Polycystic kidney disease 1
disease diseaseOn this page
Also known as APKD1autosomal dominant polycystic kidney disease caused by mutation in PKD1PKD1PKD1 autosomal dominant polycystic kidney diseasepolycystic kidney disease type 1Potter type 3 polycystic kidney disease
Summary
Polycystic kidney disease 1 (MONDO:0008263) is a disease caused by PKD1 (GenCC Definitive), with 12 cohort genes.
At a glance
- Causal gene: PKD1 (GenCC Definitive)
- Cohort genes: 12
- ClinVar variants: 4,276
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | polycystic kidney disease 1 |
| Mondo ID | MONDO:0008263 |
| MeSH | C536326 |
| OMIM | 173900 |
| DOID | DOID:0110858 |
| SNOMED CT | 253878003 |
| UMLS | C3149841 |
| MedGen | 461191 |
| GARD | 0018597 |
| Is cancer (heuristic) | no |
Also known as: APKD1 · autosomal dominant polycystic kidney disease caused by mutation in PKD1 · PKD1 · PKD1 autosomal dominant polycystic kidney disease · polycystic kidney disease 1 · polycystic kidney disease type 1 · Potter type 3 polycystic kidney disease
Data availability: 4,276 ClinVar variants · 3 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 kidney disease › polycystic kidney disease 1
Related subtypes (6): polycystic kidney disease 3 with or without polycystic liver disease, polycystic kidney disease 2, polycystic kidney disease 7, polycystic kidney disease 6 with or without polycystic liver disease, ALG9-associated autosomal dominant polycystic kidney disease, polycystic kidney disease 8
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:
207 uncertain significance, 150 pathogenic, 78 conflicting classifications of pathogenicity, 58 likely pathogenic, 34 benign/likely benign, 25 pathogenic/likely pathogenic, 24 likely benign, 21 benign, 3 not provided
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1179116 | GRCh37/hg19 16p13.3(chr16:2089795-2185919) | MIR1225 | Pathogenic | no assertion criteria provided |
| 1013090 | NM_001009944.3(PKD1):c.11263C>T (p.Gln3755Ter) | PKD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1030954 | NM_001009944.3(PKD1):c.5637C>A (p.Tyr1879Ter) | PKD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1034359 | NM_001009944.3(PKD1):c.8043_8046del (p.Ser2682fs) | PKD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1048640 | NM_001009944.3(PKD1):c.8333dup (p.Glu2779fs) | PKD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1048641 | NM_001009944.3(PKD1):c.5290G>T (p.Glu1764Ter) | PKD1 | Pathogenic | criteria provided, single submitter |
| 1048642 | NM_001009944.3(PKD1):c.3931dup (p.Ala1311fs) | PKD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1048645 | NM_001009944.3(PKD1):c.5856del (p.Asn1954fs) | PKD1 | Pathogenic | criteria provided, single submitter |
| 1048760 | NM_001009944.3(PKD1):c.499del (p.Gly168fs) | PKD1 | Pathogenic | no assertion criteria provided |
| 1064647 | NM_001009944.3(PKD1):c.11723T>C (p.Leu3908Pro) | PKD1 | Pathogenic | criteria provided, single submitter |
| 1077162 | NM_001009944.3(PKD1):c.10527_10528del (p.Glu3509fs) | PKD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1172882 | NM_001009944.3(PKD1):c.1606+1G>A | PKD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1177416 | NM_001009944.3(PKD1):c.10219del (p.Ser3407fs) | PKD1 | Pathogenic | criteria provided, single submitter |
| 1177417 | NM_001009944.3(PKD1):c.6282G>A (p.Trp2094Ter) | PKD1 | Pathogenic | criteria provided, single submitter |
| 1177427 | NM_001009944.3(PKD1):c.10358dup (p.Ser3454fs) | PKD1 | Pathogenic | criteria provided, single submitter |
| 1179034 | NM_001009944.3(PKD1):c.4743dup (p.Trp1582fs) | PKD1 | Pathogenic | criteria provided, single submitter |
| 1179054 | NM_001009944.3(PKD1):c.160_166del (p.Arg54fs) | PKD1 | Pathogenic | criteria provided, single submitter |
| 1179066 | NM_001009944.3(PKD1):c.10516del (p.Glu3506fs) | PKD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1179071 | NM_001009944.3(PKD1):c.9691G>T (p.Glu3231Ter) | PKD1 | Pathogenic | criteria provided, single submitter |
| 1179072 | NM_001009944.3(PKD1):c.9683dup (p.Leu3229fs) | PKD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1179075 | NM_001009944.3(PKD1):c.659del (p.Gly220fs) | PKD1 | Pathogenic | criteria provided, single submitter |
| 1179077 | NM_001009944.3(PKD1):c.6424C>T (p.Gln2142Ter) | PKD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1179078 | NM_001009944.3(PKD1):c.628_631dup (p.Ser211fs) | PKD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1179089 | NM_001009944.3(PKD1):c.272C>A (p.Ser91Ter) | PKD1 | Pathogenic | criteria provided, single submitter |
| 1179091 | NM_001009944.3(PKD1):c.2716G>T (p.Glu906Ter) | PKD1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1179093 | NM_001009944.3(PKD1):c.2054_2055del (p.Glu685fs) | PKD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1179098 | NM_001009944.3(PKD1):c.1418_1419del (p.Val473fs) | PKD1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1179105 | NM_001009944.3(PKD1):c.1326del (p.Ala443fs) | PKD1 | Pathogenic | criteria provided, single submitter |
| 1179107 | NM_001009944.3(PKD1):c.10168C>T (p.Gln3390Ter) | PKD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1179124 | NM_001009944.3(PKD1):c.601dup (p.His201fs) | PKD1 | Pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 21 · Orphanet: 27 · 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 |
|---|---|---|---|---|
| PKD1 | Definitive | Autosomal recessive | autosomal recessive polycystic kidney disease | 7 |
| PRKD1 | Definitive | Autosomal recessive | autosomal recessive polycystic kidney disease | 14 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| PKD1 | Orphanet:730 | Autosomal dominant polycystic kidney disease |
| PKD1 | Orphanet:88924 | Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis |
| PRKD1 | Orphanet:276145 | Malignant epithelial tumor of salivary glands |
| PRKD1 | Orphanet:708019 | Congenital heart defect-ectodermal dysplasia- brachydactyly-telangiectasia syndrome |
| SLC7A9 | Orphanet:93613 | Cystinuria type B |
| ALG9 | Orphanet:730 | Autosomal dominant polycystic kidney disease |
| ALG9 | Orphanet:79328 | ALG9-CDG |
| 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 |
| NTHL1 | Orphanet:454840 | NTHL1-related polyposis |
| PKD2 | Orphanet:730 | Autosomal dominant polycystic kidney disease |
| PKHD1 | Orphanet:53035 | Caroli disease |
| PKHD1 | Orphanet:731 | Autosomal recessive polycystic kidney disease |
| PLP1 | Orphanet:280210 | Pelizaeus-Merzbacher disease, connatal form |
| PLP1 | Orphanet:280219 | Pelizaeus-Merzbacher disease, classic form |
| PLP1 | Orphanet:280224 | Pelizaeus-Merzbacher disease, transitional form |
| PLP1 | Orphanet:280229 | Pelizaeus-Merzbacher disease in female carriers |
| PLP1 | Orphanet:280234 | Null syndrome |
| PLP1 | Orphanet:599376 | Hypomyelination of early myelinating structures |
| PLP1 | Orphanet:99015 | Spastic paraplegia type 2 |
Cohort genes → proteins
12 cohort genes, 9 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 12 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| PKD1 | HGNC:9008 | ENSG00000008710 | P98161 | Polycystin-1 | gencc,clinvar |
| PRKD1 | HGNC:9407 | ENSG00000184304 | Q15139 | Serine/threonine-protein kinase D1 | gencc,clinvar |
| SLC7A9 | HGNC:11067 | ENSG00000021488 | P82251 | b(0,+)-type amino acid transporter 1 | clinvar |
| ALG9 | HGNC:15672 | ENSG00000086848 | Q9H6U8 | Alpha-1,2-mannosyltransferase ALG9 | clinvar |
| MIR1225 | HGNC:33931 | ENSG00000221656 | microRNA 1225 | clinvar | |
| MIR6511B1 | HGNC:50228 | ENSG00000284008 | microRNA 6511b-1 | clinvar | |
| PKD1-AS1 | HGNC:56035 | ENSG00000259933 | PKD1 antisense RNA 1 | clinvar | |
| LRP5 | HGNC:6697 | ENSG00000162337 | O75197 | Low-density lipoprotein receptor-related protein 5 | clinvar |
| NTHL1 | HGNC:8028 | ENSG00000065057 | P78549 | Endonuclease III-like protein 1 | clinvar |
| PKD2 | HGNC:9009 | ENSG00000118762 | Q13563 | Polycystin-2 | clinvar |
| PKHD1 | HGNC:9016 | ENSG00000170927 | P08F94 | Fibrocystin | clinvar |
| PLP1 | HGNC:9086 | ENSG00000123560 | P60201 | Myelin proteolipid protein | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| 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. |
| 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… |
| SLC7A9 | b(0,+)-type amino acid transporter 1 | Associates with SLC3A1 to form a functional transporter complex that mediates the electrogenic exchange between cationic amino acids and neutral amino acids, with a stoichiometry of 1:1. |
| ALG9 | Alpha-1,2-mannosyltransferase ALG9 | Mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. |
| 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. |
| NTHL1 | Endonuclease III-like protein 1 | Bifunctional DNA N-glycosylase with associated apurinic/apyrimidinic (AP) lyase function that catalyzes the first step in base excision repair (BER), the primary repair pathway for the repair of oxidative DNA damage. |
| 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. |
| PLP1 | Myelin proteolipid protein | This is the major myelin protein from the central nervous system. |
Protein-family classification
Druggable: 6 · Difficult: 0 · Unknown: 6 · Druggable fraction: 0.5
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 | 2 | 4.9× | 0.308 |
| Transporter | 1 | 6.5× | 0.360 |
| Enzyme (other) | 2 | 2.0× | 0.440 |
| Kinase | 1 | 2.3× | 0.446 |
| Other/Unknown | 6 | 0.9× | 0.758 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| PKD1 | Antibody/Immunoglobulin | yes | GPS, LRRNT, PC1 | |
| PRKD1 | Kinase | yes | 2.7.11.13 | Prot_kinase_dom, PH_domain, PKC_DAG/PE |
| SLC7A9 | Transporter | yes | AA/rel_permease1, AminoAcid_Transporter | |
| ALG9 | Enzyme (other) | yes | 2.4.1.259 | GPI_mannosylTrfase |
| MIR1225 | Other/Unknown | no | ||
| MIR6511B1 | Other/Unknown | no | ||
| PKD1-AS1 | Other/Unknown | no | ||
| LRP5 | Other/Unknown | no | LDLR_classB_rpt, EGF, LDrepeatLR_classA_rpt | |
| NTHL1 | Enzyme (other) | yes | 4.2.99.18 | HhH_motif, HhH-GPD_domain, Endonuclease3_FeS-loop_motif |
| PKD2 | Other/Unknown | no | EF_hand_dom, PKD_2, EF-hand-dom_pair | |
| PKHD1 | Antibody/Immunoglobulin | yes | IPT_dom, PbH1, Pectin_lyase_fold/virulence | |
| PLP1 | Other/Unknown | no | Myelin_PLP, Myelin_PLP_CS |
Expression context
Cohort genes with no expression data: 0.
10 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) | 12 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| cerebellar cortex | 2 |
| cerebellar hemisphere | 2 |
| right hemisphere of cerebellum | 2 |
| sural nerve | 2 |
| calcaneal tendon | 2 |
| mucosa of transverse colon | 2 |
| right lobe of liver | 2 |
| seminal vesicle | 1 |
| thoracic aorta | 1 |
| ventricular zone | 1 |
| ileal mucosa | 1 |
| jejunal mucosa | 1 |
| secondary oocyte | 1 |
| body of pancreas | 1 |
| endothelial cell | 1 |
| ganglionic eminence | 1 |
| Brodmann (1909) area 9 | 1 |
| skeletal muscle tissue | 1 |
| Ammon’s horn | 1 |
| ascending aorta | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| PKD1 | 290 | marker | right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex | |
| PRKD1 | 239 | ubiquitous | marker | ventricular zone, seminal vesicle, thoracic aorta |
| SLC7A9 | 173 | tissue_specific | marker | ileal mucosa, secondary oocyte, jejunal mucosa |
| ALG9 | 240 | ubiquitous | marker | endothelial cell, body of pancreas, ganglionic eminence |
| MIR1225 | 77 | yes | sural nerve, skeletal muscle tissue, Brodmann (1909) area 9 | |
| MIR6511B1 | 46 | yes | sural nerve, calcaneal tendon, Ammon’s horn | |
| PKD1-AS1 | 133 | marker | right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex | |
| LRP5 | 224 | ubiquitous | marker | right lobe of liver, mucosa of transverse colon, ascending aorta |
| NTHL1 | 211 | ubiquitous | marker | right lobe of liver, apex of heart, mucosa of transverse colon |
| PKD2 | 288 | ubiquitous | marker | blood vessel layer, calcaneal tendon, saphenous vein |
| PKHD1 | 51 | tissue_specific | marker | kidney epithelium, renal medulla, metanephros cortex |
| PLP1 | 250 | broad | marker | corpus callosum, middle frontal gyrus, inferior vagus X ganglion |
Protein interactions among cohort
Intra-cohort edges: 6.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| LRP5 | 2,619 |
| PRKD1 | 2,131 |
| NTHL1 | 1,994 |
| PKD2 | 1,644 |
| PKD1 | 1,370 |
| PKHD1 | 1,211 |
| ALG9 | 1,167 |
| SLC7A9 | 1,106 |
| PLP1 | 157 |
| MIR1225 | 0 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| 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: 6 · AlphaFold-only: 3 · No structure: 3
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| PKD2 | Q13563 | 31 |
| PKD1 | P98161 | 13 |
| SLC7A9 | P82251 | 4 |
| ALG9 | Q9H6U8 | 2 |
| NTHL1 | P78549 | 2 |
| PLP1 | P60201 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| LRP5 | O75197 | 78.65 |
| PRKD1 | Q15139 | 68.99 |
| PKHD1 | P08F94 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 40. Enrichment computed across 12 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 |
| Defective ALG9 causes CDG-1l | 1 | 1631.4× | 0.006 | ALG9 |
| Defective NTHL1 substrate processing | 1 | 1631.4× | 0.006 | NTHL1 |
| Defective NTHL1 substrate binding | 1 | 1631.4× | 0.006 | NTHL1 |
| Defective SLC3A1 causes cystinuria (CSNU) | 1 | 815.7× | 0.008 | SLC7A9 |
| Defective amino acid transport by SLC7A9 causes cystinuria (CSNU) | 1 | 815.7× | 0.008 | SLC7A9 |
| Signaling by LRP5 mutants | 1 | 233.1× | 0.024 | LRP5 |
| Signaling by RNF43 mutants | 1 | 181.3× | 0.028 | LRP5 |
| Displacement of DNA glycosylase by APEX1 | 1 | 148.3× | 0.030 | NTHL1 |
| Negative regulation of TCF-dependent signaling by WNT ligand antagonists | 1 | 102.0× | 0.038 | LRP5 |
| Diseases associated with N-glycosylation of proteins | 1 | 90.6× | 0.038 | ALG9 |
| Signaling by WNT in cancer | 1 | 85.9× | 0.038 | LRP5 |
| Disease | 3 | 5.6× | 0.038 | SLC7A9, ALG9, LRP5 |
| Regulation of FZD by ubiquitination | 1 | 74.2× | 0.038 | LRP5 |
| Basigin interactions | 1 | 62.8× | 0.042 | SLC7A9 |
| Disassembly of the destruction complex and recruitment of AXIN to the membrane | 1 | 51.0× | 0.049 | LRP5 |
| Amino acid transport across the plasma membrane | 1 | 42.9× | 0.054 | SLC7A9 |
| Sphingolipid de novo biosynthesis | 1 | 40.8× | 0.054 | PRKD1 |
| Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein | 1 | 29.7× | 0.068 | ALG9 |
| SLC transporter disorders | 1 | 29.1× | 0.068 | SLC7A9 |
| Recognition and association of DNA glycosylase with site containing an affected pyrimidine | 1 | 26.3× | 0.068 | NTHL1 |
| Cleavage of the damaged pyrimidine | 1 | 26.3× | 0.068 | NTHL1 |
| Sphingolipid metabolism | 1 | 24.0× | 0.071 | PRKD1 |
| Disorders of transmembrane transporters | 1 | 19.9× | 0.081 | SLC7A9 |
| Diseases of glycosylation | 1 | 18.8× | 0.081 | ALG9 |
| R-HSA-425393 | 1 | 18.5× | 0.081 | SLC7A9 |
| TCF dependent signaling in response to WNT | 1 | 16.8× | 0.086 | LRP5 |
| Signaling by WNT | 1 | 16.0× | 0.087 | LRP5 |
| Cell surface interactions at the vascular wall | 1 | 13.6× | 0.098 | SLC7A9 |
| Diseases of metabolism | 1 | 11.5× | 0.112 | ALG9 |
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 |
|---|---|---|---|---|
| mesonephric tubule development | 2 | 1872.4× | 5e-05 | PKD1, PKD2 |
| metanephric ascending thin limb development | 2 | 936.2× | 2e-04 | PKD1, PKD2 |
| mesonephric duct development | 2 | 749.0× | 2e-04 | PKD1, PKD2 |
| placenta blood vessel development | 2 | 312.1× | 9e-04 | PKD1, PKD2 |
| detection of mechanical stimulus | 2 | 267.5× | 9e-04 | PKD1, PKD2 |
| protein heterotetramerization | 2 | 234.1× | 0.001 | PKD1, PKD2 |
| embryonic placenta development | 2 | 170.2× | 0.002 | PKD1, PKD2 |
| branching morphogenesis of an epithelial tube | 2 | 162.8× | 0.002 | PKD1, PKHD1 |
| neural tube development | 2 | 117.0× | 0.003 | PKD1, PKD2 |
| spinal cord development | 2 | 113.5× | 0.003 | 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 |
| regulation of cholangiocyte proliferation | 1 | 1872.4× | 0.006 | PKHD1 |
| regulation of cell adhesion | 2 | 68.1× | 0.006 | PKD1, PKHD1 |
| cell surface receptor signaling pathway via JAK-STAT | 2 | 64.6× | 0.006 | PKD1, PKD2 |
| positive regulation of osteoblast differentiation | 2 | 49.9× | 0.008 | PRKD1, LRP5 |
| liver development | 2 | 49.3× | 0.008 | PKD1, PKD2 |
| 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 |
| nitrogen cycle metabolic process | 1 | 936.2× | 0.009 | PKD1 |
| metanephric smooth muscle tissue development | 1 | 936.2× | 0.009 | PKD2 |
| calcium ion transport | 2 | 40.3× | 0.009 | PKD1, PKD2 |
| positive regulation of gene expression | 3 | 12.9× | 0.010 | PRKD1, PKD2, PLP1 |
| detection of nodal flow | 1 | 624.1× | 0.010 | PKD2 |
| lymph vessel morphogenesis | 1 | 624.1× | 0.010 | PKD1 |
| cell-cell signaling involved in mammary gland development | 1 | 624.1× | 0.010 | LRP5 |
| cellular response to hydrostatic pressure | 1 | 624.1× | 0.010 | PKD2 |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 11
Druggability breadth: 5 of 12 evidence-associated genes (42%) 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 |
| PKD1 | 0 | 0 |
| SLC7A9 | 0 | 0 |
| ALG9 | 0 | 0 |
| MIR1225 | 0 | 0 |
| MIR6511B1 | 0 | 0 |
| PKD1-AS1 | 0 | 0 |
| LRP5 | 0 | 0 |
| NTHL1 | 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): 3.
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 |
| NTHL1 | 8 | Binding:7, Functional:1 |
| LRP5 | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| PRKD1 | 2.7.11.13 | protein kinase C |
| ALG9 | 2.4.1.259, 2.4.1.261 | dolichyl-P-Man:Man6GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase, dolichyl-P-Man:Man8GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase |
| NTHL1 | 4.2.99.18 | DNA-(apurinic or apyrimidinic site) lyase |
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: 10; 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 | 4 | PKD1, SLC7A9, ALG9, NTHL1 |
| D | Druggable family + AlphaFold only, no drug | 1 | PKHD1 |
| E | Difficult family or no structure, no drug | 6 | MIR1225, MIR6511B1, PKD1-AS1, LRP5, PKD2, PLP1 |
Undrugged target profiles
11 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| PKD1 | 27 | PRKD1 |
| SLC7A9 | 0 | — |
| ALG9 | 0 | — |
| MIR1225 | 0 | — |
| MIR6511B1 | 0 | — |
| PKD1-AS1 | 0 | — |
| LRP5 | 1 | — |
| NTHL1 | 8 | — |
| PKD2 | 12 | — |
| PKHD1 | 0 | — |
| PLP1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.