Renal tubular dysgenesis

Summary

Renal tubular dysgenesis (MONDO:0017609) is a disease with 7 cohort genes. The dominant Reactome pathway is Metabolism of Angiotensinogen to Angiotensins (3 cohort genes).

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 7
• ClinVar variants: 346
• Phenotypes (HPO): 13

Clinical features

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0001382	Joint hypermobility	Very frequent (80-99%)
HP:0000114	Proximal tubulopathy	Very frequent (80-99%)
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0001561	Polyhydramnios	Very frequent (80-99%)
HP:0001622	Premature birth	Very frequent (80-99%)
HP:0002089	Pulmonary hypoplasia	Very frequent (80-99%)
HP:0005562	Multiple renal cysts	Very frequent (80-99%)
HP:0008660	Renotubular dysgenesis	Very frequent (80-99%)
HP:0000112	Nephropathy	Occasional (5-29%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0001562	Oligohydramnios	Occasional (5-29%)
HP:0001636	Tetralogy of Fallot	Occasional (5-29%)
HP:0007598	Bilateral single transverse palmar creases	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	renal tubular dysgenesis
Mondo ID	MONDO:0017609
Orphanet	3033
ICD-11	191424358
SNOMED CT	702397002
UMLS	C0266313
MedGen	82738
GARD	0000379
Is cancer (heuristic)	no

Also known as: primitive renal tubule syndrome · renotubular dysgenesis

Data availability: 346 ClinVar variants.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › renal tubular dysgenesis

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, exstrophy-epispadias complex, fetal lower urinary tract obstruction, IgG4-related kidney disease, congenital primary megaureter, renal nutcracker syndrome, renal hypoplasia, renal dysplasia, congenital megacalycosis, glomerular disorder, congenital renal artery stenosis, kidney neoplasm, renal tubule disorder, pyonephrosis, Arnold stickler bourne syndrome, C1q nephropathy, hypertensive nephropathy, atypical Fanconi syndrome-neonatal hyperinsulinism syndrome, idiopathic non-lupus full-house nephropathy, lachiewicz sibley syndrome, crush syndrome, obstructive nephropathy, inherited kidney disorder, acute tubulointerstitial nephritis, kidney cortex disease, non-syndromic supernumerary kidneys, neonatal renal venous thrombosis

Subtypes (3): renal tubular dysgenesis of genetic origin, renal tubular dysgenesis due to twin-twin transfusion, drug-related renal tubular dysgenesis

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

346 retrieved; paginated sample, class counts are floors:

147 uncertain significance, 72 conflicting classifications of pathogenicity, 54 benign, 29 benign/likely benign, 17 pathogenic, 12 likely benign, 9 likely pathogenic, 6 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1028377	NM_000789.4(ACE):c.1744C>T (p.Gln582Ter)	ACE	Pathogenic	criteria provided, single submitter
1320127	NM_000789.4(ACE):c.1454dup (p.Ser486fs)	ACE	Pathogenic	criteria provided, single submitter
18063	NM_000789.4(ACE):c.798C>G (p.Tyr266Ter)	ACE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
18064	NM_000789.4(ACE):c.1319_1322del (p.Leu440fs)	ACE	Pathogenic	no assertion criteria provided
208559	NM_000789.4(ACE):c.12_31del (p.Ser5fs)	ACE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
235336	NM_000789.4(ACE):c.1522C>T (p.Arg508Ter)	ACE	Pathogenic	criteria provided, multiple submitters, no conflicts
50208	NM_000789.4(ACE):c.1486C>T (p.Arg496Ter)	ACE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
50209	NM_000789.4(ACE):c.2371C>T (p.Arg791Ter)	ACE	Pathogenic	criteria provided, multiple submitters, no conflicts
974372	NM_000789.4(ACE):c.1361del (p.Leu454fs)	ACE	Pathogenic	criteria provided, single submitter
974373	NM_000789.4(ACE):c.1384dup (p.Ile462fs)	ACE	Pathogenic	criteria provided, single submitter
974413	NM_000789.4(ACE):c.899del (p.Phe300fs)	ACE	Pathogenic	criteria provided, single submitter
988100	NM_000789.4(ACE):c.1709+5G>C	ACE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
18070	NC_000001.11:g.230705933C>T	AGT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
18071	NC_000001.11:g.230710247G>A	AGT	Pathogenic	no assertion criteria provided
18072	NC_000001.11:g.230703316del	AGT	Pathogenic	no assertion criteria provided
18067	NM_000685.5(AGTR1):c.845C>T (p.Thr282Met)	AGTR1	Pathogenic	no assertion criteria provided
50206	NM_000685.5(AGTR1):c.251G>A (p.Trp84Ter)	AGTR1	Pathogenic	criteria provided, single submitter
375375	NM_001375380.1(EBF3):c.512G>A (p.Gly171Asp)	EBF3	Pathogenic	criteria provided, single submitter
1252080	NM_000537.4(REN):c.299_300del (p.Lys100fs)	REN	Pathogenic	no assertion criteria provided
13123	NM_000537.4(REN):c.145C>T (p.Arg49Ter)	REN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13124	NM_000537.4(REN):c.689G>A (p.Arg230Lys)	REN	Pathogenic	no assertion criteria provided
50210	NM_000537.4(REN):c.127C>T (p.Arg43Ter)	REN	Pathogenic	criteria provided, single submitter
50211	NM_000537.4(REN):c.404C>A (p.Ser135Tyr)	REN	Pathogenic	no assertion criteria provided
375298	NM_000789.4(ACE):c.2642-1G>A	ACE	Likely pathogenic	criteria provided, single submitter
559878	NM_000789.4(ACE):c.3503+1G>C	ACE	Likely pathogenic	criteria provided, multiple submitters, no conflicts
917911	NM_000789.4(ACE):c.3296G>A (p.Gly1099Asp)	ACE	Likely pathogenic	no assertion criteria provided
917912	NM_001384479.1(AGT):c.77G>A (p.Arg26Gln)	AGT	Likely pathogenic	no assertion criteria provided
1179033	NM_000685.5(AGTR1):c.599dup (p.Asn200fs)	AGTR1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1328400	NM_000685.5(AGTR1):c.879del (p.Phe293fs)	AGTR1	Likely pathogenic	criteria provided, single submitter
18066	NM_000685.5(AGTR1):c.110dup (p.Ile38fs)	AGTR1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EBF3	Orphanet:658843	Developmental delay-ataxia-hypotonia-facial dysmorphism syndrome
EBF3	Orphanet:96148	Distal deletion 10q syndrome
ACE	Orphanet:97369	Renal tubular dysgenesis of genetic origin
AGT	Orphanet:97369	Renal tubular dysgenesis of genetic origin
AGTR1	Orphanet:97369	Renal tubular dysgenesis of genetic origin
AGXT	Orphanet:93598	Primary hyperoxaluria type 1
REN	Orphanet:217330	REN-related autosomal dominant tubulointerstitial kidney disease
REN	Orphanet:97369	Renal tubular dysgenesis of genetic origin

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
EBF3	HGNC:19087	ENSG00000108001	Q9H4W6	Transcription factor COE3	clinvar
KCTD11	HGNC:21302	ENSG00000213859	Q693B1	BTB/POZ domain-containing protein KCTD11	clinvar
ACE	HGNC:2707	ENSG00000159640	P12821	Angiotensin-converting enzyme	clinvar
AGT	HGNC:333	ENSG00000135744	P01019	Angiotensinogen	clinvar
AGTR1	HGNC:336	ENSG00000144891	P30556	Type-1 angiotensin II receptor	clinvar
AGXT	HGNC:341	ENSG00000172482	P21549	Alanine–glyoxylate aminotransferase	clinvar
REN	HGNC:9958	ENSG00000143839	P00797	Renin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EBF3	Transcription factor COE3	Transcriptional activator.
KCTD11	BTB/POZ domain-containing protein KCTD11	Plays a role as a marker and a regulator of neuronal differentiation; Up-regulated by a variety of neurogenic signals, such as retinoic acid, epidermal growth factor/EGF and NGFB/nerve growth factor.
ACE	Angiotensin-converting enzyme	Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regulation of blood pressure, electrolyte hom…
AGT	Angiotensinogen	Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.
AGTR1	Type-1 angiotensin II receptor	Receptor for angiotensin II, a vasoconstricting peptide, which acts as a key regulator of blood pressure and sodium retention by the kidney.
AGXT	Alanine–glyoxylate aminotransferase	Peroxisomal aminotransferase that catalyzes the transamination of glyoxylate to glycine and contributes to the glyoxylate detoxification.
REN	Renin	Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retenti…

Protein-family classification

Druggable: 4 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.57

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
Protease	2	10.5×	0.071
GPCR	1	3.4×	0.646
Enzyme (other)	1	1.7×	0.744
Transcription factor	1	1.2×	0.744
Other/Unknown	2	0.5×	0.968

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EBF3	Transcription factor	no		IPT_dom, Transcription_factor_COE, Ig-like_fold
KCTD11	Other/Unknown	no		T1-type_BTB, SKP1/BTB/POZ_sf, KCTD11/21_C
ACE	Protease	yes	3.4.15.1	Peptidase_M2
AGT	Other/Unknown	no		Serpin_fam, Angiotensinogen, Serpin_CS
AGTR1	GPCR	yes		ATII_AT1_rcpt, ATII_rcpt, GPCR_Rhodpsn
AGXT	Enzyme (other)	yes	2.6.1.44	Aminotrans_V_dom, PyrdxlP-dep_Trfase_major, PyrdxlP-dep_Trfase_small
REN	Protease	yes	3.4.23.15	Aspartic_peptidase_A1, Aspartic_peptidase_AS, Aspartic_peptidase_N

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
subcutaneous adipose tissue	2
liver	2
right lobe of liver	2
tendon of biceps brachii	1
tibialis anterior	1
esophagus mucosa	1
lower esophagus mucosa	1
tibial nerve	1
ileal mucosa	1
left testis	1
right testis	1
lateral globus pallidus	1
placenta	1
skin of hip	1
endometrium epithelium	1
adult mammalian kidney	1
decidua	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EBF3	193	broad	marker	tibialis anterior, subcutaneous adipose tissue, tendon of biceps brachii
KCTD11	132	ubiquitous	marker	lower esophagus mucosa, tibial nerve, esophagus mucosa
ACE	177	ubiquitous	marker	ileal mucosa, right testis, left testis
AGT	255	broad	marker	right lobe of liver, liver, lateral globus pallidus
AGTR1	224		marker	skin of hip, placenta, subcutaneous adipose tissue
AGXT	125	tissue_specific	marker	right lobe of liver, liver, endometrium epithelium
REN	126	tissue_specific	marker	decidua, adult mammalian kidney, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AGT	5,091
ACE	3,659
REN	3,244
AGTR1	2,651
AGXT	2,648
EBF3	655
KCTD11	420

Intra-cohort edges

A	B	Sources
ACE	AGT	biogrid_interaction, string_interaction
ACE	AGTR1	string_interaction
ACE	REN	string_interaction
AGT	AGTR1	intact, string_interaction
AGT	REN	biogrid_interaction, intact, string_interaction
AGTR1	REN	string_interaction

Structural data

PDB: 6 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACE	P12821	97
REN	P00797	91
AGT	P01019	22
AGXT	P21549	17
AGTR1	P30556	11
EBF3	Q9H4W6	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KCTD11	Q693B1	85.00

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 23. 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
Metabolism of Angiotensinogen to Angiotensins	3	380.7×	8e-07	ACE, AGT, REN
Peptide hormone metabolism	2	108.8×	0.002	ACE, AGT
Class A/1 (Rhodopsin-like receptors)	2	29.7×	0.010	AGT, AGTR1
Peptide ligand-binding receptors	2	29.7×	0.010	AGT, AGTR1
GPCR ligand binding	2	25.7×	0.011	AGT, AGTR1
G alpha (q) signalling events	2	22.9×	0.011	AGT, AGTR1
GPCR downstream signalling	2	17.4×	0.017	AGT, AGTR1
Glyoxylate metabolism and glycine degradation	1	152.3×	0.017	AGXT
Signaling by GPCR	2	16.0×	0.017	AGT, AGTR1
Protein localization	1	38.1×	0.060	AGXT
Peroxisomal protein import	1	34.6×	0.060	AGXT
Regulation of lipid metabolism by PPARalpha	1	28.2×	0.067	AGT
Cargo recognition for clathrin-mediated endocytosis	1	20.9×	0.082	AGTR1
PPARA activates gene expression	1	18.9×	0.082	AGT
Clathrin-mediated endocytosis	1	17.0×	0.082	AGTR1
Metabolism of proteins	2	5.0×	0.082	ACE, AGT
Metabolism	2	4.7×	0.084	AGT, AGXT
Metabolism of amino acids and derivatives	1	13.5×	0.092	AGXT
Signal Transduction	2	4.1×	0.096	AGT, AGTR1
G alpha (i) signalling events	1	7.8×	0.140	AGT
Membrane Trafficking	1	7.4×	0.140	AGTR1
Vesicle-mediated transport	1	7.0×	0.142	AGTR1
Metabolism of lipids	1	6.3×	0.149	AGT

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
renin-angiotensin regulation of aldosterone production	3	2407.4×	5e-09	AGT, AGTR1, REN
angiotensin-activated signaling pathway	3	656.6×	4e-07	ACE, AGT, AGTR1
regulation of vasoconstriction	3	343.9×	2e-06	ACE, AGT, AGTR1
kidney development	4	80.2×	2e-06	ACE, AGT, AGTR1, REN
regulation of renal output by angiotensin	2	2407.4×	3e-06	ACE, AGT
maintenance of blood vessel diameter homeostasis by renin-angiotensin	2	1605.0×	8e-06	AGT, AGTR1
regulation of renal sodium excretion	2	1203.7×	1e-05	AGT, AGTR1
regulation of systemic arterial blood pressure by renin-angiotensin	2	963.0×	2e-05	ACE, AGTR1
regulation of blood pressure	3	95.0×	4e-05	ACE, AGT, REN
positive regulation of cholesterol metabolic process	2	601.9×	5e-05	AGT, AGTR1
amyloid-beta metabolic process	2	437.7×	8e-05	ACE, REN
angiotensin maturation	2	370.4×	1e-04	ACE, REN
low-density lipoprotein particle remodeling	2	300.9×	1e-04	AGT, AGTR1
positive regulation of macrophage derived foam cell differentiation	2	240.7×	2e-04	AGT, AGTR1
blood vessel diameter maintenance	2	178.3×	4e-04	ACE, AGTR1
positive regulation of reactive oxygen species metabolic process	2	145.9×	5e-04	AGT, AGTR1
blood vessel remodeling	2	109.4×	9e-04	ACE, AGT
regulation of blood volume by renin-angiotensin	1	2407.4×	0.002	AGT
mononuclear cell proliferation	1	2407.4×	0.002	ACE
regulation of cell growth	2	63.4×	0.002	AGT, AGTR1
G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger	1	1203.7×	0.004	AGT
regulation of angiotensin metabolic process	1	1203.7×	0.004	ACE
response to cGMP	1	1203.7×	0.004	REN
cell proliferation in bone marrow	1	1203.7×	0.004	ACE
negative regulation of gap junction assembly	1	1203.7×	0.004	ACE
male gonad development	2	44.6×	0.004	ACE, REN
positive regulation of inflammatory response	2	41.5×	0.004	AGT, AGTR1
substance P catabolic process	1	802.5×	0.004	ACE
obsolete glycine biosynthetic process, by transamination of glyoxylate	1	802.5×	0.004	AGXT
oxalic acid secretion	1	802.5×	0.004	AGXT

Therapeutics

Drug target analysis

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

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
ACE	TELMISARTAN
AGTR1	IRBESARTAN
REN	CAPTOPRIL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AGTR1	88	4
ACE	31	4
REN	13	4
EBF3	0	0
KCTD11	0	0
AGT	0	0
AGXT	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TELMISARTAN	4	ACE, AGTR1
MOEXIPRIL	4	ACE
RAMIPRIL	4	ACE
LISINOPRIL ANHYDROUS	4	ACE
SITAGLIPTIN	4	ACE
TRANDOLAPRIL	4	ACE
CAPTOPRIL	4	ACE, REN
PERINDOPRIL	4	ACE
QUINAPRIL	4	ACE
LOSARTAN	4	ACE, AGTR1
FOSINOPRIL	4	ACE
IMIDAPRIL	4	ACE
ENALAPRILAT ANHYDROUS	4	ACE
ENALAPRIL	4	ACE
BENAZEPRIL	4	ACE
IRBESARTAN	4	AGTR1
SARALASIN	4	AGTR1
LOSARTAN POTASSIUM	4	AGTR1
CANDESARTAN CILEXETIL	4	AGTR1
CLOTRIMAZOLE	4	AGTR1
SIMVASTATIN	4	AGTR1
VALSARTAN	4	AGTR1
RIMONABANT	4	AGTR1
ARIPIPRAZOLE	4	AGTR1
PONATINIB	4	AGTR1
OXYMETHOLONE	4	AGTR1
OLMESARTAN MEDOXOMIL	4	AGTR1
NORGESTIMATE	4	AGTR1
ROCURONIUM	4	AGTR1
PYRVINIUM	4	AGTR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
REN	541	Binding:472, Functional:68, ADMET:1
AGTR1	421	Binding:315, Functional:105, ADMET:1
ACE	304	Binding:288, Functional:8, ADMET:5, Unclassified:3
AGXT	8	Binding:8
AGT	2	Binding:2
KCTD11	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ACE	3.4.15.1	peptidyl-dipeptidase A
AGXT	2.6.1.44, 2.6.1.51	alanine-glyoxylate transaminase, serine-pyruvate transaminase
REN	3.4.23.15	renin

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ACE	304
AGTR1	421
REN	541

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

30 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)
TELMISARTAN	4	ACE, AGTR1
MOEXIPRIL	4	ACE
RAMIPRIL	4	ACE
LISINOPRIL ANHYDROUS	4	ACE
SITAGLIPTIN	4	ACE
TRANDOLAPRIL	4	ACE
CAPTOPRIL	4	ACE, REN
PERINDOPRIL	4	ACE
QUINAPRIL	4	ACE
LOSARTAN	4	ACE, AGTR1
FOSINOPRIL	4	ACE
IMIDAPRIL	4	ACE
ENALAPRILAT ANHYDROUS	4	ACE
ENALAPRIL	4	ACE
BENAZEPRIL	4	ACE
IRBESARTAN	4	AGTR1
SARALASIN	4	AGTR1
LOSARTAN POTASSIUM	4	AGTR1
CANDESARTAN CILEXETIL	4	AGTR1
CLOTRIMAZOLE	4	AGTR1
SIMVASTATIN	4	AGTR1
VALSARTAN	4	AGTR1
RIMONABANT	4	AGTR1
ARIPIPRAZOLE	4	AGTR1
PONATINIB	4	AGTR1
OXYMETHOLONE	4	AGTR1
OLMESARTAN MEDOXOMIL	4	AGTR1
NORGESTIMATE	4	AGTR1
ROCURONIUM	4	AGTR1
PYRVINIUM	4	AGTR1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	ACE, AGTR1, REN
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	AGXT
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	EBF3, KCTD11, AGT

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
AGT	2	AGTR1, ACE, REN
EBF3	0	—
KCTD11	1	—
AGXT	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.