PKD1

Summary

PKD1 (polycystin 1, transient receptor potential channel interacting, HGNC:9008) is a protein-coding gene on chromosome 16p13.3, encoding Polycystin-1 (P98161). Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B.

This gene encodes a member of the polycystin protein family. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains and a cytoplasmic C-tail. It is an integral membrane protein that functions as a regulator of calcium permeable cation channels and intracellular calcium homoeostasis. It is also involved in cell-cell/matrix interactions and may modulate G-protein-coupled signal-transduction pathways. It plays a role in renal tubular development, and mutations in this gene cause autosomal dominant polycystic kidney disease type 1 (ADPKD1). ADPKD1 is characterized by the growth of fluid-filled cysts that replace normal renal tissue and result in end-stage renal failure. Splice variants encoding different isoforms have been noted for this gene. Also, six pseudogenes, closely linked in a known duplicated region on chromosome 16p, have been described.

Source: NCBI Gene 5310 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant polycystic kidney disease (Definitive, ClinGen) — +3 more curated relationships
• Clinical variants (ClinVar): 7,001 total — 1551 pathogenic, 491 likely-pathogenic
• Phenotypes (HPO): 31
• Druggable target: yes
• MANE Select transcript: NM_001009944

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9008
Approved symbol	PKD1
Name	polycystin 1, transient receptor potential channel interacting
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	PBP, Pc-1, TRPP1
Ensembl gene	ENSG00000008710
Ensembl biotype	protein_coding
OMIM	601313
Entrez	5310

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 21 retained_intron, 10 protein_coding_CDS_not_defined, 5 protein_coding, 4 nonsense_mediated_decay

ENST00000262304, ENST00000415938, ENST00000423118, ENST00000468674, ENST00000469241, ENST00000469851, ENST00000471603, ENST00000472577, ENST00000472659, ENST00000473780, ENST00000474088, ENST00000475889, ENST00000480227, ENST00000483024, ENST00000483558, ENST00000483731, ENST00000483814, ENST00000485120, ENST00000486339, ENST00000487932, ENST00000488185, ENST00000496574, ENST00000561668, ENST00000561991, ENST00000562297, ENST00000562425, ENST00000564313, ENST00000564865, ENST00000564890, ENST00000565639, ENST00000566784, ENST00000566905, ENST00000567355, ENST00000567946, ENST00000568591, ENST00000568796, ENST00000569983, ENST00000570150, ENST00000570193, ENST00000570253

RefSeq mRNA: 2 — MANE Select: NM_001009944 NM_000296, NM_001009944

CCDS: CCDS32369, CCDS45385

Canonical transcript exons

ENST00000262304 — 46 exons

Exon	Start	End
ENSE00001646942	2090674	2090808
ENSE00001685753	2116833	2117053
ENSE00001704553	2118676	2118845
ENSE00001707265	2108252	2111871
ENSE00001712154	2119307	2119378
ENSE00001742822	2117791	2118462
ENSE00001768440	2119114	2119185
ENSE00002710399	2135475	2135898
ENSE00003465030	2113161	2113292
ENSE00003476703	2112788	2112963
ENSE00003477392	2099861	2100071
ENSE00003489424	2100396	2100566
ENSE00003491604	2115378	2115625
ENSE00003514551	2097148	2097241
ENSE00003514982	2112340	2112473
ENSE00003516228	2094092	2094210
ENSE00003530534	2092047	2092188
ENSE00003531671	2092954	2093093
ENSE00003533708	2100166	2100309
ENSE00003536327	2117489	2117672
ENSE00003544272	2099644	2099770
ENSE00003544442	2091781	2091906
ENSE00003549115	2103266	2103895
ENSE00003552757	2090285	2090590
ENSE00003559565	2104498	2104642
ENSE00003567818	2097319	2097503
ENSE00003569697	2106091	2106304
ENSE00003583385	2107883	2108032
ENSE00003593667	2116529	2116644
ENSE00003596620	2105865	2106024
ENSE00003607637	2105322	2105474
ENSE00003612827	2093544	2093738
ENSE00003628139	2093811	2094013
ENSE00003629798	2102814	2102970
ENSE00003631955	2102381	2102633
ENSE00003642197	2092480	2092592
ENSE00003645303	2114170	2114925
ENSE00003646590	2115992	2116118
ENSE00003647173	2106805	2106948
ENSE00003665951	2102061	2102256
ENSE00003668317	2097868	2097984
ENSE00003677394	2091423	2091597
ENSE00003683239	2090884	2091174
ENSE00003685878	2106398	2106677
ENSE00003786909	2097728	2097780
ENSE00003896676	2088708	2090194

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.85.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.85	gold quality
cerebellar hemisphere	UBERON:0002245	99.84	gold quality
cerebellar cortex	UBERON:0002129	99.79	gold quality
cerebellum	UBERON:0002037	99.39	gold quality
adenohypophysis	UBERON:0002196	99.27	gold quality
right frontal lobe	UBERON:0002810	99.16	gold quality
mucosa of stomach	UBERON:0001199	99.14	gold quality
ascending aorta	UBERON:0001496	99.13	gold quality
thoracic aorta	UBERON:0001515	99.12	gold quality
descending thoracic aorta	UBERON:0002345	99.05	gold quality
pituitary gland	UBERON:0000007	99.01	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.86	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.85	gold quality
lower esophagus	UBERON:0013473	98.84	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.84	gold quality
body of uterus	UBERON:0009853	98.83	gold quality
aorta	UBERON:0000947	98.82	gold quality
right coronary artery	UBERON:0001625	98.73	gold quality
popliteal artery	UBERON:0002250	98.66	gold quality
tibial artery	UBERON:0007610	98.65	gold quality
left uterine tube	UBERON:0001303	98.64	gold quality
right ovary	UBERON:0002118	98.61	gold quality
artery	UBERON:0001637	98.51	gold quality
left ovary	UBERON:0002119	98.39	gold quality
apex of heart	UBERON:0002098	98.36	gold quality
paraflocculus	UBERON:0005351	98.33	gold quality
endocervix	UBERON:0000458	98.32	gold quality
left coronary artery	UBERON:0001626	98.32	gold quality
coronary artery	UBERON:0001621	98.15	gold quality
right uterine tube	UBERON:0001302	98.06	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-30	yes	516.72
E-ANND-3	yes	4.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ATF1, CTNNB1, DDIT3, GATA4, HNF4A, MZF1, NFKB, NKX2-5, NR1I3, NR4A1, PAX6, PDX1, PKD2, RXRB, SP1, SPI1, THRA, THRB, TP53, ZNF148

miRNA regulators (miRDB)

53 targeting PKD1, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-6852-5P	99.17	66.69	2073

Literature-anchored findings (GeneRIF, showing 40)

• induces resistance to apoptosis and spontaneous tubulogenesis in MDCK cells (PMID:11106764)
• Fluorescence in situ hybridization analysis in a patient with an acrofacial dysostosis-like phenotype, tuberous sclerosis, and polycystic kidney disease shows a microdeletion of approximately 280 kb including the PKD1 gene on chromosome 16p13.3. (PMID:11836366)
• Twelve novel pathogenic DNA variants, including five truncating mutations, two in-frame deletions, and two splice-site mutations, have been detected in the duplicated region of the PKD1 gene. (PMID:11857740)
• found profound differences in the spatiotemporal expression of PKD1 and PKD2 during nephrogenesis, PKD2 being expressed earlier and more diffusely than PKD1 (PMID:11891195)
• identification, characterization, and localization of a complex with polycystin-2 (PMID:11901144)
• Polycystin-1 activation of c-Jun N-terminal kinase and AP-1 is mediated by heterotrimeric G proteins (PMID:11912216)
• promoter is a target of the beta-catenin/T-cell factor pathway (PMID:12048202)
• Cleavage of polycystin-1 requires the receptor for egg jelly domain and is disrupted by human autosomal-dominant polycystic kidney disease 1-associated mutations. (PMID:12482949)
• one of the primary functions of polycystin-1 is to mediate cell-cell adhesion in renal epithelial cells, probably via homophilic or heterophilic interactions of the PKD domains (PMID:12819240)
• REVIEW: Role in renal tubulogenesis (PMID:12946628)
• The results of glycosylation reporter analyses are unambiguous for the majority of polycystin-1 transmembrane (TM) domains and support an 11 TM structure for polycystin-1 comprised of TM domains I-XI. (PMID:14596619)
• Enhanced phosphorylation of polycystin-1 in ADPKD cells precipitates changes in its localization and its ability to form protein complexes (PMID:14718571)
• PAF-evoked intracellular Ca2+ increase was reduced by the presence of PKD1 mutations. PC1 is functionally expressed in B- lymphoblastoid cells. (PMID:15001556)
• polycystin-1 is a surface membrane receptor that transduces the signal via changes in ionic currents. (PMID:15060061)
• Polycystin-1 may be required for adequate AP-1 activity. (PMID:15087466)
• polycystin-1 is regulated by Siah-1 through the ubiquitin-dependent proteasome pathway. (PMID:15284290)
• Mutations occur throughout the PKD1 gene, but more severe disease is associated with N-terminal mutations. (PMID:15382167)
• PC1 signaling elevates intracellular Ca(2+), activates Galpha(q) and PLC, which then activates calcineurin and NFAT (PMID:15466861)
• In kidney epithelial cells the overexpression of PC1 C-terminus upregulates serum-evoked intracellular Ca2+ by counteracting the growth-suppression activity of endogenous PC1 and leading to an increase in cell proliferation. (PMID:15748886)
• Structure and function of this gene shows how mutation at this locus results in the spectrum of changes seen in autosomal-dominant polycystic kidney disease. (review) (PMID:15780076)
• polycystin-1 accelerated the decay of the cell calcium response to ATP by upregulation of ER calcium reuptake and consequent minimization of the stimulus for capacitative calcium entry (PMID:15870383)
• CD16.7-PKD1 (115-226) activates Cl(-) channels in the Xenopus oocyte plasma membrane in parallel with, but not secondary to, activation of Ca(2+)-permeable cation channels (PMID:16014040)
• The polycystin multiprotein complex is embedded in a cholesterol-containing signalling microdomain specified by flotillin-2, which is distinct from classical light-buoyant-density, detergent-resistant domains. (PMID:16038619)
• Data suggested that the autosomal dominant polycystic kidney disease is not linked to PKD1 but to PKD2. (PMID:16215947)
• polycystin-1 extracellular region displays a dynamic extensibility whereby the resting length might be regulated through unfolding/refolding of its Ig-like domains (PMID:16219758)
• PKD2 regulates the cell cycle through direct interaction with Id2; Id2 expression suppresses the induction of a cdk inhibitor, p21, by either PKD1 or PDK2. The PDK2-Id2 interaction is regulated by PDK1-dependent phosphorylation of PDK2. (PMID:16311606)
• News: regulates the cell cycle by preventing nuclear localization of ID2 (PMID:16319969)
• propose that calcium response to fluid-flow shear stress can be used as a readout of polycystin function and that loss of mechanosensation in the renal tubular epithelia is a feature of autosomal dominant polycystic kidney disease cysts (PMID:16565258)
• In PKD1 gene, 14 mutations found, including 10 missense, 1 insertion, 1 deletion and 2 nonsense mutations. Besides 12 mutations identified before, mutations nt32819G>A and nt37137T>C were the novel mutations found. (PMID:16767665)
• development of the kidney may regulate the expression of PC-1, and an altered PC-1 expression may contribute to cyst formation in autosomal dominant polycystic kidney disease (PMID:16778383)
• Results suggest that membrane-bound polycystin 1 has a central role in regulating morphogenic protein signaling at cell-matrix interfaces in non-confluent cells. (PMID:16790429)
• Data provide evidence for ciliary dysfunction and polycystin mislocalization in human autosomal dominant polycystic kidney disease cells with PKD1 protein containing the novel DeltaL2433 mutation. (PMID:17090781)
• mTOR is regulatd by polycystin-1 in polycystic kidney disease [review] (PMID:17102641)
• ADPKD patient cells with known germline mutations in PKD1 had a decreased or absence of polycystin-1 but not polycystin-2. These cells had an increased sensitivity to IGF-1 and to cyclic AMP (PMID:17396115)
• Reliable basis upon which to map important residues using mutagenic experiments and to refine knowledge about a preferred sugar ligand and the functional role of the C-lectins in polycystin-1. (PMID:17437137)
• Data suggest that PKD1 may act as a novel member of the tumor suppressor family of genes. (PMID:17437318)
• Data show that annexin A5 interacts with the N-terminal leucine-rich repeats of polycystin-1, and that polycystin-1 colocalizes with E-cadherin at cell-cell contacts and accelerates the recruitment of intracellular E-cadherin to reforming junctions. (PMID:17451746)
• The PKD1 gene product, plays a critical role in renal tubule diameter control and disruption of its function causes cyst formation in human autosomal dominant polycystic kidney disease (PMID:17525154)
• polycystin-1 COOH-terminal can activate or block polycystin-1 signaling (PMID:17540339)
• PC-1 regulates the actin cytoskeleton in renal epithelial cells (MDCK) and induces cell scattering and cell migration. (PMID:17671167)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pkd1a	ENSDARG00000030417
mus_musculus	Pkd1	ENSMUSG00000032855
rattus_norvegicus	Pkd1	ENSRNOG00000010771
drosophila_melanogaster	Pkd2	FBGN0041195
caenorhabditis_elegans		WBGENE00004035

Paralogs (10): PKD2L2 (ENSG00000078795), PKD2L1 (ENSG00000107593), PKD2 (ENSG00000118762), PKDREJ (ENSG00000130943), PKD1L1 (ENSG00000158683), PKD1L2 (ENSG00000166473), LOXHD1 (ENSG00000167210), DENND5B (ENSG00000170456), DENND5A (ENSG00000184014), PKD1L3 (ENSG00000277481)

Protein

Protein identifiers

Polycystin-1 — P98161 (reviewed: P98161)

Alternative names: Autosomal dominant polycystic kidney disease 1 protein

All UniProt accessions (8): P98161, H3BQF4, H3BSE8, H3BSE9, H3BTE0, H3BTG3, H3BV77, I3L4N0

UniProt curated annotations — full annotation on UniProt →

Function. Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B. Both PKD1 and PKD2 are required for channel activity. Involved in renal tubulogenesis. Involved in fluid-flow mechanosensation by the primary cilium in renal epithelium. Acts as a regulator of cilium length, together with PKD2. The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling. The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling. May be an ion-channel regulator. Involved in adhesive protein-protein and protein-carbohydrate interactions. Likely to be involved with polycystin-1-interacting protein 1 in the detection, sequestration and exocytosis of senescent mitochondria.

Subunit / interactions. Component of the heterotetrameric polycystin channel complex with PKD2; the tetramer contains one PKD1 chain and three PKD2 chains. Interacts with PKD2; the interaction is required for ciliary localization. Interacts with PKD2L1. Interacts with PRKX; involved in differentiation and controlled morphogenesis of the kidney. Interacts (via extracellular domain) with WNT3A, WNT4, WNT5A and WNT9B. Interacts with DVL1 and DVL2. Interacts with NPHP1 (via SH3 domain). Interacts with BBS1, BBS4, BBS5 and TTC8. Interacts with RGS7. Interacts (via the PKD repeats in the N-terminal extracellular region) with EPCIP; the interaction is not dependent on N-glycosylation of either protein.

Subcellular location. Cell membrane. Cell projection. Cilium. Endoplasmic reticulum. Golgi apparatus. Vesicle. Secreted. Extracellular exosome.

Post-translational modifications. N-glycosylated. After synthesis, undergoes cleavage between Leu-3048 and Thr-3049 in the GPS region of the GAIN-B domain. Cleavage at the GPS region occurs through a cis-autoproteolytic mechanism involving an ester-intermediate via N-O acyl rearrangement. This process takes place in the early secretory pathway, depends on initial N-glycosylation, and requires the REJ domain. There is evidence that cleavage at GPS region is incomplete. Uncleaved and cleaved products may have different functions in vivo.

Disease relevance. Polycystic kidney disease 1 with or without polycystic liver disease (PKD1) [MIM:173900] An autosomal dominant disorder characterized by renal cysts, liver cysts and intracranial aneurysm. Clinical variability is due to differences in the rate of loss of glomerular filtration, the age of reaching end-stage renal disease and the occurrence of hypertension, symptomatic extrarenal cysts, and subarachnoid hemorrhage from intracranial ‘berry’ aneurysm. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The LDL-receptor class A domain is atypical; the potential calcium-binding site is missing.

Similarity. Belongs to the polycystin family.

Isoforms (3)

UniProt ID	Names	Canonical?
P98161-1	1	yes
P98161-2	2
P98161-3	3

RefSeq proteins (2): NP_000287, NP_001009944* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000203	GPS	Conserved_site
IPR000372	LRRNT	Domain
IPR000434	PC1	Family
IPR000483	Cys-rich_flank_reg_C	Domain
IPR000601	PKD_dom	Domain
IPR001024	PLAT/LH2_dom	Domain
IPR001304	C-type_lectin-like	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR002859	PKD/REJ-like	Domain
IPR002889	WSC_carb-bd	Domain
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR006228	Polycystin_cat	Domain
IPR013122	PKD1_2_channel	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014010	REJ_dom	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR022409	PKD/Chitinase_dom	Domain
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR035986	PKD_dom_sf	Homologous_superfamily
IPR036392	PLAT/LH2_dom_sf	Homologous_superfamily
IPR042060	PLAT_polycystin1	Domain
IPR046791	Polycystin_dom	Domain
IPR057244	GAIN_B	Domain

Pfam: PF00059, PF00801, PF01477, PF01822, PF02010, PF08016, PF13855, PF20519

UniProt features (341 total): sequence variant 186, glycosylation site 60, domain 25, sequence conflict 16, topological domain 12, transmembrane region 11, strand 7, disulfide bond 6, region of interest 4, compositionally biased region 3, splice variant 2, repeat 2, mutagenesis site 2, signal peptide 1, chain 1, coiled-coil region 1, site 1, modified residue 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
8ZKH	ELECTRON MICROSCOPY	2.3
8ZKR	ELECTRON MICROSCOPY	2.8
8Z6B	ELECTRON MICROSCOPY	3
8Z6F	ELECTRON MICROSCOPY	3.08
8Z6H	ELECTRON MICROSCOPY	3.1
8ZKS	ELECTRON MICROSCOPY	3.21
8ZKT	ELECTRON MICROSCOPY	3.34
8ZKU	ELECTRON MICROSCOPY	3.34
9L0M	ELECTRON MICROSCOPY	3.34
8ZL8	ELECTRON MICROSCOPY	3.38
6A70	ELECTRON MICROSCOPY	3.6
9L0W	ELECTRON MICROSCOPY	3.69
1B4R	SOLUTION NMR

Predicted structure (AlphaFold)

No AlphaFold model available for P98161 — 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): 3048–3049 (cleavage; by autolysis)

Post-translational modifications (1): 4166

Disulfide bonds (6): 436–530, 508–522, 640–653, 647–665, 660–669, 3015–3043

Glycosylation sites (60): 1880, 1991, 2050, 2074, 2125, 2248, 2353, 2395, 2412, 2567, 2578, 2645, 2718, 2754, 2841, 2878, 2925, 2956, 2994, 3738 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
3049	does not affect auto-cleavage.
3049	does not undergo auto-cleavage.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5620916	VxPx cargo-targeting to cilium

MSigDB gene sets: 428 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, RNGTGGGC_UNKNOWN, GOBP_METANEPHRIC_NEPHRON_MORPHOGENESIS, MODULE_97, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_LUNG_EPITHELIUM_DEVELOPMENT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_METANEPHROS_DEVELOPMENT, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT

GO Biological Process (51): cartilage condensation (GO:0001502), in utero embryonic development (GO:0001701), kidney development (GO:0001822), liver development (GO:0001889), embryonic placenta development (GO:0001892), protein export from nucleus (GO:0006611), calcium ion transport (GO:0006816), homophilic cell-cell adhesion (GO:0007156), cell-matrix adhesion (GO:0007160), calcium-independent cell-matrix adhesion (GO:0007161), cell surface receptor signaling pathway (GO:0007166), positive regulation of cytosolic calcium ion concentration (GO:0007204), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), heart development (GO:0007507), anatomical structure morphogenesis (GO:0009653), Wnt signaling pathway (GO:0016055), spinal cord development (GO:0021510), neural tube development (GO:0021915), establishment of cell polarity (GO:0030010), regulation of cell adhesion (GO:0030155), response to fluid shear stress (GO:0034405), lymph vessel morphogenesis (GO:0036303), skin development (GO:0043588), positive regulation of transcription by RNA polymerase II (GO:0045944), digestive tract development (GO:0048565), branching morphogenesis of an epithelial tube (GO:0048754), genitalia development (GO:0048806), detection of mechanical stimulus (GO:0050982), cartilage development (GO:0051216), protein heterotetramerization (GO:0051290), regulation of cell cycle (GO:0051726), regulation of mitotic spindle organization (GO:0060236), lung epithelium development (GO:0060428), placenta blood vessel development (GO:0060674), regulation of proteasomal protein catabolic process (GO:0061136), calcium ion transmembrane transport (GO:0070588), nitrogen cycle metabolic process (GO:0071941), mesonephric tubule development (GO:0072164), mesonephric duct development (GO:0072177), metanephric collecting duct development (GO:0072205)

GO Molecular Function (9): calcium channel activity (GO:0005262), protein kinase binding (GO:0019901), protein domain specific binding (GO:0019904), carbohydrate binding (GO:0030246), Wnt receptor activity (GO:0042813), transmembrane transporter binding (GO:0044325), transcription regulator inhibitor activity (GO:0140416), monoatomic cation channel activity (GO:0005261), protein binding (GO:0005515)

GO Cellular Component (22): Golgi membrane (GO:0000139), polycystin complex (GO:0002133), nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), cilium (GO:0005929), cell surface (GO:0009986), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), lateral plasma membrane (GO:0016328), Golgi-associated vesicle membrane (GO:0030660), motile cilium (GO:0031514), cation channel complex (GO:0034703), calcium channel complex (GO:0034704), ciliary membrane (GO:0060170), extracellular exosome (GO:0070062), migrasome (GO:0140494), extracellular region (GO:0005576), vesicle (GO:0031982), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cargo trafficking to the periciliary membrane	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular membrane-bounded organelle	4
bounding membrane of organelle	3
chordate embryonic development	2
animal organ development	2
anatomical structure development	2
protein binding	2
binding	2
cytoplasm	2
endomembrane system	2
cilium	2
skeletal system morphogenesis	1
cartilage development	1
cell aggregation	1
renal system development	1
gland development	1
hepaticobiliary system development	1
in utero embryonic development	1
placenta development	1
embryonic organ development	1
intracellular protein transport	1
nuclear export	1
metal ion transport	1
cell-cell adhesion	1
cell-substrate adhesion	1
cell-matrix adhesion	1
signal transduction	1
regulation of biological quality	1
cell surface receptor signaling pathway via STAT	1
circulatory system development	1
developmental process	1
cell surface receptor signaling pathway	1
central nervous system development	1
nervous system development	1
tube development	1
epithelium development	1
establishment or maintenance of cell polarity	1
cell adhesion	1
regulation of cellular process	1
monoatomic cation channel activity	1

Protein interactions and networks

STRING

1260 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PKD1	PKD2	Q13563	993
PKD1	PKHD1	P08F94	969
PKD1	TSC2	P49815	941
PKD1	TRPC1	P48995	903
PKD1	PRKD1	Q15139	893
PKD1	TRPV4	Q9HBA0	870
PKD1	IFT88	Q13099	817
PKD1	TRPC4	Q9UBN4	803
PKD1	NPHP1	O15259	798
PKD1	TSC1	Q92574	776
PKD1	PRKCSH	P14314	761
PKD1	NEK8	Q86SG6	758
PKD1	KIF3A	Q9Y496	732
PKD1	CTNNB1	P35222	729
PKD1	PLAT	P00750	713

IntAct

35 interactions, top by confidence:

A	B	Type	Score
PKD2	PKD1	psi-mi:“MI:0915”(physical association)	0.720
PKD2	PKD1	psi-mi:“MI:0407”(direct interaction)	0.720
PKD1	PKD2	psi-mi:“MI:0915”(physical association)	0.720
PKD1	PKD2	psi-mi:“MI:0407”(direct interaction)	0.650
PKD1	PKD2	psi-mi:“MI:0915”(physical association)	0.650
PKD2	PKD1	psi-mi:“MI:0407”(direct interaction)	0.650
NPHP1	PKD1	psi-mi:“MI:0407”(direct interaction)	0.560
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530
EPCIP	PKD1	psi-mi:“MI:0915”(physical association)	0.460
PKD1	EPCIP	psi-mi:“MI:0915”(physical association)	0.460
PKD1	EPCIP	psi-mi:“MI:0403”(colocalization)	0.460
PKD1	ABL1	psi-mi:“MI:0915”(physical association)	0.400
FYN	PKD1	psi-mi:“MI:0915”(physical association)	0.400
PKD1	LTB4R2	psi-mi:“MI:0915”(physical association)	0.370
ORF6	PKD1	psi-mi:“MI:0915”(physical association)	0.370
kin-10	PKD1	psi-mi:“MI:0915”(physical association)	0.370
ATF7IP	PKD1	psi-mi:“MI:0915”(physical association)	0.370
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350

BioGRID (75): PKD2 (Two-hybrid), PKD1 (Affinity Capture-Western), CTNNB1 (Affinity Capture-Western), PKD1 (Affinity Capture-Western), PKD1 (Affinity Capture-MS), RGS7 (Two-hybrid), PKD1 (Affinity Capture-MS), AKT1 (Affinity Capture-Western), PKD1 (Two-hybrid), PKD2 (Two-hybrid), PTPRS (Affinity Capture-Western), PTPRG (Affinity Capture-Western), PKD1 (Affinity Capture-Western), PKD1 (Affinity Capture-RNA), PTK2 (Affinity Capture-Western)

ESM2 similar proteins: A0A1B0GTW7, A0A286YEC0, A6NE52, A7YWM1, D3ZT86, D3ZVB0, G7PWZ3, O08852, O77755, P05111, P07994, P17490, P20863, P27106, P29474, P49000, P98161, Q04997, Q05932, Q16671, Q28680, Q3TAP4, Q4TUC0, Q5TJE4, Q62893, Q6IE08, Q6P531, Q6PDE7, Q6QNU9, Q6ZS72, Q76MJ5, Q7M733, Q7TQH7, Q7Z4F1, Q866Y3, Q8IZF5, Q8K0R6, Q8K592, Q8R2S1, Q8VCS0

Diamond homologs: A2RSQ0, B8UU59, C8YR32, E7FKV8, G3V7Q0, O08852, O16025, P09917, P12527, P48999, P51399, P98161, Q09624, Q2EG98, Q6IQ26, Q6NXD8, Q6PAL8, Q6ZUT9, Q7TN88, Q7Z442, Q7Z443, Q8IVV2, Q8R526, Q8TDX9, Q9NTG1, Q9Z0T6, A6H789, A6H793, A6MFK8, A6NJW4, A8WHP9, E9Q7T7, F1NUK7, G5EFX6, O00468, O02678, O19045, O46390, O46403, O46542

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PRKX	up-regulates	PKD1	phosphorylation
PKD1	“up-regulates activity”	SIAH1	binding
PKD1	“down-regulates quantity by destabilization”	JADE1	binding
DAPK1	“up-regulates activity”	PKD1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
intracellular signal transduction	5	12.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

7001 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1551
Likely pathogenic	491
Uncertain significance	3296
Likely benign	782
Benign	130

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1013090	NM_001009944.3(PKD1):c.11263C>T (p.Gln3755Ter)	Pathogenic
1030954	NM_001009944.3(PKD1):c.5637C>A (p.Tyr1879Ter)	Pathogenic
1034359	NM_001009944.3(PKD1):c.8043_8046del (p.Ser2682fs)	Pathogenic
1048640	NM_001009944.3(PKD1):c.8333dup (p.Glu2779fs)	Pathogenic
1048641	NM_001009944.3(PKD1):c.5290G>T (p.Glu1764Ter)	Pathogenic
1048642	NM_001009944.3(PKD1):c.3931dup (p.Ala1311fs)	Pathogenic
1048645	NM_001009944.3(PKD1):c.5856del (p.Asn1954fs)	Pathogenic
1048760	NM_001009944.3(PKD1):c.499del (p.Gly168fs)	Pathogenic
1050228	NM_001009944.3(PKD1):c.8791+40_10050+3del	Pathogenic
1064647	NM_001009944.3(PKD1):c.11723T>C (p.Leu3908Pro)	Pathogenic
1077162	NM_001009944.3(PKD1):c.10527_10528del (p.Glu3509fs)	Pathogenic
1172882	NM_001009944.3(PKD1):c.1606+1G>A	Pathogenic
1177416	NM_001009944.3(PKD1):c.10219del (p.Ser3407fs)	Pathogenic
1177417	NM_001009944.3(PKD1):c.6282G>A (p.Trp2094Ter)	Pathogenic
1177427	NM_001009944.3(PKD1):c.10358dup (p.Ser3454fs)	Pathogenic
1179034	NM_001009944.3(PKD1):c.4743dup (p.Trp1582fs)	Pathogenic
1179054	NM_001009944.3(PKD1):c.160_166del (p.Arg54fs)	Pathogenic
1179066	NM_001009944.3(PKD1):c.10516del (p.Glu3506fs)	Pathogenic
1179071	NM_001009944.3(PKD1):c.9691G>T (p.Glu3231Ter)	Pathogenic
1179072	NM_001009944.3(PKD1):c.9683dup (p.Leu3229fs)	Pathogenic
1179075	NM_001009944.3(PKD1):c.659del (p.Gly220fs)	Pathogenic
1179077	NM_001009944.3(PKD1):c.6424C>T (p.Gln2142Ter)	Pathogenic
1179078	NM_001009944.3(PKD1):c.628_631dup (p.Ser211fs)	Pathogenic
1179089	NM_001009944.3(PKD1):c.272C>A (p.Ser91Ter)	Pathogenic
1179093	NM_001009944.3(PKD1):c.2054_2055del (p.Glu685fs)	Pathogenic
1179105	NM_001009944.3(PKD1):c.1326del (p.Ala443fs)	Pathogenic
1179107	NM_001009944.3(PKD1):c.10168C>T (p.Gln3390Ter)	Pathogenic
1179124	NM_001009944.3(PKD1):c.601dup (p.His201fs)	Pathogenic
1179125	NM_001009944.3(PKD1):c.5968_5969del (p.Arg1990fs)	Pathogenic
1179154	NM_001009944.3(PKD1):c.12383_12387del (p.Glu4128fs)	Pathogenic

SpliceAI

8063 predictions. Top by Δscore:

Variant	Effect	Δscore
16:2090195:C:CC	acceptor_gain	1.0000
16:2090283:A:C	donor_loss	1.0000
16:2090283:ACCT:A	donor_gain	1.0000
16:2090284:CCTC:C	donor_gain	1.0000
16:2090286:T:TA	donor_gain	1.0000
16:2090587:CGAG:C	acceptor_gain	1.0000
16:2090591:C:CC	acceptor_gain	1.0000
16:2090670:CTACC:C	donor_loss	1.0000
16:2090671:TAC:T	donor_loss	1.0000
16:2090672:A:AC	donor_gain	1.0000
16:2090672:A:C	donor_loss	1.0000
16:2090673:C:CC	donor_gain	1.0000
16:2090805:CAGC:C	acceptor_gain	1.0000
16:2090806:AGC:A	acceptor_gain	1.0000
16:2090809:C:CC	acceptor_gain	1.0000
16:2090809:C:CG	acceptor_loss	1.0000
16:2090878:CCTCA:C	donor_loss	1.0000
16:2090879:CTCAC:C	donor_loss	1.0000
16:2090880:TCA:T	donor_loss	1.0000
16:2090881:CACC:C	donor_loss	1.0000
16:2091775:TCCCA:T	donor_loss	1.0000
16:2091776:CCCA:C	donor_loss	1.0000
16:2091777:CCAC:C	donor_loss	1.0000
16:2091778:CACC:C	donor_loss	1.0000
16:2091779:ACCTG:A	donor_loss	1.0000
16:2093065:A:T	acceptor_gain	1.0000
16:2093538:GCTCA:G	donor_loss	1.0000
16:2093539:CTCAC:C	donor_loss	1.0000
16:2093541:CACCC:C	donor_loss	1.0000
16:2093542:A:AC	donor_gain	1.0000

AlphaMissense

27513 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:2102507:C:A	W3025C	0.999
16:2102507:C:G	W3025C	0.999
16:2102454:C:G	C3043S	0.998
16:2102455:A:G	C3043R	0.998
16:2102455:A:T	C3043S	0.998
16:2106672:C:A	W2405C	0.998
16:2106672:C:G	W2405C	0.998
16:2108606:C:A	W2187C	0.998
16:2108606:C:G	W2187C	0.998
16:2117038:C:A	W467C	0.998
16:2117038:C:G	W467C	0.998
16:2100273:A:T	V3202D	0.997
16:2100295:A:G	W3195R	0.997
16:2100295:A:T	W3195R	0.997
16:2102453:G:C	C3043W	0.997
16:2102509:A:G	W3025R	0.997
16:2102509:A:T	W3025R	0.997
16:2102538:C:G	C3015S	0.997
16:2102538:C:T	C3015Y	0.997
16:2102539:A:G	C3015R	0.997
16:2102539:A:T	C3015S	0.997
16:2108273:C:A	W2298C	0.997
16:2108273:C:G	W2298C	0.997
16:2108608:A:G	W2187R	0.997
16:2108608:A:T	W2187R	0.997
16:2109151:A:G	W2006R	0.997
16:2109151:A:T	W2006R	0.997
16:2110423:A:G	W1582R	0.997
16:2110423:A:T	W1582R	0.997
16:2090174:A:C	F4155L	0.996

dbSNP variants (sampled 300 via entrez): RS1000131450 (16:2094498 GCA>G), RS1000161706 (16:14924744 T>C), RS1000173053 (16:2124249 T>A,C), RS1000243757 (16:2129315 A>C,G,T), RS1000293595 (16:2134106 G>A), RS1000383504 (16:14936557 A>G), RS1000385132 (16:2105586 C>G,T), RS1000473425 (16:2129652 G>C), RS1000474665 (16:2091202 G>A,C), RS1000541526 (16:2125802 G>A), RS1000552320 (16:2122409 A>C), RS1000581246 (16:14936886 T>C), RS1000586932 (16:2133780 C>T), RS1000605684 (16:2105709 T>G), RS1000649561 (16:2096607 C>A)

Disease associations

OMIM: gene MIM:601313 | disease phenotypes: MIM:173900, MIM:613095, MIM:613254, MIM:191100, MIM:606690, MIM:607341, MIM:616371, MIM:119800, MIM:607086, MIM:610805, MIM:620442, MIM:300804, MIM:600666, MIM:174050, MIM:167000, MIM:600057, MIM:619681

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive polycystic kidney disease	Definitive	Autosomal recessive
polycystic kidney disease 1	Definitive	Autosomal dominant
Caroli disease	Strong	Autosomal dominant
autosomal dominant polycystic kidney disease	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
autosomal dominant polycystic kidney disease	Definitive	AD
autosomal recessive polycystic kidney disease	Definitive	AR

Mondo (37): polycystic kidney disease 1 (MONDO:0008263), autosomal dominant polycystic kidney disease (MONDO:0004691), bile duct cancer (MONDO:0003059), hereditary ataxia (MONDO:0100309), kidney failure (MONDO:0001106), polycystic kidney disease 2 (MONDO:0013131), tuberous sclerosis 2 (MONDO:0013199), polycystic kidney disease (MONDO:0020642), tuberous sclerosis (MONDO:0001734), lymphangioleiomyomatosis (MONDO:0011705), isolated focal cortical dysplasia type II (MONDO:0011818), pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 (MONDO:0014612), 46 XY differences of sex development (MONDO:0020040), clubfoot (MONDO:0007342), cystic kidney disease (MONDO:0002473)

Orphanet (19): Autosomal dominant polycystic kidney disease (Orphanet:730), Hereditary ataxia (Orphanet:183518), Tuberous sclerosis complex (Orphanet:805), Isolated focal cortical dysplasia type II (Orphanet:268994), Lymphangioleiomyomatosis (Orphanet:538), Idiopathic pulmonary fibrosis (Orphanet:2032), 46,XY difference of sex development (Orphanet:98085), Familial clubfoot with or without associated lower limb anomalies (Orphanet:199315), Familial aortic dissection (Orphanet:229), Renal or urinary tract malformation (Orphanet:93545), Multicystic dysplastic kidney (Orphanet:1851), Inherited cancer-predisposing syndrome (Orphanet:140162), Orofaciodigital syndrome type 6 (Orphanet:2754), Autosomal recessive polycystic kidney disease (Orphanet:731), (Orphanet:8378)

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant 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:0000790	Hematuria
HP:0000791	Uric acid nephrolithiasis
HP:0000822	Hypertension
HP:0001407	Hepatic cysts
HP:0001634	Mitral valve prolapse
HP:0001653	Mitral regurgitation
HP:0001737	Pancreatic cysts
HP:0002253	Colonic diverticula
HP:0002616	Aortic root aneurysm
HP:0003259	Elevated circulating creatinine concentration
HP:0003774	Stage 5 chronic kidney disease
HP:0004944	Dilatation of the cerebral artery
HP:0006557	Polycystic liver disease
HP:0007029	Cerebral berry aneurysm
HP:0008672	Calcium oxalate nephrolithiasis
HP:0011004	Abnormal systemic arterial morphology
HP:0011760	Pituitary growth hormone cell adenoma
HP:0012207	Reduced sperm motility
HP:0012213	Decreased glomerular filtration rate
HP:0012330	Pyelonephritis
HP:0012591	Abnormal urinary electrolyte concentration
HP:0012592	Albuminuria
HP:0012622	Chronic kidney disease
HP:0030157	Flank pain

GWAS associations

0 associations (top):

MeSH disease descriptors (25)

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
D003025	Clubfoot	C05.330.488.655.063; C05.330.495.681.063; C05.660.585.512.380.813.063; C16.131.621.585.512.500.681.063
D003240	Connective Tissue Diseases	C17.300
D058490	Disorder of Sex Development, 46,XY	C12.050.351.875.253.096; C12.200.706.316.096; C12.800.316.096; C16.131.939.316.096; C19.391.119.096
D006391	Hemangioma	C04.557.645.375
D006973	Hypertension	C14.907.489
D052177	Kidney Diseases, Cystic	C12.050.351.968.419.403; C12.200.777.419.403; C12.950.419.403
D007676	Kidney Failure, Chronic	C12.050.351.968.419.780.750.500; C12.200.777.419.780.750.500; C12.950.419.780.750.500; C23.550.291.500.906.500
D018192	Lymphangioleiomyomatosis	C04.557.375.460.465; C04.557.450.692.500; C15.604.515.562.465; C20.683.515.710.465
D021782	Multicystic Dysplastic Kidney	C12.050.351.875.558; C12.050.351.968.419.403.750; C12.200.706.629; C12.200.777.419.403.750; C12.800.629; C12.950.419.403.750; C16.131.939.629
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
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
D011507	Proteinuria	C12.050.351.968.934.734; C12.200.777.934.734; C12.950.934.734; C23.888.942.750
D051437	Renal Insufficiency	C12.050.351.968.419.780; C12.200.777.419.780; C12.950.419.780
D014402	Tuberous Sclerosis	C04.445.810; C04.651.800; C04.700.700; C10.500.507.400.750; C10.562.850; C10.574.500.865; C16.131.666.507.400.750; C16.320.400.880; C16.320.700.700
C562834	Aortic Aneurysm, Familial Thoracic 1 (supp.)
C566906	Cakut (supp.)
C537067	Focal cortical dysplasia of Taylor (supp.)
C531684	Hereditary spinal ataxia (supp.)
C567582	Joubert Syndrome 10 (supp.)
C536326	Polycystic kidney disease, type 1 (supp.)
C566021	Tuberous Sclerosis 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5772 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

9 measured of 9 human assays (9 total across all organisms); most potent 9 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
NSC_4179	KI	0.27 nM
NSC_6437389	KI	0.29 nM
NSC_105100	KI	0.35 nM
CAS_159320	KI	0.45 nM
B8-DL-B8 (low PS)	KI	10.8 nM
CAS_454217	KI	12.9 nM
(-)-Indolactam V (low PS)	KI	38 nM
3-hydroxy-2-[4-methyl-3-(methylethyl)pentanoyloxy]propyl 4-methyl-3-(methylethyl)pentanoate	KI	90 nM
NSC_104731	KI	146 nM

ChEMBL bioactivities

7 potent at pChembl≥5 of 7 total, top 7 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.19	Ki	64	nM	CHEMBL5405484
7.18	Ki	66	nM	CHEMBL4211840
7.09	IC50	81	nM	CHEMBL5188373
7.05	Ki	89	nM	CHEMBL4209095
6.68	IC50	210	nM	CHEMBL5405484
6.66	IC50	220	nM	CHEMBL4211840
6.52	IC50	300	nM	CHEMBL4209095

PubChem BioAssay actives

7 with measured affinity, of 27 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[3-[2-[(1R,4R,5S)-4-hydroxy-2-methyl-3-oxo-2-azabicyclo[3.1.0]hexan-4-yl]ethynyl]phenyl]pyrazolo[5,4-b]pyridine-3-carboxamide	2031269: Inhibition of PKD1 (unknown origin) assessed as inhibition constant	ki	0.0640	uM
6-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]-4-methoxypyridine-2-carboxamide	2031269: Inhibition of PKD1 (unknown origin) assessed as inhibition constant	ki	0.0660	uM
5-bromo-4-N-(5-dimethylphosphoryl-2,3-dihydro-1,4-benzodioxin-6-yl)-2-N-[2-methoxy-4-[4-[3-(methoxymethyl)azetidin-1-yl]piperidin-1-yl]-5-methylphenyl]pyrimidine-2,4-diamine	1862888: Inhibition of PKD1 (unknown origin)	ic50	0.0810	uM
1-[3-[2-[(3R)-3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl]ethynyl]phenyl]pyrazolo[5,4-b]pyridine-3-carboxamide	2031269: Inhibition of PKD1 (unknown origin) assessed as inhibition constant	ki	0.0890	uM

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, increases expression	3
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases mutagenesis	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
benzo(k)fluoranthene	decreases expression	1
perfluorooctanoic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
Oxaliplatin	decreases expression	1
Troglitazone	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Calcium	increases abundance, increases reaction	1
Dexamethasone	affects cotreatment, decreases expression	1
Estradiol	affects expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ozone	affects expression, increases abundance	1
Selenium	increases expression	1
Smoke	decreases expression	1
Sulindac	increases expression	1
Thiram	increases expression	1
Urethane	increases expression	1

ChEMBL screening assays

27 unique, capped per target: 27 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4057360	Binding	Inhibition of PKD1 (unknown origin) at 0.45 uM relative to control	Discovery of DS79182026: A potent orally active hepcidin production inhibitor. — Bioorg Med Chem Lett

Cellosaurus cell lines

31 cell lines: 22 induced pluripotent stem cell, 4 transformed cell line, 3 embryonic stem cell, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A1MN	PLAFMCi002-A	Induced pluripotent stem cell	Male
CVCL_A4GQ	chHES-468	Embryonic stem cell	Male
CVCL_A4QF	ADPKD#10D	Induced pluripotent stem cell	Sex unspecified
CVCL_A4QG	ADPKD#50B	Induced pluripotent stem cell	Sex unspecified
CVCL_A4XI	PLAFMCi003-A	Induced pluripotent stem cell	Male
CVCL_A6IZ	MUi026-A	Induced pluripotent stem cell	Female
CVCL_A6JA	MUi027-A	Induced pluripotent stem cell	Female
CVCL_A9YN	IRFMNi003-A-3	Induced pluripotent stem cell	Female
CVCL_A9YP	IRFMNi003-A-4	Induced pluripotent stem cell	Female
CVCL_C7YC	HAP1 PKD1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

213 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
NCT00280709	PHASE4	COMPLETED	Biliary Metal Stent Study: Metal Stents for Management of Distal Malignant Biliary Obstruction
NCT01041612	PHASE4	COMPLETED	Comparing Covered Self-expandable Metallic Stent (SEMS) Above/Across the Sphincter of Oddi
NCT01111591	PHASE4	UNKNOWN	Cyclooxygenase-2 Inhibitor for Adjuvant Anticancer Effect in Patients With Biliary-pancreas Cancer
NCT01256034	PHASE4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Pancreaticoduodenectomy
NCT01256047	PHASE4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Hepatectomy
NCT01969110	PHASE4	UNKNOWN	Additional Effects of Perioperative Immunonutrition in Patients Undergoing Pancreaticoduodenectomy
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)
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
NCT00809081	PHASE3	UNKNOWN	Early Enteral Feeding After Pylorus Preserving Pancreatoduodenectomy
NCT02853474	PHASE3	COMPLETED	Early Palliative Care in Patients With Metastatic Upper Gastrointestinal Cancers Treated With First-line Chemotherapy
NCT07155525	PHASE3	RECRUITING	Tissue Adhesive Glue Modified Cyanoacrylate (Glubran® 2) in Soft Pancreas
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]
NCT01210560	PHASE2	COMPLETED	Dose-finding Study of New Tolvaptan Formulation in Subjects With ADPKD
NCT01336972	PHASE2	COMPLETED	Short-term Renal Hemodynamic Effects of Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT01451827	PHASE2	COMPLETED	8-Week Study of Tolvaptan Dose Forms in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT01670110	PHASE2	COMPLETED	Pasireotide LAR in Severe Polycystic Liver Disease
NCT01932450	PHASE2	UNKNOWN	Radiofrequency Ablation for ADPKD Blood Pressure and Disease Progression Control
NCT02527863	PHASE2	COMPLETED	Effect of the Aquaretic Tolvaptan on Nitric Oxide System
NCT02616055	PHASE2	TERMINATED	Long-Term Treatment and Follow up of Subjects Completing 24 Months of Treatment With Tesevatinib on Study KD019-101