Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAH8SMF)

• DOT Name: Fibrocystin (PKHD1)
• Synonyms: Polycystic kidney and hepatic disease 1 protein; Polyductin; Tigmin
• Gene Name: PKHD1
• Related Disease:
  Autosomal recessive polycystic kidney disease
  Polycystic kidney disease 4
  Adenoma
  Advanced cancer
  Anal intraepithelial neoplasia
  Autosomal dominant polycystic kidney disease
  Autosomal dominant polycystic liver disease
  Carcinoma
  Cardiovascular disease
  Cholestasis
  Chronic kidney disease
  Ciliopathy
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Common wart
  Congestive heart failure
  Cystic kidney disease
  Episodic kinesigenic dyskinesia 1
  Familial pancreatic carcinoma
  Kidney failure
  Matthew-Wood syndrome
  Medullary sponge kidney
  Neoplasm
  Pancreatic ductal carcinoma
  Schizophrenia
  Sexually transmitted infection
  Nephronophthisis
  Obesity
  Caroli disease
  Colorectal adenocarcinoma
  OPTN-related open angle glaucoma
  Acute myelogenous leukaemia
  Childhood kidney Wilms tumor
  Familial adenomatous polyposis
  Familial prostate carcinoma
  High blood pressure
  Pneumocystis pneumonia
  Prostate cancer
  Prostate carcinoma
  Wilms tumor
• UniProt ID: PKHD1_HUMAN
• Pfam ID: PF13229 ; PF10162 ; PF01833
• Sequence:
  MTAWLISLMSIEVLLLAVRHLSLHIEPEEGSLAGGTWITVIFDGLELGVLYPNNGSQLEI
  HLVNVNMVVPALRSVPCDVFPVFLDLPVVTCRTRSVLSEAHEGLYFLEAYFGGQLVSSPN
  PGPRDSCTFKFSKAQTPIVHQVYPPSGVPGKLIHVYGWIITGRLETFDFDAEYIDSPVIL
  EAQGDKWVTPCSLINRQMGSCYPIQEDHGLGTLQCHVEGDYIGSQNVSFSVFNKGKSMVH
  KKAWLISAKQDLFLYQTHSEILSVFPETGSLGGRTNITITGDFFDNSAQVTIAGIPCDIR
  HVSPRKIECTTRAPGKDVRLTTPQPGNRGLLFEVGDAVEGLELTEATPGYRWQIVPNASS
  PFGFWSQEGQPFRARLSGFFVAPETNNYTFWIQADSQASLHFSWSEEPRTKVKVASISVG
  TADWFDSWEQNRDEGTWQQKTPKLELLGGAMYYLEAEHHGIAPSRGMRIGVQIHNTWLNP
  DVVTTYLREKHQIRVRAQRLPEVQVLNVSGRGNFFLTWDNVSSQPIPANATAHLIQTTIE
  ELLAVKCKLEPLWSNILLRLGFERGPEVSNSDGDLTSGTEPFCGRFSLRQPRHLVLTPPA
  AQKGYRLDQYTHLCLAYKGHMNKILKMIVSFTIGFQNMVKNTTCDWSLTRTSPESWQFDC
  TDLWETCVRCFGDLQPPPANSPVLVHQINLLPLAQETGLFYVDEIIIADTNVTVSQADSG
  TARPGGNLVESVSVVGSPPVYSVTSWLAGCGTELPLITARSVPTEGTEEGSGLVLVTTQR
  RQRTSPPLGGHFRIQLPNTVISDVPVQISAHHLHQLLQNNADDFTSRYLNASDFTVKEDL
  YTCYEHVWTLSWSTQIGDLPNFIRVSDENLTGVNPAAATRVVYDGGVFLGPIFGDMLATA
  NQHTQVVVRVNDVPAHCPGSCSFQYLQGSTPCVHSVWYSIDGDINLMIYITGTGFSGDSQ
  FLQVTVNKTSCKVIFSNQTNVVCQTDLLPVGMHRILMLVRPSGLAISATGEDLFLNVKPR
  LDMVEPSRAADIGGLWATIRGSSLEGVSLILFGSYSCAINVATSNSSRIQCKVPPRGKDG
  RIVNVTVIRGDYSAVLPRAFTYVSSLNPVIVTLSRNISNIAGGETLVIGVARLMNYTDLD
  VEVHVQDALAPVHTQSAWGLEVALPPLPAGLHRISVSINGVSIHSQGVDLHIQYLTEVFS
  IEPCCGSLLGGTILSISGIGFSRDPALVWVLVGNRSCDIVNLTEASIWCETLPAPQIPDA
  GAPTVPAAVEVWAGNRFFARGPSPSLVGKGFTFMYEAAATPVVTAMQGEITNSSLSLHVG
  GSNLSNSVILLGNLNCDVETQSFQGNVSLSGCSIPLHSLEAGIYPLQVRQKQMGFANMSV
  VLQQFAVMPRIMAIFPSQGSACGGTILTVRGLLLNSRRRSVRVDLSGPFTCVILSLGDHT
  ILCQVSLEGDPLPGASFSLNVTVLVNGLTSECQGNCTLFIREEASPVMDALSTNTSGSLT
  TVLIRGQRLATTADEPMVFVDDQLPCNVTFFNASHVVCQTRDLAPGPHYLSVFYTRNGYA
  CSGNVSRHFYIMPQVFHYFPKNFSLHGGSLLTIEGTGLRGQNTTSVYIDQQTCLTVNIGA
  ELIRCIVPTGNGSVALEIEVDGLWYHIGVIGYNKAFTPELISISQSDDILTFAVAQISGA
  ANIDIFIGMSPCVGVSGNHTVLQCVVPSLPAGEYHVRGYDCIRGWASSALVFTSRVIITA
  VTENFGCLGGRLVHVFGAGFSPGNVSAAVCGAPCRVLANATVSAFSCLVLPLDVSLAFLC
  GLKREEDSCEAARHTYVQCDLTVAMATEQLLESWPYLYICEESSQCLFVPDHWAESMFPS
  FSGLFISPKLERDEVLIYNSSCNITMETEAEMECETPNQPITVKITEIRKRWGQNTQGNF
  SLQFCRRWSRTHSWFPERLPQDGDNVTVENGQLLLLDTNTSILNLLHIKGGKLIFMAPGP
  IELRAHAILVSDGGELRIGSEDKPFQGRAQITLYGSSYSTPFFPYGVKFLAVRNGTLSLH
  GSLPEVIVTCLRATAHALDTVLALEDAVDWNPGDEVVIISGTGVKGAKPMEEIVTVETVQ
  DTDLYLKSPLRYSHNFTENWVAGEHHILKATVALLSRSITIQGNLTNEREKLLVSCQEAN
  APEGNLQHCLYSMSEKMLGSRDMGARVIVQSFPEEPSQVQLKGVQFQVLGQAFHKHLSSL
  TLVGAMRESFIQGCTVRNSFSRGLSMCGTLGLKVDSNVFYNILGHALLVGTCTEMRYISW
  EAIHGRKDDWSGHGNIIRNNVIIQVSGAEGLSNPEMLTPSGIYICSPTNVIEGNRVCGAG
  YGYFFHLMTNQTSQAPLLSFTQNIAHSCTRYGLFVYPKFQPPWDNVTGTTLFQSFTVWES
  AGGAQIFRSSNLRLKNFKVYSCRDFGIDVLESDANTSVTDSLLLGHFAHKGSLCMSSGIK
  TPKRWELMVSNTTFVNFDLINCVAIRTCSDCSQGQGGFTVKTSQLKFTNSSNLVAFPFPH
  AAILEDLDGSLSGKNRSHILASMETLSASCLVNSSFGRVVHGSACGGGVLFHRMSIGLAN
  TPEVSYDLTMTDSRNKTTTVNYVRDTLSNPRGWMALLLDQETYSLQSENLWINRSLQYSA
  TFDNFAPGNYLLLVHTDLPPYPDILLRCGSRVGLSFPFLPSPGQNQGCDWFFNSQLRQLT
  YLVSGEGQVQVILRVKEGMPPTISASTSAPESALKWSLPETWQGVEEGWGGYNNTIPGPG
  DDVLILPNRTVLVDTDLPFFKGLYVMGTLDFPVDRSNVLSVACMVIAGGELKVGTLENPL
  EKEQKLLILLRASEGVFCDRMNGIHIDPGTIGVYGKVHLYSAYPKNSWTHLGADIASGNE
  RIIVEDAVDWRPHDKIVLSSSSYEPHEAEVLTVKEVKGHHVRIYERLKHRHIGSVHVTED
  GRHIRLAAEVGLLTRNIQIQPDVSCRGRLFVGSFRKSSREEFSGVLQLLNVEIQNFGSPL
  YSSVEFSNVSAGSWIISSTLHQSCGGGIHAAASHGVLLNDNIVFGTAGHGIDLEGQAYTV
  TNNLVVLMTQPAWSTIWVAGIKVNQVKDINLHGNVVAGSERLGFHIRGHKCSSCELLWSD
  NVAHSSLHGLHLYKESGLDNCTRISGFLAFKNFDYGAMLHVENSVEIENITLVDNTIGLL
  AVVYVFSAPQNSVKKVQIVLRNSVIVATSSSFDCIQDKVKPHSANLTSTDRAPSNPRGGR
  IGILWPVFTSEPNQWPQEPWHKVRNDHSISGIMKLQDVTFSSFVKSCYSDDLDVCILPNA
  ENSGIMHPITAERTRMLKIKDKNKFYFPSLQPRKDLGKVVCPELDCASPRKYLFKDLDGR
  ALGLPPPVSVFPKTEAEWTASFFNAGTFREEQKCTYQFLMQGFICKQTDQVVLILDSADA
  IWAIQKLYPVVSVTSGFVDVFSSVNANIPCSTSGSVSTFYSILPIRQITKVCFMDQTPQV
  LRFFLLGNKSTSKLLLAVFYHELQSPHVFLGESFIPPTLVQSASLLLNESIGANYFNIMD
  NLLYVVLQGEEPIEIRSGVSIHLALTVMVSVLEKGWEIVILERLTNFLQIGQNQIRFIHE
  MPGHEETLKAIADSRAKRKRNCPTVTCTSHYRRVGQRRPLMMEMNSHRASPPMTVETISK
  VIVIEIGDSPTVRSTGMISSLSSNKLQNLAHRVITAQQTGVLENVLNMTIGALLVTQSKG
  VIGYGNTSSFKTGNLIYIRPYALSILVQPSDGEVGNELPVQPQLVFLDEQNRRVESLGPP
  SEPWTISASLEGASDSVLKGCTQAETQDGYVSFYNLAVLISGSNWHFIFTVTSPPGVNFT
  ARSKPFAVLPVTRKEKSTIILAASLSSVASWLALSCLVCCWLKRSKSRKTKPEEIPESQT
  NNQNIHIHISSKRRESQGPKKEDTVVGEDMRMKVMLGKVNQCPHQLMNGVSRRKVSRHIV
  REEEAAVPAPGTTGITSHGHICAPGAPAQQVYLQETGNWKEGQEQLLRYQLAGQNQLLLL
  CPDFRQERQQLPGQSRLSKQSGSLGLSQEKKASCGATEAFCLHSVHPETIQEQL
• Function: Promotes ciliogenesis in renal epithelial cells and therefore participates in the tubules formation and/ or ensures the maintenance of the architecture of the lumen of the kidney. Has an impact on cellular symmetry by ensuring correct bipolar cell division through the regulation of centrosome duplication and mitotic spindle assembly and by maintaining oriented cell division (OCD) during tubular elongation through planar cell polarity (PCP) pathway. During epithelial cell morphogenesis regulates also cell-cell and cell-matrix adhesion and participates in cell motility. Promotes cell-cell contact through the positive regulation of PTK2 kinase activity leading to either positive regulation of epithelial cell proliferation through the HRAS/RAF1 pathways, or negative regulation of apoptosis through the PDK1/AKT1 pathway. May act in collecting-duct and biliary differentiation. May participate in the regulation of the cholangiocytes proliferation and the CCN2 production in an CXCL8-dependent manner.
• Tissue Specificity: Predominantly expressed in fetal and adult kidney. In the kidney, it is found in the cortical and medullary collecting ducts. Also present in the adult pancreas, but at much lower levels. Detectable in fetal and adult liver. Rather indistinct signal in fetal brain.

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive polycystic kidney disease	DISPUS40	Definitive	Autosomal recessive	[1]
Polycystic kidney disease 4	DISNSG52	Definitive	Autosomal recessive	[2]
Adenoma	DIS78ZEV	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Anal intraepithelial neoplasia	DISJ0JW3	Strong	Genetic Variation	[5]
Autosomal dominant polycystic kidney disease	DISBHWUI	Strong	Biomarker	[6]
Autosomal dominant polycystic liver disease	DISJS005	Strong	Genetic Variation	[7]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[8]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[9]
Cholestasis	DISDJJWE	Strong	Genetic Variation	[10]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[11]
Ciliopathy	DIS10G4I	Strong	Biomarker	[6]
Colon cancer	DISVC52G	Strong	Genetic Variation	[12]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[13]
Common wart	DISPREJ5	Strong	Biomarker	[14]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[15]
Cystic kidney disease	DISRT1LM	Strong	Genetic Variation	[6]
Episodic kinesigenic dyskinesia 1	DISGVQMP	Strong	Genetic Variation	[16]
Familial pancreatic carcinoma	DIS1XROR	Strong	Biomarker	[17]
Kidney failure	DISOVQ9P	Strong	Genetic Variation	[18]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[17]
Medullary sponge kidney	DISA0949	Strong	Genetic Variation	[7]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[5]
Pancreatic ductal carcinoma	DIS26F9Q	Strong	Genetic Variation	[17]
Schizophrenia	DISSRV2N	Strong	Biomarker	[19]
Sexually transmitted infection	DISIVIAL	Strong	Biomarker	[14]
Nephronophthisis	DISXU4HY	moderate	CausalMutation	[20]
Obesity	DIS47Y1K	moderate	Genetic Variation	[21]
Caroli disease	DISXQYMX	Supportive	Autosomal recessive	[22]
Colorectal adenocarcinoma	DISPQOUB	Disputed	Biomarker	[13]
OPTN-related open angle glaucoma	DISDR98A	Disputed	Genetic Variation	[23]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[24]
Childhood kidney Wilms tumor	DIS0NMK3	Limited	Genetic Variation	[25]
Familial adenomatous polyposis	DISW53RE	Limited	Biomarker	[26]
Familial prostate carcinoma	DISL9KNO	Limited	Genetic Variation	[27]
High blood pressure	DISY2OHH	Limited	Genetic Variation	[28]
Pneumocystis pneumonia	DISFSOM3	Limited	Altered Expression	[29]
Prostate cancer	DISF190Y	Limited	Biomarker	[27]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[27]
Wilms tumor	DISB6T16	Limited	Genetic Variation	[25]

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Fibrocystin (PKHD1).	[30]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Fibrocystin (PKHD1).	[31]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Fibrocystin (PKHD1).	[32]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Fibrocystin (PKHD1).	[33]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Fibrocystin (PKHD1).	[35]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 decreases the expression of Fibrocystin (PKHD1).	[36]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Fibrocystin (PKHD1).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Fibrocystin (PKHD1).	[37]

References

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