Hypertensive disorder

Summary

Hypertensive disorder (MONDO:0005044) is a disease (an umbrella term covering 12 Mondo subtypes) with 75 cohort genes (2,084 GWAS associations across 176 studies) and 4,735 clinical trials. The dominant Reactome pathway is NCAM1 interactions (7 cohort genes). Top therapeutic interventions include losartan, amlodipine, and hydrochlorothiazide.

At a glance

• Umbrella term: 12 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 2,084
• ClinVar variants: 29
• Clinical trials: 4,735

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypertensive disorder
Mondo ID	MONDO:0005044
EFO	EFO:0000537
MeSH	D006973
DOID	DOID:10763
ICD-10-CM	I10-I16, I15
NCIT	C3117
SNOMED CT	38341003
UMLS	C0020538
MedGen	6969
Anatomy (UBERON)	UBERON:0004573
Is cancer (heuristic)	no

Also known as: blood pressure, high · blood pressure, increased · high blood pressure · HTN · hypertensive disease · increased blood pressure · pressure, high blood · vascular hypertensive disorder

Data availability: 29 ClinVar variants · 2,084 GWAS associations (176 studies) · 1 HPO phenotype · 6 cell lines.

Disease family

An umbrella term covering 12 Mondo subtypes.

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

Related subtypes (29): vertebral artery insufficiency, splenic artery aneurysm, basilar artery insufficiency, arteriosclerosis disorder, subclavian artery aneurysm, pulmonary artery choriocarcinoma, pulmonary artery leiomyosarcoma, coronary artery disorder, carotid artery disorder, pulmonary embolism, peripheral arterial disease, hypotensive disorder, large artery stroke, aortic disorder, cervical artery dissection, anterior spinal artery syndrome, fibromuscular dysplasia, retinal arterial tortuosity, Sneddon syndrome, celiac trunk compression syndrome, pediatric arterial ischemic stroke, absence of the pulmonary artery, arterial occlusion, aberrant subclavian artery, anterior spinal artery stroke, arteritis, pulmonary artery disease, fibromuscular dysplasia, multifocal, carotid web

Subtypes (12): essential hypertension, secondary hypertension, pulmonary hypertension, early onset hypertension, chemotherapy-induced hypertension, intracranial hypertension, malignant hypertension, ocular hypertension, kallikrein hypertension, hypertension, pregnancy-induced, resistant hypertension, hypertensive urgency

Genetics & variants

GWAS landscape

2,084 GWAS associations across 176 studies. Top hits map to 27 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs10857147	4e-121	PRDM8 - FGF5	?	0.11
rs11105378	9e-54	ATP2B1	?	0.09
rs1421085	3e-51	FTO	?
rs3184504	2e-49	ATXN2, SH2B3	?
rs13125101	5e-49	PRDM8 - FGF5	?
rs11099097	2e-48	PRDM8 - FGF5	?
rs7827545	2e-44	ZFAT x ZFAT	G
rs11014267	2e-43	CACNB2	?	0.06
rs12656497	5e-43	NPR3 - LINC02120	?
rs1275978	7e-43	KCNK3	?	0.06
rs55823223	2e-41	TRIM65	A
rs3918226	2e-39	NOS3	?
chr4:81184341	4e-37		?	0.19
rs604723	1e-36	ARHGAP42	?
rs16998073	6e-36	PRDM8 - FGF5	T	1.2
rs8027450	6e-36	FURIN	?
rs880315	9e-36	CASZ1	?	0.05
rs1275988	1e-35	RPL37P11 - KCNK3	?
rs55857306	4e-35	CLCN6	?
rs198851	1e-34	H2BC4	?
rs17367504	4e-34	MTHFR	?	0.1
rs1401982	4e-32	ATP2B1	G	0.94
rs79105258	9e-31	CUX2	A	0.17
rs35441	1e-28	TBX3-AS1 - UBA52P7	T	0.94
rs592373	2e-27	LSP1	?
rs167479	4e-27	RGL3	?
rs2301597	7e-27	NMT1	?
rs11451130	2e-26	TBX3-AS1 - UBA52P7	?
rs12978472	9e-26	INSR	?
rs2137320	1e-25	LSP1	A	1.06

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST007610	Zhu Z	2019	144,793	313,761	Genetic overlap of chronic obstructive pulmonary disease and cardiovascular disease-related traits: a large-scale genome-wide cross-trait analysis.
GCST90038604	Donertas HM	2021	129,909	354,689	Common genetic associations between age-related diseases.
GCST90042688	Jiang L	2021	128,883	291,510	A generalized linear mixed model association tool for biobank-scale data.
GCST90042675	Jiang L	2021	89,851	307,528	A generalized linear mixed model association tool for biobank-scale data.
GCST006023	Surendran P	2016	83,330	73,760	Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.
GCST90042702	Jiang L	2021	75,869	283,494	A generalized linear mixed model association tool for biobank-scale data.
GCST007707	Takeuchi F	2018	22,566	28,226	Interethnic analyses of blood pressure loci in populations of East Asian and European descent.
GCST007611	Zhu Z	2019	12,550	46,368	Genetic overlap of chronic obstructive pulmonary disease and cardiovascular disease-related traits: a large-scale genome-wide cross-trait analysis.
GCST008036	Wojcik GL	2019	11,863	5,289	Genetic analyses of diverse populations improves discovery for complex traits.
GCST011141	Jeong H	2020	8,178	9,558	Identifying Interactions between Dietary Sodium, Potassium, Sodium-Potassium Ratios, and FGF5 rs16998073 Variants and Their Associated Risk for Hypertension in Korean Adults.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	3
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	47

MAF distribution

Bucket	Variants
common (>=0.05)	46
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	4

Functional consequences

Consequence	Count
intron_variant	32
intergenic_variant	11
missense_variant	3
unknown	3
intron_variant x intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs10857147	4	80259918	A>T	0.05	intergenic_variant	PRDM8 - FGF5	4e-121	Tier 4: intronic/intergenic
rs11105378	12	89696964	C>T	0.05	intron_variant	ATP2B1	9e-54	Tier 4: intronic/intergenic
rs1421085	16	53767042	T>C	0.05	intron_variant	FTO	3e-51	Tier 4: intronic/intergenic
rs3184504	12	111446804	T>A,C,G	0.05	missense_variant	ATXN2, SH2B3	2e-49	Tier 1: coding
rs13125101	4	80253438	G>A	0.05	intergenic_variant	PRDM8 - FGF5	5e-49	Tier 4: intronic/intergenic
rs11099097	4	80246155	C>G,T	0.05	intergenic_variant	PRDM8 - FGF5	2e-48	Tier 4: intronic/intergenic
rs7827545	8 x 8	134554324	C>A,T	0.05	intron_variant x intron_variant	ZFAT x ZFAT	2e-44	Tier 4: intronic/intergenic
rs11014267	10	18448045	G>A,T	0.05	intron_variant	CACNB2	2e-43	Tier 4: intronic/intergenic
rs12656497	5	32831833	T>A,C,G	0.05	intergenic_variant	NPR3 - LINC02120	5e-43	Tier 4: intronic/intergenic
rs1275978	2	26700227	C>T	0.05	intron_variant	KCNK3	7e-43	Tier 4: intronic/intergenic
rs55823223	17	75894282	G>A,C	0.14	intron_variant	TRIM65	2e-41	Tier 4: intronic/intergenic
rs3918226	7	150993088	C>T	0.05	intron_variant	NOS3	2e-39	Tier 4: intronic/intergenic
chr4:81184341							4e-37	Tier 4: intronic/intergenic
rs604723	11	100739815	T>C	0.05	intron_variant	ARHGAP42	1e-36	Tier 4: intronic/intergenic
rs16998073	4	80263187	A>C,G,T	0.05	intergenic_variant	PRDM8 - FGF5	6e-36	Tier 4: intronic/intergenic
rs8027450	15	90875164	C>A,T	0.05	intron_variant	FURIN	6e-36	Tier 4: intronic/intergenic
rs880315	1	10736809	T>C,G	0.05	intron_variant	CASZ1	9e-36	Tier 4: intronic/intergenic
rs1275988	2	26691496	C>T	0.05	intron_variant	RPL37P11 - KCNK3	1e-35	Tier 4: intronic/intergenic
rs55857306	1	11835738	G>A,C,T	0.05	intron_variant	CLCN6	4e-35	Tier 4: intronic/intergenic
rs198851	6	26104404	T>A,C,G	0.05	intergenic_variant	H2BC4	1e-34	Tier 4: intronic/intergenic
rs17367504	1	11802721	A>G	0.05	intron_variant	MTHFR	4e-34	Tier 4: intronic/intergenic
rs1401982	12	89595822	G>A,T	0.05	intron_variant	ATP2B1	4e-32	Tier 4: intronic/intergenic
rs79105258	12	111280427	C>A,T	0.253	intron_variant	CUX2	9e-31	Tier 4: intronic/intergenic
rs35441	12	115115310	C>A,G,T	0.05	intron_variant	TBX3-AS1 - UBA52P7	1e-28	Tier 4: intronic/intergenic
rs592373	11	1869760	G>A,C,T	0.05	intron_variant	LSP1	2e-27	Tier 4: intronic/intergenic
rs167479	19	11416089	T>A,C,G	0.05	missense_variant	RGL3	4e-27	Tier 1: coding
rs2301597	17	45095905	T>A,C	0.05	intron_variant	NMT1	7e-27	Tier 4: intronic/intergenic
rs11451130	12	115116281	AT>A,ATT	0.05	intron_variant	TBX3-AS1 - UBA52P7	2e-26	Tier 4: intronic/intergenic
rs12978472	19	7257979	C>A,G,T	0.05	intron_variant	INSR	9e-26	Tier 4: intronic/intergenic
rs2137320	11	1863112	G>A,C	0.05	intron_variant	LSP1	1e-25	Tier 4: intronic/intergenic

ClinVar germline variants

29 retrieved; paginated sample, class counts are floors:

12 pathogenic, 5 uncertain significance, 4 pathogenic/likely pathogenic, 3 conflicting classifications of pathogenicity, 3 likely pathogenic, 1 benign, 1 conflicting classifications of pathogenicity; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
633592	NM_033440.3(CELA2A):c.361G>A (p.Asp121Asn)	CELA2A	Pathogenic	no assertion criteria provided
633594	NM_033440.3(CELA2A):c.639+1G>C	CELA2A	Pathogenic	no assertion criteria provided
633595	NM_033440.3(CELA2A):c.209C>T (p.Thr70Met)	CELA2A	Pathogenic	criteria provided, multiple submitters, no conflicts
24455	NM_033380.3(COL4A5):c.1871G>A (p.Gly624Asp)	COL4A5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2504113	NM_006587.4(CORIN):c.684dup (p.Met229fs)	CORIN	Pathogenic	criteria provided, single submitter
523249	GRCh37/hg19 15q11.2(chr15:22765628-23300287)	CYFIP1	Pathogenic	criteria provided, single submitter
1057	NM_018122.5(DARS2):c.228-21_228-20delinsC	DARS2	Pathogenic	criteria provided, multiple submitters, no conflicts
1062	NM_018122.5(DARS2):c.492+2T>C	DARS2	Pathogenic	criteria provided, multiple submitters, no conflicts
1170	NM_000505.4(F12):c.983C>G (p.Thr328Arg)	F12	Pathogenic	criteria provided, single submitter
523533	NM_022489.4(INF2):c.658G>A (p.Glu220Lys)	INF2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
373955	NM_000297.4(PKD2):c.357_364delinsTAGGACG (p.Pro120fs)	LOC129992813	Pathogenic	criteria provided, single submitter
374107	NM_001370259.2(MEN1):c.654+1del	MEN1	Pathogenic	criteria provided, single submitter
827676	NM_006554.5(MTX2):c.295_296del (p.Ser98_Leu99insTer)	MTX2	Pathogenic	no assertion criteria provided
374097	NM_001009944.3(PKD1):c.8311G>A (p.Glu2771Lys)	PKD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374102	NM_001009944.3(PKD1):c.3520C>T (p.Gln1174Ter)	PKD1	Pathogenic	criteria provided, multiple submitters, no conflicts
374187	NM_001009944.3(PKD1):c.11524T>C (p.Trp3842Arg)	PKD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
633593	NM_033440.3(CELA2A):c.253C>A (p.Leu85Met)	CELA2A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
523453	NM_002473.6(MYH9):c.4271A>G (p.Asp1424Gly)	MYH9	Likely pathogenic	criteria provided, multiple submitters, no conflicts
374044	NM_001009944.3(PKD1):c.9185T>A (p.Val3062Asp)	PKD1	Likely pathogenic	criteria provided, single submitter
242442	NM_000092.5(COL4A4):c.2320G>C (p.Gly774Arg)	COL4A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
255039	NM_000092.5(COL4A4):c.4217-15T>C	COL4A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
523324	NM_000092.5(COL4A4):c.4394G>A (p.Gly1465Asp)	COL4A4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
199044	NM_000157.4(GBA1):c.1093G>A (p.Glu365Lys)	GBA1	Conflicting classifications of pathogenicity; risk factor	criteria provided, conflicting classifications
374041	NM_000092.5(COL4A4):c.3055G>C (p.Glu1019Gln)	COL4A4	Uncertain significance	criteria provided, single submitter
2570686	NM_005245.4(FAT1):c.10513A>T (p.Arg3505Trp)	FAT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2570687	NM_005245.4(FAT1):c.11518G>A (p.Val3840Met)	FAT1	Uncertain significance	criteria provided, single submitter
1338787	NM_173598.6(KSR2):c.2512C>T (p.Arg838Cys)	KSR2	Uncertain significance	criteria provided, single submitter
374128	NM_016203.4(PRKAG2):c.590C>G (p.Pro197Arg)	PRKAG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
18068	NC_000001.11:g.230710048A>G	AGT	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 45 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RIT1	Orphanet:648	Noonan syndrome
CNNM2	Orphanet:620363	Primary hypomagnesemia-generalized seizures-intellectual disability-obesity syndrome
RYR2	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
RYR2	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
RYR2	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
RYR2	Orphanet:3286	Catecholaminergic polymorphic ventricular tachycardia
SALL1	Orphanet:857	Townes-Brocks syndrome
ATXN2	Orphanet:803	Amyotrophic lateral sclerosis
ATXN2	Orphanet:98756	Spinocerebellar ataxia type 2
TBX3	Orphanet:3138	Ulnar-mammary syndrome
TBX5	Orphanet:101016	Romano-Ward syndrome
TBX5	Orphanet:392	Holt-Oram syndrome
TNNT3	Orphanet:1146	Distal arthrogryposis type 1
TNNT3	Orphanet:1147	Sheldon-Hall syndrome
UMOD	Orphanet:88950	UMOD-related autosomal dominant tubulointerstitial kidney disease
VPS33B	Orphanet:2697	Arthrogryposis-renal dysfunction-cholestasis syndrome
WNT2B	Orphanet:714487	Congenital diarrhea-chronic gastrointestinal inflammation-ocular dysgenesis syndrome
YWHAE	Orphanet:213711	Endometrial stromal sarcoma
YWHAE	Orphanet:217385	17p13.3 microduplication syndrome
YWHAE	Orphanet:261257	Distal 17p13.3 microdeletion syndrome
YWHAE	Orphanet:457246	Clear cell sarcoma of kidney
YWHAE	Orphanet:531	Miller-Dieker syndrome
CACNA1D	Orphanet:324321	Sinoatrial node dysfunction and deafness
CACNA1D	Orphanet:369929	Primary hyperaldosteronism-seizures-neurological abnormalities syndrome
ABHD16A	Orphanet:631085	Autosomal recessive spastic paraplegia type 86
SLC44A4	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
PRDM8	Orphanet:324290	PRDM8-related progressive myoclonus epilepsy
PRDM16	Orphanet:154	Familial isolated dilated cardiomyopathy
PRDM16	Orphanet:1606	1p36 deletion syndrome
PRDM16	Orphanet:54260	Left ventricular noncompaction
CACNB2	Orphanet:130	Brugada syndrome
RNF213	Orphanet:2573	Moyamoya disease
CALCRL	Orphanet:363999	Non-immune hydrops fetalis
PLCE1	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome
BANK1	Orphanet:536	Systemic lupus erythematosus
CORIN	Orphanet:275555	Preeclampsia
CUX2	Orphanet:2382	Lennox-Gastaut syndrome
CHRM3	Orphanet:2970	Prune belly syndrome
CCDC88C	Orphanet:269510	Congenital non-communicating hydrocephalus
CCDC88C	Orphanet:423275	Spinocerebellar ataxia type 40
SLC39A8	Orphanet:468699	SLC39A8-CDG
PHACTR1	Orphanet:697160	Infantile epileptic spasms syndrome
SBF2	Orphanet:99956	Charcot-Marie-Tooth disease type 4B2
COL4A2	Orphanet:36383	COL4A1/2-related familial vascular leukoencephalopathy
COL4A2	Orphanet:99810	Familial porencephaly

Cohort genes → proteins

75 cohort genes, 74 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	72
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RIT1	HGNC:10023	ENSG00000143622	Q92963	GTP-binding protein Rit1	gwas
CNNM2	HGNC:103	ENSG00000148842	Q9H8M5	Metal transporter CNNM2	gwas
RYR2	HGNC:10484	ENSG00000198626	Q92736	Ryanodine receptor 2	gwas
SALL1	HGNC:10524	ENSG00000103449	Q9NSC2	Sal-like protein 1	gwas
ATXN2	HGNC:10555	ENSG00000204842	Q99700	Ataxin-2	gwas
SEMA7A	HGNC:10741	ENSG00000138623	O75326	Semaphorin-7A	gwas
SLC22A7	HGNC:10971	ENSG00000137204	Q9Y694	Solute carrier family 22 member 7	gwas
SLC30A1	HGNC:11012	ENSG00000170385	Q9Y6M5	Proton-coupled zinc antiporter SLC30A1	gwas
SLC4A7	HGNC:11033	ENSG00000033867	Q9Y6M7	Sodium bicarbonate cotransporter 3	gwas
TARBP1	HGNC:11568	ENSG00000059588	Q13395	tRNA (guanosine(18)-2’-O)-methyltransferase TARBP1	gwas
TBX18	HGNC:11595	ENSG00000112837	O95935	T-box transcription factor TBX18	gwas
TBX2	HGNC:11597	ENSG00000121068	Q13207	T-box transcription factor TBX2	gwas
TBX3	HGNC:11602	ENSG00000135111	O15119	T-box transcription factor TBX3	gwas
TBX5	HGNC:11604	ENSG00000089225	Q99593	T-box transcription factor TBX5	gwas
TCF21	HGNC:11632	ENSG00000118526	O43680	Transcription factor 21	gwas
TMOD4	HGNC:11874	ENSG00000163157	Q9NZQ9	Tropomodulin-4	gwas
TNKS	HGNC:11941	ENSG00000173273	O95271	Poly [ADP-ribose] polymerase tankyrase-1	gwas
TNNT3	HGNC:11950	ENSG00000130595	P45378	Troponin T, fast skeletal muscle	gwas
UMOD	HGNC:12559	ENSG00000169344	P07911	Uromodulin	gwas
VPS33B	HGNC:12712	ENSG00000184056	Q9H267	Vacuolar protein sorting-associated protein 33B	gwas
WNT2B	HGNC:12781	ENSG00000134245	Q93097	Protein Wnt-2b	gwas
YES1	HGNC:12841	ENSG00000176105	P07947	Tyrosine-protein kinase Yes	gwas
YWHAE	HGNC:12851	ENSG00000108953	P62258	14-3-3 protein epsilon	gwas
ZNF107	HGNC:12887	ENSG00000196247	Q9UII5	Zinc finger protein 107	gwas
RIBC2	HGNC:13241	ENSG00000128408	Q9H4K1	RIB43A-like with coiled-coils protein 2	gwas
FIGN	HGNC:13285	ENSG00000182263	Q5HY92	Fidgetin	gwas
MS4A6A	HGNC:13375	ENSG00000110077	Q9H2W1	Membrane-spanning 4-domains subfamily A member 6A	gwas
NID2	HGNC:13389	ENSG00000087303	Q14112	Nidogen-2	gwas
ZNF318	HGNC:13578	ENSG00000171467	Q5VUA4	Zinc finger protein 318	gwas
CYFIP1	HGNC:13759	ENSG00000273749	Q7L576	Cytoplasmic FMR1-interacting protein 1	clinvar
DMRTA1	HGNC:13826	ENSG00000176399	Q5VZB9	Doublesex- and mab-3-related transcription factor A1	gwas
CACNA1D	HGNC:1391	ENSG00000157388	Q01668	Voltage-dependent L-type calcium channel subunit alpha-1D	gwas
PRRC2A	HGNC:13918	ENSG00000204469	P48634	Protein PRRC2A	gwas
ABHD16A	HGNC:13921	ENSG00000204427	O95870	Phosphatidylserine lipase ABHD16A	gwas
MPIG6B	HGNC:13937	ENSG00000204420	O95866	Megakaryocyte and platelet inhibitory receptor G6b	gwas
SLC44A4	HGNC:13941	ENSG00000204385	Q53GD3	Choline transporter-like protein 4	gwas
PRDM8	HGNC:13993	ENSG00000152784	Q9NQV8	PR domain zinc finger protein 8	gwas
PRDM16	HGNC:14000	ENSG00000142611	Q9HAZ2	Histone-lysine N-methyltransferase PRDM16	gwas
CACNB2	HGNC:1402	ENSG00000165995	Q08289	Voltage-dependent L-type calcium channel subunit beta-2	gwas
RNF213	HGNC:14539	ENSG00000173821	Q63HN8	E3 ubiquitin-protein ligase RNF213	gwas
OR4X1	HGNC:14854	ENSG00000176567	Q8NH49	Olfactory receptor 4X1	gwas
CAPZA1	HGNC:1488	ENSG00000116489	P52907	F-actin-capping protein subunit alpha-1	gwas
OR5B12	HGNC:15432	ENSG00000172362	Q96R08	Olfactory receptor 5B12	gwas
ALDH1A2	HGNC:15472	ENSG00000128918	O94788	Retinal dehydrogenase 2	gwas
ZP4	HGNC:15770	ENSG00000116996	Q12836	Zona pellucida sperm-binding protein 4	gwas
ULK4	HGNC:15784	ENSG00000168038	Q96C45	Serine/threonine-protein kinase ULK4	gwas
ZNF831	HGNC:16167	ENSG00000124203	Q5JPB2	Zinc finger protein 831	gwas
LINC02871	HGNC:16180	ENSG00000125899		long intergenic non-protein coding RNA 2871	gwas
SOX6	HGNC:16421	ENSG00000110693	P35712	Transcription factor SOX-6	gwas
SORCS2	HGNC:16698	ENSG00000184985	Q96PQ0	VPS10 domain-containing receptor SorCS2	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RIT1	GTP-binding protein Rit1	Plays a crucial role in coupling NGF stimulation to the activation of both EPHB2 and MAPK14 signaling pathways and in NGF-dependent neuronal differentiation.
CNNM2	Metal transporter CNNM2	Divalent metal cation transporter.
RYR2	Ryanodine receptor 2	Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering cardiac muscle contraction.
SALL1	Sal-like protein 1	Transcriptional repressor involved in organogenesis.
ATXN2	Ataxin-2	Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane.
SEMA7A	Semaphorin-7A	Plays an important role in integrin-mediated signaling and functions both in regulating cell migration and immune responses.
SLC22A7	Solute carrier family 22 member 7	Functions as a Na(+)-independent bidirectional multispecific transporter.
SLC30A1	Proton-coupled zinc antiporter SLC30A1	Zinc ion:proton antiporter that could function at the plasma membrane mediating zinc efflux from cells against its electrochemical gradient protecting them from intracellular zinc accumulation and toxicity.
SLC4A7	Sodium bicarbonate cotransporter 3	Electroneutral sodium- and bicarbonate-dependent cotransporter with a Na(+):HCO3(-) 1:1 stoichiometry.
TARBP1	tRNA (guanosine(18)-2’-O)-methyltransferase TARBP1	S-adenosyl-L-methionine-dependent 2’-O-ribose methyltransferase that catalyzes the formation of 2’-O-methylguanosine at position 18 (Gm18) in a subset of tRNA.
TBX18	T-box transcription factor TBX18	Acts as a transcriptional repressor involved in developmental processes of a variety of tissues and organs, including the heart and coronary vessels, the ureter and the vertebral column.
TBX2	T-box transcription factor TBX2	Transcription factor which acts as a transcriptional repressor.
TBX3	T-box transcription factor TBX3	Transcriptional repressor involved in developmental processes.
TBX5	T-box transcription factor TBX5	DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation.
TCF21	Transcription factor 21	Involved in epithelial-mesenchymal interactions in kidney and lung morphogenesis that include epithelial differentiation and branching morphogenesis.
TMOD4	Tropomodulin-4	Blocks the elongation and depolymerization of the actin filaments at the pointed end.
TNKS	Poly [ADP-ribose] polymerase tankyrase-1	Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking.
TNNT3	Troponin T, fast skeletal muscle	Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
UMOD	Uromodulin	Functions in biogenesis and organization of the apical membrane of epithelial cells of the thick ascending limb of Henle’s loop (TALH), where it promotes formation of complex filamentous gel-like structure that may play a role in the water…
VPS33B	Vacuolar protein sorting-associated protein 33B	May play a role in vesicle-mediated protein trafficking to lysosomal compartments and in membrane docking/fusion reactions of late endosomes/lysosomes.
WNT2B	Protein Wnt-2b	Ligand for members of the frizzled family of seven transmembrane receptors.
YES1	Tyrosine-protein kinase Yes	Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation.
YWHAE	14-3-3 protein epsilon	Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways.
ZNF107	Zinc finger protein 107	May be involved in transcriptional regulation.
RIBC2	RIB43A-like with coiled-coils protein 2	Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.
FIGN	Fidgetin	ATP-dependent microtubule severing protein.
MS4A6A	Membrane-spanning 4-domains subfamily A member 6A	May be involved in signal transduction as a component of a multimeric receptor complex.
NID2	Nidogen-2	Cell adhesion glycoprotein which is widely distributed in basement membranes.
ZNF318	Zinc finger protein 318	Acts as a transcriptional corepressor for AR-mediated transactivation function.
CYFIP1	Cytoplasmic FMR1-interacting protein 1	Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression.
CACNA1D	Voltage-dependent L-type calcium channel subunit alpha-1D	Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…
PRRC2A	Protein PRRC2A	May play a role in the regulation of pre-mRNA splicing.
ABHD16A	Phosphatidylserine lipase ABHD16A	Phosphatidylserine (PS) lipase that mediates the hydrolysis of phosphatidylserine to generate lysophosphatidylserine (LPS).
MPIG6B	Megakaryocyte and platelet inhibitory receptor G6b	Inhibitory receptor that acts as a critical regulator of hematopoietic lineage differentiation, megakaryocyte function and platelet production.
SLC44A4	Choline transporter-like protein 4	Choline transporter that plays a role in the choline-acetylcholine system and is required to the efferent innervation of hair cells in the olivocochlear bundle for the maintenance of physiological function of outer hair cells and the prote…
PRDM8	PR domain zinc finger protein 8	Probable histone methyltransferase, preferentially acting on ‘Lys-9’ of histone H3.
PRDM16	Histone-lysine N-methyltransferase PRDM16	Transcription regulator that acts both as a histone methyltransferase or chromatin adapter, depending on the context.
CACNB2	Voltage-dependent L-type calcium channel subunit beta-2	Beta subunit of voltage-dependent calcium channels which contributes to the function of the calcium channel by increasing peak calcium current.
RNF213	E3 ubiquitin-protein ligase RNF213	Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity.
OR4X1	Olfactory receptor 4X1	Odorant receptor.
CAPZA1	F-actin-capping protein subunit alpha-1	F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends.
OR5B12	Olfactory receptor 5B12	Odorant receptor.
ALDH1A2	Retinal dehydrogenase 2	Catalyzes the NAD-dependent oxidation of aldehyde substrates, such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their corresponding carboxylic acids, all-trans-retinoate and all-trans-13,14-dihydroretinoate, respectively.
ZP4	Zona pellucida sperm-binding protein 4	Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy.
ULK4	Serine/threonine-protein kinase ULK4	May be involved in the remodeling of cytoskeletal components, such as alpha-tubulin, and in this way regulates neurite branching and elongation, as well as cell motility.
SOX6	Transcription factor SOX-6	Transcription factor that plays a key role in several developmental processes, including neurogenesis, chondrocytes differentiation and cartilage formation.
SORCS2	VPS10 domain-containing receptor SorCS2	The heterodimer formed by NGFR and SORCS2 functions as receptor for the precursor forms of NGF (proNGF) and BDNF (proBDNF).
CALCRL	Calcitonin gene-related peptide type 1 receptor	G protein-coupled receptor which specificity is determined by its interaction with receptor-activity-modifying proteins (RAMPs).
SWAP70	Switch-associated protein 70	Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor (GEF) which, independently of RAS, transduces signals from tyrosine kinase receptors to RAC.
PLCE1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1	The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.

Protein-family classification

Druggable: 21 · Difficult: 23 · Unknown: 31 · Druggable fraction: 0.28

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
Transcription factor	16	1.8×	0.180
Ion channel	2	3.0×	0.400
Antibody/Immunoglobulin	5	1.9×	0.400
Scaffold/PPI	7	1.6×	0.400
Transporter	2	2.1×	0.552
GPCR	4	1.3×	0.702
Kinase	3	1.1×	0.803
Phosphatase	1	1.1×	0.817
Other/Unknown	31	0.7×	0.996
Protease	1	0.5×	0.996
Enzyme (other)	3	0.5×	0.996

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RIT1	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
CNNM2	Other/Unknown	no		CBS_dom, CNNM, RmlC-like_jellyroll
RYR2	Ion channel	yes		RIH_dom, B30.2/SPRY, EF_hand_dom
SALL1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Sal_C2H2-zinc-finger
ATXN2	Other/Unknown	no		LsmAD_domain, PAM2_motif, LSM_dom_sf
SEMA7A	Antibody/Immunoglobulin	yes		Semap_dom, Plexin_repeat, Ig-like_dom
SLC22A7	Transporter	yes		Orgcat_transp/SVOP, MFS, MFS_dom
SLC30A1	Other/Unknown	no		Cation_efflux, Cation_efflux_TMD_sf, Cation_efflux_CTD
SLC4A7	Other/Unknown	no		HCO3_transpt_euk, HCO3_transpt-like_TM_dom, Band3_cytoplasmic_dom
TARBP1	Enzyme (other)	yes	2.1.1.34	SpoU_MeTrfase, ARM-type_fold, TARBP1
TBX18	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TBX2	Transcription factor	no		TF_T-box, TF_Brachyury, p53-like_TF_DNA-bd_sf
TBX3	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TBX5	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TCF21	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, E-box_TF_Regulators
TMOD4	Other/Unknown	no		TMOD, LRR_dom_sf
TNKS	Scaffold/PPI	no	2.4.2.30	SAM, Ankyrin_rpt, Poly(ADP-ribose)pol_cat_dom
TNNT3	Other/Unknown	no		Troponin, TNNT, Troponin_sf
UMOD	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, ZP_dom
VPS33B	Other/Unknown	no		Sec1-like, Sec1-like_dom2, Sec1-like_sf
WNT2B	Other/Unknown	no		Wnt, Wnt2, Wnt_CS
YES1	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
YWHAE	Other/Unknown	no		14-3-3, 14-3-3_CS, 14-3-3_domain
ZNF107	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Zinc_finger_PRDM4/PRDM1/PRDM14
RIBC2	Other/Unknown	no		RIB43A
FIGN	Other/Unknown	no		AAA+_ATPase, ATPase_AAA_core, ATPase_AAA_CS
MS4A6A	Other/Unknown	no		CD20-like_TM, MS4A
NID2	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, Thyroglobulin_1
ZNF318	Transcription factor	no		Matrin/U1-like-C_Znf_C2H2, Znf318-like
CYFIP1	Other/Unknown	no		Cytoplasmic_FMR1-int, CYRIA/CYRIB_Rac1-bd
DMRTA1	Other/Unknown	no		DM_DNA-bd, DMA, UBA-like_sf
CACNA1D	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, LVDCC_a1dsu
PRRC2A	Other/Unknown	no		BAT2_N, PRRC2
ABHD16A	Other/Unknown	no		AB_hydrolase_1, AB_hydrolase_fold, ABHD16_N
MPIG6B	Other/Unknown	no		G6B, G6B_V-set
SLC44A4	Other/Unknown	no		Choline_transptr-like
PRDM8	Transcription factor	no		SET_dom, Znf_C2H2_type, Znf_C2H2_sf
PRDM16	Transcription factor	no	2.1.1.367	SET_dom, Znf_C2H2_type, Znf_C2H2_sf
CACNB2	Scaffold/PPI	no		VDCC_L_bsu, SH3_domain, VDCC_L_b2su
RNF213	Transcription factor	no		Znf_RING, AAA+_ATPase, Znf_RING/FYVE/PHD
OR4X1	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
CAPZA1	Other/Unknown	no		CapZ_alpha, F-actin_cap_asu_CS, CapZ_alpha/beta
OR5B12	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
ALDH1A2	Enzyme (other)	yes	1.2.1.36	Aldehyde_DH_dom, Ald_DH_CS_CYS, Ald_DH/histidinol_DH
ZP4	Antibody/Immunoglobulin	yes		P_trefoil_dom, ZP_dom, P_trefoil_CS
ULK4	Kinase	yes		Prot_kinase_dom, Kinase-like_dom_sf, ARM-like
ZNF831	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
LINC02871	Other/Unknown	no
SOX6	Transcription factor	no		HMG_box_dom, HMG_box_dom_sf, SOX/SOX-like_TF
SORCS2	Antibody/Immunoglobulin	yes		PKD_dom, VPS10, Ig-like_fold

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	1
moderate (6-20)	2
broad (>20)	72
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	9
oocyte	6
secondary oocyte	6
Brodmann (1909) area 23	6
ventricular zone	5
colonic epithelium	5
middle temporal gyrus	5
cortical plate	5
granulocyte	5
monocyte	4
calcaneal tendon	4
right uterine tube	4
right lung	4
lymph node	4
left testis	4
right testis	4
male germ line stem cell (sensu Vertebrata) in testis	4
leukocyte	3
mononuclear cell	3
spleen	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RIT1	268	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
CNNM2	234	ubiquitous	marker	secondary oocyte, oocyte, right adrenal gland
RYR2	210	broad	marker	heart right ventricle, left ventricle myocardium, myocardium
SALL1	195	broad	marker	ventricular zone, inferior vagus X ganglion, renal medulla
ATXN2	286	ubiquitous	marker	buccal mucosa cell, colonic epithelium, olfactory bulb
SEMA7A	136	ubiquitous	yes	spleen, C1 segment of cervical spinal cord, primary visual cortex
SLC22A7	170	tissue_specific	yes	right lobe of liver, liver, adult mammalian kidney
SLC30A1	287	ubiquitous	marker	jejunal mucosa, choroid plexus epithelium, caput epididymis
SLC4A7	284	ubiquitous	marker	oocyte, duodenum, calcaneal tendon
TARBP1	290	ubiquitous	marker	right hemisphere of cerebellum, right uterine tube, cerebellar hemisphere
TBX18	162	ubiquitous	marker	right coronary artery, popliteal artery, tibial artery
TBX2	236	ubiquitous	marker	right lung, right coronary artery, upper lobe of left lung
TBX3	243	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, adrenal cortex
TBX5	129	broad	marker	tendon of biceps brachii, cardiac muscle of right atrium, buccal mucosa cell
TCF21	175	broad	marker	primordial germ cell in gonad, right lung, upper lobe of left lung
TMOD4	176	tissue_specific	yes	vastus lateralis, quadriceps femoris, skeletal muscle tissue of rectus abdominis
TNKS	295	ubiquitous	yes	middle temporal gyrus, medial globus pallidus, Brodmann (1909) area 23
TNNT3	135	broad	marker	hindlimb stylopod muscle, skeletal muscle tissue, gastrocnemius
UMOD	104	tissue_specific	marker	renal medulla, adult organism, adult mammalian kidney
VPS33B	277	ubiquitous	yes	pancreatic ductal cell, Brodmann (1909) area 23, middle temporal gyrus
WNT2B	231	broad	marker	germinal epithelium of ovary, buccal mucosa cell, parietal pleura
YES1	295	ubiquitous	marker	secondary oocyte, oocyte, jejunal mucosa
YWHAE	155	ubiquitous	marker	superior frontal gyrus, ventricular zone, cortical plate
ZNF107	253	ubiquitous	marker	secondary oocyte, oocyte, lymph node
RIBC2	175	broad	marker	bronchial epithelial cell, epithelium of bronchus, right uterine tube
FIGN	225	ubiquitous	marker	buccal mucosa cell, dorsal root ganglion, endothelial cell
MS4A6A	259	broad	marker	monocyte, mononuclear cell, leukocyte
NID2	236	ubiquitous	marker	cartilage tissue, stromal cell of endometrium, tibia
ZNF318	274	ubiquitous	marker	left testis, right testis, testis
CYFIP1	295	ubiquitous	marker	esophagus squamous epithelium, germinal epithelium of ovary, epithelium of esophagus

Protein interactions among cohort

Intra-cohort edges: 21.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDH17	4,513
ALDH1A2	4,289
YES1	3,542
ATXN2	3,360
RIT1	3,298
YWHAE	3,177
CAPZA1	3,048
TNKS	2,828
COL4A2	2,746
ZNF318	2,705

Intra-cohort edges

A	B	Sources
ABHD16A	PRRC2A	string_interaction
ALDH1A2	TBX18	string_interaction
ALDH1A2	TCF21	string_interaction
ATXN2	CUX2	string_interaction
CACNA1D	CACNB2	string_interaction
CACNA1D	LRRC7	string_interaction
CACNA1D	RYR2	string_interaction
CAPZA1	TMOD4	string_interaction
CHRM3	SLC4A7	biogrid_interaction
COL4A2	NID2	string_interaction
CYFIP1	PRDM16	biogrid_interaction
KSR2	RIT1	string_interaction
KSR2	YWHAE	biogrid_interaction
PRDM16	PRDM8	string_interaction
PRDM16	SOX6	biogrid_interaction, intact
SALL1	TBX5	string_interaction
SEMA7A	SLC12A9	biogrid_interaction, intact
SLC30A1	SLC39A8	string_interaction
TBX18	TCF21	string_interaction
TBX3	TBX5	string_interaction
TBX5	YES1	string_interaction

Structural data

PDB: 40 · AlphaFold-only: 34 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNKS	O95271	42
RYR2	Q92736	26
CALCRL	Q16602	25
SLC30A1	Q9Y6M5	12
YWHAE	P62258	11
UMOD	P07911	10
CAPZA1	P52907	10
KSR2	Q6VAB6	9
CNNM2	Q9H8M5	7
ALDH1A2	O94788	7
CACNA1D	Q01668	6
PHACTR1	Q9C0D0	6
CYFIP1	Q7L576	5
CHRM3	P20309	5
TBX5	Q99593	4
RNF213	Q63HN8	4
NCR3	O14931	4
COL4A2	P08572	4
RIT1	Q92963	3
CACNB2	Q08289	3
PLCE1	Q9P212	3
CDH17	Q12864	3
MTCH2	Q9Y6C9	3
CUX2	O14529	3
RIBC2	Q9H4K1	2
PRDM16	Q9HAZ2	2
ULK4	Q96C45	2
LRRC7	Q96NW7	2
ATXN2	Q99700	1
SEMA7A	O75326	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
VPS33B	Q9H267	91.82
ABHD16A	O95870	89.90
OR5B12	Q96R08	89.47
OR4X1	Q8NH49	88.10
WNT2B	Q93097	86.85
TMOD4	Q9NZQ9	86.28
SLC22A7	Q9Y694	84.93
SLC44A4	Q53GD3	83.79
SLC12A9	Q9BXP2	82.25
FSTL4	Q6MZW2	81.18
TNNT3	P45378	77.99
NBEAL1	Q6ZS30	75.20
ZP4	Q12836	74.90
CRIP3	Q6Q6R5	74.81
NID2	Q14112	74.40
ZNF107	Q9UII5	74.23
MS4A6A	Q9H2W1	73.84
SBF2	Q86WG5	73.74
SLC39A8	Q9C0K1	73.46
CORIN	Q9Y5Q5	70.20
MBIP	Q9NS73	68.83
TCF21	O43680	66.67
CCDC88C	Q9P219	65.69
FIGN	Q5HY92	62.06
BANK1	Q8NDB2	61.25
TBX18	O95935	61.09
TBX2	Q13207	58.13
DMRTA1	Q5VZB9	57.14
SOX6	P35712	56.48
PRDM8	Q9NQV8	55.64

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 646. Enrichment computed across 206 evidence-associated genes (133 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 133 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
NCAM1 interactions	7	13.1×	6e-04	CACNA1D, CACNB2, COL4A2, COL4A4, COL4A5, COL6A3, COL6A5
Glucocorticoid biosynthesis	4	26.4×	0.003	CYP11B1, CYP11B2, CYP17A1, CYP21A2
Signaling by PDGF	6	11.4×	0.003	COL4A2, COL4A4, COL4A5, COL6A3, COL6A5, FURIN
Sensory processing of sound	5	11.6×	0.010	CACNA1D, CACNB2, CAPZA1, MYH9, ATP2B1
Collagen degradation	6	7.9×	0.014	COL4A2, COL4A4, COL4A5, COL6A3, COL6A5, FURIN
Collagen chain trimerization	5	9.8×	0.016	COL4A2, COL4A4, COL4A5, COL6A3, COL6A5
Muscle contraction	8	4.6×	0.030	RYR2, TBX5, CACNB2, ALDH2, KCNK3, KCNK5, MYL2, ATP2B1
Laminin interactions	4	11.4×	0.031	NID2, COL4A2, COL4A4, COL4A5
Assembly of collagen fibrils and other multimeric structures	5	7.5×	0.037	COL4A2, COL4A4, COL4A5, COL6A3, COL6A5
Anchoring fibril formation	3	17.2×	0.041	COL4A2, COL4A4, COL4A5
Fibronectin matrix formation	3	12.9×	0.061	COL4A2, COL4A4, COL4A5
Crosslinking of collagen fibrils	3	12.9×	0.061	COL4A2, COL4A4, COL4A5
Signaling by ALK in cancer	4	8.2×	0.061	RNF213, MCL1, MOV10, MYH9
Collagen biosynthesis and modifying enzymes	5	6.4×	0.061	COL4A2, COL4A4, COL4A5, COL6A3, COL6A5
Sensory processing of sound by inner hair cells of the cochlea	5	6.1×	0.061	CACNA1D, CACNB2, CAPZA1, MYH9, ATP2B1
Cardiac conduction	6	4.9×	0.061	RYR2, TBX5, CACNB2, KCNK3, KCNK5, ATP2B1
ECM proteoglycans	5	5.7×	0.072	COL4A2, COL4A4, COL4A5, COL6A3, COL6A5
Attachment of bacteria to epithelial cells	3	11.2×	0.083	COL4A2, COL4A4, COL4A5
Phase I - Functionalization of compounds	4	6.6×	0.100	ADH7, CYP11B1, CYP11B2, ALDH2
Integrin cell surface interactions	5	5.0×	0.100	COL4A2, COL4A4, COL4A5, COL6A3, COL6A5
Mineralocorticoid biosynthesis	2	21.5×	0.108	CYP11B2, CYP21A2
Synthesis of IP3 and IP4 in the cytosol	3	9.5×	0.108	PLCE1, PLCB2, PLCD3
Endogenous sterols	3	8.9×	0.127	CYP11B1, CYP11B2, CYP21A2
Acetylcholine regulates insulin secretion	2	17.2×	0.147	CHRM3, PLCB2
CD163 mediating an anti-inflammatory response	2	17.2×	0.147	MYH9, FURIN
Integration of energy metabolism	4	5.3×	0.171	CACNA1D, CACNB2, CHRM3, PRKAG2
Ethanol oxidation	2	14.3×	0.197	ADH7, ALDH2
Striated Muscle Contraction	3	7.0×	0.200	TMOD4, TNNT3, MYL2
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	3	7.0×	0.200	KDM4A, MOV10, NR1H3
Metabolic disorders of biological oxidation enzymes	2	13.2×	0.208	CYP11B1, CYP11B2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 182 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cortisol biosynthetic process	4	46.3×	0.001	CYP11B1, CYP11B2, CYP17A1, CYP21A2
glucocorticoid biosynthetic process	4	33.7×	0.003	CYP11B1, CYP11B2, CYP17A1, CYP21A2
angiogenesis	13	4.5×	0.004	RNF213, CALCRL, COL4A2, ENPEP, EPHB3, HOXA3, HOXB3, CXCL8 (+5 more)
regulation of blood pressure	7	8.5×	0.007	UMOD, CORIN, CYP11B1, AGT, GUCY1A1, NPR3, ATP2B1
smooth muscle cell differentiation	4	19.5×	0.013	TBX18, TBX2, TBX3, NPNT
ureteric peristalsis	2	92.6×	0.029	TBX2, TBX3
atrioventricular bundle cell differentiation	2	61.7×	0.037	TBX3, TBX5
specification of animal organ position	2	61.7×	0.037	TBX3, HOXA3
mammary placode formation	2	61.7×	0.037	TBX2, TBX3
regulation of ribonuclease activity	2	61.7×	0.037	OAS3, PDE3A
cardiac jelly development	2	61.7×	0.037	TBX2, TBX3
nitric oxide-cGMP-mediated signaling	3	25.2×	0.037	AGT, GUCY1A1, GUCY1B1
glomerulus development	3	21.4×	0.037	TCF21, PLCE1, ENPEP
negative regulation of cytosolic calcium ion concentration	3	21.4×	0.037	KCNK3, ATP2B1, OPRM1
cell fate specification	4	11.6×	0.037	TBX18, TBX2, TBX3, TBX5
adherens junction organization	4	11.2×	0.039	CDH13, CDH17, CSK, NUMB
embryonic forelimb morphogenesis	4	10.9×	0.039	TBX3, TBX5, ALDH1A2, HOXA9
positive regulation of MAPK cascade	9	4.0×	0.039	BANK1, KSR2, LPAR1, EDN3, FGF5, GRM5, IGFBP3, INSR (+1 more)
calcium ion transport	6	6.0×	0.040	RYR2, CACNA1D, CACNB2, CALCRL, HOXA3, PKD1
mineralocorticoid biosynthetic process	2	46.3×	0.041	CYP11B2, CYP21A2
glossopharyngeal nerve morphogenesis	2	46.3×	0.041	HOXA3, HOXB3
regulation of renal sodium excretion	2	46.3×	0.041	CORIN, AGT
response to oxygen levels	2	46.3×	0.041	GUCY1A1, GUCY1B1
metanephric ascending thin limb development	2	46.3×	0.041	UMOD, PKD1
atrioventricular canal morphogenesis	2	46.3×	0.041	TBX2, TBX3
embryonic digestive tract development	3	16.3×	0.043	SALL1, ALDH1A2, CXCL8
positive regulation of smooth muscle contraction	3	15.4×	0.050	CHRM3, NPNT, EDN3
aldosterone biosynthetic process	2	37.0×	0.054	CYP11B1, CYP11B2
cadmium ion transmembrane transport	2	37.0×	0.054	SLC30A1, SLC39A8
positive regulation of the force of heart contraction	2	37.0×	0.054	RYR2, MYL2

Therapeutics

Drugs indicated for this disease

60 approved, 77 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Ambrisentan	Approved (phase 4)
Aprocitentan	Approved (phase 4)
Atenolol	Approved (phase 4)
Bendroflumethiazide	Approved (phase 4)
Bethanidine	Approved (phase 4)
Bosentan	Approved (phase 4)
Candesartan Cilexetil	Approved (phase 4)
Captopril	Approved (phase 4)
Carvedilol	Approved (phase 4)
Chlorothiazide	Approved (phase 4)
Chlorthalidone	Approved (phase 4)
Clonidine	Approved (phase 4)
Debrisoquin	Approved (phase 4)
Deserpidine	Approved (phase 4)
Diazoxide	Approved (phase 4)
Doxazosin	Approved (phase 4)
Eplerenone	Approved (phase 4)
Felodipine	Approved (phase 4)
Furosemide	Approved (phase 4)
Guanethidine	Approved (phase 4)
Guanfacine	Approved (phase 4)
Hydralazine	Approved (phase 4)
Hydrochlorothiazide	Approved (phase 4)
Indapamide	Approved (phase 4)
Indoramin	Approved (phase 4)
Irbesartan	Approved (phase 4)
Isradipine	Approved (phase 4)
Ketanserin	Approved (phase 4)
Latanoprost	Approved (phase 4)
Macitentan	Approved (phase 4)
Mecamylamine	Approved (phase 4)
Methyldopa	Approved (phase 4)
Metolazone	Approved (phase 4)
Metyrosine	Approved (phase 4)
Minoxidil	Approved (phase 4)
Moxonidine	Approved (phase 4)
Nadolol	Approved (phase 4)
Nifedipine	Approved (phase 4)
Nisoldipine	Approved (phase 4)
Nitroglycerin	Approved (phase 4)
Nitroprusside	Approved (phase 4)
Olmesartan Medoxomil	Approved (phase 4)
Pargyline	Approved (phase 4)
Prazosin	Approved (phase 4)
Ramipril	Approved (phase 4)
Rauwolfia Serpentina	Approved (phase 4)
Rescinnamine	Approved (phase 4)
Reserpine	Approved (phase 4)
Rilmenidine	Approved (phase 4)
Riociguat	Approved (phase 4)
Sitaxentan	Approved (phase 4)
Sotatercept	Approved (phase 4)
Spironolactone	Approved (phase 4)
Telmisartan	Approved (phase 4)
Torsemide	Approved (phase 4)
Trandolapril	Approved (phase 4)
Triamterene	Approved (phase 4)
Trimethaphan	Approved (phase 4)
Valsartan	Approved (phase 4)
Veratrum Viride Root	Approved (phase 4)
Acarbose	Phase 3 (in late-stage trials)
Alcohol	Phase 3 (in late-stage trials)
Aliskiren	Phase 3 (in late-stage trials)
Allopurinol	Phase 3 (in late-stage trials)
Amiloride	Phase 3 (in late-stage trials)
Amlodipine	Phase 3 (in late-stage trials)
Angiotensin	Phase 3 (in late-stage trials)
Angiotensin Ii	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Atorvastatin	Phase 3 (in late-stage trials)
Azilsartan	Phase 3 (in late-stage trials)
Azilsartan Medoxomil	Phase 3 (in late-stage trials)
Benazepril	Phase 3 (in late-stage trials)
Bisoprolol	Phase 3 (in late-stage trials)
Candesartan	Phase 3 (in late-stage trials)
Celecoxib	Phase 3 (in late-stage trials)
Cilexetil	Phase 3 (in late-stage trials)
Cilnidipine	Phase 3 (in late-stage trials)
Clevidipine	Phase 3 (in late-stage trials)
Darusentan	Phase 3 (in late-stage trials)
Delapril	Phase 3 (in late-stage trials)
Dexmedetomidine	Phase 3 (in late-stage trials)
Dihydralazine	Phase 3 (in late-stage trials)
Diltiazem	Phase 3 (in late-stage trials)
Enalapril	Phase 3 (in late-stage trials)
Estrogens, Conjugated	Phase 3 (in late-stage trials)
Etomidate	Phase 3 (in late-stage trials)
Ezetimibe	Phase 3 (in late-stage trials)
Fenofibrate	Phase 3 (in late-stage trials)
Fimasartan	Phase 3 (in late-stage trials)
Firibastat	Phase 3 (in late-stage trials)
Folic Acid	Phase 3 (in late-stage trials)
Fospropofol	Phase 3 (in late-stage trials)
Ginseng, American	Phase 3 (in late-stage trials)
Glimepiride	Phase 3 (in late-stage trials)
Insulin Aspart	Phase 3 (in late-stage trials)
Insulin Detemir	Phase 3 (in late-stage trials)
Insulin Glargine	Phase 3 (in late-stage trials)
Insulin Human	Phase 3 (in late-stage trials)
Insulin Susp Isophane Recombinant Human	Phase 3 (in late-stage trials)
Insulin Susp Isophane Semisynthetic Purified Human	Phase 3 (in late-stage trials)
Labetalol	Phase 3 (in late-stage trials)
Lacidipine	Phase 3 (in late-stage trials)
Lercanidipine	Phase 3 (in late-stage trials)
Levamlodipine	Phase 3 (in late-stage trials)
Lisinopril Anhydrous	Phase 3 (in late-stage trials)
Losartan	Phase 3 (in late-stage trials)
MANIDIPINE 6300	Phase 3 (in late-stage trials)
Medroxyprogesterone Acetate	Phase 3 (in late-stage trials)
Metformin	Phase 3 (in late-stage trials)
Metoprolol	Phase 3 (in late-stage trials)
Midazolam	Phase 3 (in late-stage trials)
Minocycline	Phase 3 (in late-stage trials)
Nebivolol	Phase 3 (in late-stage trials)
Nicardipine	Phase 3 (in late-stage trials)
Nitrendipine	Phase 3 (in late-stage trials)
OMEGA-3-ACID ETHYL ESTERS	Phase 3 (in late-stage trials)
Olmesartan	Phase 3 (in late-stage trials)
Perindopril	Phase 3 (in late-stage trials)
Pioglitazone	Phase 3 (in late-stage trials)
Potassium Chloride	Phase 3 (in late-stage trials)
Pravastatin	Phase 3 (in late-stage trials)
Progesterone	Phase 3 (in late-stage trials)
Propofol	Phase 3 (in late-stage trials)
Repaglinide	Phase 3 (in late-stage trials)
Rosiglitazone	Phase 3 (in late-stage trials)
Rosuvastatin	Phase 3 (in late-stage trials)
Sacubitril	Phase 3 (in late-stage trials)
Sildenafil	Phase 3 (in late-stage trials)
Simvastatin	Phase 3 (in late-stage trials)
Spermidine	Phase 3 (in late-stage trials)
Tamoxifen	Phase 3 (in late-stage trials)
Taurine	Phase 3 (in late-stage trials)
Terazosin	Phase 3 (in late-stage trials)
Topiramate	Phase 3 (in late-stage trials)
Urapidil	Phase 3 (in late-stage trials)
XL550	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Abatacept, Acebutolol, Acetaminophen, Baxdrostat, Calcitriol, Colchicine, Febuxostat, Fosinopril, Glycine, Ibuprofen, Isosorbide, Isosorbide Mononitrate, Magnesium Citrate, Melatonin, Menthol, Microcrystalline Cellulose, Osilodrostat, Propranolol, Sirolimus, Sitokiren, Sparsentan, Starch, Tadalafil.

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 7 · Phased (≥1): 8 · Undrugged: 67

Druggability breadth: 82 of 206 evidence-associated genes (40%) 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
TNKS	NIRAPARIB
YES1	PONATINIB
CACNA1D	BEPRIDIL
ABHD16A	ORLISTAT
CACNB2	NIMODIPINE
CALCRL	PRAMLINTIDE
CHRM3	CARBACHOL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHRM3	207	4
YES1	66	4
CACNA1D	48	4
CALCRL	12	4
TNKS	9	4
CACNB2	2	4
RYR2	1	2
ABHD16A	1	4
RIT1	0	0
CNNM2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NIRAPARIB	4	TNKS
RUCAPARIB	4	TNKS
TALAZOPARIB	4	TNKS
OLAPARIB	4	TNKS
PONATINIB	4	YES1
FEDRATINIB	4	CHRM3, YES1
AXITINIB	4	YES1
DASATINIB ANHYDROUS	4	YES1
NERATINIB	4	YES1
INFIGRATINIB PHOSPHATE	4	YES1
INFIGRATINIB	4	YES1
IBRUTINIB	4	YES1
DABRAFENIB	4	YES1
VANDETANIB	4	CHRM3, YES1
NILOTINIB	4	CACNA1D, YES1
BOSUTINIB	4	YES1
GILTERITINIB	4	YES1
BRIGATINIB	4	YES1
PAZOPANIB	4	YES1
NINTEDANIB	4	YES1
SUNITINIB	4	CACNA1D, CHRM3, YES1
DASATINIB	4	CACNA1D, YES1
ERLOTINIB	4	YES1
QUIZARTINIB	4	YES1
CRIZOTINIB	4	YES1
MIDOSTAURIN	4	YES1
BEPRIDIL	4	CACNA1D, CHRM3
IMIPRAMINE	4	CACNA1D, CHRM3
HALOFANTRINE	4	CACNA1D
DROPERIDOL	4	CACNA1D

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

Symbol	Assays	Type breakdown
CHRM3	1,026	Binding:764, Functional:244, ADMET:17, Unclassified:1
YES1	514	Binding:509, ADMET:3, Functional:2
CACNA1D	233	Binding:145, Functional:81, Toxicity:5, ADMET:2
TNKS	226	Binding:223, Functional:3
CALCRL	196	Binding:131, Functional:65
ALDH1A2	32	Binding:32
KSR2	28	Binding:28
SLC22A7	24	Functional:18, ADMET:5, Binding:1
CACNB2	22	Binding:20, ADMET:1, Toxicity:1
RYR2	15	Binding:15
ABHD16A	13	Binding:13
CAPZA1	8	Binding:8
CYFIP1	7	Binding:7
ATXN2	5	Binding:3, Functional:2
YWHAE	4	Binding:4
MTCH2	3	Binding:3
TARBP1	2	Binding:2
PRDM16	2	Binding:2
SLC4A7	1	Binding:1
TBX5	1	Binding:1
PRRC2A	1	Binding:1
PRDM8	1	Binding:1
RNF213	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TARBP1	2.1.1.34	tRNA (guanosine18-2’-O)-methyltransferase
TNKS	2.4.2.30	NAD+ ADP-ribosyltransferase
YES1	2.7.10.2	non-specific protein-tyrosine kinase
PRDM16	2.1.1.367, 2.1.1.370	[histone H3]-lysine9 N-methyltransferase, [histone H3]-lysine4 N-dimethyltransferase
ALDH1A2	1.2.1.36	retinal dehydrogenase
PLCE1	3.1.4.11	phosphoinositide phospholipase C
KSR2	2.7.11.25	mitogen-activated protein kinase kinase kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TNKS	226
YES1	514
CACNA1D	233
CALCRL	196
CHRM3	1,026

Pharmacogenomics

Cohort genes with a PharmGKB record: 74; 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)
NIRAPARIB	4	TNKS
RUCAPARIB	4	TNKS
TALAZOPARIB	4	TNKS
OLAPARIB	4	TNKS
PONATINIB	4	YES1
FEDRATINIB	4	CHRM3, YES1
AXITINIB	4	YES1
DASATINIB ANHYDROUS	4	YES1
NERATINIB	4	YES1
INFIGRATINIB PHOSPHATE	4	YES1
INFIGRATINIB	4	YES1
IBRUTINIB	4	YES1
DABRAFENIB	4	YES1
VANDETANIB	4	CHRM3, YES1
NILOTINIB	4	CACNA1D, YES1
BOSUTINIB	4	YES1
GILTERITINIB	4	YES1
BRIGATINIB	4	YES1
PAZOPANIB	4	YES1
NINTEDANIB	4	YES1
SUNITINIB	4	CACNA1D, CHRM3, YES1
DASATINIB	4	CACNA1D, YES1
ERLOTINIB	4	YES1
QUIZARTINIB	4	YES1
CRIZOTINIB	4	YES1
MIDOSTAURIN	4	YES1
BEPRIDIL	4	CACNA1D, CHRM3
IMIPRAMINE	4	CACNA1D, CHRM3
HALOFANTRINE	4	CACNA1D
DROPERIDOL	4	CACNA1D

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	7	TNKS, YES1, CACNA1D, ABHD16A, CACNB2, CALCRL, CHRM3
B	Phased (≥1) drug, not yet approved	1	RYR2
C	Druggable family + PDB, no drug	8	SEMA7A, TARBP1, ALDH1A2, ULK4, SORCS2, PLCE1, KSR2, NCR3
D	Druggable family + AlphaFold only, no drug	8	SLC22A7, OR4X1, OR5B12, ZP4, CORIN, SLC39A8, SBF2, FSTL4
E	Difficult family or no structure, no drug	51	RIT1, CNNM2, SALL1, ATXN2, SLC30A1, SLC4A7, TBX18, TBX2, TBX3, TBX5 (+41 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PRRC2A	1	ABHD16A
LRRC7	0	CACNA1D
RIT1	0	—
CNNM2	0	—
SALL1	0	—
ATXN2	5	—
SEMA7A	0	—
SLC22A7	24	—
SLC30A1	0	—
SLC4A7	1	—
TARBP1	2	—
TBX18	0	—
TBX2	0	—
TBX3	0	—
TBX5	1	—
TCF21	0	—
TMOD4	0	—
TNNT3	0	—
UMOD	0	—
VPS33B	0	—
WNT2B	0	—
YWHAE	4	—
ZNF107	0	—
RIBC2	0	—
FIGN	0	—
MS4A6A	0	—
NID2	0	—
ZNF318	0	—
CYFIP1	7	—
DMRTA1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4,735.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE4	590
PHASE3	461
PHASE2/PHASE3	36
PHASE2	13

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03713515	PHASE4	RECRUITING	Bridging the Evidence-to-practice Gap
NCT04111419	PHASE4	ACTIVE_NOT_RECRUITING	Intensive Management of Blood Pressure and Cholesterol in Elderly Chinese With Hypertension and Atrial Fibrillation
NCT04715568	PHASE4	RECRUITING	Secondhand Tobacco Smoke and Cardiovascular Disease
NCT04840342	PHASE4	ACTIVE_NOT_RECRUITING	MR Antagonist and LSD1
NCT04974138	PHASE4	RECRUITING	China Stroke Primary Prevention Trial 2 for Participants With H-type Hypertension and MTHFR 677 CC/CT Genotype (CSPPT2-CC/CT)
NCT04974151	PHASE4	RECRUITING	China Stroke Primary Prevention Trial 2 for Participants With Hypertension and MTHFR 677 TT Genotype
NCT05030545	PHASE4	RECRUITING	Cardiovascular Manifestations of MR Activation in Primary Aldosteronism: Pilot Clinical Study
NCT05089448	PHASE4	RECRUITING	Morning Versus Bedtime Dosing of Antihypertensive Medication
NCT05416840	PHASE4	NOT_YET_RECRUITING	Effects and Safety of Clonidine Patch on Young and Middle-aged Smokers With Mild Hypertension
NCT05421767	PHASE4	RECRUITING	Renal Nerve Stimulation in Uncontrolled Hypertensive Patients Undergoing Renal Denervation
NCT05593055	PHASE4	RECRUITING	Mineralocorticoid Receptor, Coronary Microvascular Function, and Cardiac Efficiency in Hypertension
NCT05688579	PHASE4	ENROLLING_BY_INVITATION	Effect of MRA on Cardiovascular Disease in Patients With Hypertension and Hyperaldosteronemia
NCT05749874	PHASE4	ACTIVE_NOT_RECRUITING	Effects of Berberine on Preventing Cardiovascular Disease and Diabetes Mellitus
NCT06055452	PHASE4	RECRUITING	Effects of SGLT2 Inhibitors in Pre-heart Failure Populations With Hypertension
NCT06063772	PHASE4	NOT_YET_RECRUITING	Effect of Treatment of Pre-induction Hypertension on Hemodynamic Stability During Induction of General Anesthesia
NCT06132477	PHASE4	RECRUITING	Impact GLP-1 Agonists Following Bariatric
NCT06256991	PHASE4	RECRUITING	Potassium Correction for RAAS Optimization in Chronic Kidney Disease
NCT06281665	PHASE4	RECRUITING	Treatment With Aspirin After Preeclampsia: TAP Trial
NCT06431477	PHASE4	RECRUITING	Efficacy and Safety of Telmisartan Compared With Losartan
NCT06523465	PHASE4	RECRUITING	Statin Combined with Amlodipine Treats Primary Aldosteronism
NCT06676553	PHASE4	RECRUITING	INtraprocedural Feedback-Optimized Renal Denervation Based on Measurements Obtained Through Renal Artery Stimulation: a Randomized Controlled Trial (INFORM)
NCT06760078	PHASE4	NOT_YET_RECRUITING	Tranexamic Acid with Intensive Blood Pressure Management in Ultra-Early Intracerebral Hemorrhage
NCT06834230	PHASE4	RECRUITING	Effect of Dotinurad in Hyperuricemia With Hypertension
NCT06845345	PHASE4	ENROLLING_BY_INVITATION	Effect of an Early Time Restricted Eating Mediterranean Diet Compared to Naltrexone/Bupropion on Liver Fibrosis in People With Cardiometabolic Risk Factors in a Hospital Outpatient Clinic (MEDFAST-study)
NCT07018557	PHASE4	RECRUITING	Impact of Eszopiclone on Blood Pressure in Patients With Insomnia and Hypertension (PRYSMA-HTN)
NCT07240909	PHASE4	NOT_YET_RECRUITING	Antihypertensive Drug Selection Based on Hemodynamic Phenotypes
NCT07241338	PHASE4	NOT_YET_RECRUITING	Sacubitril/Allisartan for Hypertensive Patients With Overweight or Obesity
NCT07247162	PHASE4	NOT_YET_RECRUITING	Osilodrostat in Patients With Hypertension Caused by Hypercortisolaemia Due to Cushing’s Syndrome
NCT07271420	PHASE4	RECRUITING	Blood Pressure Control With Thiazide Diuretics in Peritoneal Dialysis Patients
NCT07293728	PHASE4	NOT_YET_RECRUITING	A Randomized Feasibility Trial Comparing Drospirenone and Norethindrone for Postpartum Hypertension Management in Preeclampsia
NCT07607275	PHASE4	NOT_YET_RECRUITING	Effect of the Traditional Chinese Medicine Yufeng Ningxin in Patients With Hypertension
NCT00000521	PHASE4	COMPLETED	Sodium-Potassium Blood Pressure Trial in Children
NCT00018759	PHASE4	COMPLETED	Treatment Effects on Platelet Calcium in Hypertensive and Depressed Patients
NCT00034840	PHASE4	COMPLETED	Telmisartan vs. Valsartan in Patients With Mild to Moderate Hypertension Following a Missed Dose
NCT00044265	PHASE4	COMPLETED	Treatment of Pediatric Hypertension With Altace Trial
NCT00060918	PHASE4	COMPLETED	Glycemic Control Of Carvedilol Versus Metoprolol In Patients With Type II Diabetes Mellitus And Hypertension
NCT00060931	PHASE4	COMPLETED	Effect Of Carvedilol Versus Metoprolol On Glycemic Control In Patients With Type II Diabetes And Hypertension
NCT00110422	PHASE4	COMPLETED	Irbesartan in the Treatment of Hypertensive Patients With Metabolic Syndrome
NCT00115726	PHASE4	COMPLETED	Trial Assessing the Effect of Preoperative Furosemide on Intraoperative Blood Pressure
NCT00120380	PHASE4	TERMINATED	Combination Therapy of Bosentan and Aerosolized Iloprost in Idiopathic Pulmonary Arterial Hypertension (IPAH)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LOSARTAN	4	85
AMLODIPINE	4	81
HYDROCHLOROTHIAZIDE	4	69
TELMISARTAN	4	69
ALISKIREN	4	65
VALSARTAN	4	60
METOPROLOL	4	54
ENALAPRIL	4	48
NEBIVOLOL	4	41
OLMESARTAN MEDOXOMIL	4	34
BISOPROLOL	4	33
IRBESARTAN	4	32
PERINDOPRIL	4	28
RAMIPRIL	4	27
DOXAZOSIN	4	24
LISINOPRIL ANHYDROUS	4	24
CHLORTHALIDONE	4	23
ATENOLOL	4	22
AZILSARTAN MEDOXOMIL	4	22
BENAZEPRIL	4	15
CANDESARTAN CILEXETIL	4	15
CLEVIDIPINE	4	13
EPLERENONE	4	12
NIFEDIPINE	4	11
CARVEDILOL	4	9
TRANDOLAPRIL	4	8
SPIRONOLACTONE	4	7
ATORVASTATIN	4	6
INDAPAMIDE	4	6
ALCOHOL	4	5