Polycystic liver disease 1

Summary

Polycystic liver disease 1 (MONDO:0008265) is a disease caused by PRKCSH (GenCC Definitive), with 9 cohort genes and 16 clinical trials. Top therapeutic interventions include lanreotide, octreotide, and ursodiol.

At a glance

• Causal gene: PRKCSH (GenCC Definitive)
• Cohort genes: 9
• ClinVar variants: 203
• Clinical trials: 16

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	polycystic liver disease 1
Mondo ID	MONDO:0008265
OMIM	174050
DOID	DOID:0060980
SNOMED CT	716196007
UMLS	C0887850
MedGen	165781
GARD	0024613
MedDRA	10010427, 10048834
Is cancer (heuristic)	no

Also known as: ADPCLD · isolated autosomal dominant polycystic liver disease · isolated congenital polycystic liver disease · isolated polycystic liver disease · nonsyndromic congenital polycystic liver disease · nonsyndromic polycystic liver disease (disease) · PCLD · PCLD1 · polycystic liver disease · polycystic liver disease 1 · polycystic liver disease 1 with or without kidney cysts

Data availability: 203 ClinVar variants · 8 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant polycystic liver disease › polycystic liver disease 1

Related subtypes (4): polycystic liver disease 2, polycystic liver disease 4 with or without kidney cysts, polycystic liver disease 3 with or without kidney cysts, SEC61B-related polycystic liver 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

203 retrieved; paginated sample, class counts are floors:

93 uncertain significance, 26 benign/likely benign, 25 conflicting classifications of pathogenicity, 18 pathogenic, 16 likely benign, 15 likely pathogenic, 9 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
162392	NM_002335.4(LRP5):c.4587G>C (p.Arg1529Ser)	LRP5	Pathogenic	no assertion criteria provided
433952	NM_001009944.3(PKD1):c.2215C>T (p.Arg739Trp)	PKD1	Pathogenic	criteria provided, single submitter
447985	NM_001009944.3(PKD1):c.5014_5015del (p.Arg1672fs)	PKD1	Pathogenic	criteria provided, multiple submitters, no conflicts
997260	NM_001009944.3(PKD1):c.6472C>T (p.Gln2158Ter)	PKD1	Pathogenic	criteria provided, multiple submitters, no conflicts
523354	NM_000297.4(PKD2):c.2284_2287del (p.Tyr762fs)	PKD2	Pathogenic	criteria provided, single submitter
1048653	NM_001289104.2(PRKCSH):c.374_375del (p.Glu125fs)	PRKCSH	Pathogenic	criteria provided, multiple submitters, no conflicts
1255667	NM_001289104.2(PRKCSH):c.487C>T (p.Gln163Ter)	PRKCSH	Pathogenic	criteria provided, single submitter
13238	NM_001289104.2(PRKCSH):c.1362-2A>G	PRKCSH	Pathogenic	criteria provided, single submitter
13239	NM_001289104.2(PRKCSH):c.292+1G>C	PRKCSH	Pathogenic	no assertion criteria provided
13240	NM_001289104.2(PRKCSH):c.1461+2_1461+3del	PRKCSH	Pathogenic	criteria provided, single submitter
13241	NM_001289104.2(PRKCSH):c.1261C>T (p.Gln421Ter)	PRKCSH	Pathogenic	no assertion criteria provided
13242	NM_001289104.2(PRKCSH):c.1290C>G (p.Tyr430Ter)	PRKCSH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13243	NM_001289104.2(PRKCSH):c.215dup (p.Asn72fs)	PRKCSH	Pathogenic	criteria provided, single submitter
1994589	NM_001289104.2(PRKCSH):c.372_375del (p.Arg124fs)	PRKCSH	Pathogenic	criteria provided, multiple submitters, no conflicts
3583455	NM_001289104.2(PRKCSH):c.1289dup (p.Tyr430Ter)	PRKCSH	Pathogenic	criteria provided, multiple submitters, no conflicts
4531704	NM_001289104.2(PRKCSH):c.668del (p.Asp223fs)	PRKCSH	Pathogenic	criteria provided, single submitter
492970	NM_001289104.2(PRKCSH):c.1416T>G (p.Tyr472Ter)	PRKCSH	Pathogenic	no assertion criteria provided
992438	NM_001289104.2(PRKCSH):c.1191dup (p.Ile398fs)	PRKCSH	Pathogenic	criteria provided, single submitter
225125	NM_007214.5(SEC63):c.220del (p.Thr73_Val74insTer)	SEC63	Pathogenic	no assertion criteria provided
373976	NM_000138.5(FBN1):c.7274A>G (p.Tyr2425Cys)	FBN1	Likely pathogenic	no assertion criteria provided
162391	NM_002335.4(LRP5):c.3562C>T (p.Arg1188Trp)	LRP5	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179126	NM_001289104.2(PRKCSH):c.564_567del (p.Glu189fs)	PRKCSH	Likely pathogenic	criteria provided, single submitter
1685413	NM_001289104.2(PRKCSH):c.683+1G>A	PRKCSH	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2575053	NM_001289104.2(PRKCSH):c.805_845del (p.Tyr269fs)	PRKCSH	Likely pathogenic	no assertion criteria provided
3220939	NM_001289104.2(PRKCSH):c.1462-1G>C	PRKCSH	Likely pathogenic	criteria provided, single submitter
3234974	NM_001289104.2(PRKCSH):c.247_248insT (p.Lys83fs)	PRKCSH	Likely pathogenic	criteria provided, single submitter
3310005	NM_001289104.2(PRKCSH):c.684-1G>A	PRKCSH	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382804	NM_001289104.2(PRKCSH):c.1127-2A>C	PRKCSH	Likely pathogenic	criteria provided, single submitter
3583435	NM_001289104.2(PRKCSH):c.871_872delinsCCG (p.Ala291fs)	PRKCSH	Likely pathogenic	criteria provided, single submitter
3899967	NM_001289104.2(PRKCSH):c.703C>T (p.Gln235Ter)	PRKCSH	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 44 · Orphanet: 28 · 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
PRKCSH	Definitive	Autosomal dominant	polycystic liver disease 1	10
SEC63	Definitive	Autosomal dominant	polycystic liver disease 2	5
LRP5	Strong	Autosomal dominant	polycystic liver disease 4 with or without kidney cysts	26
SEC61B	Moderate	Autosomal dominant	polycystic liver disease 1	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SEC63	Orphanet:2924	Isolated polycystic liver disease
LRP5	Orphanet:178377	Osteosclerosis-developmental delay-craniosynostosis syndrome
LRP5	Orphanet:2783	Autosomal dominant osteopetrosis type 1
LRP5	Orphanet:2788	Osteoporosis-pseudoglioma syndrome
LRP5	Orphanet:2790	Endosteal hyperostosis, Worth type
LRP5	Orphanet:2924	Isolated polycystic liver disease
LRP5	Orphanet:3416	Hyperostosis corticalis generalisata
LRP5	Orphanet:498481	LRP5-related primary osteoporosis
LRP5	Orphanet:891	Familial exudative vitreoretinopathy
LRP5	Orphanet:90050	Retinopathy of prematurity
PRKCSH	Orphanet:2924	Isolated polycystic liver disease
ODAD3	Orphanet:244	Primary ciliary dyskinesia
FBN1	Orphanet:1885	Isolated ectopia lentis
FBN1	Orphanet:2084	Glaucoma-ectopia lentis-microspherophakia-stiff joints-short stature syndrome
FBN1	Orphanet:2462	Shprintzen-Goldberg syndrome
FBN1	Orphanet:2623	Geleophysic dysplasia
FBN1	Orphanet:2833	Stiff skin syndrome
FBN1	Orphanet:284963	Marfan syndrome type 1
FBN1	Orphanet:284979	Neonatal Marfan syndrome
FBN1	Orphanet:300382	Progeroid and marfanoid aspect-lipodystrophy syndrome
FBN1	Orphanet:3449	Weill-Marchesani syndrome
FBN1	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
FBN1	Orphanet:969	Acromicric dysplasia
PKD1	Orphanet:730	Autosomal dominant polycystic kidney disease
PKD1	Orphanet:88924	Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis
PKD2	Orphanet:730	Autosomal dominant polycystic kidney disease
PRKD1	Orphanet:276145	Malignant epithelial tumor of salivary glands
PRKD1	Orphanet:708019	Congenital heart defect-ectodermal dysplasia- brachydactyly-telangiectasia syndrome

Cohort genes → proteins

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SEC63	HGNC:21082	ENSG00000025796	Q9UGP8	Translocation protein SEC63 homolog	gencc,clinvar
LRP5	HGNC:6697	ENSG00000162337	O75197	Low-density lipoprotein receptor-related protein 5	gencc,clinvar
PRKCSH	HGNC:9411	ENSG00000130175	P14314	Glucosidase 2 subunit beta	gencc,clinvar
SEC61B	HGNC:16993	ENSG00000106803	P60468	Protein transport protein Sec61 subunit beta	gencc
ODAD3	HGNC:28303	ENSG00000198003	A5D8V7	Outer dynein arm-docking complex subunit 3	clinvar
FBN1	HGNC:3603	ENSG00000166147	P35555	Fibrillin-1	clinvar
PKD1	HGNC:9008	ENSG00000008710	P98161	Polycystin-1	clinvar
PKD2	HGNC:9009	ENSG00000118762	Q13563	Polycystin-2	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)
SEC63	Translocation protein SEC63 homolog	Mediates cotranslational and post-translational transport of certain precursor polypeptides across endoplasmic reticulum (ER).
LRP5	Low-density lipoprotein receptor-related protein 5	Acts as a coreceptor with members of the frizzled family of seven-transmembrane spanning receptors to transduce signal by Wnt proteins.
PRKCSH	Glucosidase 2 subunit beta	Regulatory subunit of glucosidase II that cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins.
SEC61B	Protein transport protein Sec61 subunit beta	Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across the endoplasmic reticulum (ER).
ODAD3	Outer dynein arm-docking complex subunit 3	Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule.
FBN1	Fibrillin-1	Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues.
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.
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: 3 · Difficult: 0 · Unknown: 6 · Druggable fraction: 0.33

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	1	3.2×	0.507
Kinase	1	3.1×	0.507
Other/Unknown	6	1.2×	0.507
Enzyme (other)	1	1.3×	0.543

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SEC63	Other/Unknown	no		DnaJ_domain, Sec63-dom, Ig_E-set
LRP5	Other/Unknown	no		LDLR_classB_rpt, EGF, LDrepeatLR_classA_rpt
PRKCSH	Enzyme (other)	yes	3.2.1.207	EF_hand_dom, Man6P_isomerase_rcpt-bd_dom_sf, EF-hand-dom_pair
SEC61B	Other/Unknown	no		SecG/Sec61-beta/Sbh, Sec61-beta/Sbh
ODAD3	Other/Unknown	no		ODAD3
FBN1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
PKD1	Antibody/Immunoglobulin	yes		GPS, LRRNT, PC1
PKD2	Other/Unknown	no		EF_hand_dom, PKD_2, EF-hand-dom_pair
PRKD1	Kinase	yes	2.7.11.13	Prot_kinase_dom, PH_domain, PKC_DAG/PE

Expression context

Cohort genes with no expression data: 0.

9 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)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	2
parotid gland	2
colonic epithelium	1
ascending aorta	1
mucosa of transverse colon	1
right lobe of liver	1
olfactory bulb	1
stromal cell of endometrium	1
type B pancreatic cell	1
oocyte	1
bronchial epithelial cell	1
bronchus	1
right uterine tube	1
decidua	1
skin of hip	1
synovial joint	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
blood vessel layer	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SEC63	295	ubiquitous	marker	colonic epithelium, body of pancreas, parotid gland
LRP5	224	ubiquitous	marker	right lobe of liver, mucosa of transverse colon, ascending aorta
PRKCSH	288	ubiquitous	marker	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
SEC61B	288	ubiquitous	marker	parotid gland, body of pancreas, oocyte
ODAD3	177	broad	marker	bronchial epithelial cell, bronchus, right uterine tube
FBN1	275	ubiquitous	marker	synovial joint, skin of hip, decidua
PKD1	290		marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
PKD2	288	ubiquitous	marker	blood vessel layer, calcaneal tendon, saphenous vein
PRKD1	239	ubiquitous	marker	ventricular zone, seminal vesicle, thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 8.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FBN1	3,640
SEC63	3,355
LRP5	2,619
PRKD1	2,131
PRKCSH	1,922
ODAD3	1,817
PKD2	1,644
PKD1	1,370
SEC61B	1,185

Intra-cohort edges

A	B	Sources
PKD1	PKD2	biogrid_interaction, intact, string_interaction
PKD1	PRKCSH	string_interaction
PKD1	PRKD1	string_interaction
PKD1	SEC63	string_interaction
PKD2	PRKCSH	string_interaction
PKD2	PRKD1	string_interaction
PRKCSH	PRKD1	string_interaction
PRKCSH	SEC63	string_interaction

Structural data

PDB: 6 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PKD2	Q13563	31
SEC61B	P60468	16
PKD1	P98161	13
FBN1	P35555	11
PRKCSH	P14314	2
ODAD3	A5D8V7	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LRP5	O75197	78.65
SEC63	Q9UGP8	77.71
PRKD1	Q15139	68.99

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 39. Enrichment computed across 9 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
VxPx cargo-targeting to cilium	2	148.3×	0.003	PKD1, PKD2
Maturation of spike protein	1	271.9×	0.033	PRKCSH
Signaling by LRP5 mutants	1	233.1×	0.033	LRP5
Post-translational protein phosphorylation	2	28.6×	0.033	PRKCSH, FBN1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	2	24.7×	0.033	PRKCSH, FBN1
Signaling by RNF43 mutants	1	181.3×	0.036	LRP5
Negative regulation of TCF-dependent signaling by WNT ligand antagonists	1	102.0×	0.042	LRP5
Advanced glycosylation endproduct receptor signaling	1	102.0×	0.042	PRKCSH
Calnexin/calreticulin cycle	1	102.0×	0.042	PRKCSH
Signaling by WNT in cancer	1	85.9×	0.045	LRP5
Regulation of FZD by ubiquitination	1	74.2×	0.046	LRP5
Insertion of tail-anchored proteins into the endoplasmic reticulum membrane	1	68.0×	0.046	SEC61B
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	1	60.4×	0.046	PRKCSH
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	51.0×	0.046	LRP5
Elastic fibre formation	1	48.0×	0.046	FBN1
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	48.0×	0.046	PRKCSH
TGF-beta receptor signaling activates SMADs	1	46.6×	0.046	FBN1
Antigen processing-Cross presentation	1	45.3×	0.046	SEC61B
Molecules associated with elastic fibres	1	44.1×	0.046	FBN1
Sphingolipid de novo biosynthesis	1	40.8×	0.047	PRKD1
Maturation of spike protein	1	37.9×	0.048	PRKCSH
Protein localization	1	27.2×	0.064	SEC61B
Sphingolipid metabolism	1	24.0×	0.069	PRKD1
Integrin cell surface interactions	1	19.2×	0.082	FBN1
ER-Phagosome pathway	1	18.5×	0.082	SEC61B
Degradation of the extracellular matrix	1	16.8×	0.084	FBN1
TCF dependent signaling in response to WNT	1	16.8×	0.084	LRP5
Signaling by WNT	1	16.0×	0.085	LRP5
SRP-dependent cotranslational protein targeting to membrane	1	14.3×	0.091	SEC61B
Class I MHC mediated antigen processing & presentation	1	10.0×	0.124	SEC61B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
liver development	4	98.5×	1e-05	SEC63, PRKCSH, PKD1, PKD2
nitrogen cycle metabolic process	2	1872.4×	2e-05	SEC63, PKD1
mesonephric tubule development	2	1872.4×	2e-05	PKD1, PKD2
metanephric ascending thin limb development	2	936.2×	8e-05	PKD1, PKD2
mesonephric duct development	2	749.0×	1e-04	PKD1, PKD2
post-translational protein targeting to membrane, translocation	2	468.1×	2e-04	SEC63, SEC61B
placenta blood vessel development	2	312.1×	5e-04	PKD1, PKD2
detection of mechanical stimulus	2	267.5×	6e-04	PKD1, PKD2
protein heterotetramerization	2	234.1×	7e-04	PKD1, PKD2
embryonic placenta development	2	170.2×	0.001	PKD1, PKD2
neural tube development	2	117.0×	0.002	PKD1, PKD2
spinal cord development	2	113.5×	0.002	PKD1, PKD2
heart development	3	26.2×	0.003	FBN1, PKD1, PKD2
metanephric cortex development	1	1872.4×	0.006	PKD2
metanephric cortical collecting duct development	1	1872.4×	0.006	PKD2
metanephric distal tubule development	1	1872.4×	0.006	PKD2
metanephric distal tubule morphogenesis	1	1872.4×	0.006	PKD1
cell surface receptor signaling pathway via JAK-STAT	2	64.6×	0.006	PKD1, PKD2
determination of left/right symmetry	2	56.7×	0.006	ODAD3, PKD2
positive regulation of osteoblast differentiation	2	49.9×	0.007	LRP5, PRKD1
calcium ion transmembrane transport	2	46.8×	0.008	PKD1, PKD2
regulation of skeletal muscle contraction by modulation of calcium ion sensitivity of myofibril	1	936.2×	0.009	PRKD1
renal artery morphogenesis	1	936.2×	0.009	PKD2
metanephric smooth muscle tissue development	1	936.2×	0.009	PKD2
calcium ion transport	2	40.3×	0.009	PKD1, PKD2
detection of nodal flow	1	624.1×	0.011	PKD2
lymph vessel morphogenesis	1	624.1×	0.011	PKD1
post-embryonic eye morphogenesis	1	624.1×	0.011	FBN1
cell-cell signaling involved in mammary gland development	1	624.1×	0.011	LRP5
cellular response to hydrostatic pressure	1	624.1×	0.011	PKD2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 8

Druggability breadth: 7 of 9 evidence-associated genes (78%) 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
PRKD1	INGENOL MEBUTATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRKD1	26	4
SEC63	0	0
LRP5	0	0
PRKCSH	0	0
SEC61B	0	0
ODAD3	0	0
FBN1	0	0
PKD1	0	0
PKD2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INGENOL MEBUTATE	4	PRKD1
MIDOSTAURIN	4	PRKD1
TAMOXIFEN	4	PRKD1
NERATINIB	4	PRKD1
BRIGATINIB	4	PRKD1
NINTEDANIB	4	PRKD1
SUNITINIB	4	PRKD1
CRIZOTINIB	4	PRKD1
GEFITINIB	4	PRKD1
SURAMIN	3	PRKD1
FASUDIL	3	PRKD1
ALVOCIDIB	3	PRKD1
LESTAURTINIB	3	PRKD1
PHORBOL MYRISTATE ACETATE	2	PRKD1
EDELFOSINE	2	PRKD1
UPROSERTIB	2	PRKD1
UCN-01	2	PRKD1
SU-014813	2	PRKD1
AT-9283	2	PRKD1
BI-2536	2	PRKD1
KW-2449	1	PRKD1
BMS-387032	1	PRKD1
PF-03758309	1	PRKD1
SRA-737	1	PRKD1
GSK-690693	1	PRKD1
AST-487	1	PRKD1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
PRKD1	660	Binding:650, Functional:10
PKD1	27	Binding:27
PKD2	12	Binding:12
SEC63	1	Binding:1
LRP5	1	Binding:1
PRKCSH	1	Binding:1
SEC61B	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRKCSH	3.2.1.207	mannosyl-oligosaccharide alpha-1,3-glucosidase
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
PRKD1	660

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

26 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)
INGENOL MEBUTATE	4	PRKD1
MIDOSTAURIN	4	PRKD1
TAMOXIFEN	4	PRKD1
NERATINIB	4	PRKD1
BRIGATINIB	4	PRKD1
NINTEDANIB	4	PRKD1
SUNITINIB	4	PRKD1
CRIZOTINIB	4	PRKD1
GEFITINIB	4	PRKD1
SURAMIN	3	PRKD1
FASUDIL	3	PRKD1
ALVOCIDIB	3	PRKD1
LESTAURTINIB	3	PRKD1
PHORBOL MYRISTATE ACETATE	2	PRKD1
EDELFOSINE	2	PRKD1
UPROSERTIB	2	PRKD1
UCN-01	2	PRKD1
SU-014813	2	PRKD1
AT-9283	2	PRKD1
BI-2536	2	PRKD1
KW-2449	1	PRKD1
BMS-387032	1	PRKD1
PF-03758309	1	PRKD1
SRA-737	1	PRKD1
GSK-690693	1	PRKD1
AST-487	1	PRKD1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PRKD1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	PRKCSH, PKD1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	6	SEC63, LRP5, SEC61B, ODAD3, FBN1, PKD2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PKD1	27	PRKD1
SEC63	1	—
LRP5	1	—
PRKCSH	1	—
SEC61B	1	—
ODAD3	0	—
FBN1	0	—
PKD2	12	—

Clinical trials & evidence

Clinical trials

Clinical trials: 16.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	7
PHASE2/PHASE3	5
PHASE2	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05281328	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Trial to Assess the Efficacy and Safety of Octreotide Subcutaneous Depot in Patients With PLD
NCT00426153	PHASE2/PHASE3	COMPLETED	Octreotide in Severe Polycystic Liver Disease
NCT00565097	PHASE2/PHASE3	COMPLETED	Lanreotide as Treatment of Polycystic Livers
NCT00771888	PHASE2/PHASE3	UNKNOWN	Open-Label Extension of LOCKCYST Trial
NCT01315795	PHASE2/PHASE3	COMPLETED	Lanreotide Autogel in the Treatment of Symptomatic Polycystic Liver Disease
NCT05478083	PHASE2	RECRUITING	A GnRH Agonist IN Pre-menopausal Women STudy to Treat Severe Polycystic Liver Disease
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
NCT04645251	Not specified	RECRUITING	Polycystic Liver Disease Registry (UK)
NCT00934791	Not specified	TERMINATED	Polycystic Liver Disease in Kidney Transplant
NCT01354405	Not specified	COMPLETED	Somatostatin Analogues as a Volume Reducing Treatment of Polycystic Livers (RESOLVE)
NCT02173080	Not specified	COMPLETED	Development and Assessment of The Polycystic Liver Disease Questionnaire (PLD-Q).
NCT03960710	Not specified	UNKNOWN	Automatic Segmentation of Polycystic Liver
NCT05215964	Not specified	UNKNOWN	The Association Between Skeletal Muscle Mass and Severity of Polycystic Liver Disease and Polycystic Kidney Disease
NCT05500157	Not specified	UNKNOWN	Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LANREOTIDE	4	3
OCTREOTIDE	4	2
URSODIOL	4	2
CHEMBL3350037	0	1
CHEMBL5409583	0	1