PKHD1

Summary

PKHD1 (PKHD1 ciliary IPT domain containing fibrocystin/polyductin, HGNC:9016) is a protein-coding gene on chromosome 6p12.3-p12.2, encoding Fibrocystin (P08F94). 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.

The protein encoded by this gene is predicted to have a single transmembrane (TM)-spanning domain and multiple copies of an immunoglobulin-like plexin-transcription-factor domain. Alternative splicing results in two transcript variants encoding different isoforms. Other alternatively spliced transcripts have been described, but the full length sequences have not been determined. Several of these transcripts are predicted to encode truncated products which lack the TM and may be secreted. Mutations in this gene cause autosomal recessive polycystic kidney disease, also known as polycystic kidney and hepatic disease-1.

Source: NCBI Gene 5314 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive polycystic kidney disease (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 46
• Clinical variants (ClinVar): 6,692 total — 368 pathogenic, 905 likely-pathogenic
• Phenotypes (HPO): 90
• MANE Select transcript: NM_138694

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9016
Approved symbol	PKHD1
Name	PKHD1 ciliary IPT domain containing fibrocystin/polyductin
Location	6p12.3-p12.2
Locus type	gene with protein product
Status	Approved
Aliases	ARPKD, FCYT, FPC
Ensembl gene	ENSG00000170927
Ensembl biotype	protein_coding
OMIM	606702
Entrez	5314

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000340994, ENST00000371117

RefSeq mRNA: 2 — MANE Select: NM_138694 NM_138694, NM_170724

CCDS: CCDS4935, CCDS4936

Canonical transcript exons

ENST00000371117 — 67 exons

Exon	Start	End
ENSE00001084048	51638849	51638956
ENSE00001084050	51626997	51627116
ENSE00001084051	51632565	51632723
ENSE00001084053	51649085	51649220
ENSE00001133917	51746721	51746889
ENSE00001133927	51747787	51748665
ENSE00001133935	51753201	51753353
ENSE00001138118	52017410	52017629
ENSE00001138123	52022801	52022944
ENSE00001138130	52024574	52026181
ENSE00001138134	52027829	52027896
ENSE00001138138	52028156	52028351
ENSE00001138142	52033030	52033165
ENSE00001138148	52035591	52035721
ENSE00001138154	52042859	52043134
ENSE00001138161	52043625	52043730
ENSE00001138165	52044966	52045088
ENSE00001138171	52046004	52046188
ENSE00001138179	52048492	52048619
ENSE00001138529	52053076	52053251
ENSE00001138538	52054038	52054165
ENSE00001138579	51648031	51648118
ENSE00001165338	51744385	51744542
ENSE00001167034	52010309	52010459
ENSE00001167035	52055587	52055729
ENSE00001183430	51658952	51659969
ENSE00001183450	51754784	51754938
ENSE00001183457	51772702	51772789
ENSE00001183461	51775808	51775921
ENSE00001183467	51791236	51791373
ENSE00001183469	51830861	51830989
ENSE00001183471	51836404	51836469
ENSE00001183475	51847775	51847970
ENSE00001183482	51855893	51856070
ENSE00001183490	51867863	51868109
ENSE00001183494	51870504	51870639
ENSE00001183498	51883093	51883227
ENSE00001183502	51885867	51885972
ENSE00001183506	51887133	51887245
ENSE00001183510	51903597	51903727
ENSE00001183514	51903986	51904042
ENSE00001183518	51906215	51906340
ENSE00001183524	51909283	51909474
ENSE00001183527	51911799	51911956
ENSE00001183530	51912366	51912576
ENSE00001183533	51934110	51934322
ENSE00001183535	51959870	51960026
ENSE00001183582	52050157	52050295
ENSE00001183595	52056698	52056788
ENSE00001183599	52056890	52056979
ENSE00001183603	52058323	52058601
ENSE00001183608	52059928	52060042
ENSE00001183613	52062519	52062660
ENSE00001183619	52064955	52065050
ENSE00001183621	52065976	52066077
ENSE00001183627	52069457	52069527
ENSE00001183631	52070406	52070445
ENSE00001183637	52071006	52071070
ENSE00001183643	52072115	52072189
ENSE00001183648	52073463	52073541
ENSE00001183652	52076276	52076333
ENSE00001183658	52079900	52080008
ENSE00001183663	52082392	52082542
ENSE00001183666	52083178	52083255
ENSE00001359748	52087434	52087613
ENSE00001380634	52084882	52085017
ENSE00001454387	51615299	51619520

Expression profiles

Bgee: expression breadth broad, 51 present calls, max score 95.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3670 / max 138.0763, expressed in 49 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73951	0.2622	48
73950	0.0530	18
73949	0.0350	13
73952	0.0168	9

Top tissues by expression

230 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	95.47	gold quality
renal medulla	UBERON:0000362	91.80	gold quality
metanephros cortex	UBERON:0010533	85.61	gold quality
epithelial cell of pancreas	CL:0000083	84.42	gold quality
kidney	UBERON:0002113	83.58	gold quality
adult mammalian kidney	UBERON:0000082	82.64	gold quality
cortex of kidney	UBERON:0001225	77.72	gold quality
body of pancreas	UBERON:0001150	77.55	gold quality
metanephros	UBERON:0000081	77.02	gold quality
corpus epididymis	UBERON:0004359	74.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.63	gold quality
pancreas	UBERON:0001264	73.35	gold quality
tibialis anterior	UBERON:0001385	67.67	silver quality
caput epididymis	UBERON:0004358	67.47	gold quality
buccal mucosa cell	CL:0002336	66.31	gold quality
islet of Langerhans	UBERON:0000006	64.23	gold quality
right lobe of liver	UBERON:0001114	63.22	gold quality
liver	UBERON:0002107	62.77	gold quality
gall bladder	UBERON:0002110	62.11	gold quality
pancreatic ductal cell	CL:0002079	60.65	silver quality
ileal mucosa	UBERON:0000331	60.09	silver quality
cauda epididymis	UBERON:0004360	59.98	gold quality
sperm	CL:0000019	59.12	gold quality
adult organism	UBERON:0007023	58.47	gold quality
endothelial cell	CL:0000115	57.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	57.00	gold quality
colonic epithelium	UBERON:0000397	56.49	gold quality
seminal vesicle	UBERON:0000998	54.81	silver quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	516.04
E-CURD-119	yes	38.87
E-ANND-3	yes	10.22
E-GEOD-131882	no	6048.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF1A, HNF1B

miRNA regulators (miRDB)

144 targeting PKHD1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 40)

• 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. (PMID:11898128)
• characterization of mutation in autosomal recessive polycystic kidney disease (PMID:11919560)
• Map position is consistent with putative association with autosomal recessive polycystic kidney (PMID:12079288)
• Mutations in 110 alleles. Mutations scattered throughout gene without evidence of clustering at specific sites. All missense mutations were nonconservative. All with two truncating mutations displayed severe phenotype with perinatal or neonatal demise. (PMID:12506140)
• In cultured renal cells, the PKHD1 gene product colocalized with polycystin-2, the gene product of autosomal dominant polycystic disease type 2. (PMID:14983006)
• The detection of three different products using two antisera, with evidence for distinct subcellular localizations, suggests that PKHD1 encodes membrane-bound and soluble isoforms. (PMID:15458427)
• the hepatocyte nuclear factor-1beta (HNF-1beta) C-terminal domain has a role in Pkhd1 (ARPKD) gene transcription and renal cystogenesis (PMID:15647252)
• PKHD1 deletions account for a detectable proportion of autosomal recessive polycystic kidney disease cases (PMID:16199545)
• The intracellular C-terminus of fibrocystin interacts with CAML, a protein with an intracellular distribution that is similar to that of PKD2. (PMID:16243292)
• PKHD1 mutations are involved in the pathogenesis of all typical forms of autosomal recessive polycystic kidney disease (ARPKD). (PMID:17160262)
• These findings suggest that FPC and polycystins share, at least in part, a common mechanotransduction pathway. (PMID:17283055)
• PKHD1 gene product polyductin/fibrocystin undergoes a complicated pattern of Notch-like proteolytic processing and is shed from the cilia to the lumen. (PMID:17470460)
• Mutations in this gene are not linked to renal-hepatic-pancreatic dysplasia in a case report. (PMID:17593545)
• These results suggest that the loss of fibrocystin may lead to abnormal proliferation in kidney epithelial cells and cyst formation in autosomal recessive polycystic kidney disease by modulation of intracellular Ca(2+). (PMID:17669261)
• Pseudoexon activation in the PKHD1 gene: a French founder intronic mutation IVS46+653A>G causing severe autosomal recessive polycystic kidney disease. (PMID:19021639)
• polycystin-1, polycystin-2, and fibrocystin are shed in membrane particles in the urine, and these particles interact with primary cilia (PMID:19158352)
• These results represent the first systematic study of polyductin expression in human pathologies associated with abnormal development of intrahepatic biliary tree. (PMID:19292732)
• These observations should provide an important platform for determining FPC function and the pathogenesis of autosomal recessive polycystic kidney disease. (PMID:19524688)
• PKHD1 sequencing results on 78 ARPKD/CHF patients from 68 families, is reported. (PMID:19914852)
• Data suggest that fibrocystin-1 is a component of the normal focal adhesion complex and that actin and fibrocystin-1 are lost from autosomal recessive polycystic kidney disease complexes. (PMID:19923420)
• the presence of two truncating mutations of the PKHD1 gene is associated with the most severe renal forms of prenatally detected autosomal recessive polycystic kidney disease (PMID:19940839)
• FC1-depletion induced reduction in ERK1/2 kinase activation and activation of NF-kappaB. (PMID:19943112)
• There is wide variability in severity of renal disease among patients carrying the same PKHD1 mutations, even within the same family. (PMID:20413436)
• PKHD1 localizes to the mitotic spindle in patients with autosomal recessive polycystic kidney disease. (PMID:20554582)
• Multiplex ligation-dependent probe amplification is a sensitive and rapid method to identify PKHD1 deletions. (PMID:20575693)
• Screening for the most common PKHD1 mutation (T36M) in a European cohort indicated that heterozygous PKHD1 mutations are not a risk factor but rather are protective for colorectal cancer. (PMID:21274727)
• Data suggest that the PI3K/Akt pathway is involved in apoptotic function in PKHD1-silenced cells, and PI3K/Akt inhibition correlates with upregulation of NF-kappaB activity. (PMID:21300060)
• Our data suggest that carrier status for PKHD1 mutations in autosomal recessive polycystic kidney disease is a predisposition to polycystic liver disease and renal involvement (PMID:21945273)
• miR-365-1 modulated PKHD1 suppressed cell-cell adhesion in part through E-cadherin (PMID:22411058)
• Data identified that the compound heterozygous PKHD1 gene mutations are the molecular basis of the patient with ARPKD. (PMID:22882926)
• PKHD1 mutations in a Chinese twin family with Caroli disease. (PMID:24710345)
• The cytoplasmic tail of fibrocystin modulates the PI3K/Akt/mTOR pathway and the cleaved C-tail regulates the function of the full-length protein. (PMID:24851866)
• Intragenic motifs regulate the transcriptional complexity of Pkhd1/PKHD1 (PMID:24984783)
• Report PKHD1 mutations in autosomal recessive polycystic kidney disease leading to alterations in genetic transcription. (PMID:25104275)
• PKHD1 mutations were detected in three children with autosomal recessive polycystic kidney disease with PCR and direct sequencing. (PMID:25124979)
• A novel c.9059T>C mutation in PKHD1 gene expands mutation spectrum for autosomal recessive polycystic kidney disease. (PMID:25153916)
• Our data provide strong evidence that the p.M627K substitution at the PKHD1 locus is a founder mutation for Autosomal recessive polycystic kidney disease in the Afrikaner population (PMID:25193386)
• Both polycystins were detected on the spindle and mid-body of mitotic cells, while fibrocystin was on centrosome throughout cell cycle. (PMID:25367197)
• Results identified six novel mutations (PKHD1: p.Thr777Met, p.Tyr2260Cys; ABCB11: p.Val1112Phe, c.611+1G > A, p.Gly628Trpfs*3 and NPC1: p.Glu391Lys) for the diagnostic of inherited infantile cholestatic disorders. (PMID:25771912)
• Compound heterozygous PKHD1 variants cause a wide spectrum of ductal plate malformations. (PMID:26385851)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pkhd1	ENSMUSG00000043760
rattus_norvegicus	Pkhd1	ENSRNOG00000058742

Paralogs (36): SYNE2 (ENSG00000054654), SPTB (ENSG00000070182), ACTN1 (ENSG00000072110), ACTN2 (ENSG00000077522), DSP (ENSG00000096696), DRP2 (ENSG00000102385), SPTBN1 (ENSG00000115306), MACF1 (ENSG00000127603), FLNC (ENSG00000128591), ACTN4 (ENSG00000130402), SYNE1 (ENSG00000131018), MICAL2 (ENSG00000133816), DTNA (ENSG00000134769), MICAL1 (ENSG00000135596), FLNB (ENSG00000136068), SPTBN5 (ENSG00000137877), DTNB (ENSG00000138101), GAS2L3 (ENSG00000139354), DST (ENSG00000151914), UTRN (ENSG00000152818), SPTBN4 (ENSG00000160460), SPTA1 (ENSG00000163554), CLMN (ENSG00000165959), SPTBN2 (ENSG00000173898), SYNE3 (ENSG00000176438), PLEC (ENSG00000178209), SMTNL2 (ENSG00000188176), FLNA (ENSG00000196924), SPTAN1 (ENSG00000197694), DMD (ENSG00000198947), PKHD1L1 (ENSG00000205038), DYTN (ENSG00000232125), MICAL3 (ENSG00000243156), ACTN3 (ENSG00000248746), EPPK1 (ENSG00000261150), GAS2L2 (ENSG00000270765)

Protein

Protein identifiers

Fibrocystin — P08F94 (reviewed: P08F94)

Alternative names: Polycystic kidney and hepatic disease 1 protein, Polyductin, Tigmin

All UniProt accessions (1): P08F94

UniProt curated annotations — full annotation on UniProt →

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, it also regulates 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.

Subunit / interactions. Interacts with CAMLG. Interacts with PKD2. Interacts (via CST) with ARF4; this interaction allows an efficient PKHD1 trafficking to the cilium. Interacts (via CST) with RAB8A; this interaction controls trafficking through the endomembrane systeme and the cilium. Interacts (via CST) with TULP3; this interaction allows PKHD1 trafficking to the cilium.

Subcellular location. Cell membrane. Cytoplasm. Cell projection. Cilium. Cytoskeleton. Cilium basal body. Spindle. Chromosome. Centromere. Apical cell membrane. Nucleus. Secreted. Extracellular exosome. Endoplasmic reticulum. Golgi apparatus.

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.

Post-translational modifications. Several proteolytic cleavages occur within the extracellular domain, whereas at least one cleavage occurs within the cytoplasmic domain. Cleaved by a probable proprotein convertase which produces an extracellular domain (polyductin extracellular domain, (PECD)) and a C-terminal fragment (polyductin transmembrane fragment (PTM)) which are tethered together by disulfide bonds. This extracellular domain (PECD) is then shed from the primary cilium by activation of a member of the ADAM metalloproteinase disintegrins family, resulting in concomitant release of an intra-cellular C-terminal fragment (ICD) via a gamma-secretase-dependent process. The proteolytic cleavage of the C-terminal intracellular fragment (ICD) is controlled by cytosolic calcium concentration and activation of PKC. Palmitoylated. Palmitoylation facilitates membrane targeting and the trafficking to the cilia. N-glycosylated.

Disease relevance. Polycystic kidney disease 4, with or without polycystic liver disease (PKD4) [MIM:263200] A severe form of polycystic kidney disease affecting the kidneys and, in some cases, the hepatic biliary tract. The clinical spectrum is widely variable, with most cases presenting during infancy. The fetal phenotypic features classically include enlarged and echogenic kidneys, as well as oligohydramnios secondary to a poor urine output. Up to 50% of the affected neonates die shortly after birth, as a result of severe pulmonary hypoplasia and secondary respiratory insufficiency. In the subset that survives the perinatal period, morbidity and mortality are mainly related to severe systemic hypertension, renal insufficiency, and portal hypertension due to portal-tract fibrosis. PKD4 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Loss-of-function PKHD1 variations may cause autosomal dominant polycystic liver disease (PCLD) in patients that lack variations in known causative genes, such as PRKCSH and SEC63.

Isoforms (2)

UniProt ID	Names	Canonical?
P08F94-1	1	yes
P08F94-2	2

RefSeq proteins (2): NP_619639, NP_733842 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002909	IPT_dom	Domain
IPR006626	PbH1	Repeat
IPR011050	Pectin_lyase_fold/virulence	Homologous_superfamily
IPR012334	Pectin_lyas_fold	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR019316	G8_domain	Domain
IPR037524	PA14/GLEYA	Domain
IPR039448	Beta_helix	Domain
IPR052387	Fibrocystin	Family
IPR055401	CEMIP_beta-hel_dom	Domain

Pfam: PF01833, PF10162, PF13229, PF24606

UniProt features (260 total): sequence variant 159, glycosylation site 64, domain 15, repeat 9, region of interest 3, topological domain 2, splice variant 2, signal peptide 1, chain 1, mutagenesis site 1, transmembrane region 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for P08F94 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 3620–3621 (cleavage)

Glycosylation sites (64): 54, 226, 276, 357, 387, 507, 520, 529, 641, 711, 830, 869, 967, 977, 1065, 1084, 1116, 1135, 1234, 1241 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
3617–3618	loss of protein convertase cleavage into a 85 kda ptm fragment.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 396 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_SPINDLE_LOCALIZATION, GOCC_CELL_SURFACE, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, HNF1_Q6, GOCC_MICROTUBULE_ORGANIZING_CENTER

GO Biological Process (24): establishment of mitotic spindle orientation (GO:0000132), kidney development (GO:0001822), regulation of cell-matrix adhesion (GO:0001952), epithelial cell morphogenesis (GO:0003382), intracellular calcium ion homeostasis (GO:0006874), positive regulation of cell population proliferation (GO:0008284), regulation of centrosome duplication (GO:0010824), regulation of cell-cell adhesion (GO:0022407), regulation of cell adhesion (GO:0030155), regulation of TOR signaling (GO:0032006), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), homeostatic process (GO:0042592), negative regulation of apoptotic process (GO:0043066), cell-cell junction organization (GO:0045216), branching morphogenesis of an epithelial tube (GO:0048754), positive regulation of epithelial cell proliferation (GO:0050679), establishment of centrosome localization (GO:0051660), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), cilium assembly (GO:0060271), regulation of ERK1 and ERK2 cascade (GO:0070372), regulation of establishment of planar polarity (GO:0090175), cell-cell adhesion (GO:0098609), negative regulation of epithelial cell apoptotic process (GO:1904036), regulation of cholangiocyte proliferation (GO:1904054)

GO Molecular Function (2): signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (22): chromosome, centromeric region (GO:0000775), nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), centrosome (GO:0005813), cytosol (GO:0005829), cilium (GO:0005929), external side of plasma membrane (GO:0009897), apical plasma membrane (GO:0016324), ciliary basal body (GO:0036064), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), mitotic spindle (GO:0072686), 9+0 non-motile cilium (GO:0097731), extracellular region (GO:0005576), chromosome (GO:0005694), spindle (GO:0005819), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	4
intracellular membrane-bounded organelle	3
intracellular membraneless organelle	3
endomembrane system	2
microtubule organizing center	2
mitotic cell cycle	1
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
animal organ development	1
renal system development	1
cell-matrix adhesion	1
regulation of cell-substrate adhesion	1
cell morphogenesis	1
epithelial cell development	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of centrosome cycle	1
centrosome duplication	1
regulation of cell adhesion	1
cell-cell adhesion	1
cell adhesion	1
regulation of cellular process	1
TOR signaling	1
regulation of intracellular signal transduction	1
biological_process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
cell junction organization	1
tube morphogenesis	1
epithelial tube morphogenesis	1
morphogenesis of a branching epithelium	1
positive regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
centrosome localization	1

Protein interactions and networks

STRING

1194 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PKHD1	PKD2	Q13563	984
PKHD1	PKD1	P98161	969
PKHD1	UMOD	P07911	844
PKHD1	HNF1B	P35680	827
PKHD1	CYS1	Q717R9	820
PKHD1	IFT88	Q13099	796
PKHD1	NPHP3	Q7Z494	747
PKHD1	NPHP1	O15259	742
PKHD1	TRAM2	Q15035	741
PKHD1	PRKD1	Q15139	733
PKHD1	CAMLG	P49069	724
PKHD1	KIF3A	Q9Y496	676
PKHD1	DZIP1L	Q8IYY4	670
PKHD1	PRKCSH	P14314	669
PKHD1	NEK8	Q86SG6	638

IntAct

5 interactions, top by confidence:

A	B	Type	Score
PKHD1	CAMLG	psi-mi:“MI:0915”(physical association)	0.510
PKHD1	RPLP2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (12): SMURF1 (Affinity Capture-Western), SMURF2 (Affinity Capture-Western), NEDD4L (Affinity Capture-Western), NDFIP2 (Affinity Capture-Western), PKHD1 (Affinity Capture-MS), PKHD1 (Affinity Capture-MS), PKHD1 (Proximity Label-MS), PKHD1 (Affinity Capture-MS), PKHD1 (Cross-Linking-MS (XL-MS)), PRPF19 (Cross-Linking-MS (XL-MS)), PKHD1 (Proximity Label-MS), PKHD1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTW7, A0A1D5NSK0, A0A1L8HYT7, A0A286YEC0, A0M8R7, A0M8S8, A1X150, E2RK30, O60486, O62446, P08581, P08F94, P10643, P16056, P97523, Q00PJ8, Q07DV8, Q07DY1, Q07DZ1, Q07E01, Q07E24, Q07E37, Q07E48, Q09YH7, Q09YI9, Q09YK0, Q09YL1, Q09YN5, Q108U6, Q2IBA6, Q2IBC0, Q2IBD8, Q2IBF2, Q2IBG7, Q2QL89, Q2QLA9, Q2QLC0, Q2QLE0, Q2QLF1, Q2QLG5

Diamond homologs: E2RK30, E9PZ36, P08F94, Q5FWI3, Q8BI06, Q8WUJ3, A3KPQ7, A5PKI3, B0BLS9, Q54KF6, Q6GQC1, Q91VU0, Q92520, Q9UHN6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

6692 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	368
Likely pathogenic	905
Uncertain significance	2039
Likely benign	2364
Benign	214

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1064648	NM_138694.3:c.(?5909)(12225_?)del	Pathogenic
1066549	NM_138694.4(PKHD1):c.2T>C (p.Met1Thr)	Pathogenic
1069080	NM_138694.4(PKHD1):c.6008del (p.Lys2003fs)	Pathogenic
1070196	NM_138694.4(PKHD1):c.547C>T (p.Gln183Ter)	Pathogenic
1070528	NM_138694.4(PKHD1):c.7529_7530del (p.Ser2510fs)	Pathogenic
1071279	NC_000006.11:g.(?51612575)(51618161_?)del	Pathogenic
1071341	NM_138694.4(PKHD1):c.2664_2665insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGTTGCAGTGAGCCGAGATGGCAGCAGTACAGTCCAGCTTCGGCTCCGCATGAGAGGGAGACCGTGGGGAGAGGGAGACAGAGGGAGAGGGAGAGGGAGCATGATGGTGGAGTTTTT (p.Leu889fs)	Pathogenic
1071441	NM_138694.4(PKHD1):c.9210_9223del (p.Gln3070fs)	Pathogenic
1073091	NC_000006.11:g.(?51701192)(51701277_?)del	Pathogenic
1073092	NC_000006.11:g.(?51637490)(51637597_?)del	Pathogenic
1073631	NM_138694.4(PKHD1):c.11408dup (p.Ala3804fs)	Pathogenic
1073734	NM_138694.4(PKHD1):c.8863C>T (p.Arg2955Ter)	Pathogenic
1073873	NM_138694.4(PKHD1):c.1626_1629del (p.Leu543fs)	Pathogenic
1073874	NM_138694.4(PKHD1):c.1197del (p.Leu400fs)	Pathogenic
1074162	NM_138694.4(PKHD1):c.10561C>T (p.Gln3521Ter)	Pathogenic
1074409	NM_138694.4(PKHD1):c.424del (p.Val142fs)	Pathogenic
1074792	NM_138694.4(PKHD1):c.9149del (p.Gly3050fs)	Pathogenic
1075810	NM_138694.4(PKHD1):c.3589dup (p.Glu1197fs)	Pathogenic
1075837	NM_138694.4(PKHD1):c.484G>T (p.Gly162Ter)	Pathogenic
1076600	NM_138694.4(PKHD1):c.2085_2086insA (p.Glu696fs)	Pathogenic
1076676	NM_138694.4(PKHD1):c.11566A>T (p.Lys3856Ter)	Pathogenic
1076693	NM_138694.4(PKHD1):c.9070dup (p.Cys3024fs)	Pathogenic
1179144	NM_138694.4(PKHD1):c.1854del (p.Gly619fs)	Pathogenic
1180650	NM_138694.4(PKHD1):c.8642+1G>T	Pathogenic
1184734	NM_138694.4(PKHD1):c.8743G>T (p.Glu2915Ter)	Pathogenic
1255548	NM_138694.4(PKHD1):c.2285_2286del (p.Val762fs)	Pathogenic
1300719	NM_138694.4(PKHD1):c.8829dup (p.Ile2944fs)	Pathogenic
1323460	NM_138694.4(PKHD1):c.470dup (p.Trp158fs)	Pathogenic
1328416	NM_138694.4(PKHD1):c.444_445del (p.Pro149fs)	Pathogenic
1328417	NM_138694.4(PKHD1):c.1694-74_1837-287del	Pathogenic

SpliceAI

12434 predictions. Top by Δscore:

Variant	Effect	Δscore
6:51619418:T:TA	donor_gain	1.0000
6:51619518:TAT:T	acceptor_gain	1.0000
6:51619518:TATC:T	acceptor_loss	1.0000
6:51619521:C:CC	acceptor_gain	1.0000
6:51619521:C:T	acceptor_loss	1.0000
6:51627122:T:TC	acceptor_gain	1.0000
6:51632563:A:AC	donor_gain	1.0000
6:51632564:C:CT	donor_gain	1.0000
6:51632564:CTT:C	donor_gain	1.0000
6:51632566:T:TA	donor_gain	1.0000
6:51632721:CTC:C	acceptor_gain	1.0000
6:51648027:CTA:C	donor_loss	1.0000
6:51648117:TT:T	acceptor_gain	1.0000
6:51648119:C:CC	acceptor_gain	1.0000
6:51648125:A:AC	acceptor_gain	1.0000
6:51648125:A:C	acceptor_gain	1.0000
6:51649228:A:C	acceptor_gain	1.0000
6:51649230:A:C	acceptor_gain	1.0000
6:51744379:GCTTA:G	donor_loss	1.0000
6:51744380:CTTA:C	donor_loss	1.0000
6:51744381:TTACC:T	donor_loss	1.0000
6:51744382:TACCT:T	donor_loss	1.0000
6:51744383:A:C	donor_loss	1.0000
6:51744384:C:A	donor_loss	1.0000
6:51744538:CTTTC:C	acceptor_gain	1.0000
6:51746757:T:C	donor_gain	1.0000
6:51746764:T:C	donor_gain	1.0000
6:51746773:T:TA	donor_gain	1.0000
6:51755535:T:TC	acceptor_gain	1.0000
6:51772696:CCTTA:C	donor_loss	1.0000

AlphaMissense

26616 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:51830957:A:G	W2736R	0.988
6:51830957:A:T	W2736R	0.988
6:52083215:G:C	S31R	0.988
6:52083215:G:T	S31R	0.988
6:52083217:T:G	S31R	0.988
6:51648079:A:G	W3784R	0.986
6:51648079:A:T	W3784R	0.986
6:52071030:A:G	C215R	0.986
6:51747989:G:C	S3209R	0.985
6:51747989:G:T	S3209R	0.985
6:51747991:T:G	S3209R	0.985
6:51632619:A:G	W3871R	0.983
6:51632619:A:T	W3871R	0.983
6:51830937:C:A	W2742C	0.983
6:51830937:C:G	W2742C	0.983
6:51868102:A:C	F2498L	0.983
6:51868102:A:T	F2498L	0.983
6:51868104:A:G	F2498L	0.983
6:51959994:C:A	W1928C	0.983
6:51959994:C:G	W1928C	0.983
6:52033094:A:C	F1100L	0.983
6:52033094:A:T	F1100L	0.983
6:52033096:A:G	F1100L	0.983
6:52069494:A:C	S247R	0.982
6:52069494:A:T	S247R	0.982
6:52069496:T:G	S247R	0.982
6:52071029:C:G	C215S	0.980
6:52071030:A:T	C215S	0.980
6:51959996:A:G	W1928R	0.979
6:51959996:A:T	W1928R	0.979

dbSNP variants (sampled 300 via entrez): RS1000006639 (6:51891816 A>G), RS1000015284 (6:51844424 A>G,T), RS1000017812 (6:51729407 A>C,G), RS1000020671 (6:51619691 A>G), RS1000022496 (6:51638336 C>T), RS1000022823 (6:51913617 A>C), RS1000027340 (6:51664338 G>A), RS1000028988 (6:51823253 T>C), RS1000029384 (6:51662647 C>T), RS1000047726 (6:51842644 T>A), RS1000056142 (6:51647454 T>C), RS1000062765 (6:51896772 T>A,C), RS1000072318 (6:51717132 T>C), RS1000076440 (6:51931995 G>T), RS1000089353 (6:51997681 G>C)

Disease associations

OMIM: gene MIM:606702 | disease phenotypes: MIM:263200, MIM:174050, MIM:600643, MIM:614391, MIM:173900, MIM:236200, MIM:252350

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive polycystic kidney disease	Definitive	Autosomal recessive
polycystic kidney disease 4	Definitive	Autosomal recessive
nephrocalcinosis	Strong	Autosomal dominant
Caroli disease	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
autosomal recessive polycystic kidney disease	Definitive	AR

Mondo (20): autosomal recessive polycystic kidney disease (MONDO:0009889), polycystic kidney disease 4 (MONDO:0033004), autosomal dominant polycystic liver disease (MONDO:0000447), Caroli disease (MONDO:0010913), cystic kidney disease (MONDO:0002473), urogenital tract malformation (MONDO:0019356), pregnancy loss, recurrent, susceptibility to, 3 (MONDO:0013729), autosomal dominant polycystic kidney disease (MONDO:0004691), familial cystic renal disease (MONDO:0019741), polycystic kidney disease (MONDO:0020642), prostate cancer (MONDO:0008315), biliary tract disorder (MONDO:0004868), malignant colon neoplasm (MONDO:0021063), polycystic kidney disease 1 (MONDO:0008263), classic homocystinuria (MONDO:0009352)

Orphanet (10): Autosomal recessive polycystic kidney disease (Orphanet:731), (Orphanet:8378), Isolated polycystic liver disease (Orphanet:2924), Caroli disease (Orphanet:53035), Urogenital tract malformation (Orphanet:83001), Autosomal dominant polycystic kidney disease (Orphanet:730), Genetic cystic renal disease (Orphanet:93587), Familial prostate cancer (Orphanet:1331), Homocystinuria due to cystathionine beta-synthase deficiency (Orphanet:394), Moyamoya disease (Orphanet:2573)

HPO phenotypes

90 total (30 of 90 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000083	Renal insufficiency
HP:0000105	Enlarged kidney
HP:0000107	Renal cyst
HP:0000113	Polycystic kidney dysplasia
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000457	Depressed nasal ridge
HP:0000822	Hypertension
HP:0000952	Jaundice
HP:0000989	Pruritus
HP:0001081	Cholelithiasis
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001396	Cholestasis
HP:0001405	Periportal fibrosis
HP:0001406	Intrahepatic cholestasis
HP:0001407	Hepatic cysts
HP:0001409	Portal hypertension
HP:0001433	Hepatosplenomegaly
HP:0001510	Growth delay
HP:0001541	Ascites
HP:0001562	Oligohydramnios
HP:0001737	Pancreatic cysts
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001919	Acute kidney injury
HP:0001944	Dehydration

GWAS associations

46 associations (top):

Study	Trait	p-value
GCST000095_2	Prostate cancer	3.000000e-06
GCST000427_1	Waist circumference	3.000000e-06
GCST001985_1	Weight loss (gastric bypass surgery)	5.000000e-07
GCST001985_2	Weight loss (gastric bypass surgery)	5.000000e-08
GCST002168_2	Intraocular pressure	7.000000e-07
GCST003264_1363	Post bronchodilator FEV1/FVC ratio	6.000000e-08
GCST003264_1393	Post bronchodilator FEV1/FVC ratio	1.000000e-07
GCST003264_1399	Post bronchodilator FEV1/FVC ratio	2.000000e-07
GCST003488_11	Response to fenofibrate (triglyceride levels)	7.000000e-06
GCST004280_32	Diastolic blood pressure	7.000000e-10
GCST005170_50	Intraocular pressure	7.000000e-10
GCST005580_222	Intraocular pressure	5.000000e-20
GCST005580_228	Intraocular pressure	3.000000e-18
GCST006065_18	Glaucoma (primary open-angle)	5.000000e-09
GCST006394_8	Intraocular pressure	1.000000e-13
GCST006395_3	Glaucoma	4.000000e-07
GCST006412_59	Intraocular pressure	2.000000e-14
GCST006658_6	Longevity	4.000000e-06
GCST006986_8	Red vs. brown/black hair color	3.000000e-28
GCST007094_88	Diastolic blood pressure	1.000000e-09
GCST007576_344	Chronotype	2.000000e-09
GCST007930_165	Medication use (agents acting on the renin-angiotensin system)	1.000000e-09
GCST008058_288	Estimated glomerular filtration rate	1.000000e-11
GCST008259_13	Alcohol use disorder	1.000000e-08
GCST008526_43	Coffee consumption	4.000000e-11
GCST008529_4	Tea consumption	5.000000e-13
GCST008647_25	Urinary sodium excretion	1.000000e-17
GCST008748_2	Epigenetic age acceleration in alcohol use disorder	6.000000e-07
GCST009725_18	Intraocular pressure	2.000000e-16
GCST010002_325	Refractive error	4.000000e-37

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0005245	body weight loss
EFO:0004695	intraocular pressure measurement
EFO:0004713	FEV/FVC ratio
EFO:0007681	triglyceride change measurement
EFO:0006336	diastolic blood pressure
EFO:0003924	hair color
EFO:0008328	chronotype measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009458	alcohol use disorder measurement
EFO:0006781	coffee consumption measurement
EFO:0010091	tea consumption measurement
EFO:0009282	sodium measurement
EFO:0000473	epigenetic status
EFO:0022597	aging
EFO:0008111	diet measurement
EFO:0007874	gut microbiome measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement

MeSH disease descriptors (12)

Descriptor	Name	Tree numbers
D001660	Biliary Tract Diseases	C06.130
D016767	Caroli Disease	C06.130.120.127.500; C06.198.184.500; C16.131.077.245.250; C16.131.314.184.500; C16.320.184.250
D030342	Genetic Diseases, Inborn	C16.320
D052177	Kidney Diseases, Cystic	C12.050.351.968.419.403; C12.200.777.419.403; C12.950.419.403
D009072	Moyamoya Disease	C10.228.140.300.200.600; C10.228.140.300.510.200.737; C14.907.137.615; C14.907.253.123.620; C14.907.253.560.200.737
D009397	Nephrocalcinosis	C12.050.351.968.419.590; C12.200.777.419.590; C12.950.419.590; C18.452.174.130.560
D016104	Oligohydramnios	C12.050.703.560
D007690	Polycystic Kidney Diseases	C12.050.351.968.419.403.875; C12.200.777.419.403.875; C12.950.419.403.875; C16.131.077.717; C16.320.184.625
D016891	Polycystic Kidney, Autosomal Dominant	C12.050.351.968.419.403.875.500; C12.200.777.419.403.875.500; C12.950.419.403.875.500; C16.131.077.717.500; C16.320.184.625.500
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D051437	Renal Insufficiency	C12.050.351.968.419.780; C12.200.777.419.780; C12.950.419.780
C536326	Polycystic kidney disease, type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation, increases mutagenesis	3
sodium arsenite	affects methylation, decreases expression	2
methyleugenol	decreases expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
bisphenol A	increases methylation	1
CGP 52608	increases reaction, affects binding	1
bisphenol S	affects cotreatment, increases methylation	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Zoledronic Acid	decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Arbutin	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Methotrexate	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Theophylline	decreases expression	1
Valproic Acid	affects expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

9 cell lines: 5 induced pluripotent stem cell, 2 transformed cell line, 2 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3NW	DHMCi006-A	Induced pluripotent stem cell	Female
CVCL_B3NX	DHMCi007-A	Induced pluripotent stem cell	Female
CVCL_B7DP	CPGHi008-A	Induced pluripotent stem cell	Female
CVCL_E3XK	UAB-HEK293-PKHD1 KO#1	Transformed cell line	Female
CVCL_E3XL	UAB-HEK293-PKHD1 KO#2	Transformed cell line	Female
CVCL_E3XQ	UAB-iPSC-PKHD1 KO#1	Induced pluripotent stem cell	Male
CVCL_V447	GM12607	Finite cell line	Female
CVCL_V448	GM12609	Finite cell line	Female
CVCL_V453	iPS ARPKD 5	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

150 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00414440	PHASE4	COMPLETED	Efficacy, Safety and Tolerability of Everolimus in Preventing End-stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease
NCT03273413	PHASE4	ACTIVE_NOT_RECRUITING	Statin Therapy in Patients With Early Stage ADPKD
NCT03949894	PHASE4	COMPLETED	Evaluating the Safety and effectivenesS in Adult KorEaN Patients Treated With Tolvaptan for Management of Autosomal domInAnt poLycystic Kidney Disease
NCT04782258	PHASE3	RECRUITING	A Study to See Iftolvaptan is Safe in Infants and Children Who at Enrollment Are 28 Days to Less Than 18 Years Old withAutosomal Recessive Polycystic Kidney Disease (ARPKD)
NCT04786574	PHASE3	WITHDRAWN	A Study to See if Tolvaptan Can Delay Dialysis in Infants and Children Who at Enrollment Are 28 Days to Less Than 12 Weeks Old With Autosomal Recessive Polycystic Kidney Disease (ARPKD)
NCT00249951	PHASE3	COMPLETED	Alkaline Citrate Treatment to Lower the Risk of Nephrocalcinosis in Preterm Infants
NCT01756547	PHASE3	UNKNOWN	Study to Assess the Efficacy and Safety of Oral Potassium Citrate on the Prevention of Nephrocalcinosis in Extreme Premature
NCT04705051	PHASE3	TERMINATED	Long-term Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) With Venglustat
NCT00309283	PHASE3	COMPLETED	Somatostatin in Polycystic Kidney: a Long-term Three Year Follow up Study
NCT00346918	PHASE3	COMPLETED	Sirolimus (Rapamune®) for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT00428948	PHASE3	COMPLETED	Tolvaptan Phase 3 Efficacy and Safety Study in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT01022424	PHASE3	COMPLETED	A Long-term Administration Study of OPC-41061 in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) (2) [Extension of Study 156-05-002]
NCT01214421	PHASE3	COMPLETED	Tolvaptan Extension Study in Participants With ADPKD
NCT01377246	PHASE3	COMPLETED	Somatostatin In Patients With Autosomal Dominant Polycystic Kidney Disease And Moderate To Severe Renal Insufficiency
NCT01616927	PHASE3	UNKNOWN	Study of Lanreotide to Treat Polycystic Kidney Disease
NCT01853553	PHASE3	COMPLETED	Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT02115659	PHASE3	UNKNOWN	Triptolide-Containing Formulation as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT02134899	PHASE3	COMPLETED	The Efficacy of Everolimus in Reducing Total Native Kidney Volume in Polycystic Kidney Disease Transplanted Recipients
NCT02160145	PHASE3	COMPLETED	Efficacy and Safety of Tolvaptan in Subjects With Chronic Kidney Disease Between Late Stage 2 to Early Stage 4 Due to Autosomal Dominant Polycystic Kidney Disease
NCT02964273	PHASE3	COMPLETED	Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease)
NCT03764605	PHASE3	UNKNOWN	Metformin vs Tolvaptan for Treatment of Autosomal Dominant Polycystic Kidney Disease
NCT03918447	PHASE3	TERMINATED	A Trial of Bardoxolone Methyl in Patients With ADPKD - FALCON
NCT04064346	PHASE3	TERMINATED	Efficacy and Safety of Lixivaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease
NCT04152837	PHASE3	TERMINATED	Safety of Lixivaptan in Subjects Previously Treated With Tolvaptan for Autosomal Dominant Polycystic Kidney Disease
NCT04939935	PHASE3	RECRUITING	Implementation of Metformin theraPy to Ease Decline of Kidney Function in Polycystic Kidney Disease (IMPEDE-PKD)
NCT05373264	PHASE3	RECRUITING	HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life
NCT04495608	PHASE2	COMPLETED	Multicenter, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Fluconazole in Hypercalcicuric Patients With Increased 1.25(OH) 2D Levels
NCT01157858	PHASE2	COMPLETED	Everolimus and LongActing Octreotide Trial in Polycystic Livers
NCT01670110	PHASE2	COMPLETED	Pasireotide LAR in Severe Polycystic Liver Disease
NCT02021110	PHASE2	COMPLETED	Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease
NCT05478083	PHASE2	RECRUITING	A GnRH Agonist IN Pre-menopausal Women STudy to Treat Severe Polycystic Liver Disease
NCT02684435	PHASE2	COMPLETED	Contrast-enhanced Ultrasound of the Kidney
NCT03196076	PHASE2	COMPLETED	Contrast-enhanced Ultrasound for Complex Kidney Lesion Diagnosis in Patients With CKD Extension
NCT00841568	PHASE2	COMPLETED	A Long-term Administration Study of OPC-41061 in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) [Extension of Study 156-04-001]
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