Autosomal dominant polycystic liver disease

Summary

Autosomal dominant polycystic liver disease (MONDO:0000447) is a disease (an umbrella term covering 5 Mondo subtypes) with 23 cohort genes and 17 clinical trials. The dominant Reactome pathway is Developmental Lineage of Multipotent Pancreatic Progenitor Cells (3 cohort genes). Top therapeutic interventions include lanreotide, octreotide, and ursodiol.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 23
• ClinVar variants: 182
• Phenotypes (HPO): 22
• Clinical trials: 17

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	1	Europe	Validated

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0002240	Hepatomegaly	Very frequent (80-99%)
HP:0003270	Abdominal distention	Very frequent (80-99%)
HP:0006557	Polycystic liver disease	Very frequent (80-99%)
HP:0005562	Multiple renal cysts	Frequent (30-79%)
HP:0033842	Early satiety	Frequent (30-79%)
HP:0000952	Jaundice	Occasional (5-29%)
HP:0001654	Abnormal heart valve morphology	Occasional (5-29%)
HP:0001732	Abnormality of the pancreas	Occasional (5-29%)
HP:0002020	Gastroesophageal reflux	Occasional (5-29%)
HP:0002027	Abdominal pain	Occasional (5-29%)
HP:0002086	Abnormality of the respiratory system	Occasional (5-29%)
HP:0002093	Respiratory insufficiency	Occasional (5-29%)
HP:0002094	Dyspnea	Occasional (5-29%)
HP:0002239	Gastrointestinal hemorrhage	Occasional (5-29%)
HP:0002617	Dilatation	Occasional (5-29%)
HP:0003155	Elevated circulating alkaline phosphatase concentration	Occasional (5-29%)
HP:0003418	Back pain	Occasional (5-29%)
HP:0003573	Increased total bilirubin	Occasional (5-29%)
HP:0004944	Dilatation of the cerebral artery	Occasional (5-29%)
HP:0008872	Feeding difficulties in infancy	Occasional (5-29%)
HP:0010741	Pedal edema	Occasional (5-29%)
HP:0030948	Elevated gamma-glutamyltransferase level	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant polycystic liver disease
Mondo ID	MONDO:0000447
OMIM	174050
Orphanet	2924
DOID	DOID:0050770
ICD-10-CM	Q44.6
ICD-11	1361740083, 423904268
NCIT	C82833
SNOMED CT	72925005
UMLS	C0158683
MedGen	56388
GARD	0009457
MedDRA	10010427, 10048834, 10083939
Is cancer (heuristic)	no

Also known as: AD polycystic liver disease · ADPLD · isolated congenital polycystic liver disease · isolated polycystic liver disease · PCLD · polycystic liver disease

Data availability: 182 ClinVar variants · 2 GenCC gene-disease records · 1 HPO phenotype.

Disease family

An umbrella term covering 5 Mondo subtypes.

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

Related subtypes (191): cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Subtypes (5): polycystic liver disease 1, polycystic liver disease 2, polycystic liver disease 4 with or without kidney cysts, polycystic liver disease 3 with or without kidney cysts, SEC61B-related polycystic liver disease

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

182 retrieved; paginated sample, class counts are floors:

58 uncertain significance, 32 pathogenic, 29 likely pathogenic, 25 conflicting classifications of pathogenicity, 17 pathogenic/likely pathogenic, 15 likely benign, 4 benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2506352	NM_024079.5(ALG8):c.160C>T (p.Gln54Ter)	ALG8	Pathogenic	no assertion criteria provided
2506353	NM_024079.5(ALG8):c.272del (p.Asn91fs)	ALG8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2506354	NM_024079.5(ALG8):c.371del (p.Cys124fs)	ALG8	Pathogenic	no assertion criteria provided
2506356	NM_024079.5(ALG8):c.1501del (p.Ala500_Val501insTer)	ALG8	Pathogenic	no assertion criteria provided
280116	NM_024079.5(ALG8):c.1090C>T (p.Arg364Ter)	ALG8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
956334	NM_024079.5(ALG8):c.981dup (p.Val328fs)	ALG8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
631493	NM_024740.2(ALG9):c.1109G>A (p.Arg370Lys)	ALG9	Pathogenic	no assertion criteria provided
590348	NM_198334.3(GANAB):c.621del (p.Asp207fs)	GANAB	Pathogenic	no assertion criteria provided
590349	NM_198334.3(GANAB):c.1769G>C (p.Arg590Pro)	GANAB	Pathogenic	no assertion criteria provided
590350	NM_198334.3(GANAB):c.1936+1G>C	GANAB	Pathogenic	no assertion criteria provided
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
1255548	NM_138694.4(PKHD1):c.2285_2286del (p.Val762fs)	PKHD1	Pathogenic	no assertion criteria provided
188369	NM_138694.4(PKHD1):c.4870C>T (p.Arg1624Trp)	PKHD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189098	NM_138694.4(PKHD1):c.1880T>A (p.Met627Lys)	PKHD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
196052	NM_138694.4(PKHD1):c.2854G>A (p.Gly952Arg)	PKHD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
198314	NM_138694.4(PKHD1):c.10219C>T (p.Gln3407Ter)	PKHD1	Pathogenic	criteria provided, multiple submitters, no conflicts
371036	NM_138694.4(PKHD1):c.5485C>T (p.Gln1829Ter)	PKHD1	Pathogenic	criteria provided, multiple submitters, no conflicts
4108	NM_138694.4(PKHD1):c.107C>T (p.Thr36Met)	PKHD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4114	NM_138694.4(PKHD1):c.1486C>T (p.Arg496Ter)	PKHD1	Pathogenic	criteria provided, multiple submitters, no conflicts
593691	NM_138694.4(PKHD1):c.11074C>T (p.Arg3692Ter)	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
636941	NM_138694.4(PKHD1):c.8518C>T (p.Arg2840Cys)	PKHD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
653999	NM_138694.4(PKHD1):c.10126del (p.Ala3376fs)	PKHD1	Pathogenic	criteria provided, multiple submitters, no conflicts
684635	NM_138694.4(PKHD1):c.820dup (p.Arg274fs)	PKHD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
863593	NM_138694.4(PKHD1):c.8122C>T (p.Gln2708Ter)	PKHD1	Pathogenic	criteria provided, multiple submitters, no conflicts
96397	NM_138694.4(PKHD1):c.353del (p.Ser118fs)	PKHD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1048653	NM_001289104.2(PRKCSH):c.374_375del (p.Glu125fs)	PRKCSH	Pathogenic	criteria provided, multiple submitters, no conflicts
1255531	NM_001289104.2(PRKCSH):c.1290C>A (p.Tyr430Ter)	PRKCSH	Pathogenic	no assertion criteria provided
1255627	NM_001289104.2(PRKCSH):c.430_432delinsAATAAGG (p.Leu144fs)	PRKCSH	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 50 · 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
SEC16B	Moderate	Autosomal dominant	autosomal dominant polycystic liver disease
SEC61B	Moderate	Autosomal dominant	polycystic liver disease 1	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
ALG9	Orphanet:730	Autosomal dominant polycystic kidney disease
ALG9	Orphanet:79328	ALG9-CDG
SEC61A1	Orphanet:697417	Common variable immunodeficiency phenotype due to SEC61A1 deficiency
SEC63	Orphanet:2924	Isolated polycystic liver disease
ALG8	Orphanet:2924	Isolated polycystic liver disease
ALG8	Orphanet:79325	ALG8-CDG
CTNNB1	Orphanet:1501	Adrenocortical carcinoma
CTNNB1	Orphanet:210159	Adult hepatocellular carcinoma
CTNNB1	Orphanet:2780	Osteopathia striata-cranial sclerosis syndrome
CTNNB1	Orphanet:33402	Pediatric hepatocellular carcinoma
CTNNB1	Orphanet:404473	Intellectual disability-eye abnormalities-microcephaly-peripheral spasticity syndrome
CTNNB1	Orphanet:54595	Craniopharyngioma
CTNNB1	Orphanet:569248	Microcystic stromal tumor
CTNNB1	Orphanet:689430	Adenoid ameloblastoma
CTNNB1	Orphanet:873	Desmoid tumor
CTNNB1	Orphanet:891	Familial exudative vitreoretinopathy
CTNNB1	Orphanet:91414	Pilomatrixoma
CTNNB1	Orphanet:952	Acrofacial dysostosis, Weyers type
GANAB	Orphanet:730	Autosomal dominant polycystic kidney disease
HNF4A	Orphanet:263455	Congenital hyperinsulinism due to HNF4A deficiency
HNF4A	Orphanet:544628	Atypical Fanconi syndrome-neonatal hyperinsulinism syndrome
HNF4A	Orphanet:552	MODY
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
LRP6	Orphanet:1810	Autosomal dominant hypohidrotic ectodermal dysplasia
LRP6	Orphanet:99798	Oligodontia
NF2	Orphanet:2495	Meningioma
NF2	Orphanet:634475	Mosaic NF2-related schwannomatosis
NF2	Orphanet:637	Full NF2-related schwannomatosis
NF2	Orphanet:93921	Full schwannomatosis
PKD2	Orphanet:730	Autosomal dominant polycystic kidney disease
PKHD1	Orphanet:53035	Caroli disease
PKHD1	Orphanet:731	Autosomal recessive polycystic kidney disease
PRKCSH	Orphanet:2924	Isolated polycystic liver disease

Cohort genes → proteins

23 cohort genes, 23 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	23

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SEC61B	HGNC:16993	ENSG00000106803	P60468	Protein transport protein Sec61 subunit beta	gencc
SEC16B	HGNC:30301	ENSG00000120341	Q96JE7	Protein transport protein Sec16B	gencc
RUVBL1	HGNC:10474	ENSG00000175792	Q9Y265	RuvB-like 1	clinvar
HNF1B	HGNC:11630	ENSG00000275410	P35680	Hepatocyte nuclear factor 1-beta	clinvar
ALG9	HGNC:15672	ENSG00000086848	Q9H6U8	Alpha-1,2-mannosyltransferase ALG9	clinvar
CDC25A	HGNC:1725	ENSG00000164045	P30304	M-phase inducer phosphatase 1	clinvar
SEC61A2	HGNC:17702	ENSG00000065665	Q9H9S3	Protein transport protein Sec61 subunit alpha isoform 2	clinvar
SEC61A1	HGNC:18276	ENSG00000058262	P61619	Protein transport protein Sec61 subunit alpha isoform 1	clinvar
SEC63	HGNC:21082	ENSG00000025796	Q9UGP8	Translocation protein SEC63 homolog	clinvar
ALG8	HGNC:23161	ENSG00000159063	Q9BVK2	Dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase	clinvar
CTNNB1	HGNC:2514	ENSG00000168036	P35222	Catenin beta-1	clinvar
DKK3	HGNC:2893	ENSG00000050165	Q9UBP4	Dickkopf-related protein 3	clinvar
GANAB	HGNC:4138	ENSG00000089597	Q14697	Neutral alpha-glucosidase AB	clinvar
HHEX	HGNC:4901	ENSG00000152804	Q03014	Hematopoietically-expressed homeobox protein HHEX	clinvar
HNF4A	HGNC:5024	ENSG00000101076	P41235	Hepatocyte nuclear factor 4-alpha	clinvar
LRP5	HGNC:6697	ENSG00000162337	O75197	Low-density lipoprotein receptor-related protein 5	clinvar
LRP6	HGNC:6698	ENSG00000070018	O75581	Low-density lipoprotein receptor-related protein 6	clinvar
NF2	HGNC:7773	ENSG00000186575	P35240	Merlin	clinvar
ONECUT1	HGNC:8138	ENSG00000169856	Q9UBC0	Hepatocyte nuclear factor 6	clinvar
ONECUT2	HGNC:8139	ENSG00000119547	O95948	One cut domain family member 2	clinvar
PKD2	HGNC:9009	ENSG00000118762	Q13563	Polycystin-2	clinvar
PKHD1	HGNC:9016	ENSG00000170927	P08F94	Fibrocystin	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)
SEC61B	Protein transport protein Sec61 subunit beta	Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across the endoplasmic reticulum (ER).
SEC16B	Protein transport protein Sec16B	Plays a role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER).
RUVBL1	RuvB-like 1	Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (3’ to 5’) activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activ…
HNF1B	Hepatocyte nuclear factor 1-beta	Transcription factor that binds to the inverted palindrome 5’-GTTAATNATTAAC-3'.
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.
CDC25A	M-phase inducer phosphatase 1	Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression.
SEC61A2	Protein transport protein Sec61 subunit alpha isoform 2	Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across the endoplasmic reticulum (ER).
SEC61A1	Protein transport protein Sec61 subunit alpha isoform 1	Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across the endoplasmic reticulum (ER).
SEC63	Translocation protein SEC63 homolog	Mediates cotranslational and post-translational transport of certain precursor polypeptides across endoplasmic reticulum (ER).
ALG8	Dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase	Dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation.
CTNNB1	Catenin beta-1	Key downstream component of the canonical Wnt signaling pathway.
DKK3	Dickkopf-related protein 3	Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6.
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.
HHEX	Hematopoietically-expressed homeobox protein HHEX	Recognizes the DNA sequence 5’-ATTAA-3'.
HNF4A	Hepatocyte nuclear factor 4-alpha	Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes.
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.
LRP6	Low-density lipoprotein receptor-related protein 6	Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes.
NF2	Merlin	Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis.
ONECUT1	Hepatocyte nuclear factor 6	Transcriptional activator.
ONECUT2	One cut domain family member 2	Transcriptional activator.
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.
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: 7 · Difficult: 4 · Unknown: 12 · Druggable fraction: 0.3

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
Nuclear receptor	1	16.8×	0.348
Enzyme (other)	4	2.1×	0.360
Phosphatase	1	3.6×	0.452
Transcription factor	4	1.4×	0.452
Antibody/Immunoglobulin	1	1.3×	0.662
Other/Unknown	12	0.9×	0.714

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SEC61B	Other/Unknown	no		SecG/Sec61-beta/Sbh, Sec61-beta/Sbh
SEC16B	Other/Unknown	no		Sec16_Sec23-bd, Sec16_CCD
RUVBL1	Other/Unknown	no		AAA+_ATPase, TIP49_P-loop, RuvB-like
HNF1B	Transcription factor	no		HD, HNF1b_C, HNF-1_N
ALG9	Enzyme (other)	yes	2.4.1.259	GPI_mannosylTrfase
CDC25A	Phosphatase	yes	3.1.3.48	MPI_Phosphatase, Rhodanese-like_dom, Rhodanese-like_dom_sf
SEC61A2	Other/Unknown	no		SecY/SEC61-alpha, Translocon_Sec61/SecY_plug_dom, SecY_dom_sf
SEC61A1	Other/Unknown	no		SecY/SEC61-alpha, Translocon_Sec61/SecY_plug_dom, SecY_dom_sf
SEC63	Other/Unknown	no		DnaJ_domain, Sec63-dom, Ig_E-set
ALG8	Enzyme (other)	yes	2.4.1.265	Glyco_trans_ALG6/ALG8
CTNNB1	Other/Unknown	no		Armadillo, ARM-like, Beta-catenin
DKK3	Other/Unknown	no		Dickkopf_N, DKK1-4, Dkk3_Cys2
GANAB	Enzyme (other)	yes	3.2.1.207	Glyco_hydro_31_TIM, Gal_mutarotase_sf_dom, Glyco_hydro_b
HHEX	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
HNF4A	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
LRP5	Other/Unknown	no		LDLR_classB_rpt, EGF, LDrepeatLR_classA_rpt
LRP6	Other/Unknown	no		LDLR_classB_rpt, EGF, LDrepeatLR_classA_rpt
NF2	Other/Unknown	no		FERM_domain, Ez/rad/moesin-like, Moesin_tail_sf
ONECUT1	Transcription factor	no		HD, CUT_dom, Homeodomain-like_sf
ONECUT2	Transcription factor	no		HD, CUT_dom, Homeodomain-like_sf
PKD2	Other/Unknown	no		EF_hand_dom, PKD_2, EF-hand-dom_pair
PKHD1	Antibody/Immunoglobulin	yes		IPT_dom, PbH1, Pectin_lyase_fold/virulence
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.

21 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)	23
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	6
right lobe of liver	4
ventricular zone	4
stromal cell of endometrium	4
oocyte	3
parotid gland	2
adrenal tissue	2
metanephros cortex	2
endothelial cell	2
secondary oocyte	2
islet of Langerhans	2
duodenum	2
mucosa of transverse colon	2
calcaneal tendon	2
primordial germ cell in gonad	1
right uterine tube	1
adult mammalian kidney	1
kidney	1
ganglionic eminence	1
buccal mucosa cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SEC61B	288	ubiquitous	marker	parotid gland, body of pancreas, oocyte
SEC16B	165	broad	yes	right lobe of liver, body of pancreas, adrenal tissue
RUVBL1	134	ubiquitous	marker	right uterine tube, ventricular zone, primordial germ cell in gonad
HNF1B	74	broad	marker	metanephros cortex, adult mammalian kidney, kidney
ALG9	240	ubiquitous	marker	endothelial cell, body of pancreas, ganglionic eminence
CDC25A	182	ubiquitous	marker	secondary oocyte, buccal mucosa cell, oocyte
SEC61A2	213	ubiquitous	yes	cortical plate, sperm, C1 segment of cervical spinal cord
SEC61A1	284	ubiquitous	marker	body of pancreas, stromal cell of endometrium, islet of Langerhans
SEC63	295	ubiquitous	marker	colonic epithelium, body of pancreas, parotid gland
ALG8	282	ubiquitous	marker	right testis, left testis, testis
CTNNB1	295	ubiquitous	marker	adrenal tissue, ventricular zone, periodontal ligament
DKK3	286	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, middle temporal gyrus
GANAB	293	ubiquitous	marker	stromal cell of endometrium, islet of Langerhans, ventricular zone
HHEX	222	ubiquitous	marker	secondary oocyte, right lobe of thyroid gland, oocyte
HNF4A	110	tissue_specific	marker	right lobe of liver, mucosa of transverse colon, duodenum
LRP5	224	ubiquitous	marker	right lobe of liver, mucosa of transverse colon, ascending aorta
LRP6	139	ubiquitous	marker	calcaneal tendon, corpus callosum, ventricular zone
NF2	283	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, dorsal motor nucleus of vagus nerve
ONECUT1	56	broad	marker	body of pancreas, right lobe of liver, gall bladder
ONECUT2	80	broad	marker	jejunal mucosa, pancreatic ductal cell, duodenum
PKD2	288	ubiquitous	marker	blood vessel layer, calcaneal tendon, saphenous vein
PKHD1	51	tissue_specific	marker	kidney epithelium, renal medulla, metanephros cortex
PRKCSH	288	ubiquitous	marker	stromal cell of endometrium, type B pancreatic cell, olfactory bulb

Protein interactions among cohort

Intra-cohort edges: 27.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTNNB1	15,668
HNF4A	4,731
GANAB	3,817
SEC63	3,355
NF2	3,208
CDC25A	3,147
SEC61A2	2,652
LRP5	2,619
LRP6	2,525
DKK3	2,444

Intra-cohort edges

A	B	Sources
ALG8	ALG9	string_interaction
ALG8	GANAB	string_interaction
ALG8	PRKCSH	string_interaction
ALG8	SEC63	string_interaction
ALG9	GANAB	string_interaction
CTNNB1	DKK3	string_interaction
CTNNB1	HNF4A	biogrid_interaction, string_interaction
CTNNB1	NF2	string_interaction
DKK3	LRP5	string_interaction
DKK3	LRP6	string_interaction
GANAB	PRKCSH	intact, string_interaction
GANAB	SEC63	string_interaction
HHEX	HNF1B	string_interaction
HHEX	ONECUT1	string_interaction
HNF1B	HNF4A	string_interaction
HNF1B	ONECUT1	string_interaction
HNF1B	PKHD1	string_interaction
HNF1B	RUVBL1	biogrid_interaction
HNF4A	ONECUT1	string_interaction
LRP5	LRP6	string_interaction
PKD2	PKHD1	string_interaction
PKD2	PRKCSH	string_interaction
PKHD1	PRKCSH	string_interaction
PRKCSH	SEC63	string_interaction
SEC61A1	SEC63	biogrid_interaction
SEC61A2	SEC61B	intact
SEC61A2	SEC63	string_interaction

Structural data

PDB: 15 · AlphaFold-only: 8 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTNNB1	P35222	50
RUVBL1	Q9Y265	36
PKD2	Q13563	31
LRP6	O75581	30
SEC61B	P60468	16
SEC61A1	P61619	15
HNF4A	P41235	8
NF2	P35240	6
HNF1B	P35680	3
ALG9	Q9H6U8	2
CDC25A	P30304	2
GANAB	Q14697	2
ONECUT2	O95948	2
PRKCSH	P14314	2
HHEX	Q03014	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ALG8	Q9BVK2	92.07
LRP5	O75197	78.65
SEC63	Q9UGP8	77.71
DKK3	Q9UBP4	74.08
SEC61A2	Q9H9S3	72.77
ONECUT1	Q9UBC0	60.78
SEC16B	Q96JE7	55.68
PKHD1	P08F94

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 143. Enrichment computed across 23 evidence-associated genes (19 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 19 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	3	94.9×	5e-04	HNF1B, HHEX, ONECUT1
Disassembly of the destruction complex and recruitment of AXIN to the membrane	3	56.4×	8e-04	CTNNB1, LRP5, LRP6
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	3	53.0×	8e-04	CTNNB1, GANAB, PRKCSH
Antigen processing-Cross presentation	3	50.1×	8e-04	SEC61B, SEC61A2, SEC61A1
TCF dependent signaling in response to WNT	4	24.8×	8e-04	RUVBL1, CTNNB1, LRP5, LRP6
Maturation of spike protein	2	200.3×	9e-04	GANAB, PRKCSH
Metabolism of proteins	8	5.2×	0.001	RUVBL1, ALG9, SEC61B, CDC25A, SEC61A2, SEC61A1, ALG8, SEC16B
Regulation of gene expression in early pancreatic precursor cells	2	150.3×	0.001	HNF1B, ONECUT1
Signaling by RNF43 mutants	2	133.6×	0.001	LRP5, LRP6
Nephron development	2	92.5×	0.003	HNF1B, HNF4A
Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells	2	75.1×	0.003	HNF1B, ONECUT1
Negative regulation of TCF-dependent signaling by WNT ligand antagonists	2	75.1×	0.003	LRP5, LRP6
Calnexin/calreticulin cycle	2	75.1×	0.003	GANAB, PRKCSH
Diseases associated with N-glycosylation of proteins	2	66.8×	0.004	ALG9, ALG8
ER-Phagosome pathway	3	20.5×	0.004	SEC61B, SEC61A2, SEC61A1
Signaling by WNT in cancer	2	63.3×	0.004	LRP5, LRP6
Regulation of FZD by ubiquitination	2	54.6×	0.005	LRP5, LRP6
Signaling by WNT	3	17.7×	0.005	RUVBL1, LRP5, LRP6
SRP-dependent cotranslational protein targeting to membrane	3	15.8×	0.006	SEC61B, SEC61A2, SEC61A1
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	2	44.5×	0.006	GANAB, PRKCSH
Defective ALG9 causes CDG-1l	1	601.0×	0.011	ALG9
Defective ALG8 causes CDG-1h	1	601.0×	0.011	ALG8
Developmental Lineage of Pancreatic Acinar Cells	2	31.6×	0.011	HNF1B, ONECUT1
Maturation of spike protein	2	28.0×	0.013	GANAB, PRKCSH
Class I MHC mediated antigen processing & presentation	3	11.1×	0.013	SEC61B, SEC61A2, SEC61A1
Post-translational protein modification	5	5.0×	0.013	RUVBL1, ALG9, CDC25A, ALG8, SEC16B
Developmental Lineage of Pancreatic Ductal Cells	2	24.0×	0.016	HNF1B, ONECUT1
Translation	3	9.8×	0.017	SEC61B, SEC61A2, SEC61A1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	2	21.9×	0.018	ALG9, ALG8
Asparagine N-linked glycosylation	3	9.5×	0.018	ALG9, ALG8, SEC16B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 23 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
post-translational protein targeting to membrane, translocation	4	366.4×	8e-08	SEC61B, SEC61A2, SEC61A1, SEC63
liver development	5	48.2×	1e-05	SEC63, ONECUT1, ONECUT2, PKD2, PRKCSH
SRP-dependent cotranslational protein targeting to membrane, translocation	3	274.8×	2e-05	SEC61B, SEC61A2, SEC61A1
epithelial cell development	3	199.8×	4e-05	CTNNB1, ONECUT1, ONECUT2
regulation of cell-matrix adhesion	3	169.1×	5e-05	ONECUT1, ONECUT2, PKHD1
positive regulation of DNA-templated transcription	7	8.5×	8e-04	RUVBL1, HNF1B, CTNNB1, HHEX, HNF4A, LRP5, LRP6
establishment of blood-retinal barrier	2	244.2×	0.002	CTNNB1, LRP5
SRP-dependent cotranslational protein targeting to membrane	2	183.2×	0.002	SEC61A1, SEC63
regulation of calcium ion import	2	183.2×	0.002	CTNNB1, PKD2
cell-cell adhesion	4	17.7×	0.003	CTNNB1, LRP5, LRP6, PKHD1
Wnt signaling pathway	4	17.3×	0.003	DKK3, HHEX, LRP6, PKD2
positive regulation of transcription by RNA polymerase II	8	5.2×	0.003	CTNNB1, HHEX, HNF4A, LRP5, LRP6, ONECUT1, ONECUT2, PKD2
post-translational protein targeting to endoplasmic reticulum membrane	2	122.1×	0.003	SEC61A1, SEC63
osteoblast proliferation	2	122.1×	0.003	LRP5, NF2
establishment of blood-brain barrier	2	122.1×	0.003	CTNNB1, LRP5
ectoderm development	2	104.7×	0.004	CTNNB1, NF2
midbrain dopaminergic neuron differentiation	2	104.7×	0.004	CTNNB1, LRP6
hindbrain development	2	97.7×	0.004	HNF1B, CTNNB1
gastrulation with mouth forming second	2	81.4×	0.005	CTNNB1, LRP5
endocrine pancreas development	2	81.4×	0.005	HNF1B, ONECUT2
anterior/posterior pattern specification	3	23.6×	0.005	HNF1B, HHEX, LRP5
dolichol-linked oligosaccharide biosynthetic process	2	73.3×	0.006	ALG9, ALG8
N-glycan processing	2	63.7×	0.008	GANAB, PRKCSH
branching morphogenesis of an epithelial tube	2	63.7×	0.008	HNF1B, PKHD1
canonical Wnt signaling pathway	3	20.0×	0.008	CTNNB1, LRP5, LRP6
pancreas development	2	58.6×	0.009	HNF1B, CTNNB1
cell-cell junction organization	2	54.3×	0.010	NF2, PKHD1
positive regulation of mesenchymal cell proliferation	2	52.3×	0.010	CTNNB1, LRP5
glial cell fate determination	1	732.7×	0.012	CTNNB1
regulation of pronephros size	1	732.7×	0.012	HNF1B

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 4 · Undrugged: 19

Druggability breadth: 13 of 23 evidence-associated genes (57%) 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
CDC25A	MILTEFOSINE
CTNNB1	DITHIAZANINE IODIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CDC25A	5	4
CTNNB1	4	4
RUVBL1	1	2
GANAB	1	2
SEC61B	0	0
SEC16B	0	0
HNF1B	0	0
ALG9	0	0
SEC61A2	0	0
SEC61A1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MILTEFOSINE	4	CDC25A
MENADIONE	4	CDC25A
DITHIAZANINE IODIDE	4	CTNNB1
YOHIMBINE	3	CDC25A
QUERCETIN	3	CTNNB1
MOLIBRESIB	2	RUVBL1
SODIUM TUNGSTATE	2	CDC25A
SALINOMYCIN	2	CTNNB1
DALOSIRVAT	2	CTNNB1
DUVOGLUSTAT	2	GANAB
PLUMBAGIN	1	CDC25A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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

Symbol	Assays	Type breakdown
CTNNB1	361	Binding:358, Functional:3
CDC25A	111	Binding:111
HNF4A	106	Binding:97, Functional:9
GANAB	38	Binding:32, Functional:6
RUVBL1	15	Binding:15
PKD2	12	Binding:12
LRP6	9	Binding:9
SEC61A1	7	Binding:7
SEC61B	1	Binding:1
SEC63	1	Binding:1
ALG8	1	Binding:1
LRP5	1	Binding:1
PRKCSH	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
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
CDC25A	3.1.3.48	protein-tyrosine-phosphatase
ALG8	2.4.1.265	dolichyl-P-Glc:Glc1Man9GlcNAc2-PP-dolichol alpha-1,3-glucosyltransferase
GANAB	3.2.1.207	mannosyl-oligosaccharide alpha-1,3-glucosidase
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
CDC25A	111
CTNNB1	361
HNF4A	106

Pharmacogenomics

Cohort genes with a PharmGKB record: 23; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

11 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)
MILTEFOSINE	4	CDC25A
MENADIONE	4	CDC25A
DITHIAZANINE IODIDE	4	CTNNB1
YOHIMBINE	3	CDC25A
QUERCETIN	3	CTNNB1
MOLIBRESIB	2	RUVBL1
SODIUM TUNGSTATE	2	CDC25A
SALINOMYCIN	2	CTNNB1
DALOSIRVAT	2	CTNNB1
DUVOGLUSTAT	2	GANAB
PLUMBAGIN	1	CDC25A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	CDC25A, CTNNB1
B	Phased (≥1) drug, not yet approved	2	RUVBL1, GANAB
C	Druggable family + PDB, no drug	3	ALG9, HNF4A, PRKCSH
D	Druggable family + AlphaFold only, no drug	2	ALG8, PKHD1
E	Difficult family or no structure, no drug	14	SEC61B, SEC16B, HNF1B, SEC61A2, SEC61A1, SEC63, DKK3, HHEX, LRP5, LRP6 (+4 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
HNF4A	106	CTNNB1
ALG9	0	GANAB
ALG8	1	GANAB
PRKCSH	1	GANAB
SEC61B	1	—
SEC16B	0	—
HNF1B	0	—
SEC61A2	0	—
SEC61A1	7	—
SEC63	1	—
DKK3	0	—
HHEX	0	—
LRP5	1	—
LRP6	9	—
NF2	0	—
ONECUT1	0	—
ONECUT2	0	—
PKD2	12	—
PKHD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 17.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8
PHASE2/PHASE3	5
PHASE2	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05281328	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Trial to Assess the Efficacy and Safety of Octreotide Subcutaneous Depot in Patients With PLD
NCT00426153	PHASE2/PHASE3	COMPLETED	Octreotide in Severe Polycystic Liver Disease
NCT00565097	PHASE2/PHASE3	COMPLETED	Lanreotide as Treatment of Polycystic Livers
NCT00771888	PHASE2/PHASE3	UNKNOWN	Open-Label Extension of LOCKCYST Trial
NCT01315795	PHASE2/PHASE3	COMPLETED	Lanreotide Autogel in the Treatment of Symptomatic Polycystic Liver Disease
NCT05478083	PHASE2	RECRUITING	A GnRH Agonist IN Pre-menopausal Women STudy to Treat Severe Polycystic Liver Disease
NCT01157858	PHASE2	COMPLETED	Everolimus and LongActing Octreotide Trial in Polycystic Livers
NCT01670110	PHASE2	COMPLETED	Pasireotide LAR in Severe Polycystic Liver Disease
NCT02021110	PHASE2	COMPLETED	Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease
NCT04111692	Not specified	RECRUITING	A Prospective Observational Study of Foam Sclerotherapy .
NCT04645251	Not specified	RECRUITING	Polycystic Liver Disease Registry (UK)
NCT00934791	Not specified	TERMINATED	Polycystic Liver Disease in Kidney Transplant
NCT01354405	Not specified	COMPLETED	Somatostatin Analogues as a Volume Reducing Treatment of Polycystic Livers (RESOLVE)
NCT02173080	Not specified	COMPLETED	Development and Assessment of The Polycystic Liver Disease Questionnaire (PLD-Q).
NCT03960710	Not specified	UNKNOWN	Automatic Segmentation of Polycystic Liver
NCT05215964	Not specified	UNKNOWN	The Association Between Skeletal Muscle Mass and Severity of Polycystic Liver Disease and Polycystic Kidney Disease
NCT05500157	Not specified	UNKNOWN	Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts

Drugs tested across these trials (top 30)

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