Exstrophy-epispadias complex

Summary

Exstrophy-epispadias complex (MONDO:0017919) is a disease caused by variants in PTCH1 and SLC20A1, with 13 cohort genes and 2 clinical trials.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal genes: PTCH1 (GenCC Strong), SLC20A1 (GenCC Strong)
• Cohort genes: 13
• ClinVar variants: 11
• Phenotypes (HPO): 40
• Clinical trials: 2

Clinical features

Signs & symptoms

Clinical features (HPO)

40 HPO clinical features (Orphanet curated; top 40 by frequency):

HPO ID	Term	Frequency
HP:0000039	Epispadias	Frequent (30-79%)
HP:0000076	Vesicoureteral reflux	Frequent (30-79%)
HP:0002836	Bladder exstrophy	Frequent (30-79%)
HP:0004298	Abnormality of the abdominal wall	Frequent (30-79%)
HP:0010866	Abdominal wall defect	Frequent (30-79%)
HP:0100645	Cystocele	Frequent (30-79%)
HP:0000020	Urinary incontinence	Occasional (5-29%)
HP:0000023	Inguinal hernia	Occasional (5-29%)
HP:0000048	Bifid scrotum	Occasional (5-29%)
HP:0000075	Renal duplication	Occasional (5-29%)
HP:0000077	Abnormality of the kidney	Occasional (5-29%)
HP:0000083	Renal insufficiency	Occasional (5-29%)
HP:0000085	Horseshoe kidney	Occasional (5-29%)
HP:0000089	Renal hypoplasia	Occasional (5-29%)
HP:0000136	Bifid uterus	Occasional (5-29%)
HP:0001367	Abnormal joint morphology	Occasional (5-29%)
HP:0001539	Omphalocele	Occasional (5-29%)
HP:0004321	Bladder fistula	Occasional (5-29%)
HP:0011024	Abnormality of the gastrointestinal tract	Occasional (5-29%)
HP:0011842	Abnormality of skeletal morphology	Occasional (5-29%)
HP:0025489	Bladder duplication	Occasional (5-29%)
HP:0030014	Female sexual dysfunction	Occasional (5-29%)
HP:0030261	Absent penis	Occasional (5-29%)
HP:0040307	Male sexual dysfunction	Occasional (5-29%)
HP:0100599	Bifid penis	Occasional (5-29%)
HP:0100600	Penoscrotal transposition	Occasional (5-29%)
HP:0000028	Cryptorchidism	Very rare (<1-4%)
HP:0000069	Abnormality of the ureter	Very rare (<1-4%)
HP:0000110	Renal dysplasia	Very rare (<1-4%)
HP:0000238	Hydrocephalus	Very rare (<1-4%)
HP:0000252	Microcephaly	Very rare (<1-4%)
HP:0000271	Abnormality of the face	Very rare (<1-4%)
HP:0000290	Abnormality of the forehead	Very rare (<1-4%)
HP:0000315	Abnormality of the orbital region	Very rare (<1-4%)
HP:0001627	Abnormal heart morphology	Very rare (<1-4%)
HP:0002023	Anal atresia	Very rare (<1-4%)
HP:0002025	Anal stenosis	Very rare (<1-4%)
HP:0002414	Spina bifida	Very rare (<1-4%)
HP:0010475	Cloacal exstrophy	Very rare (<1-4%)
HP:0012443	Abnormality of brain morphology	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	exstrophy-epispadias complex
Mondo ID	MONDO:0017919
OMIM	258040
Orphanet	322
DOID	DOID:0080173
NCIT	C99142
UMLS	C1850321
MedGen	338020
GARD	0002207
Is cancer (heuristic)	no

Also known as: BEEC · bladder exstrophy-epispadias-cloacal extrophy complex · EEC · OEIS complex · OEIS syndrome

Data availability: 11 ClinVar variants · 2 GenCC gene-disease records.

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 › exstrophy-epispadias complex

Related subtypes (56): renal hypertension, kidney failure, nephritis, impaired renal function disease, nephrocalcinosis, atheroembolism of kidney, renal artery disease, nephrosis, cystic kidney disease, 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, 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): cloacal exstrophy, bladder exstrophy, epispadias, bladder exstrophy-epispadias-cloacal exstrophy complex

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

11 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
134336	NM_021922.3(FANCE):c.929C>A (p.Pro310Gln)	FANCE	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2628004	NM_080764.4(ZNF280B):c.937G>A (p.Val313Met)	IGL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2519551	NM_015507.4(EGFL6):c.1343G>A (p.Arg448Gln)	EGFL6	Uncertain significance	criteria provided, multiple submitters, no conflicts
2627997	NM_002212.4(EIF6):c.467A>G (p.Asn156Ser)	EIF6	Uncertain significance	criteria provided, single submitter
1776619	NM_144997.7(FLCN):c.1621G>A (p.Ala541Thr)	FLCN	Uncertain significance	criteria provided, multiple submitters, no conflicts
2627999	NM_005525.4(HSD11B1):c.678_679insT (p.Val227fs)	HSD11B1	Uncertain significance	criteria provided, single submitter
2628000	NM_001351695.2(INTS2):c.2132C>T (p.Pro711Leu)	INTS2	Uncertain significance	criteria provided, single submitter
2628001	NM_000968.4(RPL4):c.611G>T (p.Arg204Leu)	RPL4	Uncertain significance	criteria provided, single submitter
2628002	NM_018393.4(TCP11L1):c.391A>G (p.Ile131Val)	TCP11L1	Uncertain significance	criteria provided, single submitter
2628003	NM_001080825.2(TMEM120B):c.605T>C (p.Val202Ala)	TMEM120B	Uncertain significance	criteria provided, single submitter
2628005	NM_001163809.2(WDR81):c.1772G>A (p.Arg591His)	WDR81	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 17 · 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
PTCH1	Strong	Autosomal dominant	exstrophy-epispadias complex	12
SLC20A1	Strong	Autosomal dominant	exstrophy-epispadias complex

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PTCH1	Orphanet:220386	Semilobar holoprosencephaly
PTCH1	Orphanet:2353	Schilbach-Rott syndrome
PTCH1	Orphanet:280195	Septopreoptic holoprosencephaly
PTCH1	Orphanet:280200	Microform holoprosencephaly
PTCH1	Orphanet:377	Gorlin syndrome
PTCH1	Orphanet:77301	Monosomy 9q22.3 syndrome
PTCH1	Orphanet:93924	Lobar holoprosencephaly
PTCH1	Orphanet:93925	Alobar holoprosencephaly
PTCH1	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
WDR81	Orphanet:1766	Dysequilibrium syndrome
WDR81	Orphanet:269505	Congenital communicating hydrocephalus
WDR81	Orphanet:269510	Congenital non-communicating hydrocephalus
FLCN	Orphanet:122	Birt-Hogg-Dubé syndrome
FLCN	Orphanet:2903	Familial spontaneous pneumothorax
FLCN	Orphanet:422526	Hereditary clear cell renal cell carcinoma
FANCE	Orphanet:84	Fanconi anemia
HSD11B1	Orphanet:168588	Hyperandrogenism due to cortisone reductase deficiency

Cohort genes → proteins

13 cohort genes, 12 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	13

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC20A1	HGNC:10946	ENSG00000144136	Q8WUM9	Sodium-dependent phosphate transporter 1	gencc
PTCH1	HGNC:9585	ENSG00000185920	Q13635	Protein patched homolog 1	gencc
RPL4	HGNC:10353	ENSG00000174444	P36578	Large ribosomal subunit protein uL4	clinvar
TCP11L1	HGNC:25655	ENSG00000176148	Q9NUJ3	T-complex protein 11-like protein 1	clinvar
WDR81	HGNC:26600	ENSG00000167716	Q562E7	WD repeat-containing protein 81	clinvar
FLCN	HGNC:27310	ENSG00000154803	Q8NFG4	Folliculin	clinvar
INTS2	HGNC:29241	ENSG00000108506	Q9H0H0	Integrator complex subunit 2	clinvar
TMEM120B	HGNC:32008	ENSG00000188735	A0PK00	Transmembrane protein 120B	clinvar
EGFL6	HGNC:3235	ENSG00000198759	Q8IUX8	Epidermal growth factor-like protein 6	clinvar
FANCE	HGNC:3586	ENSG00000112039	Q9HB96	Fanconi anemia group E protein	clinvar
HSD11B1	HGNC:5208	ENSG00000117594	P28845	11-beta-hydroxysteroid dehydrogenase 1	clinvar
IGL	HGNC:5853			immunoglobulin lambda locus	clinvar
EIF6	HGNC:6159	ENSG00000242372	P56537	Eukaryotic translation initiation factor 6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC20A1	Sodium-dependent phosphate transporter 1	Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion.
PTCH1	Protein patched homolog 1	Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH).
RPL4	Large ribosomal subunit protein uL4	Component of the large ribosomal subunit.
WDR81	WD repeat-containing protein 81	Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex.
FLCN	Folliculin	Multi-functional protein, involved in both the cellular response to amino acid availability and in the regulation of glycolysis.
INTS2	Integrator complex subunit 2	Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes.
TMEM120B	Transmembrane protein 120B	Necessary for efficient adipogenesis.
EGFL6	Epidermal growth factor-like protein 6	May bind integrin alpha-8/beta-1 and play a role in hair follicle morphogenesis.
FANCE	Fanconi anemia group E protein	As part of the Fanconi anemia (FA) complex functions in DNA cross-links repair.
HSD11B1	11-beta-hydroxysteroid dehydrogenase 1	Controls the reversible conversion of biologically active glucocorticoids such as cortisone to cortisol, and 11-dehydrocorticosterone to corticosterone in the presence of NADP(H).
EIF6	Eukaryotic translation initiation factor 6	Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 10 · Druggable fraction: 0.23

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
Transporter	1	6.0×	0.310
Other/Unknown	10	1.4×	0.310
Kinase	1	2.1×	0.506
Enzyme (other)	1	0.9×	0.678

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC20A1	Transporter	yes	7.3.2.1	Phos_transporter
PTCH1	Other/Unknown	no		SSD, TM_rcpt_patched, HMGCR/SNAP/NPC1-like_SSD
RPL4	Other/Unknown	no		Ribosomal_uL4, Ribosomal_uL4_euk_arc_CS, Ribosomal_uL4_dom_sf
TCP11L1	Other/Unknown	no		Tcp11
WDR81	Kinase	yes		BEACH_dom, WD40_rpt, Kinase-like_dom_sf
FLCN	Other/Unknown	no		Folliculin, Folliculin_DENN, Folliculin/SMCR8_longin
INTS2	Other/Unknown	no		Int2_metazoa, INTS2
TMEM120B	Other/Unknown	no		TMEM120A/B
EGFL6	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, MAM_dom
FANCE	Other/Unknown	no		Fanconi_anaemia_gr_E_prot_C, FANCE
HSD11B1	Enzyme (other)	yes	1.1.1.146	SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_sf
IGL	Other/Unknown	no
EIF6	Other/Unknown	no		eIF6

Expression context

Cohort genes with no expression data: 1.

11 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	12
unknown	1

Top tissues across cohort

Tissue	Cohort genes
granulocyte	2
mucosa of transverse colon	2
buccal mucosa cell	2
cerebellar hemisphere	2
right hemisphere of cerebellum	2
cartilage tissue	1
dorsal root ganglion	1
tibia	1
trigeminal ganglion	1
cortical plate	1
embryo	1
ganglionic eminence	1
primordial germ cell in gonad	1
type B pancreatic cell	1
vena cava	1
left ovary	1
right ovary	1
Brodmann (1909) area 23	1
endothelial cell	1
oviduct epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC20A1	296	ubiquitous	marker	mucosa of transverse colon, granulocyte, cartilage tissue
PTCH1	275	ubiquitous	marker	tibia, dorsal root ganglion, trigeminal ganglion
RPL4	309	ubiquitous	marker	cortical plate, embryo, ganglionic eminence
TCP11L1	214	ubiquitous	yes	primordial germ cell in gonad, vena cava, type B pancreatic cell
WDR81	138	ubiquitous	marker	granulocyte, left ovary, right ovary
FLCN	261	ubiquitous	marker	buccal mucosa cell, right hemisphere of cerebellum, cerebellar hemisphere
INTS2	249	ubiquitous	marker	oviduct epithelium, endothelial cell, Brodmann (1909) area 23
TMEM120B	208	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
EGFL6	186	broad	marker	visceral pleura, placenta, pleura
FANCE	184	ubiquitous	marker	buccal mucosa cell, oocyte, secondary oocyte
HSD11B1	233	broad	marker	decidua, right lobe of liver, liver
IGL
EIF6	151	ubiquitous	marker	esophagus mucosa, mucosa of transverse colon, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPL4	7,650
EIF6	3,965
HSD11B1	3,931
PTCH1	3,368
FANCE	2,857
INTS2	2,285
SLC20A1	1,918
EGFL6	1,414
WDR81	1,404
FLCN	1,317

Intra-cohort edges

A	B	Sources
EIF6	RPL4	biogrid_interaction

Structural data

PDB: 8 · AlphaFold-only: 4 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL4	P36578	199
EIF6	P56537	49
HSD11B1	P28845	42
PTCH1	Q13635	16
INTS2	Q9H0H0	8
FANCE	Q9HB96	7
FLCN	Q8NFG4	4
TMEM120B	A0PK00	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TCP11L1	Q9NUJ3	82.20
SLC20A1	Q8WUM9	70.02
WDR81	Q562E7	69.23
EGFL6	Q8IUX8	65.96

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 35. Enrichment computed across 13 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Sodium-coupled phosphate cotransporters	1	475.8×	0.055	SLC20A1
GLI proteins bind promoters of Hh responsive genes to promote transcription	1	203.9×	0.055	PTCH1
Ligand-receptor interactions	1	178.4×	0.055	PTCH1
Prednisone ADME	1	158.6×	0.055	HSD11B1
Glucocorticoid biosynthesis	1	109.8×	0.064	HSD11B1
Activation of SMO	1	79.3×	0.073	PTCH1
Fanconi Anemia Pathway	1	34.8×	0.099	FANCE
Amino acids regulate mTORC1	1	25.0×	0.099	FLCN
Class B/2 (Secretin family receptors)	1	23.8×	0.099	PTCH1
Hedgehog ‘off’ state	1	22.3×	0.099	PTCH1
Hedgehog ‘on’ state	1	19.8×	0.099	PTCH1
RNA polymerase II transcribes snRNA genes	1	19.3×	0.099	INTS2
PKR-mediated signaling	1	17.6×	0.099	FANCE
R-HSA-425393	1	16.2×	0.099	SLC20A1
Peptide chain elongation	1	15.9×	0.099	RPL4
Viral mRNA Translation	1	15.9×	0.099	RPL4
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	1	15.7×	0.099	RPL4
Selenocysteine synthesis	1	15.0×	0.099	RPL4
Eukaryotic Translation Termination	1	15.0×	0.099	RPL4
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	1	14.7×	0.099	RPL4
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	1	14.7×	0.099	RPL4
Formation of a pool of free 40S subunits	1	14.0×	0.099	RPL4
Response of EIF2AK4 (GCN2) to amino acid deficiency	1	13.9×	0.099	RPL4
Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide	1	13.3×	0.099	RPL4
L13a-mediated translational silencing of Ceruloplasmin expression	1	12.6×	0.099	RPL4
SRP-dependent cotranslational protein targeting to membrane	1	12.5×	0.099	RPL4
GTP hydrolysis and joining of the 60S ribosomal subunit	1	12.5×	0.099	RPL4
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	1	12.2×	0.099	RPL4
CDC42 GTPase cycle	1	9.0×	0.127	WDR81
Regulation of expression of SLITs and ROBOs	1	8.7×	0.128	RPL4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 12 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of cell proliferation involved in kidney development	1	1404.3×	0.033	FLCN
response to chlorate	1	702.2×	0.033	PTCH1
neural plate axis specification	1	702.2×	0.033	PTCH1
cell proliferation involved in metanephros development	1	702.2×	0.033	PTCH1
assembly of large subunit precursor of preribosome	1	702.2×	0.033	EIF6
cell differentiation involved in kidney development	1	468.1×	0.033	PTCH1
cell proliferation involved in kidney development	1	468.1×	0.033	FLCN
negative regulation of post-translational protein modification	1	351.1×	0.033	FLCN
negative regulation of lysosome organization	1	351.1×	0.033	FLCN
epidermal cell fate specification	1	280.9×	0.033	PTCH1
regulation of pro-B cell differentiation	1	280.9×	0.033	FLCN
ribosomal subunit export from nucleus	1	234.1×	0.033	EIF6
neural tube patterning	1	234.1×	0.033	PTCH1
hindlimb morphogenesis	1	234.1×	0.033	PTCH1
negative regulation of brown fat cell differentiation	1	234.1×	0.033	FLCN
steroid catabolic process	1	200.6×	0.033	HSD11B1
cytosolic ribosome assembly	1	200.6×	0.033	EIF6
regulation of fatty acid biosynthetic process	1	200.6×	0.033	EIF6
negative regulation of cell division	1	200.6×	0.033	PTCH1
mammary gland duct morphogenesis	1	200.6×	0.033	PTCH1
positive regulation of epidermal cell differentiation	1	175.5×	0.035	PTCH1
regulation of megakaryocyte differentiation	1	156.0×	0.036	EIF6
regulation of Ras protein signal transduction	1	156.0×	0.036	FLCN
aggrephagy	1	140.4×	0.036	WDR81
metanephric collecting duct development	1	140.4×	0.036	PTCH1
maturation of LSU-rRNA	1	127.7×	0.036	EIF6
response to alkaloid	1	127.7×	0.036	PTCH1
prostate gland development	1	117.0×	0.036	PTCH1
snRNA 3’-end processing	1	108.0×	0.036	INTS2
miRNA-mediated post-transcriptional gene silencing	1	108.0×	0.036	EIF6

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 11

Druggability breadth: 5 of 13 evidence-associated genes (38%) 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
RPL4	GENTAMICIN SULFATE
HSD11B1	FUROSEMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HSD11B1	13	4
RPL4	1	4
SLC20A1	0	0
PTCH1	0	0
TCP11L1	0	0
WDR81	0	0
FLCN	0	0
INTS2	0	0
TMEM120B	0	0
EGFL6	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPL4
FUROSEMIDE	4	HSD11B1
CARBENOXOLONE	4	HSD11B1
CURCUMIN	3	HSD11B1
EPIGALOCATECHIN GALLATE	3	HSD11B1
URSOLIC ACID	2	HSD11B1
MK-0736	2	HSD11B1
AZD-4017	2	HSD11B1
ENOXOLONE	2	HSD11B1
BI-187004	2	HSD11B1
BMS-823778 FREE BASE	2	HSD11B1
GLYCYRRHIZIN	2	HSD11B1
BMS-816336	1	HSD11B1
HSD-016	1	HSD11B1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
HSD11B1	311	Binding:308, Functional:3
RPL4	90	Binding:90
PTCH1	4	Binding:4
EIF6	3	Binding:3
SLC20A1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SLC20A1	7.3.2.1	ABC-type phosphate transporter
HSD11B1	1.1.1.146, 1.1.1.B40	11beta-hydroxysteroid dehydrogenase,

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
HSD11B1	311

Pharmacogenomics

Cohort genes with a PharmGKB record: 13; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

14 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)
GENTAMICIN SULFATE	4	RPL4
FUROSEMIDE	4	HSD11B1
CARBENOXOLONE	4	HSD11B1
CURCUMIN	3	HSD11B1
EPIGALOCATECHIN GALLATE	3	HSD11B1
URSOLIC ACID	2	HSD11B1
MK-0736	2	HSD11B1
AZD-4017	2	HSD11B1
ENOXOLONE	2	HSD11B1
BI-187004	2	HSD11B1
BMS-823778 FREE BASE	2	HSD11B1
GLYCYRRHIZIN	2	HSD11B1
BMS-816336	1	HSD11B1
HSD-016	1	HSD11B1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	RPL4, HSD11B1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	2	SLC20A1, WDR81
E	Difficult family or no structure, no drug	9	PTCH1, TCP11L1, FLCN, INTS2, TMEM120B, EGFL6, FANCE, IGL, EIF6

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC20A1	1	—
PTCH1	4	—
TCP11L1	0	—
WDR81	0	—
FLCN	0	—
INTS2	0	—
TMEM120B	0	—
EGFL6	0	—
FANCE	0	—
IGL	0	—
EIF6	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE4	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04760028	PHASE4	COMPLETED	Study on the Influencing Factors of Electroencephalogram Parameters Under Anesthesia
NCT06106425	Not specified	UNKNOWN	Diagnostic and Prognostic Criteria of EEG in Neonatal Convulsions at Assiut University Children Hospital