Essential hypertension, genetic

Summary

Essential hypertension, genetic (MONDO:0007781) is a disease with 9 cohort genes. The dominant Reactome pathway is Peptide ligand-binding receptors (3 cohort genes).

At a glance

• Cohort genes: 9
• ClinVar variants: 78

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	essential hypertension, genetic
Mondo ID	MONDO:0007781
OMIM	145500
Is cancer (heuristic)	no

Also known as: blood pressure regulation QTL · EHT · genetic essential hypertension · hypertension, essential, salt-sensitive · hypertension, essential, susceptibility to, 2 · hypertension, essential, susceptibility to, 3 · hypertension, essential, susceptibility to, 4 · hypertension, essential, susceptibility to, 5 · hypertension, essential, susceptibility to, 6 · hypertension, susceptibility to

Data availability: 78 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › arterial disorder › hypertensive disorder › essential hypertension › essential hypertension, genetic

Related subtypes (2): malignant essential hypertension, benign essential hypertension

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

78 retrieved; paginated sample, class counts are floors:

47 uncertain significance, 10 likely benign, 7 conflicting classifications of pathogenicity, 5 likely pathogenic, 5 benign/likely benign, 2 pathogenic/likely pathogenic, 1 benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
429714	NM_001384479.1(AGT):c.1060C>T	AGT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
429788	NM_001384479.1(AGT):c.829+1G>T	AGT	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
50206	NM_000685.5(AGTR1):c.251G>A (p.Trp84Ter)	AGTR1	Pathogenic	criteria provided, single submitter
1184963	NM_000685.5(AGTR1):c.696_700del (p.Pro233fs)	AGTR1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3588650	NM_000685.5(AGTR1):c.166del (p.Tyr56fs)	AGTR1	Likely pathogenic	criteria provided, single submitter
3588655	NM_000685.5(AGTR1):c.337dup (p.Tyr113fs)	AGTR1	Likely pathogenic	criteria provided, single submitter
3588656	NM_000685.5(AGTR1):c.340del (p.Ala114fs)	AGTR1	Likely pathogenic	criteria provided, single submitter
50207	NM_000685.5(AGTR1):c.376C>T (p.Arg126Ter)	AGTR1	Likely pathogenic	criteria provided, single submitter
1328411	NM_001384479.1(AGT):c.76C>T (p.Arg26Trp)	AGT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
296077	NC_000001.11:g.230706106G>A	AGT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
296082	NC_000001.11:g.230710177T>G	AGT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
876869	NC_000001.11:g.230710793T>G	AGT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1685513	NM_000685.5(AGTR1):c.419G>A (p.Arg140His)	AGTR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2634148	NM_000685.5(AGTR1):c.-17C>T	AGTR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
900269	NM_000685.5(AGTR1):c.500G>A (p.Arg167Gln)	AGTR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1306360	NM_001384479.1(AGT):c.380C>T (p.Pro127Leu)	AGT	Uncertain significance	criteria provided, multiple submitters, no conflicts
1405037	NM_001384479.1(AGT):c.952G>C (p.Asp318His)	AGT	Uncertain significance	criteria provided, multiple submitters, no conflicts
296084	NC_000001.11:g.230710439C>A	AGT	Uncertain significance	criteria provided, multiple submitters, no conflicts
591365	NM_001384479.1(AGT):c.374T>C	AGT	Uncertain significance	criteria provided, single submitter
806381	NM_001384479.1(AGT):c.862C>T	AGT	Uncertain significance	criteria provided, multiple submitters, no conflicts
876805	NC_000001.11:g.230703298G>A	AGT	Uncertain significance	criteria provided, multiple submitters, no conflicts
1369328	NM_000685.5(AGTR1):c.925T>C (p.Phe309Leu)	AGTR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1482663	NM_000685.5(AGTR1):c.1080A>G (p.Ter360Trp)	AGTR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1521584	NM_000685.5(AGTR1):c.736G>C (p.Val246Leu)	AGTR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2021791	NM_000685.5(AGTR1):c.-41T>G	AGTR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2072860	NM_000685.5(AGTR1):c.400A>G (p.Met134Val)	AGTR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2144773	NM_000685.5(AGTR1):c.1066T>G (p.Phe356Val)	AGTR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2537130	NM_000685.5(AGTR1):c.779C>T (p.Thr260Ile)	AGTR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3097384	NM_000685.5(AGTR1):c.814C>T (p.Arg272Cys)	AGTR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
343670	NM_000685.5(AGTR1):c.340G>A (p.Ala114Thr)	AGTR1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 4 · 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
AGTR1	Strong	Autosomal recessive	renal tubular dysgenesis of genetic origin	5
PTGIS	Limited	Unknown	essential hypertension, genetic
ECE1	No Known Disease Relationship	Unknown	essential hypertension, genetic	2
RGS5	No Known Disease Relationship	Unknown	essential hypertension, genetic

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ECE1	Orphanet:388	Hirschsprung disease
AGTR1	Orphanet:97369	Renal tubular dysgenesis of genetic origin
AGT	Orphanet:97369	Renal tubular dysgenesis of genetic origin
AGXT	Orphanet:93598	Primary hyperoxaluria type 1

Cohort genes → proteins

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ECE1	HGNC:3146	ENSG00000117298	P42892	Endothelin-converting enzyme 1	gencc,clinvar
AGTR1	HGNC:336	ENSG00000144891	P30556	Type-1 angiotensin II receptor	gencc,clinvar
PTGIS	HGNC:9603	ENSG00000124212	Q16647	Prostacyclin synthase	gencc,clinvar
RGS5	HGNC:10001	ENSG00000143248	O15539	Regulator of G-protein signaling 5	gencc
CDCA3	HGNC:14624	ENSG00000111665	Q99618	Cell division cycle-associated protein 3	clinvar
NANOS3	HGNC:22048	ENSG00000187556	P60323	Nanos homolog 3	clinvar
AGT	HGNC:333	ENSG00000135744	P01019	Angiotensinogen	clinvar
AGXT	HGNC:341	ENSG00000172482	P21549	Alanine–glyoxylate aminotransferase	clinvar
NOS3	HGNC:7876	ENSG00000164867	P29474	Nitric oxide synthase 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ECE1	Endothelin-converting enzyme 1	Converts big endothelin-1 to endothelin-1.
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.
PTGIS	Prostacyclin synthase	Catalyzes the biosynthesis and metabolism of eicosanoids.
RGS5	Regulator of G-protein signaling 5	Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form.
CDCA3	Cell division cycle-associated protein 3	F-box-like protein which is required for entry into mitosis.
NANOS3	Nanos homolog 3	Plays a role in the maintenance of the undifferentiated state of germ cells regulating the spermatogonia cell cycle and inducing a prolonged transit in G1 phase.
AGT	Angiotensinogen	Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.
AGXT	Alanine–glyoxylate aminotransferase	Peroxisomal aminotransferase that catalyzes the transamination of glyoxylate to glycine and contributes to the glyoxylate detoxification.
NOS3	Nitric oxide synthase 3	Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway.

Protein-family classification

Druggable: 5 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.56

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
Enzyme (other)	3	4.0×	0.166
Protease	1	4.1×	0.532
GPCR	1	2.7×	0.532
Transcription factor	1	0.9×	0.859
Other/Unknown	3	0.6×	0.955

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ECE1	Protease	yes	3.4.24.71	Peptidase_M13, Peptidase_M13_N, Peptidase_M13_C
AGTR1	GPCR	yes		ATII_AT1_rcpt, ATII_rcpt, GPCR_Rhodpsn
PTGIS	Enzyme (other)	yes	5.3.99.4	Cyt_P450, Cyt_P450_E_grp-IV, Cyt_P450_CYP7A1-type
RGS5	Other/Unknown	no		RGS, RGS_subdom1/3, RGS_RGS5
CDCA3	Other/Unknown	no		CDCA3
NANOS3	Transcription factor	no		Nanos/Xcar2, Znf_nanos-typ, Nanos_sf
AGT	Other/Unknown	no		Serpin_fam, Angiotensinogen, Serpin_CS
AGXT	Enzyme (other)	yes	2.6.1.44	Aminotrans_V_dom, PyrdxlP-dep_Trfase_major, PyrdxlP-dep_Trfase_small
NOS3	Enzyme (other)	yes	1.14.13.39	Flavdoxin-like, OxRdtase_FAD/NAD-bd, Flavoprot_Pyr_Nucl_cyt_Rdtase

Expression context

Cohort genes with no expression data: 0.

8 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)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
blood vessel layer	2
liver	2
right lobe of liver	2
adrenal tissue	1
left adrenal gland cortex	1
stromal cell of endometrium	1
placenta	1
skin of hip	1
subcutaneous adipose tissue	1
parietal pleura	1
right coronary artery	1
cardia of stomach	1
descending thoracic aorta	1
oocyte	1
secondary oocyte	1
ventricular zone	1
amygdala	1
prefrontal cortex	1
primordial germ cell in gonad	1
lateral globus pallidus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ECE1	288	ubiquitous	marker	stromal cell of endometrium, adrenal tissue, left adrenal gland cortex
AGTR1	224		marker	skin of hip, placenta, subcutaneous adipose tissue
PTGIS	232	broad	marker	parietal pleura, right coronary artery, blood vessel layer
RGS5	301	ubiquitous	marker	blood vessel layer, descending thoracic aorta, cardia of stomach
CDCA3	199	ubiquitous	marker	ventricular zone, oocyte, secondary oocyte
NANOS3	129	broad	yes	primordial germ cell in gonad, prefrontal cortex, amygdala
AGT	255	broad	marker	right lobe of liver, liver, lateral globus pallidus
AGXT	125	tissue_specific	marker	right lobe of liver, liver, endometrium epithelium
NOS3	168	broad	marker	spleen, apex of heart, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AGT	5,091
NOS3	3,606
AGTR1	2,651
AGXT	2,648
PTGIS	2,053
CDCA3	1,836
RGS5	1,497
ECE1	1,316
NANOS3	932

Intra-cohort edges

A	B	Sources
AGT	AGTR1	intact, string_interaction
AGT	ECE1	string_interaction
ECE1	PTGIS	string_interaction
NOS3	PTGIS	string_interaction

Structural data

PDB: 7 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NOS3	P29474	105
AGT	P01019	22
AGXT	P21549	17
AGTR1	P30556	11
PTGIS	Q16647	2
ECE1	P42892	1
RGS5	O15539	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NANOS3	P60323	71.75
CDCA3	Q99618	59.01

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 36. Enrichment computed across 9 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
Peptide ligand-binding receptors	3	27.8×	0.005	ECE1, AGTR1, AGT
G alpha (q) signalling events	3	21.5×	0.005	AGTR1, RGS5, AGT
NOSIP mediated eNOS trafficking	1	713.8×	0.017	NOS3
NOSTRIN mediated eNOS trafficking	1	285.5×	0.029	NOS3
Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation	1	142.8×	0.029	NOS3
Eicosanoids	1	119.0×	0.029	PTGIS
eNOS activation	1	109.8×	0.029	NOS3
Specification of primordial germ cells	1	109.8×	0.029	NANOS3
Nitric oxide stimulates guanylate cyclase	1	102.0×	0.029	NOS3
Synthesis of Prostaglandins (PG) and Thromboxanes (TX)	1	95.2×	0.029	PTGIS
Glyoxylate metabolism and glycine degradation	1	95.2×	0.029	AGXT
Class A/1 (Rhodopsin-like receptors)	2	18.5×	0.029	AGTR1, AGT
GPCR ligand binding	2	16.0×	0.029	AGTR1, AGT
Metabolism of Angiotensinogen to Angiotensins	1	79.3×	0.032	AGT
GPCR downstream signalling	2	10.9×	0.032	AGTR1, AGT
Signaling by GPCR	2	10.0×	0.035	AGTR1, AGT
G alpha (i) signalling events	2	9.7×	0.035	RGS5, AGT
VEGFR2 mediated vascular permeability	1	51.0×	0.039	NOS3
ROS and RNS production in phagocytes	1	42.0×	0.045	NOS3
Peptide hormone metabolism	1	34.0×	0.052	AGT
Reproduction	1	23.8×	0.068	NANOS3
Protein localization	1	23.8×	0.068	AGXT
Peroxisomal protein import	1	21.6×	0.069	AGXT
Extra-nuclear estrogen signaling	1	21.3×	0.069	NOS3
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	20.1×	0.070	NOS3
Regulation of lipid metabolism by PPARalpha	1	17.6×	0.077	AGT
Cargo recognition for clathrin-mediated endocytosis	1	13.1×	0.099	AGTR1
PPARA activates gene expression	1	11.8×	0.105	AGT
Clathrin-mediated endocytosis	1	10.7×	0.112	AGTR1
Metabolism of amino acids and derivatives	1	8.4×	0.135	AGXT

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of vasoconstriction	3	267.5×	2e-05	ECE1, AGTR1, AGT
renin-angiotensin regulation of aldosterone production	2	1248.3×	4e-05	AGTR1, AGT
maintenance of blood vessel diameter homeostasis by renin-angiotensin	2	1248.3×	4e-05	AGTR1, AGT
regulation of renal sodium excretion	2	936.2×	6e-05	AGTR1, AGT
regulation of systemic arterial blood pressure by endothelin	2	624.1×	1e-04	ECE1, NOS3
positive regulation of cholesterol metabolic process	2	468.1×	2e-04	AGTR1, AGT
angiotensin-activated signaling pathway	2	340.4×	3e-04	AGTR1, AGT
low-density lipoprotein particle remodeling	2	234.1×	6e-04	AGTR1, AGT
positive regulation of macrophage derived foam cell differentiation	2	187.2×	8e-04	AGTR1, AGT
G protein-coupled receptor signaling pathway	4	16.1×	1e-03	ECE1, AGTR1, RGS5, AGT
blood vessel diameter maintenance	2	138.7×	0.001	AGTR1, NOS3
positive regulation of reactive oxygen species metabolic process	2	113.5×	0.002	AGTR1, AGT
blood vessel remodeling	2	85.1×	0.003	AGT, NOS3
regulation of blood volume by renin-angiotensin	1	1872.4×	0.005	AGT
calcitonin catabolic process	1	1872.4×	0.005	ECE1
endothelin maturation	1	1872.4×	0.005	ECE1
apoptotic signaling pathway	2	49.9×	0.006	PTGIS, NANOS3
regulation of cell growth	2	49.3×	0.006	AGTR1, AGT
regulation of blood pressure	2	49.3×	0.006	AGT, NOS3
regulation of renal output by angiotensin	1	936.2×	0.006	AGT
regulation of the force of heart contraction by chemical signal	1	936.2×	0.006	NOS3
G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger	1	936.2×	0.006	AGT
negative regulation of muscle hyperplasia	1	936.2×	0.006	NOS3
smooth muscle hyperplasia	1	936.2×	0.006	NOS3
tetrahydrobiopterin metabolic process	1	936.2×	0.006	NOS3
substance P catabolic process	1	624.1×	0.008	ECE1
obsolete glycine biosynthetic process, by transamination of glyoxylate	1	624.1×	0.008	AGXT
regulation of nervous system process	1	624.1×	0.008	NOS3
oxalic acid secretion	1	624.1×	0.008	AGXT
phospholipase C-activating angiotensin-activated signaling pathway	1	624.1×	0.008	AGTR1

Therapeutics

Drug target analysis

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

Druggability breadth: 6 of 9 evidence-associated genes (67%) 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
ECE1	IDARUBICIN HYDROCHLORIDE
AGTR1	IRBESARTAN
NOS3	CHLORZOXAZONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AGTR1	88	4
NOS3	6	4
ECE1	4	4
PTGIS	1	2
RGS5	0	0
CDCA3	0	0
NANOS3	0	0
AGT	0	0
AGXT	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IDARUBICIN HYDROCHLORIDE	4	ECE1
LIRAGLUTIDE	4	ECE1
IRBESARTAN	4	AGTR1
LOSARTAN	4	AGTR1
SARALASIN	4	AGTR1
LOSARTAN POTASSIUM	4	AGTR1
CANDESARTAN CILEXETIL	4	AGTR1
TELMISARTAN	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
INDOCYANINE GREEN ACID FORM	4	AGTR1
BALSALAZIDE	4	AGTR1
ROSIGLITAZONE	4	AGTR1
SULCONAZOLE	4	AGTR1
MILTEFOSINE	4	AGTR1
BUTOCONAZOLE	4	AGTR1
SORAFENIB	4	AGTR1
NITAZOXANIDE	4	AGTR1
PIMOZIDE	4	AGTR1
FELODIPINE	4	AGTR1
DESOGESTREL	4	AGTR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
AGTR1	421	Binding:315, Functional:105, ADMET:1
NOS3	188	Binding:178, ADMET:6, Functional:4
ECE1	80	Binding:78, ADMET:1, Functional:1
PTGIS	12	Binding:12
AGXT	8	Binding:8
AGT	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ECE1	3.4.24.71	endothelin-converting enzyme 1
PTGIS	5.3.99.4	prostaglandin-I synthase
AGXT	2.6.1.44, 2.6.1.51	alanine-glyoxylate transaminase, serine-pyruvate transaminase
NOS3	1.14.13.39	nitric-oxide synthase (NADPH)

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
AGTR1	421
NOS3	188

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; 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)
IDARUBICIN HYDROCHLORIDE	4	ECE1
LIRAGLUTIDE	4	ECE1
IRBESARTAN	4	AGTR1
LOSARTAN	4	AGTR1
SARALASIN	4	AGTR1
LOSARTAN POTASSIUM	4	AGTR1
CANDESARTAN CILEXETIL	4	AGTR1
TELMISARTAN	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
INDOCYANINE GREEN ACID FORM	4	AGTR1
BALSALAZIDE	4	AGTR1
ROSIGLITAZONE	4	AGTR1
SULCONAZOLE	4	AGTR1
MILTEFOSINE	4	AGTR1
BUTOCONAZOLE	4	AGTR1
SORAFENIB	4	AGTR1
NITAZOXANIDE	4	AGTR1
PIMOZIDE	4	AGTR1
FELODIPINE	4	AGTR1
DESOGESTREL	4	AGTR1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	ECE1, AGTR1, NOS3
B	Phased (≥1) drug, not yet approved	1	PTGIS
C	Druggable family + PDB, no drug	1	AGXT
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	RGS5, CDCA3, NANOS3, AGT

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)
AGT	2	AGTR1
RGS5	0	—
CDCA3	0	—
NANOS3	0	—
AGXT	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.