Polycystic kidney disease

Summary

Polycystic kidney disease (MONDO:0020642) is a disease with 23 cohort genes and 25 clinical trials. Top therapeutic interventions include niacinamide, everolimus, and hydralazine.

At a glance

• Cohort genes: 23
• ClinVar variants: 761
• Clinical trials: 25

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	polycystic kidney disease
Mondo ID	MONDO:0020642
EFO	EFO:0008620
MeSH	D007690
OMIM	173900
DOID	DOID:0080322
NCIT	C75464
SNOMED CT	82525005
UMLS	C0022680
MedGen	9639
Is cancer (heuristic)	no

Also known as: fibrocystic renal disease · PKD - polycystic kidney disease · polycystic kidney disease

Data availability: 761 ClinVar variants · 2 GenCC gene-disease records · 7 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › cystic kidney disease › familial cystic renal disease › polycystic kidney disease

Related subtypes (3): autosomal dominant medullary cystic kidney disease with or without hyperuricemia, autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis, adult familial nephronophthisis-spastic quadriparesia syndrome

Subtypes (2): autosomal dominant polycystic kidney disease, autosomal recessive polycystic kidney disease

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

122 benign/likely benign, 120 pathogenic, 93 uncertain significance, 75 conflicting classifications of pathogenicity, 73 benign, 62 likely benign, 42 pathogenic/likely pathogenic, 13 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2164	NM_213599.3(ANO5):c.191dup (p.Asn64fs)	ANO5	Pathogenic	reviewed by expert panel
523401	NM_001378615.1(CC2D2A):c.1149+1G>A	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56312	NM_001378615.1(CC2D2A):c.4179+1del	CC2D2A	Pathogenic	criteria provided, multiple submitters, no conflicts
978623	NM_001378615.1(CC2D2A):c.1751G>A (p.Trp584Ter)	CC2D2A	Pathogenic	criteria provided, multiple submitters, no conflicts
978624	NM_001378615.1(CC2D2A):c.3293T>G (p.Leu1098Ter)	CC2D2A	Pathogenic	criteria provided, multiple submitters, no conflicts
1342	NM_025114.4(CEP290):c.613C>T (p.Arg205Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
374210	NM_025114.4(CEP290):c.3104-2A>G	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56739	NM_025114.4(CEP290):c.5493del (p.Ala1832fs)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
978630	NM_025114.4(CEP290):c.5329C>T (p.Gln1777Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
1344700	NM_000092.5(COL4A4):c.2383G>A (p.Gly795Arg)	COL4A4	Pathogenic	no assertion criteria provided
1172653	NM_016306.6(DNAJB11):c.70C>T (p.Arg24Ter)	DNAJB11	Pathogenic	criteria provided, multiple submitters, no conflicts
3056672	NM_014714.4(IFT140):c.1867_1870del (p.Glu623fs)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31680	NM_014714.4(IFT140):c.2399+1G>T	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
374180	NM_138694.4(PKHD1):c.5081dup (p.Val1695fs)	LOC126859690	Pathogenic	criteria provided, single submitter
373955	NM_000297.4(PKD2):c.357_364delinsTAGGACG (p.Pro120fs)	LOC129992813	Pathogenic	criteria provided, single submitter
374110	NM_000297.4(PKD2):c.145C>T (p.Gln49Ter)	LOC129992813	Pathogenic	criteria provided, multiple submitters, no conflicts
636465	NM_000297.4(PKD2):c.181C>T (p.Gln61Ter)	LOC129992813	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
997139	NM_000297.4(PKD2):c.423dup (p.Gly142fs)	LOC129992813	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
997216	NM_000297.4(PKD2):c.567G>A (p.Trp189Ter)	LOC129992813	Pathogenic	criteria provided, multiple submitters, no conflicts
434008	NM_001009944.3(PKD1):c.12445-2A>C	MIR1225	Pathogenic	no assertion criteria provided
975069	NM_001009944.3(PKD1):c.12444+1G>A	MIR1225	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
523524	NM_170784.3(MKKS):c.958_959del (p.Leu320fs)	MKKS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
220868	NM_153240.5(NPHP3):c.2694-2_2694-1del	NPHP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
373937	NM_001009944.3(PKD1):c.5086C>T (p.Gln1696Ter)	PKD1	Pathogenic	criteria provided, multiple submitters, no conflicts
374097	NM_001009944.3(PKD1):c.8311G>A (p.Glu2771Lys)	PKD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374102	NM_001009944.3(PKD1):c.3520C>T (p.Gln1174Ter)	PKD1	Pathogenic	criteria provided, multiple submitters, no conflicts
374119	NM_001009944.3(PKD1):c.4846G>T (p.Glu1616Ter)	PKD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374187	NM_001009944.3(PKD1):c.11524T>C (p.Trp3842Arg)	PKD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3772676	NM_001009944.3(PKD1):c.10729_10732dup (p.Ala3578fs)	PKD1	Pathogenic	criteria provided, single submitter
427767	NM_001009944.3(PKD1):c.7818dup (p.His2607fs)	PKD1	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 60 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CFAP47	Limited	X-linked	polycystic kidney disease	2
AQP11	No Known Disease Relationship	Autosomal recessive	polycystic kidney disease

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFAP47	Orphanet:137893	Male infertility due to large-headed multiflagellar polyploid spermatozoa
HDAC8	Orphanet:199	Cornelia de Lange syndrome
HDAC8	Orphanet:3459	Wilson-Turner syndrome
DNAJB11	Orphanet:730	Autosomal dominant polycystic kidney disease
PLCE1	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
COL4A4	Orphanet:653722	Digenic Alport syndrome
COL4A4	Orphanet:88918	Autosomal dominant Alport syndrome
COL4A4	Orphanet:88919	Autosomal recessive Alport syndrome
ANO5	Orphanet:206549	Anoctamin-5-related limb-girdle muscular dystrophy R12
ANO5	Orphanet:206599	Isolated asymptomatic elevation of creatine phosphokinase
ANO5	Orphanet:399096	Distal anoctaminopathy
ANO5	Orphanet:53697	Gnathodiaphyseal dysplasia
ANO5	Orphanet:689021	Asymptomatic hyperCKemia-myalgia-rhabdomyolysis syndrome
CEP290	Orphanet:110	Bardet-Biedl syndrome
CEP290	Orphanet:2318	Joubert syndrome with oculorenal defect
CEP290	Orphanet:3156	Senior-Loken syndrome
CEP290	Orphanet:564	Meckel syndrome
CEP290	Orphanet:65	Leber congenital amaurosis
IFT140	Orphanet:140969	Saldino-Mainzer syndrome
IFT140	Orphanet:474	Jeune syndrome
IFT140	Orphanet:65	Leber congenital amaurosis
IFT140	Orphanet:730	Autosomal dominant polycystic kidney disease
IFT140	Orphanet:791	Retinitis pigmentosa
CC2D2A	Orphanet:1454	Joubert syndrome with hepatic defect
CC2D2A	Orphanet:2318	Joubert syndrome with oculorenal defect
CC2D2A	Orphanet:564	Meckel syndrome
CC2D2A	Orphanet:791	Retinitis pigmentosa
MKKS	Orphanet:110	Bardet-Biedl syndrome
MKKS	Orphanet:2473	McKusick-Kaufman syndrome
MKS1	Orphanet:110	Bardet-Biedl syndrome
MKS1	Orphanet:220493	Joubert syndrome with ocular defect
MKS1	Orphanet:475	Isolated Joubert syndrome
MKS1	Orphanet:564	Meckel syndrome
NPHP3	Orphanet:294415	Renal-hepatic-pancreatic dysplasia
NPHP3	Orphanet:3032	NPHP3-related Meckel-like syndrome
NPHP3	Orphanet:3156	Senior-Loken syndrome
NPHP3	Orphanet:93589	Late-onset nephronophthisis
NPHP3	Orphanet:93591	Infantile nephronophthisis
PIK3CA	Orphanet:140944	CLOVES syndrome
PIK3CA	Orphanet:144	Lynch syndrome
PIK3CA	Orphanet:168984	CLAPO syndrome
PIK3CA	Orphanet:201	Cowden syndrome
PIK3CA	Orphanet:210159	Adult hepatocellular carcinoma
PIK3CA	Orphanet:221061	Familial cerebral cavernous malformation
PIK3CA	Orphanet:2495	Meningioma
PIK3CA	Orphanet:276280	Hemihyperplasia-multiple lipomatosis syndrome
PIK3CA	Orphanet:295239	Macrodactyly of fingers, unilateral
PIK3CA	Orphanet:295243	Macrodactyly of toes, unilateral
PIK3CA	Orphanet:314662	Segmental progressive overgrowth syndrome with fibroadipose hyperplasia
PIK3CA	Orphanet:60040	Megalencephaly-capillary malformation-polymicrogyria syndrome

Cohort genes → proteins

23 cohort genes, 21 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	23

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
AQP11	HGNC:19940	ENSG00000178301	Q8NBQ7	Aquaporin-11	gencc
CFAP47	HGNC:26708	ENSG00000165164	Q6ZTR5	Cilia- and flagella-associated protein 47	gencc
HDAC8	HGNC:13315	ENSG00000147099	Q9BY41	Histone deacetylase 8	clinvar
DNAJB11	HGNC:14889	ENSG00000090520	Q9UBS4	DnaJ homolog subfamily B member 11	clinvar
DHX34	HGNC:16719	ENSG00000134815	Q14147	Probable ATP-dependent RNA helicase DHX34	clinvar
PLCE1	HGNC:17175	ENSG00000138193	Q9P212	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1	clinvar
CYS1	HGNC:18525	ENSG00000205795	Q717R9	Cystin-1	clinvar
COL4A4	HGNC:2206	ENSG00000081052	P53420	Collagen alpha-4(IV) chain	clinvar
DEUP1	HGNC:26344	ENSG00000165325	Q05D60	Deuterosome assembly protein 1	clinvar
ANO5	HGNC:27337	ENSG00000171714	Q75V66	Anoctamin-5	clinvar
CEP290	HGNC:29021	ENSG00000198707	O15078	Centrosomal protein of 290 kDa	clinvar
IFT140	HGNC:29077	ENSG00000187535	Q96RY7	Intraflagellar transport protein 140 homolog	clinvar
CC2D2A	HGNC:29253	ENSG00000048342	Q9P2K1	Coiled-coil and C2 domain-containing protein 2A	clinvar
MIR1225	HGNC:33931	ENSG00000221656		microRNA 1225	clinvar
PKD1-AS1	HGNC:56035	ENSG00000259933		PKD1 antisense RNA 1	clinvar
MKKS	HGNC:7108	ENSG00000125863	Q9NPJ1	Molecular chaperone MKKS	clinvar
MKS1	HGNC:7121	ENSG00000011143	Q9NXB0	Tectonic-like complex member MKS1	clinvar
NPHP3	HGNC:7907	ENSG00000113971	Q7Z494	Nephrocystin-3	clinvar
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	clinvar
PKD1	HGNC:9008	ENSG00000008710	P98161	Polycystin-1	clinvar
PKD2	HGNC:9009	ENSG00000118762	Q13563	Polycystin-2	clinvar
PKHD1	HGNC:9016	ENSG00000170927	P08F94	Fibrocystin	clinvar
PRKD1	HGNC:9407	ENSG00000184304	Q15139	Serine/threonine-protein kinase D1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AQP11	Aquaporin-11	Channel protein that facilitates the transport of water, glycerol and hydrogen peroxide across membrane of cell or organelles guaranteeing intracellular homeostasis in several organes like liver, kidney and brain.
CFAP47	Cilia- and flagella-associated protein 47	Plays a role in flagellar formation and sperm motility.
HDAC8	Histone deacetylase 8	Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
DNAJB11	DnaJ homolog subfamily B member 11	As a co-chaperone for HSPA5 it is required for proper folding, trafficking or degradation of proteins.
DHX34	Probable ATP-dependent RNA helicase DHX34	Probable ATP-binding RNA helicase required for nonsense-mediated decay (NMD) degradation of mRNA transcripts containing premature stop codons.
PLCE1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1	The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.
COL4A4	Collagen alpha-4(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
DEUP1	Deuterosome assembly protein 1	Key structural component of the deuterosome, a structure that promotes de novo centriole amplification in multiciliated cells.
ANO5	Anoctamin-5	Plays a role in plasma membrane repair in a process involving annexins.
CEP290	Centrosomal protein of 290 kDa	Involved in early and late steps in cilia formation.
IFT140	Intraflagellar transport protein 140 homolog	Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs).
CC2D2A	Coiled-coil and C2 domain-containing protein 2A	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
MKKS	Molecular chaperone MKKS	Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis.
MKS1	Tectonic-like complex member MKS1	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.
NPHP3	Nephrocystin-3	Required for normal ciliary development and function.
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.
PKD1	Polycystin-1	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.
PKD2	Polycystin-2	Forms a nonselective cation channel.
PKHD1	Fibrocystin	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.
PRKD1	Serine/threonine-protein kinase D1	Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and tr…

Protein-family classification

Druggable: 8 · Difficult: 2 · Unknown: 13 · Druggable fraction: 0.35

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	3	3.8×	0.298
Kinase	2	2.4×	0.702
Protease	1	1.6×	0.816
Enzyme (other)	2	1.0×	0.816
Other/Unknown	13	1.0×	0.816
Scaffold/PPI	1	0.8×	0.871
Transcription factor	1	0.4×	0.949

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AQP11	Other/Unknown	no		MIP, Aquaporin_11/12, Aquaporin_11
CFAP47	Antibody/Immunoglobulin	yes		CH_dom, Ig-like_fold, CH_dom_sf
HDAC8	Enzyme (other)	yes	3.5.1.98	HDACs, HDAC_I/II, Ureohydrolase_dom_sf
DNAJB11	Other/Unknown	no		DnaJ_domain, DnaJ_C, HSP40/DnaJ_pept-bd
DHX34	Transcription factor	no	3.6.4.13	Helicase_C-like, Helicase-assoc_dom, DEAD/DEAH_box_helicase_dom
PLCE1	Enzyme (other)	yes	3.1.4.11	C2_dom, RA_dom, PLipase_C_PInositol-sp_X_dom
CYS1	Other/Unknown	no		Cys1
COL4A4	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
DEUP1	Other/Unknown	no		CEP63/Deup1_N, CEP63/Deup1_CC
ANO5	Other/Unknown	no		Anoctamin, Anoct_dimer, Anoctamin_TM
CEP290	Other/Unknown	no		Cep290, Cep209_CC5
IFT140	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
CC2D2A	Protease	yes		C2_dom, CC2D2AN-C2, C2_domain_sf
MIR1225	Other/Unknown	no
PKD1-AS1	Other/Unknown	no
MKKS	Other/Unknown	no		Cpn60/GroEL/TCP-1, GroEL-like_apical_dom_sf, TCP-1-like_intermed_sf
MKS1	Other/Unknown	no		C2_B9-type_dom
NPHP3	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, P-loop_NTPase
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
PKD1	Antibody/Immunoglobulin	yes		GPS, LRRNT, PC1
PKD2	Other/Unknown	no		EF_hand_dom, PKD_2, EF-hand-dom_pair
PKHD1	Antibody/Immunoglobulin	yes		IPT_dom, PbH1, Pectin_lyase_fold/virulence
PRKD1	Kinase	yes	2.7.11.13	Prot_kinase_dom, PH_domain, PKC_DAG/PE

Expression context

Cohort genes with no expression data: 0.

21 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	23
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right uterine tube	4
ventricular zone	3
renal medulla	3
bronchial epithelial cell	2
bronchus	2
adrenal tissue	2
left testis	2
right testis	2
kidney epithelium	2
metanephros cortex	2
cerebellar cortex	2
cerebellar hemisphere	2
right hemisphere of cerebellum	2
left ovary	2
calcaneal tendon	2
duodenum	1
ileal mucosa	1
jejunal mucosa	1
oviduct epithelium	1
colonic epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AQP11	172	ubiquitous	yes	jejunal mucosa, ileal mucosa, duodenum
CFAP47	95	tissue_specific	marker	bronchial epithelial cell, bronchus, oviduct epithelium
HDAC8	244	ubiquitous	marker	colonic epithelium, adrenal tissue, left adrenal gland
DNAJB11	141	ubiquitous	marker	vermiform appendix, body of pancreas, bone marrow cell
DHX34	217	ubiquitous	marker	right testis, blood, left testis
PLCE1	271	broad	marker	renal glomerulus, metanephric glomerulus, ventricular zone
CYS1	186	broad	marker	kidney epithelium, renal medulla, adult mammalian kidney
COL4A4	187	broad	marker	renal medulla, metanephros cortex, pigmented layer of retina
DEUP1	140	tissue_specific	marker	sperm, left testis, right testis
ANO5	220	broad	marker	cardiac muscle of right atrium, left ventricle myocardium, vastus lateralis
CEP290	278	ubiquitous	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone
IFT140	214	ubiquitous	marker	right uterine tube, right lobe of thyroid gland, left lobe of thyroid gland
CC2D2A	247	ubiquitous	marker	right uterine tube, bronchial epithelial cell, bronchus
MIR1225	77		yes	sural nerve, skeletal muscle tissue, Brodmann (1909) area 9
PKD1-AS1	133		marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
MKKS	277	ubiquitous	marker	middle temporal gyrus, endothelial cell, prefrontal cortex
MKS1	182	ubiquitous	marker	right uterine tube, olfactory segment of nasal mucosa, left ovary
NPHP3	254	ubiquitous	marker	superficial temporal artery, layer of synovial tissue, left ovary
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon
PKD1	290		marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
PKD2	288	ubiquitous	marker	blood vessel layer, calcaneal tendon, saphenous vein
PKHD1	51	tissue_specific	marker	kidney epithelium, renal medulla, metanephros cortex
PRKD1	239	ubiquitous	marker	ventricular zone, seminal vesicle, thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 15.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PIK3CA	5,157
DNAJB11	3,387
HDAC8	3,087
CEP290	2,778
MKKS	2,728
DHX34	2,501
NPHP3	2,275
PRKD1	2,131
PKD2	1,644
IFT140	1,602

Intra-cohort edges

A	B	Sources
AQP11	PKD1	string_interaction
CC2D2A	CEP290	string_interaction
CC2D2A	MKS1	biogrid_interaction, intact, string_interaction
CEP290	MKS1	string_interaction
CEP290	NPHP3	string_interaction
CYS1	PKD1	string_interaction
CYS1	PKD2	string_interaction
CYS1	PKHD1	string_interaction
NPHP3	PKHD1	string_interaction
PKD1	PKD2	biogrid_interaction, intact, string_interaction
PKD1	PKHD1	string_interaction
PKD1	PRKD1	string_interaction
PKD2	PKHD1	string_interaction
PKD2	PRKD1	string_interaction
PKHD1	PRKD1	string_interaction

Structural data

PDB: 9 · AlphaFold-only: 12 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PIK3CA	P42336	135
HDAC8	Q9BY41	53
PKD2	Q13563	31
PKD1	P98161	13
IFT140	Q96RY7	4
PLCE1	Q9P212	3
COL4A4	P53420	2
AQP11	Q8NBQ7	1
NPHP3	Q7Z494	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MKKS	Q9NPJ1	89.05
DNAJB11	Q9UBS4	84.34
ANO5	Q75V66	82.22
DHX34	Q14147	80.85
DEUP1	Q05D60	78.06
MKS1	Q9NXB0	74.05
CC2D2A	Q9P2K1	69.46
PRKD1	Q15139	68.99
CYS1	Q717R9	66.42
CEP290	O15078	60.90
CFAP47	Q6ZTR5
PKHD1	P08F94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 129. Enrichment computed across 23 evidence-associated genes (17 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 17 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Trafficking of myristoylated proteins to the cilium	2	268.7×	0.001	CYS1, NPHP3
Cilium Assembly	4	25.6×	0.001	CEP290, CC2D2A, MKKS, MKS1
Organelle biogenesis and maintenance	4	15.5×	0.004	CEP290, CC2D2A, MKKS, MKS1
VxPx cargo-targeting to cilium	2	61.1×	0.012	PKD1, PKD2
Anchoring of the basal body to the plasma membrane	3	19.9×	0.012	CEP290, CC2D2A, MKS1
Hedgehog ‘off’ state	2	21.0×	0.086	IFT140, MKS1
MET activates PI3K/AKT signaling	1	112.0×	0.099	PIK3CA
Activated NTRK3 signals through PI3K	1	112.0×	0.099	PIK3CA
Activated NTRK2 signals through PI3K	1	96.0×	0.099	PIK3CA
Signaling by LTK in cancer	1	96.0×	0.099	PIK3CA
PI3K/AKT activation	1	74.6×	0.099	PIK3CA
IRS-mediated signalling	1	61.1×	0.099	PIK3CA
PI3K events in ERBB4 signaling	1	61.1×	0.099	PIK3CA
Co-stimulation by ICOS	1	61.1×	0.099	PIK3CA
Signaling by FGFR4 in disease	1	56.0×	0.099	PIK3CA
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)	1	56.0×	0.099	PIK3CA
Passive transport by Aquaporins	1	51.7×	0.099	AQP11
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	51.7×	0.099	PIK3CA
Signaling by PDGFRA extracellular domain mutants	1	51.7×	0.099	PIK3CA
Induction of Cell-Cell Fusion	1	51.7×	0.099	ANO5
Signaling by LTK	1	51.7×	0.099	PIK3CA
Anchoring fibril formation	1	44.8×	0.099	COL4A4
Signaling by FLT3 ITD and TKD mutants	1	44.8×	0.099	PIK3CA
Constitutive Signaling by EGFRvIII	1	42.0×	0.099	PIK3CA
PI3K events in ERBB2 signaling	1	39.5×	0.099	PIK3CA
Signaling by ERBB2 ECD mutants	1	39.5×	0.099	PIK3CA
GAB1 signalosome	1	37.3×	0.099	PIK3CA
Signaling by cytosolic FGFR1 fusion mutants	1	37.3×	0.099	PIK3CA
PI-3K cascade:FGFR3	1	37.3×	0.099	PIK3CA
Tie2 Signaling	1	35.4×	0.099	PIK3CA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 20 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
non-motile cilium assembly	6	87.2×	1e-08	CEP290, IFT140, CC2D2A, MKKS, MKS1, NPHP3
determination of left/right symmetry	6	76.6×	1e-08	IFT140, CC2D2A, MKKS, MKS1, NPHP3, PKD2
cilium assembly	8	29.4×	1e-08	CFAP47, CEP290, IFT140, CC2D2A, MKKS, MKS1, NPHP3, PKHD1
kidney development	5	35.1×	2e-05	CEP290, CC2D2A, NPHP3, PKD1, PKHD1
convergent extension involved in gastrulation	2	842.6×	7e-05	MKKS, NPHP3
mesonephric tubule development	2	842.6×	7e-05	PKD1, PKD2
embryonic brain development	3	120.4×	9e-05	IFT140, CC2D2A, MKS1
branching morphogenesis of an epithelial tube	3	109.9×	1e-04	MKS1, PKD1, PKHD1
cellular response to hydrostatic pressure	2	561.7×	1e-04	PIK3CA, PKD2
heart development	5	19.7×	1e-04	IFT140, CC2D2A, MKKS, PKD1, PKD2
metanephric ascending thin limb development	2	421.3×	2e-04	PKD1, PKD2
mesonephric duct development	2	337.0×	3e-04	PKD1, PKD2
regulation of Wnt signaling pathway, planar cell polarity pathway	2	337.0×	3e-04	MKS1, NPHP3
determination of liver left/right asymmetry	2	280.9×	5e-04	NPHP3, PKD2
heart looping	3	40.1×	0.001	MKKS, NPHP3, PKD2
placenta blood vessel development	2	140.4×	0.002	PKD1, PKD2
liver development	3	33.3×	0.002	PIK3CA, PKD1, PKD2
detection of mechanical stimulus	2	120.4×	0.002	PKD1, PKD2
protein heterotetramerization	2	105.3×	0.003	PKD1, PKD2
embryonic placenta development	2	76.6×	0.005	PKD1, PKD2
phosphatidylinositol-mediated signaling	2	70.2×	0.006	PLCE1, PIK3CA
regulation of smoothened signaling pathway	2	62.4×	0.007	IFT140, MKS1
positive regulation of lamellipodium assembly	2	60.2×	0.007	PLCE1, PIK3CA
motile cilium assembly	2	58.1×	0.007	CC2D2A, MKS1
neural tube development	2	52.7×	0.008	PKD1, PKD2
spinal cord development	2	51.1×	0.008	PKD1, PKD2
smoothened signaling pathway involved in regulation of secondary heart field cardioblast proliferation	1	842.6×	0.010	MKS1
response to muscle inactivity	1	842.6×	0.010	PIK3CA
determination of intestine left/right asymmetry	1	842.6×	0.010	NPHP3
determination of stomach left/right asymmetry	1	842.6×	0.010	NPHP3

Therapeutics

Drugs indicated for this disease

1 approved, 3 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Tolvaptan	Approved (phase 4)
Lisinopril Anhydrous	Phase 3 (in late-stage trials)
Lixivaptan	Phase 3 (in late-stage trials)
Telmisartan	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Everolimus, Niacinamide, Pioglitazone, Sirolimus.

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 20

Druggability breadth: 7 of 23 evidence-associated genes (30%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
HDAC8	CELECOXIB
PIK3CA	IDELALISIB
PRKD1	INGENOL MEBUTATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PIK3CA	67	4
HDAC8	37	4
PRKD1	26	4
AQP11	0	0
CFAP47	0	0
DNAJB11	0	0
DHX34	0	0
PLCE1	0	0
CYS1	0	0
COL4A4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CELECOXIB	4	HDAC8
PHENYLBUTANOIC ACID	4	HDAC8
SODIUM PHENYLBUTYRATE	4	HDAC8
ROMIDEPSIN	4	HDAC8, PIK3CA
BELINOSTAT	4	HDAC8, PIK3CA
PANOBINOSTAT	4	HDAC8
VORINOSTAT	4	HDAC8
GIVINOSTAT	4	HDAC8
DAUNORUBICIN	4	HDAC8
BORTEZOMIB	4	HDAC8
BENDAMUSTINE	4	HDAC8
IDELALISIB	4	PIK3CA
ALPELISIB	4	PIK3CA
DUVELISIB	4	PIK3CA
COPANLISIB	4	PIK3CA
FEDRATINIB	4	PIK3CA
COPANLISIB HYDROCHLORIDE	4	PIK3CA
LENIOLISIB	4	PIK3CA
INAVOLISIB	4	PIK3CA
SUNITINIB	4	PIK3CA, PRKD1
DASATINIB	4	PIK3CA
CRIZOTINIB	4	PIK3CA, PRKD1
MIDOSTAURIN	4	PIK3CA, PRKD1
INGENOL MEBUTATE	4	PRKD1
TAMOXIFEN	4	PRKD1
NERATINIB	4	PRKD1
BRIGATINIB	4	PRKD1
NINTEDANIB	4	PRKD1
GEFITINIB	4	PRKD1
CURCUMIN	3	HDAC8

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
HDAC8	2,631	Binding:2599, ADMET:25, Functional:6, Toxicity:1
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
PRKD1	660	Binding:650, Functional:10
PKD1	27	Binding:27
PKD2	12	Binding:12
DNAJB11	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HDAC8	3.5.1.98	histone deacetylase
DHX34	3.6.4.13	RNA helicase
PLCE1	3.1.4.11	phosphoinositide phospholipase C
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase
PRKD1	2.7.11.13	protein kinase C

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
HDAC8	2,631
PIK3CA	2,034
PRKD1	660

Pharmacogenomics

Cohort genes with a PharmGKB record: 22; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
CELECOXIB	4	HDAC8
PHENYLBUTANOIC ACID	4	HDAC8
SODIUM PHENYLBUTYRATE	4	HDAC8
ROMIDEPSIN	4	HDAC8, PIK3CA
BELINOSTAT	4	HDAC8, PIK3CA
PANOBINOSTAT	4	HDAC8
VORINOSTAT	4	HDAC8
GIVINOSTAT	4	HDAC8
DAUNORUBICIN	4	HDAC8
BORTEZOMIB	4	HDAC8
BENDAMUSTINE	4	HDAC8
IDELALISIB	4	PIK3CA
ALPELISIB	4	PIK3CA
DUVELISIB	4	PIK3CA
COPANLISIB	4	PIK3CA
FEDRATINIB	4	PIK3CA
COPANLISIB HYDROCHLORIDE	4	PIK3CA
LENIOLISIB	4	PIK3CA
INAVOLISIB	4	PIK3CA
SUNITINIB	4	PIK3CA, PRKD1
DASATINIB	4	PIK3CA
CRIZOTINIB	4	PIK3CA, PRKD1
MIDOSTAURIN	4	PIK3CA, PRKD1
INGENOL MEBUTATE	4	PRKD1
TAMOXIFEN	4	PRKD1
NERATINIB	4	PRKD1
BRIGATINIB	4	PRKD1
NINTEDANIB	4	PRKD1
GEFITINIB	4	PRKD1
CURCUMIN	3	HDAC8

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	HDAC8, PIK3CA, PRKD1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	PLCE1, PKD1
D	Druggable family + AlphaFold only, no drug	3	CFAP47, CC2D2A, PKHD1
E	Difficult family or no structure, no drug	15	AQP11, DNAJB11, DHX34, CYS1, COL4A4, DEUP1, ANO5, CEP290, IFT140, MIR1225 (+5 more)

Undrugged target profiles

20 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PKD1	27	PRKD1
AQP11	0	—
CFAP47	0	—
DNAJB11	1	—
DHX34	0	—
PLCE1	0	—
CYS1	0	—
COL4A4	0	—
DEUP1	0	—
ANO5	0	—
CEP290	0	—
IFT140	0	—
CC2D2A	0	—
MIR1225	0	—
PKD1-AS1	0	—
MKKS	0	—
MKS1	0	—
NPHP3	0	—
PKD2	12	—
PKHD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 25.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	17
PHASE2	3
PHASE2/PHASE3	2
PHASE1/PHASE2	1
PHASE1	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01009957	PHASE2/PHASE3	TERMINATED	Everolimus on CKD Progression in ADPKD Patients
NCT01680250	PHASE2/PHASE3	UNKNOWN	Sirolimus for Massive Polycystic Liver
NCT00286156	PHASE1/PHASE2	COMPLETED	Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT02140814	PHASE2	COMPLETED	Uncontrolled, Open Label, Pilot and Feasibility Study of Niacinamide in Polycystic Kidney Disease
NCT02558595	PHASE2	COMPLETED	Pilot Study of Niacinamide in Polycystic Kidney Disease (NIAC-PKD2)
NCT02697617	PHASE2	COMPLETED	Use of Low Dose Pioglitazone to Treat Autosomal Dominant Polycystic Kidney Disease
NCT02166489	PHASE1	COMPLETED	Mesenchymal Stem Cells Transplantation in Patients With Chronic Renal Failure Due to Polycystic Kidney Disease
NCT03423810	EARLY_PHASE1	COMPLETED	Assessing a Dose-Response Relationship of Hydralazine and Its Effects on DNA Methyltransferase 1 in Polycystic Kidney Disease Patients
NCT00792155	Not specified	RECRUITING	Polycystic Kidney Disease Data Repository
NCT01873235	Not specified	RECRUITING	PKD Clinical and Translational Core Study
NCT02936791	Not specified	RECRUITING	Early PKD Observational Cohort Study
NCT04039061	Not specified	RECRUITING	ADPKD Patient Registry
NCT06036992	Not specified	ACTIVE_NOT_RECRUITING	Study and Management of Cystic Complications in Autosomal Dominant Polycystic Kidney Disease
NCT06325644	Not specified	RECRUITING	Well-Formulated Ketogenic Diet Polycystic Kidney Disease
NCT06728228	Not specified	RECRUITING	Amnioinfusion for Fetal Renal Failure
NCT06841224	Not specified	ENROLLING_BY_INVITATION	The Factors Affecting IPP in Peritoneal Dialysis Patients with Polycystic Kidney Disease
NCT06867471	Not specified	RECRUITING	Effects of Exogenous Ketosis on Proteinuria and Renal Function
NCT01931644	Not specified	COMPLETED	At-Home Research Study for Patients With Autoimmune, Inflammatory, Genetic, Hematological, Infectious, Neurological, CNS, Oncological, Respiratory, Metabolic Conditions
NCT02142101	Not specified	COMPLETED	Evaluation of Gut Bacteria in Patients With Polycystic Kidney Disease
NCT02739750	Not specified	COMPLETED	Pioglitazone and Lumbar Bone Marrow Fat in Chronic Kidney Disease
NCT03726463	Not specified	UNKNOWN	Evaluation of Iliac and Renal Artery for Mechanism of Intracranial Aneurysm in ADPKD
NCT03889392	Not specified	COMPLETED	Evaluation of Nephrectomy Specimen for Intracranial Aneurysm Development in ADPKD
NCT03948113	Not specified	COMPLETED	Outcome of Autosomal Dominant Polycystic Kidney Disease Patients on Peritoneal Dialysis: a National Retrospective Study Based on Two French Registries (the French Language Peritoneal Dialysis Registry and the French Renal Epidemiology and Information Network).
NCT05215964	Not specified	UNKNOWN	The Association Between Skeletal Muscle Mass and Severity of Polycystic Liver Disease and Polycystic Kidney Disease
NCT07310641	Not specified	COMPLETED	Descriptive Analysis of Preimplantation Genetic Test (PGT)in Couples With Polycystic Kidney Disease (PKD). In the ADPKD Subgroup Evaluation of Outcomes and Complications Comparing Couples in Which the Father is Affected With Couples in Which the Mother is Affected

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
NIACINAMIDE	4	2
EVEROLIMUS	4	1
HYDRALAZINE	4	1
CHEMBL1201214	0	1