277; DOI=10.1002/humu.20029; RA Bergmann C., Senderek J., Kuepper F., Schneider F., Dornia C., Windelen E., RA Eggermann T., Rudnik-Schoeneborn S., Kirfel J., Furu L., Onuchic L.F., RA Rossetti S., Harris P.C., Somlo S., Guay-Woodford L., Germino G.G., RA Moser M., Buettner R., Zerres K.; RT "PKHD1 mutations in autosomal recessive polycystic kidney disease RT (ARPKD)."; RL Hum. Mutat. 23:453-463(2004). RN [18] RP VARIANTS PKD4 MET-36; THR-307; HIS-486; LEU-805; TYR-1472; PHE-2303; RP THR-2957; GLY-2962; TYR-3124; THR-3177 AND CYS-3482, AND VARIANTS LYS-2869 RP AND TYR-3139. RX PubMed=15108281; DOI=10.1002/humu.20019; RA Bergmann C., Senderek J., Schneider F., Dornia C., Kuepper F., RA Eggermann T., Rudnik-Schoeneborn S., Kirfel J., Moser M., Buettner R., RA Zerres K.; RT "PKHD1 mutations in families requesting prenatal diagnosis for autosomal RT recessive polycystic kidney disease (ARPKD)."; RL Hum. Mutat. 23:487-495(2004). RN [19] RP VARIANT PKD4 LEU-372. RX PubMed=16677362; DOI=10.1111/j.1399-3046.2005.00464.x; RA Prelog M., Bergmann C., Ausserlechner M.J., Fischer H., Margreiter R., RA Gassner I., Brunner A., Jungraithmayr T.C., Zerres K., Sergi E.C., RA Zimmerhackl L.B.; RT "Successful transplantation in a child with rapid progression of autosomal RT recessive polycystic kidney disease associated with a novel mutation."; RL Pediatr. Transplant. 10:362-366(2006). RN [20] RP VARIANTS [LARGE SCALE ANALYSIS] HIS-19; CYS-1081; ARG-1096; TRP-1624 AND RP LYS-1806. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [21] RP VARIANTS PKD4 TRP-92; THR-246; CYS-255; VAL-293; GLU-466; VAL-470; THR-539; RP PRO-686; ARG-724; ARG-1712; GLY-1817; GLY-1875; LEU-1928; THR-2009; RP ARG-2106; GLU-2210; LEU-2219; ARG-2224; ARG-2422; VAL-2431; CYS-2573; RP GLY-2798; ARG-2803; LYS-2804; ARG-3049; THR-3207 AND CYS-3957, AND VARIANTS RP VAL-292; CYS-723; HIS-2661 AND ALA-3219. RX PubMed=19914852; DOI=10.1016/j.ymgme.2009.10.010; RA Gunay-Aygun M., Tuchman M., Font-Montgomery E., Lukose L., Edwards H., RA Garcia A., Ausavarat S., Ziegler S.G., Piwnica-Worms K., Bryant J., RA Bernardini I., Fischer R., Huizing M., Guay-Woodford L., Gahl W.A.; RT "PKHD1 sequence variations in 78 children and adults with autosomal RT recessive polycystic kidney disease and congenital hepatic fibrosis."; RL Mol. Genet. Metab. 99:160-173(2010). RN [22] RP VARIANTS PKD4 HIS-19; MET-36; LYS-218; VAL-222; TRP-1624; TRP-1624; RP THR-2957 AND ILE-3289, AND VARIANTS MET-579; SER-830 AND LYS-2869. RX PubMed=25701400; DOI=10.1016/j.gene.2015.02.040; RA Tavira B., Gomez J., Malaga S., Santos F., Fernandez-Aracama J., Alonso B., RA Iglesias S., Benavides A., Hernando I., Plasencia A., Alvarez V., Coto E.; RT "A labor and cost effective next generation sequencing of PKHD1 in RT autosomal recessive polycystic kidney disease patients."; RL Gene 561:165-169(2015). RN [23] RP VARIANTS MET-36; 496-ARG--LEU-4074 DEL; ILE-2436; SER-2648; TYR-3024; RP 3070-GLN--LEU-4074 DEL; CYS-3210; ALA-3263; 3407-GLN--LEU-4074 DEL; RP SER-3780; 4009-TYR--LEU-4074 DEL; PRO-4037 AND 4048-GLN--LEU-4074 DEL. RX PubMed=28375157; DOI=10.1172/jci90129; RA Besse W., Dong K., Choi J., Punia S., Fedeles S.V., Choi M., RA Gallagher A.R., Huang E.B., Gulati A., Knight J., Mane S., Tahvanainen E., RA Tahvanainen P., Sanna-Cherchi S., Lifton R.P., Watnick T., Pei Y.P., RA Torres V.E., Somlo S.; RT "Isolated polycystic liver disease genes define effectors of polycystin-1 RT function."; RL J. Clin. Invest. 127:1772-1785(2017). CC -!- FUNCTION: Promotes ciliogenesis in renal epithelial cells and therefore CC participates in the tubules formation and/ or ensures the maintenance CC of the architecture of the lumen of the kidney (By similarity). Has an CC impact on cellular symmetry by ensuring correct bipolar cell division CC through the regulation of centrosome duplication and mitotic spindle CC assembly and by maintaining oriented cell division (OCD) during tubular CC elongation through planar cell polarity (PCP) pathway CC (PubMed:20554582). During epithelial cell morphogenesis regulates also CC cell-cell and cell-matrix adhesion and participates in cell motility CC (By similarity). Promotes cell-cell contact through the positive CC regulation of PTK2 kinase activity leading to either positive CC regulation of epithelial cell proliferation through the HRAS/RAF1 CC pathways, or negative regulation of apoptosis through the PDK1/AKT1 CC pathway (By similarity). May act in collecting-duct and biliary CC differentiation (PubMed:11919560). May participate in the regulation of CC the cholangiocytes proliferation and the CCN2 production in an CXCL8- CC dependent manner (PubMed:30898581). {ECO:0000250|UniProtKB:E2RK30, CC ECO:0000250|UniProtKB:E9PZ36, ECO:0000269|PubMed:11919560, CC ECO:0000269|PubMed:20554582, ECO:0000269|PubMed:30898581}. CC -!- SUBUNIT: Interacts with CAMLG (PubMed:16243292). Interacts with PKD2 CC (PubMed:18235088). Interacts (via CST) with ARF4; this interaction CC allows an efficient PKHD1 trafficking to the cilium. Interacts (via CC CST) with RAB8A; this interaction controls trafficking through the CC endomembrane systeme and the cilium. Interacts (via CST) with TULP3; CC this interaction allows PKHD1 trafficking to the cilium (By CC similarity). {ECO:0000250|UniProtKB:E9PZ36, CC ECO:0000269|PubMed:16243292, ECO:0000269|PubMed:18235088}. CC -!- INTERACTION: CC P08F94; P49069: CAMLG; NbExp=3; IntAct=EBI-11693144, EBI-1748958; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15458427}; CC Single-pass type I membrane protein {ECO:0000255}. Cytoplasm CC {ECO:0000269|PubMed:15458427}. Cell projection, cilium CC {ECO:0000269|PubMed:14978161, ECO:0000269|PubMed:15458427, CC ECO:0000269|PubMed:17470460}. Cytoplasm, cytoskeleton, cilium basal CC body {ECO:0000269|PubMed:14978161}. Cytoplasm, cytoskeleton, spindle CC {ECO:0000269|PubMed:20554582}. Chromosome, centromere CC {ECO:0000269|PubMed:20554582}. Apical cell membrane CC {ECO:0000250|UniProtKB:E9PZ36}. Nucleus {ECO:0000250|UniProtKB:E9PZ36}. CC Secreted, extracellular exosome {ECO:0000250|UniProtKB:E9PZ36}. CC Secreted {ECO:0000250|UniProtKB:E9PZ36}. Endoplasmic reticulum CC {ECO:0000250|UniProtKB:E9PZ36}. Golgi apparatus CC {ECO:0000250|UniProtKB:E9PZ36}. Note=The intracellular C-terminal CC fragment (ICD) translocates to the nucleus and is not detected in CC primary cilia (PubMed:17470460, PubMed:16956880). The extracellular CC domain (PECD) traffics beyond the mid-Golgi and localizes on exosome CC like vesicles (ELVs) attached to the primary cilium (By similarity). In CC the urine, the extracellular domain (PECD) exists as an highly abundant CC secreted form and a less abundant PECD form that is either tethered to CC or shed with the C-terminal fragment (PTM) in ELVs (By similarity). The CC majority of full length PKHD1 protein resides at the endoplasmic CC reticulum and cannot pass beyond the mid-Golgi apparatus and is not CC detected in primary cilia (By similarity). The intra-cellular C- CC terminal fragment of 21-kDa translocates to the nucleus. The CC extracellular domain traffics beyond the mid-Golgi and localizes on CC exosome like vesicles (ELVs) attached to the primary cilium (By CC similarity). {ECO:0000250|UniProtKB:E9PZ36, CC ECO:0000269|PubMed:16956880, ECO:0000269|PubMed:17470460}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Comment=Additional isoforms seem to exist. As a matter of fact, CC alternatively spliced products seem to fall into two broad groups: CC one group, which includes the longest continuous ORF but which may CC also include molecules lacking some middle domains, has a single TM CC element and is likely to be associated with the plasma membrane. The CC other group lacks a TM domain and thus its members may be secreted.; CC Name=1; CC IsoId=P08F94-1; Sequence=Displayed; CC Name=2; CC IsoId=P08F94-2; Sequence=VSP_003947, VSP_003948; CC -!- TISSUE SPECIFICITY: Predominantly expressed in fetal and adult kidney. CC In the kidney, it is found in the cortical and medullary collecting CC ducts. Also present in the adult pancreas, but at much lower levels. CC Detectable in fetal and adult liver. Rather indistinct signal in fetal CC brain. {ECO:0000269|PubMed:14978161, ECO:0000269|PubMed:15458427}. CC -!- PTM: Several proteolytic cleavages occur within the extracellular CC domain, whereas at least one cleavage occurs within the cytoplasmic CC domain (PubMed:16956880). Cleaved by a probable proprotein convertase CC which produces an extracellular domain (polyductin extracellular CC domain, (PECD)) and a C-terminal fragment (polyductin transmembrane CC fragment (PTM)) which are tethered together by disulfide bonds CC (PubMed:17470460). This extracellular domain (PECD) is then shed from CC the primary cilium by activation of a member of the ADAM CC metalloproteinase disintegrins family, resulting in concomitant release CC of an intra-cellular C-terminal fragment (ICD) via a gamma-secretase- CC dependent process (PubMed:17470460). The proteolytic cleavage of the C- CC terminal intracellular fragment (ICD) is controlled by cytosolic CC calcium concentration and activation of PKC (PubMed:16956880). CC {ECO:0000269|PubMed:16956880, ECO:0000269|PubMed:17470460}. CC -!- PTM: Palmitoylated. Palmitoylation facilitates membrane targeting and CC the trafficking to the cilia. {ECO:0000250|UniProtKB:E9PZ36}. CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:E9PZ36}. CC -!- DISEASE: Polycystic kidney disease 4, with or without polycystic liver CC disease (PKD4) [MIM:263200]: A severe form of polycystic kidney disease CC affecting the kidneys and, in some cases, the hepatic biliary tract. CC The clinical spectrum is widely variable, with most cases presenting CC during infancy. The fetal phenotypic features classically include CC enlarged and echogenic kidneys, as well as oligohydramnios secondary to CC a poor urine output. Up to 50% of the affected neonates die shortly CC after birth, as a result of severe pulmonary hypoplasia and secondary CC respiratory insufficiency. In the subset that survives the perinatal CC period, morbidity and mortality are mainly related to severe systemic CC hypertension, renal insufficiency, and portal hypertension due to CC portal-tract fibrosis. PKD4 inheritance is autosomal recessive. CC {ECO:0000269|PubMed:11898128, ECO:0000269|PubMed:11919560, CC ECO:0000269|PubMed:12506140, ECO:0000269|PubMed:12846734, CC ECO:0000269|PubMed:12874454, ECO:0000269|PubMed:15108281, CC ECO:0000269|PubMed:16677362, ECO:0000269|PubMed:19914852, CC ECO:0000269|PubMed:25701400}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Note=Loss-of-function PKHD1 variations may cause autosomal CC dominant polycystic liver disease (PCLD) in patients that lack CC variations in known causative genes, such as PRKCSH and SEC63. CC {ECO:0000269|PubMed:28375157}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY074797; AAL74290.1; -; mRNA. DR EMBL; AY129465; AAM93492.1; -; Genomic_DNA. DR EMBL; AF480064; AAM44232.1; -; mRNA. DR EMBL; AY092083; AAM18186.1; -; mRNA. DR EMBL; AL590391; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL157774; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL391221; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL355997; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL121946; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471081; EAX04359.1; -; Genomic_DNA. DR CCDS; CCDS4935.1; -. [P08F94-1] DR CCDS; CCDS4936.1; -. [P08F94-2] DR RefSeq; NP_619639.3; NM_138694.3. [P08F94-1] DR RefSeq; NP_733842.2; NM_170724.2. [P08F94-2] DR RefSeq; XP_011512982.1; XM_011514680.2. [P08F94-1] DR RefSeq; XP_016866433.1; XM_017010944.1. [P08F94-1] DR SMR; P08F94; -. DR BioGRID; 111331; 9. DR CORUM; P08F94; -. DR IntAct; P08F94; 2. DR STRING; 9606.ENSP00000360158; -. DR GlyCosmos; P08F94; 64 sites, No reported glycans. DR GlyGen; P08F94; 64 sites. DR iPTMnet; P08F94; -. DR PhosphoSitePlus; P08F94; -. DR SwissPalm; P08F94; -. DR BioMuta; PKHD1; -. DR DMDM; 296439717; -. DR EPD; P08F94; -. DR MassIVE; P08F94; -. DR PaxDb; 9606-ENSP00000360158; -. DR PeptideAtlas; P08F94; -. DR ProteomicsDB; 52181; -. [P08F94-1] DR ProteomicsDB; 52182; -. [P08F94-2] DR Antibodypedia; 30875; 170 antibodies from 13 providers. DR DNASU; 5314; -. DR Ensembl; ENST00000340994.4; ENSP00000341097.4; ENSG00000170927.15. [P08F94-2] DR Ensembl; ENST00000371117.8; ENSP00000360158.3; ENSG00000170927.15. [P08F94-1] DR GeneID; 5314; -. DR KEGG; hsa:5314; -. DR MANE-Select; ENST00000371117.8; ENSP00000360158.3; NM_138694.4; NP_619639.3. DR UCSC; uc003pah.2; human. [P08F94-1] DR AGR; HGNC:9016; -. DR CTD; 5314; -. DR DisGeNET; 5314; -. DR GeneCards; PKHD1; -. DR GeneReviews; PKHD1; -. DR HGNC; HGNC:9016; PKHD1. DR HPA; ENSG00000170927; Group enriched (epididymis, kidney, pancreas). DR MalaCards; PKHD1; -. DR MIM; 263200; phenotype. DR MIM; 606702; gene. DR neXtProt; NX_P08F94; -. DR OpenTargets; ENSG00000170927; -. DR Orphanet; 731; Autosomal recessive polycystic kidney disease. DR Orphanet; 53035; Caroli disease. DR PharmGKB; PA33348; -. DR VEuPathDB; HostDB:ENSG00000170927; -. DR eggNOG; ENOG502QR85; Eukaryota. DR GeneTree; ENSGT00940000160697; -. DR HOGENOM; CLU_000057_1_0_1; -. DR InParanoid; P08F94; -. DR OMA; QSCAINV; -. DR OrthoDB; 4766at2759; -. DR PhylomeDB; P08F94; -. DR TreeFam; TF329582; -. DR PathwayCommons; P08F94; -. DR SignaLink; P08F94; -. DR BioGRID-ORCS; 5314; 15 hits in 1148 CRISPR screens. DR ChiTaRS; PKHD1; human. DR GenomeRNAi; 5314; -. DR Pharos; P08F94; Tbio. DR PRO; PR:P08F94; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; P08F94; Protein. DR Bgee; ENSG00000170927; Expressed in kidney epithelium and 44 other cell types or tissues. DR GO; GO:0097731; C:9+0 non-motile cilium; IEA:Ensembl. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0000775; C:chromosome, centromeric region; IEA:UniProtKB-SubCell. DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB. DR GO; GO:0005929; C:cilium; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0009897; C:external side of plasma membrane; TAS:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB. DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0038023; F:signaling receptor activity; NAS:UniProtKB. DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISS:UniProtKB. DR GO; GO:0098609; P:cell-cell adhesion; ISS:UniProtKB. DR GO; GO:0045216; P:cell-cell junction organization; ISS:UniProtKB. DR GO; GO:0060271; P:cilium assembly; IEA:Ensembl. DR GO; GO:0003382; P:epithelial cell morphogenesis; ISS:UniProtKB. DR GO; GO:0051660; P:establishment of centrosome localization; ISS:UniProtKB. DR GO; GO:0000132; P:establishment of mitotic spindle orientation; ISS:UniProtKB. DR GO; GO:0042592; P:homeostatic process; NAS:UniProtKB. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IMP:UniProtKB. DR GO; GO:0001822; P:kidney development; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; ISS:UniProtKB. DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:UniProtKB. DR GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISS:UniProtKB. DR GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB. DR GO; GO:0022407; P:regulation of cell-cell adhesion; ISS:UniProtKB. DR GO; GO:0001952; P:regulation of cell-matrix adhesion; ISS:UniProtKB. DR GO; GO:0010824; P:regulation of centrosome duplication; IMP:UniProtKB. DR GO; GO:1904054; P:regulation of cholangiocyte proliferation; IMP:UniProtKB. DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:UniProtKB. DR GO; GO:0090175; P:regulation of establishment of planar polarity; ISS:UniProtKB. DR GO; GO:0032006; P:regulation of TOR signaling; IMP:UniProtKB. DR CDD; cd00603; IPT_PCSR; 6. DR Gene3D; 2.60.40.10; Immunoglobulins; 5. DR Gene3D; 2.160.20.10; Single-stranded right-handed beta-helix, Pectin lyase-like; 2. DR InterPro; IPR039448; Beta_helix. DR InterPro; IPR019316; G8_domain. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR002909; IPT_dom. DR InterPro; IPR037524; PA14/GLEYA. DR InterPro; IPR006626; PbH1. DR InterPro; IPR012334; Pectin_lyas_fold. DR InterPro; IPR011050; Pectin_lyase_fold/virulence. DR PANTHER; PTHR46769:SF1; FIBROCYSTIN; 1. DR PANTHER; PTHR46769; POLYCYSTIC KIDNEY AND HEPATIC DISEASE 1 (AUTOSOMAL RECESSIVE)-LIKE 1; 1. DR Pfam; PF13229; Beta_helix; 1. DR Pfam; PF10162; G8; 2. DR Pfam; PF01833; TIG; 8. DR SMART; SM01225; G8; 2. DR SMART; SM00429; IPT; 6. DR SMART; SM00710; PbH1; 10. DR SUPFAM; SSF56988; Anthrax protective antigen; 1. DR SUPFAM; SSF81296; E set domains; 6. DR SUPFAM; SSF51126; Pectin lyase-like; 2. DR PROSITE; PS51484; G8; 2. DR PROSITE; PS51820; PA14; 1. DR Genevisible; P08F94; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Cell projection; Centromere; KW Chromosome; Ciliopathy; Cilium; Cytoplasm; Cytoskeleton; Disease variant; KW Endoplasmic reticulum; Glycoprotein; Golgi apparatus; Membrane; Nucleus; KW Receptor; Reference proteome; Repeat; Secreted; Signal; Transmembrane; KW Transmembrane helix. FT SIGNAL 1..23 FT /evidence="ECO:0000255" FT CHAIN 24..4074 FT /note="Fibrocystin" FT /id="PRO_0000022062" FT TOPO_DOM 24..3858 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 3859..3879 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 3880..4074 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 24..111 FT /note="IPT/TIG 1; atypical" FT DOMAIN 137..232 FT /note="IPT/TIG 2" FT DOMAIN 259..335 FT /note="IPT/TIG 3" FT DOMAIN 322..485 FT /note="PA14" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01164" FT DOMAIN 931..1015 FT /note="IPT/TIG 4" FT DOMAIN 1019..1103 FT /note="IPT/TIG 5" FT DOMAIN 1108..1192 FT /note="IPT/TIG 6; atypical" FT DOMAIN 1196..1289 FT /note="IPT/TIG 7" FT DOMAIN 1301..1382 FT /note="IPT/TIG 8; atypical" FT DOMAIN 1389..1481 FT /note="IPT/TIG 9" FT DOMAIN 1486..1570 FT /note="IPT/TIG 10" FT DOMAIN 1573..1659 FT /note="IPT/TIG 11" FT DOMAIN 1658..1742 FT /note="IPT/TIG 12; atypical" FT DOMAIN 1932..2053 FT /note="G8 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00817" FT REPEAT 2226..2248 FT /note="PbH1 1" FT REPEAT 2249..2271 FT /note="PbH1 2" FT REPEAT 2292..2325 FT /note="PbH1 3" FT REPEAT 2326..2347 FT /note="PbH1 4" FT REPEAT 2409..2431 FT /note="PbH1 5" FT REPEAT 2469..2502 FT /note="PbH1 6" FT DOMAIN 2747..2873 FT /note="G8 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00817" FT REPEAT 3010..3032 FT /note="PbH1 7" FT REPEAT 3033..3055 FT /note="PbH1 8" FT REPEAT 3086..3108 FT /note="PbH1 9" FT REGION 3876..3893 FT /note="Ciliary targeting sequence (CST)" FT /evidence="ECO:0000250|UniProtKB:E9PZ36" FT REGION 3890..3925 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3952..3976 FT /note="Nuclear localization signal (NLS)" FT /evidence="ECO:0000250|UniProtKB:E9PZ36" FT COMPBIAS 3908..3925 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 3620..3621 FT /note="Cleavage" FT /evidence="ECO:0000269|PubMed:17470460" FT CARBOHYD 54 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 226 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 276 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 357 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 387 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 507 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 520 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 529 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 641 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 711 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 830 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 869 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 967 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 977 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1065 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1084 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1116 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1135 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1234 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1241 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1312 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1323 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1346 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1377 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1460 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1475 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1494 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1527 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1532 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1564 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1582 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1602 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1631 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1698 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1764 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1779 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1879 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1883 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1919 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1945 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1959 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2034 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2115 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2144 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2350 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2385 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2435 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2471 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2509 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2535 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2553 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2595 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2633 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2753 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2768 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 3008 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 3140 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 3169 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 3225 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 3488 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 3528 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 3707 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 3726 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 3838 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 3386..3396 FT /note="GTFREEQKCTY -> VTTEQALKISE (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12079288" FT /id="VSP_003947" FT VAR_SEQ 3397..4074 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12079288" FT /id="VSP_003948" FT VARIANT 17 FT /note="A -> V (in PKD4; dbSNP:rs755654557)" FT /evidence="ECO:0000269|PubMed:12846734" FT /id="VAR_018520" FT VARIANT 19 FT /note="R -> H (in a colorectal cancer sample and PKD4; FT uncertain significance; somatic mutation; FT dbSNP:rs1375765328)" FT /evidence="ECO:0000269|PubMed:16959974, FT ECO:0000269|PubMed:25701400" FT /id="VAR_036228" FT VARIANT 25 FT /note="I -> V" FT /evidence="ECO:0000269|PubMed:11919560" FT /id="VAR_018521" FT VARIANT 36 FT /note="T -> M (in PKD4; common mutation; also found in a FT patient affected by polycystic liver disease; FT dbSNP:rs137852944)" FT /evidence="ECO:0000269|PubMed:11898128, FT ECO:0000269|PubMed:11919560, ECO:0000269|PubMed:12506140, FT ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:12874454, FT ECO:0000269|PubMed:15108281, ECO:0000269|PubMed:25701400, FT ECO:0000269|PubMed:28375157" FT /id="VAR_014039" FT VARIANT 92 FT /note="R -> W (in PKD4; dbSNP:rs370277502)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066416" FT VARIANT 218 FT /note="E -> K (in PKD4; uncertain significance; FT dbSNP:rs149522482)" FT /evidence="ECO:0000269|PubMed:25701400" FT /id="VAR_075540" FT VARIANT 222 FT /note="I -> V (in PKD4; dbSNP:rs369925690)" FT /evidence="ECO:0000269|PubMed:11898128, FT ECO:0000269|PubMed:11919560, ECO:0000269|PubMed:12846734, FT ECO:0000269|PubMed:25701400" FT /id="VAR_014040" FT VARIANT 223 FT /note="G -> S (in PKD4; dbSNP:rs749454235)" FT /evidence="ECO:0000269|PubMed:12506140" FT /id="VAR_018522" FT VARIANT 246 FT /note="I -> T (in PKD4; dbSNP:rs1037991711)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066417" FT VARIANT 253 FT /note="F -> L (in PKD4; dbSNP:rs775254013)" FT /evidence="ECO:0000269|PubMed:11898128, FT ECO:0000269|PubMed:12506140" FT /id="VAR_014041" FT VARIANT 255 FT /note="Y -> C (in PKD4; dbSNP:rs886042259)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066418" FT VARIANT 292 FT /note="I -> V (in a patient with polycystic kidney disease; FT dbSNP:rs367590965)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066419" FT VARIANT 293 FT /note="A -> V (in PKD4; dbSNP:rs398124499)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066420" FT VARIANT 307 FT /note="I -> T (in PKD4; dbSNP:rs1288017883)" FT /evidence="ECO:0000269|PubMed:15108281" FT /id="VAR_018523" FT VARIANT 326 FT /note="G -> V (in PKD4; dbSNP:rs778329699)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018524" FT VARIANT 372 FT /note="F -> L (in PKD4; dbSNP:rs1582038191)" FT /evidence="ECO:0000269|PubMed:16677362" FT /id="VAR_027439" FT VARIANT 387 FT /note="Missing (in PKD4; dbSNP:rs1554218506)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018525" FT VARIANT 457 FT /note="E -> D" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018526" FT VARIANT 466 FT /note="G -> E (in PKD4; dbSNP:rs750730042)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066421" FT VARIANT 470 FT /note="G -> V (in PKD4; dbSNP:rs776845008)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066422" FT VARIANT 473 FT /note="I -> S (in PKD4)" FT /evidence="ECO:0000269|PubMed:12506140" FT /id="VAR_018527" FT VARIANT 486 FT /note="Y -> H (in PKD4)" FT /evidence="ECO:0000269|PubMed:15108281" FT /id="VAR_018528" FT VARIANT 488 FT /note="R -> P (in dbSNP:rs186202437)" FT /id="VAR_018529" FT VARIANT 496..4074 FT /note="Missing (found in a patient affected by polycystic FT liver disease; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28375157" FT /id="VAR_080923" FT VARIANT 496 FT /note="R -> P (in PKD4)" FT /evidence="ECO:0000269|PubMed:12506140" FT /id="VAR_018530" FT VARIANT 539 FT /note="I -> T (in PKD4; dbSNP:rs749730748)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066423" FT VARIANT 579 FT /note="T -> M (in dbSNP:rs45500692)" FT /evidence="ECO:0000269|PubMed:12506140, FT ECO:0000269|PubMed:25701400" FT /id="VAR_018531" FT VARIANT 656 FT /note="W -> C (in PKD4)" FT /evidence="ECO:0000269|PubMed:12506140" FT /id="VAR_018532" FT VARIANT 686 FT /note="H -> P (in PKD4)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066424" FT VARIANT 703 FT /note="D -> N (in PKD4)" FT /evidence="ECO:0000269|PubMed:12506140" FT /id="VAR_018533" FT VARIANT 723 FT /note="R -> C (in dbSNP:rs794727366)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066425" FT VARIANT 724 FT /note="P -> R (in PKD4; dbSNP:rs1229139298)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066426" FT VARIANT 732 FT /note="V -> F (in dbSNP:rs201432731)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018534" FT VARIANT 739 FT /note="P -> L (in PKD4; dbSNP:rs758352210)" FT /evidence="ECO:0000269|PubMed:12846734" FT /id="VAR_018535" FT VARIANT 752 FT /note="T -> M (in dbSNP:rs200654041)" FT /evidence="ECO:0000269|PubMed:11919560" FT /id="VAR_014042" FT VARIANT 757 FT /note="I -> L (in PKD4; uncertain significance; FT dbSNP:rs777183511)" FT /evidence="ECO:0000269|PubMed:12846734" FT /id="VAR_018536" FT VARIANT 760 FT /note="R -> C (in dbSNP:rs9370096)" FT /evidence="ECO:0000269|PubMed:11919560, FT ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:12874454" FT /id="VAR_014043" FT VARIANT 760 FT /note="R -> H (in PKD4; dbSNP:rs745770404)" FT /evidence="ECO:0000269|PubMed:11898128, FT ECO:0000269|PubMed:12506140" FT /id="VAR_014044" FT VARIANT 760 FT /note="R -> W (in dbSNP:rs9370096)" FT /id="VAR_051282" FT VARIANT 805 FT /note="P -> L (in PKD4; dbSNP:rs199531851)" FT /evidence="ECO:0000269|PubMed:12506140, FT ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:15108281" FT /id="VAR_018537" FT VARIANT 830 FT /note="N -> S (in dbSNP:rs62406032)" FT /evidence="ECO:0000269|PubMed:12506140, FT ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:25701400" FT /id="VAR_018538" FT VARIANT 852 FT /note="W -> R" FT /evidence="ECO:0000269|PubMed:11919560" FT /id="VAR_014045" FT VARIANT 899 FT /note="T -> P (in PKD4; dbSNP:rs922828020)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018539" FT VARIANT 997 FT /note="M -> K (in PKD4)" FT /evidence="ECO:0000269|PubMed:12506140" FT /id="VAR_018540" FT VARIANT 1030 FT /note="A -> E (in PKD4)" FT /evidence="ECO:0000269|PubMed:12506140" FT /id="VAR_018541" FT VARIANT 1081 FT /note="R -> C (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs200986136)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036229" FT VARIANT 1096 FT /note="L -> R (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036230" FT VARIANT 1122 FT /note="G -> S (in PKD4)" FT /evidence="ECO:0000269|PubMed:11898128, FT ECO:0000269|PubMed:12506140" FT /id="VAR_014046" FT VARIANT 1123 FT /note="G -> S (in PKD4; dbSNP:rs142107837)" FT /evidence="ECO:0000269|PubMed:12506140, FT ECO:0000269|PubMed:12874454" FT /id="VAR_018542" FT VARIANT 1136 FT /note="Y -> C (in dbSNP:rs41273726)" FT /id="VAR_018543" FT VARIANT 1150 FT /note="A -> P" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018544" FT VARIANT 1204 FT /note="C -> Y" FT /evidence="ECO:0000269|PubMed:12079288" FT /id="VAR_014047" FT VARIANT 1249 FT /note="C -> W (in PKD4; dbSNP:rs748540413)" FT /evidence="ECO:0000269|PubMed:11919560, FT ECO:0000269|PubMed:12506140" FT /id="VAR_014048" FT VARIANT 1262 FT /note="A -> V (in dbSNP:rs9296669)" FT /evidence="ECO:0000269|PubMed:11919560, FT ECO:0000269|PubMed:12846734" FT /id="VAR_014049" FT VARIANT 1283 FT /note="S -> L" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018545" FT VARIANT 1389 FT /note="P -> T (in PKD4)" FT /evidence="ECO:0000269|PubMed:12846734" FT /id="VAR_018546" FT VARIANT 1407 FT /note="L -> R (in PKD4; dbSNP:rs1464962854)" FT /evidence="ECO:0000269|PubMed:11919560, FT ECO:0000269|PubMed:12506140" FT /id="VAR_014050" FT VARIANT 1472 FT /note="C -> Y (in PKD4)" FT /evidence="ECO:0000269|PubMed:15108281" FT /id="VAR_018547" FT VARIANT 1486 FT /note="P -> L (in PKD4; dbSNP:rs1421520936)" FT /evidence="ECO:0000269|PubMed:12506140" FT /id="VAR_018548" FT VARIANT 1584 FT /note="S -> I (in PKD4; dbSNP:rs1197981811)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018549" FT VARIANT 1624 FT /note="R -> W (in PKD4; pathogenic; dbSNP:rs200391019)" FT /evidence="ECO:0000269|PubMed:11898128, FT ECO:0000269|PubMed:12506140, ECO:0000269|PubMed:16959974, FT ECO:0000269|PubMed:25701400" FT /id="VAR_014051" FT VARIANT 1664 FT /note="S -> F (in PKD4; dbSNP:rs28937907)" FT /evidence="ECO:0000269|PubMed:11919560, FT ECO:0000269|PubMed:12506140" FT /id="VAR_014052" FT VARIANT 1709 FT /note="L -> F (in dbSNP:rs45517932)" FT /evidence="ECO:0000269|PubMed:12846734, FT ECO:0000269|PubMed:12874454" FT /id="VAR_018550" FT VARIANT 1712 FT /note="G -> R (in a patient with polycystic kidney disease; FT dbSNP:rs141103838)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066427" FT VARIANT 1741 FT /note="V -> M (in PKD4; dbSNP:rs137852946)" FT /evidence="ECO:0000269|PubMed:11919560, FT ECO:0000269|PubMed:12506140, ECO:0000269|PubMed:12846734" FT /id="VAR_014053" FT VARIANT 1781 FT /note="T -> I (in PKD4; dbSNP:rs1554197025)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018551" FT VARIANT 1789 FT /note="V -> L (in PKD4; dbSNP:rs1288521396)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018552" FT VARIANT 1806 FT /note="E -> K (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036231" FT VARIANT 1817 FT /note="V -> G (in PKD4)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066428" FT VARIANT 1833 FT /note="S -> L (in PKD4; dbSNP:rs201105958)" FT /evidence="ECO:0000269|PubMed:12846734" FT /id="VAR_018553" FT VARIANT 1838 FT /note="Y -> C (in PKD4; dbSNP:rs777999875)" FT /evidence="ECO:0000269|PubMed:12846734" FT /id="VAR_018554" FT VARIANT 1867 FT /note="S -> N (in PKD4)" FT /evidence="ECO:0000269|PubMed:12846734" FT /id="VAR_018555" FT VARIANT 1870 FT /note="L -> V (in dbSNP:rs2435322)" FT /evidence="ECO:0000269|PubMed:11898128, FT ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:12874454" FT /id="VAR_018556" FT VARIANT 1875 FT /note="V -> G (in PKD4; dbSNP:rs202016058)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066429" FT VARIANT 1917 FT /note="Q -> R (in PKD4; dbSNP:rs1412045164)" FT /evidence="ECO:0000269|PubMed:11919560, FT ECO:0000269|PubMed:12506140" FT /id="VAR_014054" FT VARIANT 1928 FT /note="W -> L (in PKD4)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066430" FT VARIANT 1942 FT /note="D -> G (in PKD4; dbSNP:rs1210846081)" FT /evidence="ECO:0000269|PubMed:12846734, FT ECO:0000269|PubMed:12874454" FT /id="VAR_018557" FT VARIANT 1971 FT /note="G -> D (in PKD4; dbSNP:rs180675584)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018558" FT VARIANT 1995 FT /note="E -> G (in PKD4; dbSNP:rs1554144359)" FT /evidence="ECO:0000269|PubMed:11919560, FT ECO:0000269|PubMed:12506140" FT /id="VAR_014055" FT VARIANT 1998 FT /note="I -> T (in PKD4; dbSNP:rs1210348558)" FT /evidence="ECO:0000269|PubMed:12506140" FT /id="VAR_018559" FT VARIANT 2009 FT /note="A -> T (in PKD4; dbSNP:rs761786260)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066431" FT VARIANT 2032 FT /note="V -> L (in PKD4; dbSNP:rs1187112770)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018560" FT VARIANT 2106 FT /note="L -> R (in PKD4; dbSNP:rs1254909885)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066432" FT VARIANT 2134 FT /note="L -> P (in PKD4)" FT /evidence="ECO:0000269|PubMed:12506140" FT /id="VAR_018561" FT VARIANT 2210 FT /note="G -> E (in PKD4)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066433" FT VARIANT 2219 FT /note="S -> L (in PKD4)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066434" FT VARIANT 2224 FT /note="G -> R (in PKD4; may affect splicing; FT dbSNP:rs759687904)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066435" FT VARIANT 2303 FT /note="I -> F (in PKD4; dbSNP:rs751084512)" FT /evidence="ECO:0000269|PubMed:15108281" FT /id="VAR_018562" FT VARIANT 2331 FT /note="I -> K (in PKD4; dbSNP:rs200179145)" FT /evidence="ECO:0000269|PubMed:11919560, FT ECO:0000269|PubMed:12506140" FT /id="VAR_014056" FT VARIANT 2422 FT /note="C -> G (in PKD4; dbSNP:rs201881567)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018563" FT VARIANT 2422 FT /note="C -> R (in PKD4; dbSNP:rs201881567)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066436" FT VARIANT 2431 FT /note="E -> V (in PKD4; may affect splicing; FT dbSNP:rs1280884139)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066437" FT VARIANT 2436 FT /note="T -> I (found in a patient affected by polycystic FT liver disease; uncertain significance; dbSNP:rs147851214)" FT /evidence="ECO:0000269|PubMed:28375157" FT /id="VAR_080924" FT VARIANT 2573 FT /note="R -> C (in PKD4; dbSNP:rs752994816)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066438" FT VARIANT 2615 FT /note="A -> G" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018564" FT VARIANT 2641 FT /note="T -> A (in dbSNP:rs7766366)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018565" FT VARIANT 2648 FT /note="G -> S (found in a patient affected by polycystic FT liver disease; uncertain significance; dbSNP:rs139555370)" FT /evidence="ECO:0000269|PubMed:28375157" FT /id="VAR_080925" FT VARIANT 2661 FT /note="Y -> H (in a patient with polycystic kidney FT disease)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066439" FT VARIANT 2688 FT /note="C -> F (in PKD4)" FT /evidence="ECO:0000269|PubMed:12846734" FT /id="VAR_018566" FT VARIANT 2761 FT /note="D -> Y (in PKD4; dbSNP:rs1554263080)" FT /evidence="ECO:0000269|PubMed:12506140" FT /id="VAR_018567" FT VARIANT 2772 FT /note="L -> P (in PKD4)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018568" FT VARIANT 2798 FT /note="V -> G (in PKD4; dbSNP:rs1554243589)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066440" FT VARIANT 2803 FT /note="C -> R (in PKD4; dbSNP:rs398124495)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066441" FT VARIANT 2804 FT /note="M -> K (in PKD4; dbSNP:rs794727759)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066442" FT VARIANT 2861 FT /note="S -> G (in dbSNP:rs150925674)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018569" FT VARIANT 2863 FT /note="Y -> C (in PKD4; dbSNP:rs1342555536)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018570" FT VARIANT 2869 FT /note="T -> K (in dbSNP:rs142522748)" FT /evidence="ECO:0000269|PubMed:12846734, FT ECO:0000269|PubMed:12874454, ECO:0000269|PubMed:15108281, FT ECO:0000269|PubMed:25701400" FT /id="VAR_018571" FT VARIANT 2938 FT /note="T -> M (in dbSNP:rs776068047)" FT /evidence="ECO:0000269|PubMed:11919560" FT /id="VAR_014057" FT VARIANT 2957 FT /note="I -> T (in PKD4; dbSNP:rs760222236)" FT /evidence="ECO:0000269|PubMed:11898128, FT ECO:0000269|PubMed:11919560, ECO:0000269|PubMed:12506140, FT ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:12874454, FT ECO:0000269|PubMed:15108281, ECO:0000269|PubMed:25701400" FT /id="VAR_014058" FT VARIANT 2962 FT /note="D -> G (in PKD4; dbSNP:rs1554220680)" FT /evidence="ECO:0000269|PubMed:15108281" FT /id="VAR_018572" FT VARIANT 2983 FT /note="S -> L (in PKD4; dbSNP:rs141169758)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018573" FT VARIANT 3018 FT /note="S -> F (in PKD4; dbSNP:rs137852945)" FT /evidence="ECO:0000269|PubMed:11919560, FT ECO:0000269|PubMed:12506140" FT /id="VAR_014059" FT VARIANT 3024 FT /note="C -> Y (found in a patient affected by polycystic FT liver disease; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28375157" FT /id="VAR_080926" FT VARIANT 3036 FT /note="V -> G (in PKD4; dbSNP:rs893497345)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018574" FT VARIANT 3049 FT /note="H -> R (in PKD4; dbSNP:rs367678592)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066443" FT VARIANT 3052 FT /note="D -> Y (in dbSNP:rs765526)" FT /id="VAR_027440" FT VARIANT 3070..4074 FT /note="Missing (found in a patient affected by polycystic FT liver disease; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:28375157" FT /id="VAR_080927" FT VARIANT 3072 FT /note="A -> V (in dbSNP:rs139306706)" FT /id="VAR_018575" FT VARIANT 3081 FT /note="I -> V (in PKD4; dbSNP:rs142146981)" FT /evidence="ECO:0000269|PubMed:12506140" FT /id="VAR_018576" FT VARIANT 3088 FT /note="D -> N (in dbSNP:rs201066635)" FT /id="VAR_018577" FT VARIANT 3107 FT /note="R -> P" FT /id="VAR_018578" FT VARIANT 3124 FT /note="H -> Y (in PKD4; dbSNP:rs1554218666)" FT /evidence="ECO:0000269|PubMed:12874454, FT ECO:0000269|PubMed:15108281" FT /id="VAR_018579" FT VARIANT 3139 FT /note="D -> Y (in dbSNP:rs45503297)" FT /evidence="ECO:0000269|PubMed:11898128, FT ECO:0000269|PubMed:11919560, ECO:0000269|PubMed:12506140, FT ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:12874454, FT ECO:0000269|PubMed:15108281" FT /id="VAR_014060" FT VARIANT 3143 FT /note="R -> I" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018580" FT VARIANT 3167 FT /note="I -> L (in PKD4)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018581" FT VARIANT 3175 FT /note="N -> D (in PKD4)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018582" FT VARIANT 3175 FT /note="N -> S (in PKD4; dbSNP:rs1343246818)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018583" FT VARIANT 3177 FT /note="I -> T (in PKD4; dbSNP:rs200511261)" FT /evidence="ECO:0000269|PubMed:12846734, FT ECO:0000269|PubMed:12874454, ECO:0000269|PubMed:15108281" FT /id="VAR_018584" FT VARIANT 3207 FT /note="A -> T (in PKD4; dbSNP:rs1242089464)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066444" FT VARIANT 3210 FT /note="S -> C (found in a patient affected by polycystic FT liver disease; uncertain significance; dbSNP:rs141081295)" FT /evidence="ECO:0000269|PubMed:28375157" FT /id="VAR_080928" FT VARIANT 3219 FT /note="V -> A (in a patient with polycystic kidney FT disease)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066445" FT VARIANT 3263 FT /note="V -> A (in dbSNP:rs146519878)" FT /evidence="ECO:0000269|PubMed:28375157" FT /id="VAR_080929" FT VARIANT 3289 FT /note="S -> I (in PKD4; uncertain significance; FT dbSNP:rs148932323)" FT /evidence="ECO:0000269|PubMed:25701400" FT /id="VAR_018585" FT VARIANT 3293 FT /note="D -> V (in PKD4)" FT /evidence="ECO:0000269|PubMed:12506140, FT ECO:0000269|PubMed:12874454" FT /id="VAR_018586" FT VARIANT 3346 FT /note="C -> R (in PKD4; uncertain significance; FT dbSNP:rs149798764)" FT /evidence="ECO:0000269|PubMed:12846734" FT /id="VAR_018587" FT VARIANT 3407..4074 FT /note="Missing (found in a patient affected by polycystic FT liver disease; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28375157" FT /id="VAR_080930" FT VARIANT 3440 FT /note="V -> D (in dbSNP:rs756792624)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018588" FT VARIANT 3468 FT /note="I -> V (in PKD4; dbSNP:rs748863662)" FT /evidence="ECO:0000269|PubMed:12846734" FT /id="VAR_018589" FT VARIANT 3471 FT /note="V -> G (in PKD4; dbSNP:rs137852950)" FT /evidence="ECO:0000269|PubMed:12506140" FT /id="VAR_018590" FT VARIANT 3482 FT /note="R -> C (in PKD4; dbSNP:rs148617572)" FT /evidence="ECO:0000269|PubMed:12506140, FT ECO:0000269|PubMed:15108281" FT /id="VAR_018591" FT VARIANT 3502 FT /note="E -> V (in PKD4; dbSNP:rs1554183496)" FT /evidence="ECO:0000269|PubMed:12846734" FT /id="VAR_018592" FT VARIANT 3505 FT /note="S -> R (in dbSNP:rs139014478)" FT /evidence="ECO:0000269|PubMed:12846734" FT /id="VAR_018593" FT VARIANT 3529 FT /note="E -> Q (in dbSNP:rs145184792)" FT /evidence="ECO:0000269|PubMed:12846734" FT /id="VAR_018594" FT VARIANT 3551 FT /note="E -> K (in dbSNP:rs751593192)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018595" FT VARIANT 3553 FT /note="I -> T (in PKD4; dbSNP:rs137852948)" FT /evidence="ECO:0000269|PubMed:11919560, FT ECO:0000269|PubMed:12506140" FT /id="VAR_014061" FT VARIANT 3622 FT /note="C -> Y (in PKD4)" FT /evidence="ECO:0000269|PubMed:12846734" FT /id="VAR_018596" FT VARIANT 3780 FT /note="P -> S (found in a patient affected by polycystic FT liver disease; uncertain significance; dbSNP:rs41273722)" FT /evidence="ECO:0000269|PubMed:28375157" FT /id="VAR_080931" FT VARIANT 3783 FT /note="P -> S (in PKD4)" FT /evidence="ECO:0000269|PubMed:12874454" FT /id="VAR_018597" FT VARIANT 3837 FT /note="V -> I (in dbSNP:rs9474034)" FT /id="VAR_027441" FT VARIANT 3842 FT /note="R -> L (in dbSNP:rs76572975)" FT /id="VAR_018598" FT VARIANT 3899 FT /note="Q -> R (in dbSNP:rs4715227)" FT /evidence="ECO:0000269|PubMed:12846734, FT ECO:0000269|PubMed:12874454" FT /id="VAR_018599" FT VARIANT 3905 FT /note="I -> N (in dbSNP:rs2661488)" FT /id="VAR_027442" FT VARIANT 3913 FT /note="R -> H (in dbSNP:rs2661487)" FT /id="VAR_027443" FT VARIANT 3957 FT /note="R -> C (in PKD4; dbSNP:rs146680689)" FT /evidence="ECO:0000269|PubMed:19914852" FT /id="VAR_066446" FT VARIANT 3960 FT /note="V -> I (in dbSNP:rs34548196)" FT /evidence="ECO:0000269|PubMed:11919560, FT ECO:0000269|PubMed:12846734, ECO:0000269|PubMed:12874454" FT /id="VAR_014062" FT VARIANT 4009..4074 FT /note="Missing (found in a patient affected by polycystic FT liver disease; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28375157" FT /id="VAR_080932" FT VARIANT 4037 FT /note="L -> P (found in a patient affected by polycystic FT liver disease; uncertain significance; dbSNP:rs199900211)" FT /evidence="ECO:0000269|PubMed:28375157" FT /id="VAR_080933" FT VARIANT 4048..4074 FT /note="Missing (found in a patient affected by polycystic FT liver disease; uncertain significance)" FT /evidence="ECO:0000269|PubMed:28375157" FT /id="VAR_080934" FT VARIANT 4048 FT /note="Q -> R (in dbSNP:rs9381994)" FT /evidence="ECO:0000269|PubMed:11919560, FT ECO:0000269|PubMed:12846734" FT /id="VAR_014063" FT MUTAGEN 3617..3618 FT /note="KR->AA: Loss of protein convertase cleavage into a FT 85 kDa PTM fragment." FT /evidence="ECO:0000269|PubMed:17470460" SQ SEQUENCE 4074 AA; 446702 MW; 719AA72F1203EDE1 CRC64; MTAWLISLMS IEVLLLAVRH LSLHIEPEEG SLAGGTWITV IFDGLELGVL YPNNGSQLEI HLVNVNMVVP ALRSVPCDVF PVFLDLPVVT CRTRSVLSEA HEGLYFLEAY FGGQLVSSPN PGPRDSCTFK FSKAQTPIVH QVYPPSGVPG KLIHVYGWII TGRLETFDFD AEYIDSPVIL EAQGDKWVTP CSLINRQMGS CYPIQEDHGL GTLQCHVEGD YIGSQNVSFS VFNKGKSMVH KKAWLISAKQ DLFLYQTHSE ILSVFPETGS LGGRTNITIT GDFFDNSAQV TIAGIPCDIR HVSPRKIECT TRAPGKDVRL TTPQPGNRGL LFEVGDAVEG LELTEATPGY RWQIVPNASS PFGFWSQEGQ PFRARLSGFF VAPETNNYTF WIQADSQASL HFSWSEEPRT KVKVASISVG TADWFDSWEQ NRDEGTWQQK TPKLELLGGA MYYLEAEHHG IAPSRGMRIG VQIHNTWLNP DVVTTYLREK HQIRVRAQRL PEVQVLNVSG RGNFFLTWDN VSSQPIPANA TAHLIQTTIE ELLAVKCKLE PLWSNILLRL GFERGPEVSN SDGDLTSGTE PFCGRFSLRQ PRHLVLTPPA AQKGYRLDQY THLCLAYKGH MNKILKMIVS FTIGFQNMVK NTTCDWSLTR TSPESWQFDC TDLWETCVRC FGDLQPPPAN SPVLVHQINL LPLAQETGLF YVDEIIIADT NVTVSQADSG TARPGGNLVE SVSVVGSPPV YSVTSWLAGC GTELPLITAR SVPTEGTEEG SGLVLVTTQR RQRTSPPLGG HFRIQLPNTV ISDVPVQISA HHLHQLLQNN ADDFTSRYLN ASDFTVKEDL YTCYEHVWTL SWSTQIGDLP NFIRVSDENL TGVNPAAATR VVYDGGVFLG PIFGDMLATA NQHTQVVVRV NDVPAHCPGS CSFQYLQGST PCVHSVWYSI DGDINLMIYI TGTGFSGDSQ FLQVTVNKTS CKVIFSNQTN VVCQTDLLPV GMHRILMLVR PSGLAISATG EDLFLNVKPR LDMVEPSRAA DIGGLWATIR GSSLEGVSLI LFGSYSCAIN VATSNSSRIQ CKVPPRGKDG RIVNVTVIRG DYSAVLPRAF TYVSSLNPVI VTLSRNISNI AGGETLVIGV ARLMNYTDLD VEVHVQDALA PVHTQSAWGL EVALPPLPAG LHRISVSING VSIHSQGVDL HIQYLTEVFS IEPCCGSLLG GTILSISGIG FSRDPALVWV LVGNRSCDIV NLTEASIWCE TLPAPQIPDA GAPTVPAAVE VWAGNRFFAR GPSPSLVGKG FTFMYEAAAT PVVTAMQGEI TNSSLSLHVG GSNLSNSVIL LGNLNCDVET QSFQGNVSLS GCSIPLHSLE AGIYPLQVRQ KQMGFANMSV VLQQFAVMPR IMAIFPSQGS ACGGTILTVR GLLLNSRRRS VRVDLSGPFT CVILSLGDHT ILCQVSLEGD PLPGASFSLN VTVLVNGLTS ECQGNCTLFI REEASPVMDA LSTNTSGSLT TVLIRGQRLA TTADEPMVFV DDQLPCNVTF FNASHVVCQT RDLAPGPHYL SVFYTRNGYA CSGNVSRHFY IMPQVFHYFP KNFSLHGGSL LTIEGTGLRG QNTTSVYIDQ QTCLTVNIGA ELIRCIVPTG NGSVALEIEV DGLWYHIGVI GYNKAFTPEL ISISQSDDIL TFAVAQISGA ANIDIFIGMS PCVGVSGNHT VLQCVVPSLP AGEYHVRGYD CIRGWASSAL VFTSRVIITA VTENFGCLGG RLVHVFGAGF SPGNVSAAVC GAPCRVLANA TVSAFSCLVL PLDVSLAFLC GLKREEDSCE AARHTYVQCD LTVAMATEQL LESWPYLYIC EESSQCLFVP DHWAESMFPS FSGLFISPKL ERDEVLIYNS SCNITMETEA EMECETPNQP ITVKITEIRK RWGQNTQGNF SLQFCRRWSR THSWFPERLP QDGDNVTVEN GQLLLLDTNT SILNLLHIKG GKLIFMAPGP IELRAHAILV SDGGELRIGS EDKPFQGRAQ ITLYGSSYST PFFPYGVKFL AVRNGTLSLH GSLPEVIVTC LRATAHALDT VLALEDAVDW NPGDEVVIIS GTGVKGAKPM EEIVTVETVQ DTDLYLKSPL RYSHNFTENW VAGEHHILKA TVALLSRSIT IQGNLTNERE KLLVSCQEAN APEGNLQHCL YSMSEKMLGS RDMGARVIVQ SFPEEPSQVQ LKGVQFQVLG QAFHKHLSSL TLVGAMRESF IQGCTVRNSF SRGLSMCGTL GLKVDSNVFY NILGHALLVG TCTEMRYISW EAIHGRKDDW SGHGNIIRNN VIIQVSGAEG LSNPEMLTPS GIYICSPTNV IEGNRVCGAG YGYFFHLMTN QTSQAPLLSF TQNIAHSCTR YGLFVYPKFQ PPWDNVTGTT LFQSFTVWES AGGAQIFRSS NLRLKNFKVY SCRDFGIDVL ESDANTSVTD SLLLGHFAHK GSLCMSSGIK TPKRWELMVS NTTFVNFDLI NCVAIRTCSD CSQGQGGFTV KTSQLKFTNS SNLVAFPFPH AAILEDLDGS LSGKNRSHIL ASMETLSASC LVNSSFGRVV HGSACGGGVL FHRMSIGLAN TPEVSYDLTM TDSRNKTTTV NYVRDTLSNP RGWMALLLDQ ETYSLQSENL WINRSLQYSA TFDNFAPGNY LLLVHTDLPP YPDILLRCGS RVGLSFPFLP SPGQNQGCDW FFNSQLRQLT YLVSGEGQVQ VILRVKEGMP PTISASTSAP ESALKWSLPE TWQGVEEGWG GYNNTIPGPG DDVLILPNRT VLVDTDLPFF KGLYVMGTLD FPVDRSNVLS VACMVIAGGE LKVGTLENPL EKEQKLLILL RASEGVFCDR MNGIHIDPGT IGVYGKVHLY SAYPKNSWTH LGADIASGNE RIIVEDAVDW RPHDKIVLSS SSYEPHEAEV LTVKEVKGHH VRIYERLKHR HIGSVHVTED GRHIRLAAEV GLLTRNIQIQ PDVSCRGRLF VGSFRKSSRE EFSGVLQLLN VEIQNFGSPL YSSVEFSNVS AGSWIISSTL HQSCGGGIHA AASHGVLLND NIVFGTAGHG IDLEGQAYTV TNNLVVLMTQ PAWSTIWVAG IKVNQVKDIN LHGNVVAGSE RLGFHIRGHK CSSCELLWSD NVAHSSLHGL HLYKESGLDN CTRISGFLAF KNFDYGAMLH VENSVEIENI TLVDNTIGLL AVVYVFSAPQ NSVKKVQIVL RNSVIVATSS SFDCIQDKVK PHSANLTSTD RAPSNPRGGR IGILWPVFTS EPNQWPQEPW HKVRNDHSIS GIMKLQDVTF SSFVKSCYSD DLDVCILPNA ENSGIMHPIT AERTRMLKIK DKNKFYFPSL QPRKDLGKVV CPELDCASPR KYLFKDLDGR ALGLPPPVSV FPKTEAEWTA SFFNAGTFRE EQKCTYQFLM QGFICKQTDQ VVLILDSADA IWAIQKLYPV VSVTSGFVDV FSSVNANIPC STSGSVSTFY SILPIRQITK VCFMDQTPQV LRFFLLGNKS TSKLLLAVFY HELQSPHVFL GESFIPPTLV QSASLLLNES IGANYFNIMD NLLYVVLQGE EPIEIRSGVS IHLALTVMVS VLEKGWEIVI LERLTNFLQI GQNQIRFIHE MPGHEETLKA IADSRAKRKR NCPTVTCTSH YRRVGQRRPL MMEMNSHRAS PPMTVETISK VIVIEIGDSP TVRSTGMISS LSSNKLQNLA HRVITAQQTG VLENVLNMTI GALLVTQSKG VIGYGNTSSF KTGNLIYIRP YALSILVQPS DGEVGNELPV QPQLVFLDEQ NRRVESLGPP SEPWTISASL EGASDSVLKG CTQAETQDGY VSFYNLAVLI SGSNWHFIFT VTSPPGVNFT ARSKPFAVLP VTRKEKSTII LAASLSSVAS WLALSCLVCC WLKRSKSRKT KPEEIPESQT NNQNIHIHIS SKRRESQGPK KEDTVVGEDM RMKVMLGKVN QCPHQLMNGV SRRKVSRHIV REEEAAVPAP GTTGITSHGH ICAPGAPAQQ VYLQETGNWK EGQEQLLRYQ LAGQNQLLLL CPDFRQERQQ LPGQSRLSKQ SGSLGLSQEK KASCGATEAF CLHSVHPETI QEQL //