Biliary tract disorder

Summary

Biliary tract disorder (MONDO:0004868) is a disease (an umbrella term covering 15 Mondo subtypes) with 7 cohort genes (15 GWAS associations across 30 studies).

At a glance

• Umbrella term: 15 Mondo subtypes
• Cohort genes: 7
• GWAS associations: 15
• ClinVar variants: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	biliary tract disorder
Mondo ID	MONDO:0004868
EFO	EFO:0009534
MeSH	D001660
DOID	DOID:9741
SNOMED CT	105997008
UMLS	C0549613
MedGen	108201
Anatomy (UBERON)	UBERON:0001173
Is cancer (heuristic)	no

Also known as: biliary tree disease · biliary tree disease or disorder · disease of biliary tree · disease or disorder of biliary tree · disorder of biliary tree

Data availability: 20 ClinVar variants · 15 GWAS associations (30 studies).

Disease family

An umbrella term covering 15 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › hepatobiliary disorder › biliary tract disorder

Related subtypes (3): hepatobiliary neoplasm, liver disorder, gallbladder disorder

Subtypes (15): bile duct disorder, biliary tract neoplasm, gallstones, primary biliary cholangitis, bile reflux, postcholecystectomy syndrome, Alagille syndrome, isolated agenesis of gallbladder, cholelithiasis, ketamine-induced biliary dilatation, follicular cholangitis and pancreatitis, idiopathic ductopenia, Caroli syndrome, isolated congenital hepatic fibrosis, Rokitansky-Aschoff sinuses of the gallbladder

Genetics & variants

GWAS landscape

15 GWAS associations across 30 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
rs738409	3e-13	PNPLA3	C	0.23
rs148412598	6e-13	PKD2L1	C	2.69
rs184129359	9e-13	RNU6-356P - SFRP1	G	2.24
rs3747207	2e-12	PNPLA3	G	0.19
rs545262390	5e-12	NRXN1	G	3.81
rs545082824	6e-12	LINC02150	A	3.28
rs189285587	1e-11	FDFT1	A	1.57
rs190395760	2e-11	RNU7-156P - MIR5197	G	3.18
rs545019709	3e-11	SEPHS1P7 - RNU2-41P	C	2.94
rs559378663	3e-11	SLC39A8	T	2.53
rs535647957	4e-11	CPNE5	G	2.06
rs75843875	4e-11	ICE1 - HMGB3P3	C	2.3
rs568971618	4e-11	SPA17P1 - ZNF503	C	1.86
rs79822445	5e-08	RPSAP20 - LINC01767	?
rs141493750	4e-07	LINC02098 - ETS1	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90478475	Verma A	2024	9,972	427,921	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473883	UK Biobank Whole-Genome Sequencing Consortium	2025	5,795	452,645	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90436387	Zhou W	2018	3,892	391,307	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90652107	Liu TY	2025	3,000	224,366	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90080308	Backman JD	2021	2,749	384,669	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084294	Backman JD	2021	2,749	384,669	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90476105	Verma A	2024	2,711	442,412	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90478474	Verma A	2024	2,583	115,771	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480864	Verma A	2024	2,583	115,771	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90478479	Verma A	2024	1,813	446,019	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	13

MAF distribution

Bucket	Variants
common (>=0.05)	2
low_freq (0.01-0.05)	0
rare (<0.01)	11
unknown	2

Functional consequences

Consequence	Count
intron_variant	8
intergenic_variant	5
missense_variant	2

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs738409	22	43928847	C>A,G,T	0.225	missense_variant	PNPLA3	3e-13	Tier 1: coding
rs148412598	10	100297481	C>A,T	0	missense_variant	PKD2L1	6e-13	Tier 1: coding
rs184129359	8	41145490	G>A,T	0	intergenic_variant	RNU6-356P - SFRP1	9e-13	Tier 4: intronic/intergenic
rs3747207	22	43928975	G>A,C,T	0.219	intron_variant	PNPLA3	2e-12	Tier 4: intronic/intergenic
rs545262390	2	50941937	G>A,C	0	intron_variant	NRXN1	5e-12	Tier 4: intronic/intergenic
rs545082824	5	16437138	A>C	0.001	intron_variant	LINC02150	6e-12	Tier 4: intronic/intergenic
rs189285587	8	11821936	A>G,T	0.004	intron_variant	FDFT1	1e-11	Tier 4: intronic/intergenic
rs190395760	5	143598638	G>A	0	intergenic_variant	RNU7-156P - MIR5197	2e-11	Tier 4: intronic/intergenic
rs545019709	2	114359344	C>T	0.001	intergenic_variant	SEPHS1P7 - RNU2-41P	3e-11	Tier 4: intronic/intergenic
rs559378663	4	102309954	T>A,C	0	intron_variant	SLC39A8	3e-11	Tier 4: intronic/intergenic
rs535647957	6	36792575	G>A,C	0.001	intron_variant	CPNE5	4e-11	Tier 4: intronic/intergenic
rs75843875	5	5896893	C>T	0.003	intergenic_variant	ICE1 - HMGB3P3	4e-11	Tier 4: intronic/intergenic
rs568971618	10	75390050	C>T	0.001	intron_variant	SPA17P1 - ZNF503	4e-11	Tier 4: intronic/intergenic
rs79822445	1	56406649	G>A,T		intron_variant	RPSAP20 - LINC01767	5e-08	Tier 4: intronic/intergenic
rs141493750	11	128360558	T>C		intergenic_variant	LINC02098 - ETS1	4e-07	Tier 4: intronic/intergenic

ClinVar germline variants

20 retrieved; paginated sample, class counts are floors:

7 conflicting classifications of pathogenicity, 6 pathogenic/likely pathogenic, 3 uncertain significance, 3 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
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
4075243	NM_001009944.3(PKD1):c.6517del (p.Val2173fs)	PKD1	Pathogenic	criteria provided, single submitter
562248	NM_000297.4(PKD2):c.1249C>T (p.Arg417Ter)	PKD2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
357423	NM_138694.4(PKHD1):c.8870T>C (p.Ile2957Thr)	PKHD1	Pathogenic	criteria provided, multiple submitters, no conflicts
406891	NM_138694.4(PKHD1):c.664A>G (p.Ile222Val)	PKHD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
488579	NM_138694.4(PKHD1):c.10174C>T (p.Gln3392Ter)	PKHD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
636580	NM_138694.4(PKHD1):c.3467C>T (p.Ser1156Leu)	PKHD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1255633	NM_007214.5(SEC63):c.292C>T (p.Arg98Ter)	SEC63	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3592889	NM_007214.5(SEC63):c.1786_1787del (p.Asp596fs)	SEC63	Likely pathogenic	criteria provided, multiple submitters, no conflicts
636675	NM_001009944.3(PKD1):c.974A>G (p.Tyr325Cys)	PKD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
811490	NM_001009944.3(PKD1):c.9157G>A (p.Ala3053Thr)	PKD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
167473	NM_138694.4(PKHD1):c.10926G>A (p.Met3642Ile)	PKHD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
188746	NM_138694.4(PKHD1):c.3766del (p.Gln1256fs)	PKHD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
377018	NM_138694.4(PKHD1):c.9530T>C (p.Ile3177Thr)	PKHD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
377354	NM_138694.4(PKHD1):c.2414C>T (p.Pro805Leu)	PKHD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2571945	NM_007214.5(SEC63):c.1586dup (p.Lys530fs)	SEC63	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3377197	NM_198334.3(GANAB):c.2531T>C (p.Leu844Pro)	GANAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
4074894	NM_138694.4(PKHD1):c.304G>A (p.Glu102Lys)	PKHD1	Uncertain significance	criteria provided, single submitter
4075005	NM_001289104.2(PRKCSH):c.403C>T (p.Arg135Cys)	PRKCSH	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SEC63	Orphanet:2924	Isolated polycystic liver 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
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
PRKCSH	Orphanet:2924	Isolated polycystic liver disease

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SEC63	HGNC:21082	ENSG00000025796	Q9UGP8	Translocation protein SEC63 homolog	clinvar
GANAB	HGNC:4138	ENSG00000089597	Q14697	Neutral alpha-glucosidase AB	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
PRKCSH	HGNC:9411	ENSG00000130175	P14314	Glucosidase 2 subunit beta	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).
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.
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…
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.

Protein-family classification

Druggable: 5 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.71

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	8.3×	0.088
Enzyme (other)	2	3.4×	0.220
Kinase	1	4.0×	0.302
Other/Unknown	2	0.5×	0.968

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SEC63	Other/Unknown	no		DnaJ_domain, Sec63-dom, Ig_E-set
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
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
PRKCSH	Enzyme (other)	yes	3.2.1.207	EF_hand_dom, Man6P_isomerase_rcpt-bd_dom_sf, EF-hand-dom_pair

Expression context

Cohort genes with no expression data: 0.

7 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
stromal cell of endometrium	2
ventricular zone	2
body of pancreas	1
colonic epithelium	1
parotid gland	1
islet of Langerhans	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
blood vessel layer	1
calcaneal tendon	1
saphenous vein	1
kidney epithelium	1
metanephros cortex	1
renal medulla	1
seminal vesicle	1
thoracic aorta	1
olfactory bulb	1
type B pancreatic cell	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
GANAB	293	ubiquitous	marker	stromal cell of endometrium, islet of Langerhans, ventricular zone
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
PRKCSH	288	ubiquitous	marker	stromal cell of endometrium, type B pancreatic cell, olfactory bulb

Protein interactions among cohort

Intra-cohort edges: 15.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GANAB	3,817
SEC63	3,355
PRKD1	2,131
PRKCSH	1,922
PKD2	1,644
PKD1	1,370
PKHD1	1,211

Intra-cohort edges

A	B	Sources
GANAB	PKD1	string_interaction
GANAB	PRKCSH	intact, string_interaction
GANAB	SEC63	string_interaction
PKD1	PKD2	biogrid_interaction, intact, string_interaction
PKD1	PKHD1	string_interaction
PKD1	PRKCSH	string_interaction
PKD1	PRKD1	string_interaction
PKD1	SEC63	string_interaction
PKD2	PKHD1	string_interaction
PKD2	PRKCSH	string_interaction
PKD2	PRKD1	string_interaction
PKHD1	PRKCSH	string_interaction
PKHD1	PRKD1	string_interaction
PRKCSH	PRKD1	string_interaction
PRKCSH	SEC63	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PKD2	Q13563	31
PKD1	P98161	13
GANAB	Q14697	2
PRKCSH	P14314	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SEC63	Q9UGP8	77.71
PRKD1	Q15139	68.99
PKHD1	P08F94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 7 evidence-associated genes (5 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 5 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	2	761.3×	3e-05	GANAB, PRKCSH
Calnexin/calreticulin cycle	2	285.5×	1e-04	GANAB, PRKCSH
VxPx cargo-targeting to cilium	2	207.6×	2e-04	PKD1, PKD2
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	2	169.2×	2e-04	GANAB, PRKCSH
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	2	134.3×	2e-04	GANAB, PRKCSH
Maturation of spike protein	2	106.2×	3e-04	GANAB, PRKCSH
Advanced glycosylation endproduct receptor signaling	1	142.8×	0.013	PRKCSH
Sphingolipid de novo biosynthesis	1	57.1×	0.028	PRKD1
Sphingolipid metabolism	1	33.6×	0.043	PRKD1
Post-translational protein phosphorylation	1	20.0×	0.064	PRKCSH
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	17.3×	0.067	PRKCSH
Metabolism of lipids	1	6.3×	0.161	PRKD1
Metabolism	1	2.3×	0.362	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 7 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	126.7×	2e-06	SEC63, PKD1, PKD2, PRKCSH
nitrogen cycle metabolic process	2	2407.4×	8e-06	SEC63, PKD1
mesonephric tubule development	2	2407.4×	8e-06	PKD1, PKD2
metanephric ascending thin limb development	2	1203.7×	3e-05	PKD1, PKD2
mesonephric duct development	2	963.0×	5e-05	PKD1, PKD2
placenta blood vessel development	2	401.2×	3e-04	PKD1, PKD2
detection of mechanical stimulus	2	343.9×	3e-04	PKD1, PKD2
protein heterotetramerization	2	300.9×	3e-04	PKD1, PKD2
embryonic placenta development	2	218.9×	5e-04	PKD1, PKD2
N-glycan processing	2	209.3×	5e-04	GANAB, PRKCSH
branching morphogenesis of an epithelial tube	2	209.3×	5e-04	PKD1, PKHD1
neural tube development	2	150.5×	9e-04	PKD1, PKD2
spinal cord development	2	145.9×	9e-04	PKD1, PKD2
regulation of cell adhesion	2	87.5×	0.002	PKD1, PKHD1
cell surface receptor signaling pathway via JAK-STAT	2	83.0×	0.003	PKD1, PKD2
metanephric cortex development	1	2407.4×	0.003	PKD2
metanephric cortical collecting duct development	1	2407.4×	0.003	PKD2
metanephric distal tubule development	1	2407.4×	0.003	PKD2
metanephric distal tubule morphogenesis	1	2407.4×	0.003	PKD1
regulation of cholangiocyte proliferation	1	2407.4×	0.003	PKHD1
calcium ion transmembrane transport	2	60.2×	0.003	PKD1, PKD2
calcium ion transport	2	51.8×	0.004	PKD1, PKD2
regulation of skeletal muscle contraction by modulation of calcium ion sensitivity of myofibril	1	1203.7×	0.005	PRKD1
renal artery morphogenesis	1	1203.7×	0.005	PKD2
metanephric smooth muscle tissue development	1	1203.7×	0.005	PKD2
intracellular calcium ion homeostasis	2	41.5×	0.006	PKD2, PKHD1
kidney development	2	40.1×	0.006	PKD1, PKHD1
detection of nodal flow	1	802.5×	0.006	PKD2
lymph vessel morphogenesis	1	802.5×	0.006	PKD1
cellular response to hydrostatic pressure	1	802.5×	0.006	PKD2

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Fosgemcitabine Palabenamide	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Gemcitabine.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 5

Druggability breadth: 6 of 7 evidence-associated genes (86%) 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
SEC63	0	0
PKD1	0	0
PKD2	0	0
PKHD1	0	0
PRKCSH	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
SEC63	1	Binding:1
PRKCSH	1	Binding:1

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
PRKCSH	3.2.1.207	mannosyl-oligosaccharide alpha-1,3-glucosidase

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: 7; 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	2	PKD1, PRKCSH
D	Druggable family + AlphaFold only, no drug	1	PKHD1
E	Difficult family or no structure, no drug	2	SEC63, PKD2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PKD1	27	PRKD1
PRKCSH	1	GANAB
SEC63	1	—
PKD2	12	—
PKHD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.