Cystic kidney disease

Summary

Cystic kidney disease (MONDO:0002473) is a disease caused by IFT140 (GenCC Strong), with 17 cohort genes (20 GWAS associations across 15 studies) and 6 clinical trials. Top therapeutic interventions include venglustat.

At a glance

• Causal gene: IFT140 (GenCC Strong)
• Cohort genes: 17
• GWAS associations: 20
• ClinVar variants: 82
• Clinical trials: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cystic kidney disease
Mondo ID	MONDO:0002473
EFO	EFO:0008615
MeSH	D052177
DOID	DOID:2975
ICD-10-CM	Q61
NCIT	C34750
SNOMED CT	722223000
UMLS	C3887499
MedGen	854361
Is cancer (heuristic)	no

Also known as: cystic renal disease · kidney cyst

Data availability: 82 ClinVar variants · 20 GWAS associations (15 studies) · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 4 Mondo subtypes.

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

Related subtypes (56): renal hypertension, kidney failure, nephritis, impaired renal function disease, nephrocalcinosis, atheroembolism of kidney, renal artery disease, nephrosis, anuria, stricture or kinking of ureter, proteinuria, renal infectious disease, diabetes insipidus, orthostatic proteinuria, kidney hypertrophy, chronic kidney disease, hydronephrosis, renal tubular transport disease, kidney cortex necrosis, kidney papillary necrosis, perinephritis, renal aminoaciduria, autosomal dominant progressive nephropathy with hypertension, nephrolithiasis, X-linked diffuse leiomyomatosis-Alport syndrome, tubulointerstitial nephritis and uveitis syndrome, distal renal tubular acidosis, oligomeganephronia, duplication of urethra, renal tubular dysgenesis, exstrophy-epispadias complex, fetal lower urinary tract obstruction, IgG4-related kidney disease, congenital primary megaureter, renal nutcracker syndrome, renal hypoplasia, renal dysplasia, congenital megacalycosis, glomerular disorder, congenital renal artery stenosis, kidney neoplasm, renal tubule disorder, pyonephrosis, Arnold stickler bourne syndrome, C1q nephropathy, hypertensive nephropathy, atypical Fanconi syndrome-neonatal hyperinsulinism syndrome, idiopathic non-lupus full-house nephropathy, lachiewicz sibley syndrome, crush syndrome, obstructive nephropathy, inherited kidney disorder, acute tubulointerstitial nephritis, kidney cortex disease, non-syndromic supernumerary kidneys, neonatal renal venous thrombosis

Subtypes (4): non-congenital cyst of kidney, medullary sponge kidney, multicystic dysplastic kidney, familial cystic renal disease

Genetics & variants

GWAS landscape

20 GWAS associations across 15 studies. Top hits map to 7 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs9895661	2e-41	BCAS3, TBX2-AS1	C	0.2
rs2806685	3e-28	INVS	A	0.14
chr9:103017818	1e-21		C	0.14
rs28703582	4e-20	RNA5SP431 - MAF	G	0.13
chr4:88065406	2e-19		GA	8719.79
chr16:1607935	7e-16		C	2.63
rs7021445	1e-15	TPD52L3 - UHRF2	C	0.18
rs553907985	5e-15	HERC3, HERC3	?
rs151319288	6e-15	FANCD2OS	C	0.3
chr16:2110151	8e-15		C	5051.04
chr9:102908721	4e-14		G	0.2
chr16:79473152	3e-13		T	0.11
rs7870585	5e-13	ERP44	G	0.12
rs6694034	1e-11	ELF3 - Y_RNA	A	0.09
rs140816405	3e-08	LINC01521 - RNU6-338P	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90476133	Verma A	2024	10,273	426,328	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90476265	Verma A	2024	5,765	438,134	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90476132	Verma A	2024	3,376	114,335	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480381	Verma A	2024	3,376	114,335	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479079	Verma A	2024	1,773	117,881	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480562	Verma A	2024	1,773	117,881	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90436422	Zhou W	2018	1,260	397,602	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90474277	UK Biobank Whole-Genome Sequencing Consortium	2025	983	457,457	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90478535	Verma A	2024	958	57,589	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651210	Liu TY	2025	703	234,654	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	14

MAF distribution

Bucket	Variants
common (>=0.05)	10
low_freq (0.01-0.05)	0
rare (<0.01)	1
unknown	4

Functional consequences

Consequence	Count
unknown	6
intron_variant	4
intergenic_variant	4
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs9895661	17	61379228	C>A,T	0.265	intron_variant	BCAS3, TBX2-AS1	2e-41	Tier 4: intronic/intergenic
rs2806685	9	100236750	A>C	0.454	intron_variant	INVS	3e-28	Tier 4: intronic/intergenic
chr9:103017818				0.436			1e-21	Tier 4: intronic/intergenic
rs28703582	16	79434920	G>A,T	0.465	intergenic_variant	RNA5SP431 - MAF	4e-20	Tier 4: intronic/intergenic
chr4:88065406							2e-19	Tier 4: intronic/intergenic
chr16:1607935				0			7e-16	Tier 4: intronic/intergenic
rs7021445	9	6356657	C>A,G,T	0.083	intergenic_variant	TPD52L3 - UHRF2	1e-15	Tier 4: intronic/intergenic
rs553907985	4	88621992	ATACAATT>A		intron_variant	HERC3, HERC3	5e-15	Tier 4: intronic/intergenic
rs151319288	3	10102394	C>T	0.098	intergenic_variant	FANCD2OS	6e-15	Tier 4: intronic/intergenic
chr16:2110151							8e-15	Tier 4: intronic/intergenic
chr9:102908721				0.312			4e-14	Tier 4: intronic/intergenic
chr16:79473152				0.381			3e-13	Tier 4: intronic/intergenic
rs7870585	9	100016816	G>A,C,T	0.433	intron_variant	ERP44	5e-13	Tier 4: intronic/intergenic
rs6694034	1	202034859	A>C,T	0.485	regulatory_region_variant	ELF3 - Y_RNA	1e-11	Tier 3: regulatory
rs140816405	22	31355292	A>T		intergenic_variant	LINC01521 - RNU6-338P	3e-08	Tier 4: intronic/intergenic

ClinVar germline variants

82 retrieved; paginated sample, class counts are floors:

30 pathogenic, 19 uncertain significance, 11 pathogenic/likely pathogenic, 10 likely pathogenic, 10 conflicting classifications of pathogenicity, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1172618	NM_001009944.3(PKD1):c.[9428_9429insCACGA;9432_9433del]		Pathogenic	criteria provided, single submitter
56312	NM_001378615.1(CC2D2A):c.4179+1del	CC2D2A	Pathogenic	criteria provided, multiple submitters, no conflicts
1172653	NM_016306.6(DNAJB11):c.70C>T (p.Arg24Ter)	DNAJB11	Pathogenic	criteria provided, multiple submitters, no conflicts
1069388	NM_014714.4(IFT140):c.2500C>T (p.Arg834Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1325702	NM_014714.4(IFT140):c.1039C>T (p.Arg347Ter)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
1328335	NM_014714.4(IFT140):c.3214C>T (p.Arg1072Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2444130	NM_014714.4(IFT140):c.1246C>T (p.Gln416Ter)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
2634278	NM_014714.4(IFT140):c.1648C>T (p.Arg550Ter)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
3033631	NM_014714.4(IFT140):c.2768+1dup	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
3376703	NM_014714.4(IFT140):c.2763del (p.Ser922fs)	IFT140	Pathogenic	criteria provided, single submitter
3376814	NM_014714.4(IFT140):c.1045del (p.Ala349fs)	IFT140	Pathogenic	criteria provided, single submitter
3376891	NM_014714.4(IFT140):c.581del (p.Leu194fs)	IFT140	Pathogenic	criteria provided, single submitter
4531521	NM_014714.4(IFT140):c.2931C>A (p.Tyr977Ter)	IFT140	Pathogenic	criteria provided, single submitter
4531525	NM_014714.4(IFT140):c.1306_1312del (p.Val436fs)	IFT140	Pathogenic	criteria provided, single submitter
580815	NM_014714.4(IFT140):c.1377G>A (p.Trp459Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
591976	NM_014714.4(IFT140):c.557G>A (p.Trp186Ter)	IFT140	Pathogenic	criteria provided, single submitter
620369	NM_014714.4(IFT140):c.2598C>G (p.Tyr866Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
867028	NM_014714.4(IFT140):c.409C>T (p.Arg137Ter)	IFT140	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
97055	NM_014714.4(IFT140):c.1380del (p.Asn460fs)	IFT140	Pathogenic	criteria provided, multiple submitters, no conflicts
1372134	NM_014714.4(IFT140):c.1147C>T (p.Gln383Ter)	LOC105371046	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374036	NC_000003.12:g.10133799_10141895del	LOC107303339	Pathogenic	criteria provided, single submitter
374180	NM_138694.4(PKHD1):c.5081dup (p.Val1695fs)	LOC126859690	Pathogenic	criteria provided, single submitter
3037303	NM_001009944.3(PKD1):c.10966del (p.Leu3656fs)	PKD1	Pathogenic	criteria provided, multiple submitters, no conflicts
3254608	NM_001009944.3(PKD1):c.4369_4370del (p.Ala1458fs)	PKD1	Pathogenic	criteria provided, multiple submitters, no conflicts
3376941	NM_001009944.3(PKD1):c.10745del (p.Pro3582fs)	PKD1	Pathogenic	criteria provided, multiple submitters, no conflicts
4072191	NM_001009944.3(PKD1):c.8778_8779del (p.Thr2927fs)	PKD1	Pathogenic	criteria provided, multiple submitters, no conflicts
4075239	NM_001009944.3(PKD1):c.9677del (p.Asn3226fs)	PKD1	Pathogenic	criteria provided, single submitter
4075242	NM_001009944.3(PKD1):c.8316_8323dup (p.Thr2775delinsSerProTer)	PKD1	Pathogenic	criteria provided, single submitter
4075245	NM_001009944.3(PKD1):c.3940dup (p.Thr1314fs)	PKD1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 49 · 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
IFT140	Definitive	Autosomal dominant	autosomal dominant polycystic kidney disease	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
HNF1B	Orphanet:1309	Medullary sponge kidney
HNF1B	Orphanet:1331	Familial prostate cancer
HNF1B	Orphanet:2578	Mayer-Rokitansky-Küster-Hauser syndrome type 2
HNF1B	Orphanet:261265	17q12 microdeletion syndrome
HNF1B	Orphanet:93111	HNF1B-related autosomal dominant tubulointerstitial kidney disease
HNF1B	Orphanet:93172	Renal dysplasia, unilateral
HNF1B	Orphanet:93173	Renal dysplasia, bilateral
HNF1B	Orphanet:97363	Unilateral multicystic dysplastic kidney
HNF1B	Orphanet:97364	Bilateral multicystic dysplastic kidney
TSC2	Orphanet:210159	Adult hepatocellular carcinoma
TSC2	Orphanet:269001	Isolated focal cortical dysplasia type IIa
TSC2	Orphanet:269008	Isolated focal cortical dysplasia type IIb
TSC2	Orphanet:538	Lymphangioleiomyomatosis
TSC2	Orphanet:805	Tuberous sclerosis complex
TSC2	Orphanet:88924	Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis
UMOD	Orphanet:88950	UMOD-related autosomal dominant tubulointerstitial kidney disease
DNAJB11	Orphanet:730	Autosomal dominant polycystic kidney disease
PCNT	Orphanet:2637	Microcephalic osteodysplastic primordial dwarfism type II
PCNT	Orphanet:808	Seckel syndrome
ALG6	Orphanet:79320	ALG6-CDG
TMEM67	Orphanet:140976	RHYNS syndrome
TMEM67	Orphanet:1454	Joubert syndrome with hepatic defect
TMEM67	Orphanet:475	Isolated Joubert syndrome
TMEM67	Orphanet:564	Meckel syndrome
TMEM67	Orphanet:84081	Senior-Boichis syndrome
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
DYNC2H1	Orphanet:474	Jeune syndrome
DYNC2H1	Orphanet:93269	Short rib-polydactyly syndrome, Majewski type
DYNC2H1	Orphanet:93270	Short rib-polydactyly syndrome, Saldino-Noonan type
DYNC2H1	Orphanet:93271	Short rib-polydactyly syndrome, Verma-Naumoff type
GANAB	Orphanet:730	Autosomal dominant polycystic kidney disease
PAX2	Orphanet:1475	Renal coloboma syndrome
PAX2	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
PAX2	Orphanet:97362	Renal hypoplasia, bilateral
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
PKHD1	Orphanet:53035	Caroli disease
PKHD1	Orphanet:731	Autosomal recessive 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

17 cohort genes, 17 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	17

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IFT140	HGNC:29077	ENSG00000187535	Q96RY7	Intraflagellar transport protein 140 homolog	gencc,clinvar
HNF1B	HGNC:11630	ENSG00000275410	P35680	Hepatocyte nuclear factor 1-beta	clinvar
TSC2	HGNC:12363	ENSG00000103197	P49815	Tuberin	clinvar
UMOD	HGNC:12559	ENSG00000169344	P07911	Uromodulin	clinvar
DNAJB11	HGNC:14889	ENSG00000090520	Q9UBS4	DnaJ homolog subfamily B member 11	clinvar
PCNT	HGNC:16068	ENSG00000160299	O95613	Pericentrin	clinvar
UNC13C	HGNC:23149	ENSG00000137766	Q8NB66	Protein unc-13 homolog C	clinvar
ALG6	HGNC:23157	ENSG00000088035	Q9Y672	Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase	clinvar
TMEM67	HGNC:28396	ENSG00000164953	Q5HYA8	Meckelin	clinvar
CC2D2A	HGNC:29253	ENSG00000048342	Q9P2K1	Coiled-coil and C2 domain-containing protein 2A	clinvar
DYNC2H1	HGNC:2962	ENSG00000187240	Q8NCM8	Cytoplasmic dynein 2 heavy chain 1	clinvar
GANAB	HGNC:4138	ENSG00000089597	Q14697	Neutral alpha-glucosidase AB	clinvar
PAX2	HGNC:8616	ENSG00000075891	Q02962	Paired box protein Pax-2	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)
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).
HNF1B	Hepatocyte nuclear factor 1-beta	Transcription factor that binds to the inverted palindrome 5’-GTTAATNATTAAC-3'.
TSC2	Tuberin	Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule…
UMOD	Uromodulin	Functions in biogenesis and organization of the apical membrane of epithelial cells of the thick ascending limb of Henle’s loop (TALH), where it promotes formation of complex filamentous gel-like structure that may play a role in the water…
DNAJB11	DnaJ homolog subfamily B member 11	As a co-chaperone for HSPA5 it is required for proper folding, trafficking or degradation of proteins.
PCNT	Pericentrin	Integral component of the filamentous matrix of the centrosome involved in the initial establishment of organized microtubule arrays in both mitosis and meiosis.
UNC13C	Protein unc-13 homolog C	May play a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway.
ALG6	Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase	Dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation.
TMEM67	Meckelin	Required for ciliary structure and function.
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.
DYNC2H1	Cytoplasmic dynein 2 heavy chain 1	May function as a motor for intraflagellar retrograde transport.
GANAB	Neutral alpha-glucosidase AB	Catalytic 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.
PAX2	Paired box protein Pax-2	Transcription factor that may have a role in kidney cell differentiation.
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: 6 · Difficult: 3 · Unknown: 8 · 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	2	3.4×	0.743
Protease	1	2.1×	0.743
Kinase	1	1.6×	0.743
Enzyme (other)	2	1.4×	0.743
Scaffold/PPI	1	1.0×	0.743
Transcription factor	2	1.0×	0.743
Other/Unknown	8	0.8×	0.834

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IFT140	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
HNF1B	Transcription factor	no		HD, HNF1b_C, HNF-1_N
TSC2	Other/Unknown	no		Rap/Ran_GAP_dom, Tuberin, ARM-like
UMOD	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, ZP_dom
DNAJB11	Other/Unknown	no		DnaJ_domain, DnaJ_C, HSP40/DnaJ_pept-bd
PCNT	Other/Unknown	no		PACT_domain, AKAP9/Pericentrin
UNC13C	Other/Unknown	no		C2_dom, PKC_DAG/PE, MUN_dom
ALG6	Enzyme (other)	yes	2.4.1.267	Glyco_trans_ALG6/ALG8
TMEM67	Other/Unknown	no		Growth_fac_rcpt_cys_sf, Meckelin
CC2D2A	Protease	yes		C2_dom, CC2D2AN-C2, C2_domain_sf
DYNC2H1	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
GANAB	Enzyme (other)	yes	3.2.1.207	Glyco_hydro_31_TIM, Gal_mutarotase_sf_dom, Glyco_hydro_b
PAX2	Transcription factor	no		Paired_dom, Homeodomain-like_sf, Pax2_C
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.

16 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)	17
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right uterine tube	4
adult mammalian kidney	3
metanephros cortex	3
renal medulla	3
secondary oocyte	3
cerebellar cortex	2
cerebellar hemisphere	2
right hemisphere of cerebellum	2
calcaneal tendon	2
bronchial epithelial cell	2
ventricular zone	2
left lobe of thyroid gland	1
right lobe of thyroid gland	1
kidney	1
adult organism	1
body of pancreas	1
bone marrow cell	1
vermiform appendix	1
body of tongue	1
gastrocnemius	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFT140	214	ubiquitous	marker	right uterine tube, right lobe of thyroid gland, left lobe of thyroid gland
HNF1B	74	broad	marker	metanephros cortex, adult mammalian kidney, kidney
TSC2	282	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
UMOD	104	tissue_specific	marker	renal medulla, adult organism, adult mammalian kidney
DNAJB11	141	ubiquitous	marker	vermiform appendix, body of pancreas, bone marrow cell
PCNT	283	ubiquitous	marker	gastrocnemius, body of tongue, hindlimb stylopod muscle
UNC13C	174	broad	marker	secondary oocyte, oocyte, endothelial cell
ALG6	268	ubiquitous	yes	secondary oocyte, primordial germ cell in gonad, upper leg skin
TMEM67	203	ubiquitous	marker	buccal mucosa cell, right uterine tube, calcaneal tendon
CC2D2A	247	ubiquitous	marker	right uterine tube, bronchial epithelial cell, bronchus
DYNC2H1	230	ubiquitous	marker	secondary oocyte, bronchial epithelial cell, right uterine tube
GANAB	293	ubiquitous	marker	stromal cell of endometrium, islet of Langerhans, ventricular zone
PAX2	92	broad	marker	metanephros cortex, renal medulla, adult mammalian kidney
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: 14.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TSC2	4,135
PCNT	3,934
GANAB	3,817
DNAJB11	3,387
PAX2	2,208
PRKD1	2,131
UMOD	2,084
DYNC2H1	1,885
HNF1B	1,660
PKD2	1,644

Intra-cohort edges

A	B	Sources
CC2D2A	TMEM67	string_interaction
DNAJB11	GANAB	string_interaction
DYNC2H1	IFT140	string_interaction
GANAB	PKD1	string_interaction
HNF1B	PKHD1	string_interaction
HNF1B	UMOD	string_interaction
PKD1	PKD2	biogrid_interaction, intact, string_interaction
PKD1	PKHD1	string_interaction
PKD1	PRKD1	string_interaction
PKD1	TSC2	string_interaction
PKD2	PKHD1	string_interaction
PKD2	PRKD1	string_interaction
PKHD1	PRKD1	string_interaction
PKHD1	UMOD	string_interaction

Structural data

PDB: 9 · AlphaFold-only: 8 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PKD2	Q13563	31
PKD1	P98161	13
UMOD	P07911	10
IFT140	Q96RY7	4
DYNC2H1	Q8NCM8	4
HNF1B	P35680	3
TSC2	P49815	2
GANAB	Q14697	2
TMEM67	Q5HYA8	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ALG6	Q9Y672	93.08
DNAJB11	Q9UBS4	84.34
CC2D2A	Q9P2K1	69.46
PRKD1	Q15139	68.99
UNC13C	Q8NB66	61.64
PAX2	Q02962	61.52
PCNT	O95613
PKHD1	P08F94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 51. Enrichment computed across 17 evidence-associated genes (15 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 15 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Nephron development	2	117.1×	0.006	HNF1B, PAX2
VxPx cargo-targeting to cilium	2	69.2×	0.006	PKD1, PKD2
Anchoring of the basal body to the plasma membrane	3	22.6×	0.006	PCNT, TMEM67, CC2D2A
Defective ALG6 causes CDG-1c	1	761.3×	0.017	ALG6
Intraflagellar transport	2	26.7×	0.025	IFT140, DYNC2H1
Hedgehog ‘off’ state	2	23.8×	0.026	IFT140, DYNC2H1
Inhibition of TSC complex formation by AKT (PKB)	1	152.3×	0.046	TSC2
Maturation of spike protein	1	126.9×	0.046	GANAB
Cilium Assembly	2	14.5×	0.046	TMEM67, CC2D2A
Regulation of gene expression in early pancreatic precursor cells	1	95.2×	0.049	HNF1B
Formation of intermediate mesoderm	1	95.2×	0.049	PAX2
AKT phosphorylates targets in the cytosol	1	54.4×	0.067	TSC2
Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells	1	47.6×	0.067	HNF1B
Calnexin/calreticulin cycle	1	47.6×	0.067	GANAB
Diseases associated with N-glycosylation of proteins	1	42.3×	0.067	ALG6
Formation of the nephric duct	1	42.3×	0.067	PAX2
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	1	40.1×	0.067	HNF1B
Organelle biogenesis and maintenance	2	8.8×	0.067	TMEM67, CC2D2A
Asparagine N-linked glycosylation	2	8.0×	0.067	UMOD, ALG6
Chaperone Mediated Autophagy	1	33.1×	0.072	PCNT
Formation of the ureteric bud	1	33.1×	0.072	PAX2
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	1	28.2×	0.077	GANAB
Constitutive Signaling by AKT1 E17K in Cancer	1	28.2×	0.077	TSC2
Energy dependent regulation of mTOR by LKB1-AMPK	1	26.2×	0.080	TSC2
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	22.4×	0.088	GANAB
Late endosomal microautophagy	1	21.8×	0.088	PCNT
Developmental Lineage of Pancreatic Acinar Cells	1	20.0×	0.092	HNF1B
Sphingolipid de novo biosynthesis	1	19.0×	0.093	PRKD1
Maturation of spike protein	1	17.7×	0.096	GANAB
TBC/RABGAPs	1	17.3×	0.096	TSC2

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
metanephric ascending thin limb development	3	743.5×	1e-06	UMOD, PKD1, PKD2
cilium assembly	6	26.0×	1e-05	IFT140, PCNT, TMEM67, CC2D2A, DYNC2H1, PKHD1
kidney development	5	41.3×	1e-05	HNF1B, CC2D2A, DYNC2H1, PKD1, PKHD1
determination of left/right symmetry	4	60.1×	4e-05	IFT140, CC2D2A, DYNC2H1, PKD2
mesonephric tubule development	2	991.3×	6e-05	PKD1, PKD2
branching morphogenesis of an epithelial tube	3	129.3×	8e-05	HNF1B, PKD1, PKHD1
heart development	5	23.2×	8e-05	IFT140, TSC2, CC2D2A, PKD1, PKD2
negative regulation of mesenchymal cell apoptotic process involved in metanephros development	2	660.9×	1e-04	HNF1B, PAX2
metanephric distal convoluted tubule development	2	495.6×	2e-04	UMOD, PAX2
mesonephric duct development	2	396.5×	3e-04	PKD1, PKD2
pronephros development	2	283.2×	5e-04	HNF1B, PAX2
metanephric mesenchyme development	2	283.2×	5e-04	PAX2, PKD2
non-motile cilium assembly	3	51.3×	6e-04	IFT140, CC2D2A, DYNC2H1
genitalia development	2	198.3×	9e-04	HNF1B, PKD1
metanephric collecting duct development	2	198.3×	9e-04	PAX2, PKD1
placenta blood vessel development	2	165.2×	0.001	PKD1, PKD2
detection of mechanical stimulus	2	141.6×	0.002	PKD1, PKD2
intraciliary retrograde transport	2	132.2×	0.002	IFT140, DYNC2H1
neural tube closure	3	33.0×	0.002	TSC2, CC2D2A, PAX2
protein heterotetramerization	2	123.9×	0.002	PKD1, PKD2
embryonic brain development	2	94.4×	0.003	IFT140, CC2D2A
intracellular calcium ion homeostasis	3	25.6×	0.003	UMOD, PKD2, PKHD1
embryonic placenta development	2	90.1×	0.003	PKD1, PKD2
neural tube development	2	62.0×	0.006	PKD1, PKD2
spinal cord development	2	60.1×	0.006	PKD1, PKD2
regulation of pronephros size	1	991.3×	0.008	HNF1B
pronephric nephron tubule development	1	991.3×	0.008	HNF1B
citric acid secretion	1	991.3×	0.008	UMOD
ureteric bud elongation	1	991.3×	0.008	HNF1B
obsolete negative regulation of mesenchymal cell apoptotic process involved in mesonephric nephron morphogenesis	1	991.3×	0.008	HNF1B

Therapeutics

Drugs indicated or in trials for this disease

No drug has an approved disease-direct ChEMBL indication for this disease.

1 drug in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Venglustat	Phase 3

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 15

Druggability breadth: 7 of 17 evidence-associated genes (41%) 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
GANAB	1	2
IFT140	0	0
HNF1B	0	0
TSC2	0	0
UMOD	0	0
DNAJB11	0	0
PCNT	0	0
UNC13C	0	0
ALG6	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
DUVOGLUSTAT	2	GANAB
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
GANAB	38	Binding:32, Functional:6
PKD1	27	Binding:27
PKD2	12	Binding:12
TSC2	1	Binding:1
DNAJB11	1	Binding:1
PAX2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALG6	2.4.1.267	dolichyl-P-Glc:Man9GlcNAc2-PP-dolichol alpha-1,3-glucosyltransferase
GANAB	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: 17; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

27 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
DUVOGLUSTAT	2	GANAB
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	1	GANAB
C	Druggable family + PDB, no drug	1	PKD1
D	Druggable family + AlphaFold only, no drug	3	ALG6, CC2D2A, PKHD1
E	Difficult family or no structure, no drug	11	IFT140, HNF1B, TSC2, UMOD, DNAJB11, PCNT, UNC13C, TMEM67, DYNC2H1, PAX2 (+1 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PKD1	27	PRKD1
IFT140	0	—
HNF1B	0	—
TSC2	1	—
UMOD	0	—
DNAJB11	1	—
PCNT	0	—
UNC13C	0	—
ALG6	0	—
TMEM67	0	—
CC2D2A	0	—
DYNC2H1	0	—
PAX2	1	—
PKD2	12	—
PKHD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3
PHASE2	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04705051	PHASE3	TERMINATED	Long-term Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) With Venglustat
NCT02684435	PHASE2	COMPLETED	Contrast-enhanced Ultrasound of the Kidney
NCT03196076	PHASE2	COMPLETED	Contrast-enhanced Ultrasound for Complex Kidney Lesion Diagnosis in Patients With CKD Extension
NCT04670887	Not specified	NOT_YET_RECRUITING	Comparison of Surgery and Active Surveillance in the Treatment of Bosniak III Renal Cysts
NCT02371551	Not specified	COMPLETED	Evaluation of Complex Renal Cyst With CEUS/Functional MRI Versus CT
NCT05286632	Not specified	COMPLETED	KidneYou - Innovative Digital Therapy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
VENGLUSTAT	3	1