Polycystic kidney disease 3 with or without polycystic liver disease

Summary

Polycystic kidney disease 3 with or without polycystic liver disease (MONDO:0010916) is a disease caused by GANAB (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: GANAB (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 189

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	polycystic kidney disease 3 with or without polycystic liver disease
Mondo ID	MONDO:0010916
OMIM	600666
DOID	DOID:0110860
UMLS	C3887964
MedGen	854672
GARD	0018598
Is cancer (heuristic)	no

Also known as: APKD3 · Apkd3 · autosomal dominant polycystic kidney disease caused by mutation in GANAB · GANAB autosomal dominant polycystic kidney disease · PKD3 · Pkd3 · polycystic kidney disease 3 with or without polycystic liver disease · polycystic kidney disease 3, autosomal dominant · polycystic kidney disease type 3 · polycystic kidney disease, adult, type 3 · polycystic kidney disease, type 3

Data availability: 189 ClinVar variants · 4 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 3 with or without polycystic liver disease

Related subtypes (6): polycystic kidney disease 1, 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

189 retrieved; paginated sample, class counts are floors:

115 uncertain significance, 29 likely pathogenic, 17 conflicting classifications of pathogenicity, 10 pathogenic/likely pathogenic, 8 benign/likely benign, 8 pathogenic, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1327722	NM_198334.3(GANAB):c.490C>T (p.Arg164Ter)	GANAB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1711179	NM_198334.3(GANAB):c.2516C>T (p.Thr839Ile)	GANAB	Pathogenic	no assertion criteria provided
2440412	NM_198334.3(GANAB):c.2434C>T (p.Arg812Ter)	GANAB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
253129	NM_198334.3(GANAB):c.1848_1849del (p.Asp618fs)	GANAB	Pathogenic	criteria provided, multiple submitters, no conflicts
253133	NM_198334.3(GANAB):c.152_153del (p.Arg51fs)	GANAB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2691267	NM_198334.3(GANAB):c.1936+1del	GANAB	Pathogenic	no assertion criteria provided
3236796	NM_198334.3(GANAB):c.1310_1320del (p.Arg437fs)	GANAB	Pathogenic	criteria provided, single submitter
3254987	NM_198334.3(GANAB):c.1495G>T (p.Glu499Ter)	GANAB	Pathogenic	criteria provided, single submitter
3342290	NM_198334.3(GANAB):c.199_200del (p.Leu67fs)	GANAB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3599892	NM_198334.3(GANAB):c.516_517delinsAT (p.Arg173Ter)	GANAB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3900707	NM_198334.3(GANAB):c.1240C>T (p.Gln414Ter)	GANAB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
590351	NM_198334.3(GANAB):c.2443C>T (p.Arg815Ter)	GANAB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
590352	NM_198334.3(GANAB):c.2590C>T (p.Arg864Ter)	GANAB	Pathogenic	criteria provided, single submitter
810838	NC_000011.10:g.62628412_62655064del	GANAB	Pathogenic	no assertion criteria provided
562302	NM_001009944.3(PKD1):c.2180T>C (p.Leu727Pro)	PKD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
620580	NM_001009944.3(PKD1):c.7111del (p.Val2371fs)	PKD1	Pathogenic	criteria provided, multiple submitters, no conflicts
623209	NM_001009944.3(PKD1):c.6916-9G>A	PKD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8206	NM_001009944.3(PKD1):c.2534T>C (p.Leu845Ser)	PKD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1691315	NM_198334.3(GANAB):c.560+444A>C	GANAB	Likely pathogenic	criteria provided, single submitter
1803160	NM_198334.3(GANAB):c.1429T>C (p.Tyr477His)	GANAB	Likely pathogenic	criteria provided, single submitter
2505230	NM_198334.3(GANAB):c.517C>T (p.Arg173Ter)	GANAB	Likely pathogenic	criteria provided, single submitter
253132	NM_198334.3(GANAB):c.2449C>T (p.Arg817Trp)	GANAB	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2575050	NM_198334.3(GANAB):c.677G>A (p.Trp226Ter)	GANAB	Likely pathogenic	no assertion criteria provided
2575052	NM_198334.3(GANAB):c.644_645del (p.Gln215fs)	GANAB	Likely pathogenic	criteria provided, single submitter
3068388	NM_198334.3(GANAB):c.12_38+2del	GANAB	Likely pathogenic	criteria provided, single submitter
3236803	NM_198334.3(GANAB):c.174_175del (p.Pro59fs)	GANAB	Likely pathogenic	criteria provided, single submitter
3256692	NM_198334.3(GANAB):c.842dup (p.Asn281fs)	GANAB	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3599837	NM_198334.3(GANAB):c.2496_2502del (p.Ser835fs)	GANAB	Likely pathogenic	criteria provided, single submitter
3599843	NM_198334.3(GANAB):c.2336_2339del (p.Ile779fs)	GANAB	Likely pathogenic	criteria provided, single submitter
3599844	NM_198334.3(GANAB):c.2330_2331delinsG (p.Tyr777fs)	GANAB	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 5 · 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
GANAB	Definitive	Autosomal dominant	polycystic kidney disease 3 with or without polycystic liver disease	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GANAB	Orphanet:730	Autosomal dominant polycystic kidney 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

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GANAB	HGNC:4138	ENSG00000089597	Q14697	Neutral alpha-glucosidase AB	gencc,clinvar
PKD1	HGNC:9008	ENSG00000008710	P98161	Polycystin-1	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)
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.
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…

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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	9.7×	0.157
Kinase	1	9.2×	0.157
Enzyme (other)	1	4.0×	0.230

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GANAB	Enzyme (other)	yes	3.2.1.207	Glyco_hydro_31_TIM, Gal_mutarotase_sf_dom, Glyco_hydro_b
PKD1	Antibody/Immunoglobulin	yes		GPS, LRRNT, PC1
PRKD1	Kinase	yes	2.7.11.13	Prot_kinase_dom, PH_domain, PKC_DAG/PE

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
islet of Langerhans	1
stromal cell of endometrium	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
seminal vesicle	1
thoracic aorta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GANAB	293	ubiquitous	marker	stromal cell of endometrium, islet of Langerhans, ventricular zone
PKD1	290		marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
PRKD1	239	ubiquitous	marker	ventricular zone, seminal vesicle, thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GANAB	3,817
PRKD1	2,131
PKD1	1,370

Intra-cohort edges

A	B	Sources
GANAB	PKD1	string_interaction
PKD1	PRKD1	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PKD1	P98161	13
GANAB	Q14697	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRKD1	Q15139	68.99

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Maturation of spike protein	1	634.4×	0.016	GANAB
Calnexin/calreticulin cycle	1	237.9×	0.016	GANAB
VxPx cargo-targeting to cilium	1	173.0×	0.016	PKD1
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	1	141.0×	0.016	GANAB
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	112.0×	0.016	GANAB
Sphingolipid de novo biosynthesis	1	95.2×	0.016	PRKD1
Maturation of spike protein	1	88.5×	0.016	GANAB
Sphingolipid metabolism	1	56.0×	0.022	PRKD1
Metabolism of lipids	1	10.5×	0.102	PRKD1
Metabolism	1	3.9×	0.237	PRKD1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
metanephric distal tubule morphogenesis	1	5617.3×	0.008	PKD1
regulation of skeletal muscle contraction by modulation of calcium ion sensitivity of myofibril	1	2808.7×	0.008	PRKD1
nitrogen cycle metabolic process	1	2808.7×	0.008	PKD1
mesonephric tubule development	1	2808.7×	0.008	PKD1
lymph vessel morphogenesis	1	1872.4×	0.008	PKD1
metanephric proximal tubule development	1	1872.4×	0.008	PKD1
calcium-independent cell-matrix adhesion	1	1404.3×	0.008	PKD1
cellular response to norepinephrine stimulus	1	1404.3×	0.008	PRKD1
metanephric ascending thin limb development	1	1404.3×	0.008	PKD1
mesonephric duct development	1	1123.5×	0.008	PKD1
positive regulation of sarcomere organization	1	936.2×	0.008	PRKD1
mitocytosis	1	936.2×	0.008	PKD1
lung epithelium development	1	702.2×	0.009	PKD1
cellular response to hydroperoxide	1	702.2×	0.009	PRKD1
regulation of integrin-mediated signaling pathway	1	702.2×	0.009	PRKD1
response to fluid shear stress	1	624.1×	0.009	PKD1
genitalia development	1	561.7×	0.009	PKD1
metanephric collecting duct development	1	561.7×	0.009	PKD1
regulation of keratinocyte proliferation	1	510.7×	0.009	PRKD1
Golgi vesicle transport	1	510.7×	0.009	PRKD1
positive regulation of peptide hormone secretion	1	510.7×	0.009	PRKD1
placenta blood vessel development	1	468.1×	0.009	PKD1
cellular response to endothelin	1	468.1×	0.009	PRKD1
positive regulation of cell size	1	432.1×	0.009	PRKD1
cellular response to phorbol 13-acetate 12-myristate	1	432.1×	0.009	PRKD1
detection of mechanical stimulus	1	401.2×	0.009	PKD1
transepithelial transport	1	401.2×	0.009	PRKD1
protein heterotetramerization	1	351.1×	0.010	PKD1
positive regulation of endothelial cell chemotaxis	1	330.4×	0.010	PRKD1
negative regulation of endocytosis	1	312.1×	0.010	PRKD1

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 3 evidence-associated genes (100%) 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
PKD1	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): 2.

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

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
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: 3; 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	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PKD1	27	PRKD1

Clinical trials & evidence

Clinical trials

Clinical trials: 0.