REN

Summary

REN (renin, HGNC:9958) is a protein-coding gene on chromosome 1q32.1, encoding Renin (P00797). 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 retention by the kidney.

This gene encodes renin, an aspartic protease that is secreted by the kidneys. Renin is a part of the renin-angiotensin-aldosterone system involved in regulation of blood pressure, and electrolyte balance. This enzyme catalyzes the first step in the activation pathway of angiotensinogen by cleaving angiotensinogen to form angiotensin I, which is then converted to angiotensin II by angiotensin I converting enzyme. This cascade can result in aldosterone release, narrowing of blood vessels, and increase in blood pressure as angiotension II is a vasoconstrictive peptide. Transcript variants that encode different protein isoforms and that arise from alternative splicing and the use of alternative promoters have been described, but their full-length nature has not been determined. Mutations in this gene have been shown to cause hyperuricemic nephropathy familial juvenile 2, familial hyperproreninemia, and renal tubular dysgenesis.

Source: NCBI Gene 5972 — RefSeq curated summary.

At a glance

• Gene–disease (curated): renal tubular dysgenesis of genetic origin (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 230 total — 8 pathogenic, 6 likely-pathogenic
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000537

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9958
Approved symbol	REN
Name	renin
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000143839
Ensembl biotype	protein_coding
OMIM	179820
Entrez	5972

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000272190, ENST00000638118, ENST00000851325, ENST00000851326

RefSeq mRNA: 1 — MANE Select: NM_000537 NM_000537

CCDS: CCDS30981

Canonical transcript exons

ENST00000272190 — 10 exons

Exon	Start	End
ENSE00000962218	204161292	204161415
ENSE00000962221	204156677	204156796
ENSE00000962223	204155820	204155918
ENSE00001075100	204159399	204159595
ENSE00001075102	204160560	204160678
ENSE00001306111	204156178	204156319
ENSE00001947658	204154819	204155177
ENSE00001952423	204166196	204166337
ENSE00002388313	204162013	204162163
ENSE00002396134	204157361	204157369

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 89.61.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1025 / max 951.8915, expressed in 128 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16874	1.0728	126
16875	0.0204	4
16876	0.0094	4

Top tissues by expression

273 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	89.61	gold quality
adult mammalian kidney	UBERON:0000082	86.89	gold quality
stromal cell of endometrium	CL:0002255	84.54	gold quality
left ovary	UBERON:0002119	78.82	gold quality
kidney	UBERON:0002113	78.48	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.91	silver quality
endometrium epithelium	UBERON:0004811	75.66	gold quality
right ovary	UBERON:0002118	75.09	gold quality
ovary	UBERON:0000992	71.88	gold quality
cortex of kidney	UBERON:0001225	68.50	gold quality
metanephros	UBERON:0000081	68.17	gold quality
frontal pole	UBERON:0002795	67.88	gold quality
paraflocculus	UBERON:0005351	67.79	gold quality
middle frontal gyrus	UBERON:0002702	67.44	gold quality
metanephric glomerulus	UBERON:0004736	67.00	silver quality
renal glomerulus	UBERON:0000074	66.31	silver quality
placenta	UBERON:0001987	65.87	gold quality
kidney epithelium	UBERON:0004819	65.19	silver quality
body of uterus	UBERON:0009853	63.90	gold quality
superficial temporal artery	UBERON:0001614	63.17	gold quality
metanephros cortex	UBERON:0010533	61.05	gold quality
right lobe of liver	UBERON:0001114	60.05	gold quality
palpebral conjunctiva	UBERON:0001812	59.65	gold quality
mucosa of transverse colon	UBERON:0004991	59.30	gold quality
amniotic fluid	UBERON:0000173	59.18	gold quality
left uterine tube	UBERON:0001303	59.13	gold quality
mucosa of urinary bladder	UBERON:0001259	58.84	gold quality
adult organism	UBERON:0007023	58.46	silver quality
myometrium	UBERON:0001296	57.92	gold quality
female reproductive system	UBERON:0000474	56.97	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-24	yes	4163.51
E-GEOD-100618	yes	630.31
E-MTAB-6701	yes	40.60
E-HCAD-10	no	2.88
E-ANND-3	no	1.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APEX1, ATF2, CREB1, ESR1, ETS1, HOXB9, HOXD10, JUN, NFIX, NFKB, NOTCH1, NR1H3, NR2F2, NR2F6, PBX1, PKNOX1, POU1F1, PPARA, PPARG, RBPJ, RELA, SP1, SP3, SSRP1, STAT3, TBXT, USF2, VDR, WT1

miRNA regulators (miRDB)

11 targeting REN, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-3616-3P	96.96	65.45	983
HSA-MIR-2355-3P	96.84	68.54	909

Literature-anchored findings (GeneRIF, showing 40)

• higher relative left ventricular wall thickness was not attributable to plasma concentrations of renin, angiotensin-II, aldosterone, epinephrine and norepinephrine (PMID:11800056)
• New elements in human renin promoter involved in cell-specific expression (PMID:11903315)
• Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin (PMID:12045255)
• in contrast to results for ACE blood and bone marrow levels in leukemia patients, renin levels did not vary significantly between bone marrow and peripheral blood. (PMID:12186695)
• Review. Evidence that the cardiac renin-angiotensin system participates importantly in the development and risk of hypertensive heart disease. (PMID:12431442)
• Review. The various ways through which circulating renin may reach cardiac tissue sites, considering in particular the possibility that prorenin, the inactive precursor of renin, is involved in cardiac angiotensin generation. (PMID:12431445)
• Human renin enhancer not only comprises the 225 bp element, but also extends to the region containing the -5312 SNP. (PMID:12473863)
• Repression of renin expression by intracellular calcium may be mediated by the calcium-induced translocation of Ref-1 to the nucleus, where it binds to the renin promoter nCaRE, to repress the transcription of the renin gene. (PMID:12569263)
• renin expression observed in leukemia cells disappeared with remission induction, but did not disappear with induction of cell differentiation in vivo, indicating that renin expression is associated with a blastic phenotype rather than cell proliferation. (PMID:12613527)
• The binding “gate and handle” regions of this protein are critical for its non-proteolytic activation. (PMID:12684512)
• male mice heterozygous for the human renin gene showed moderate weight gain compared with transgenic and wild-type mice. Obese hRN8-12 mice exhibited hyperglycemia, hyperinsulinemia, hyperleptinemia, and hyperlipidemia (PMID:12736712)
• In normal subjects the expression of local renin and angiotensinogen mRNA was organ specific, but with increase of the expression locally, the organ-specificity became lost in cirrhotic patients. (PMID:12854169)
• a novel variable number of tandem repeat polymorphism in the renin gene was not associated with essential hypertension (PMID:12862204)
• HADHB trifunctional enzyme, human renin, and poly(C)-binding protein are novel renin mRNA-binding proteins that target a cis-element in the 3’-UTR of renin mRNA and regulate renin production (PMID:12933794)
• dual production of renin and angiotensinogen in the renal proximal tubule can result in a systemic increase in arterial pressure (PMID:15075192)
• putative cis-elements and each corresponding trans-factor in the specific expression of the human renin gene in the promoter region (PMID:15368359)
• Genetic polymorphisms of renin and kidney failure in hypertension were studied. (PMID:15662219)
• Plasma cathepsin D isoforms and their active metabolites increase after myocardial infarction and contribute to plasma renin activity. (PMID:15739123)
• human renin and human angiotensinogen have roles in development of hypertension in transgenic mice, and may predispose to spontaneous stroke (PMID:15914769)
• The missense mutation in the human renin gene was found not to be associated in patients with preeclampsia. (PMID:16036389)
• REN 10631A alleles are significantly associated with essential hypertension in the Emirati population (PMID:16138564)
• renin angiotensin-forming enzyme is expressed in podocytes (PMID:16189286)
• It appears possible that renin and ET may contribute to the pathophysiological changes associated with premature labor and preeclampsia (PMID:16375820)
• The expression of Renin gene by the use of real-time quantitative PCR (RQ-PCR) at diagnosis in acute myeloid leukemia patients (AML) and to assess its possible relevance in the prognosis and outcome of such patients. (PMID:16396763)
• These data support the concept of an intracellular form of renin in the brain, which may provoke functional changes in fluid homeostasis and BP regulation. (PMID:16446393)
• Mutation of REN leads to an autosomal recessive renal tubular dysgenesis in heterozygotes. (PMID:16790508)
• The group of hypertensive obese women showed significantly reduced plasma levels of renin and increased aldosterone/renin quotient (ARQ) compared to obese normotensive women. (PMID:16933186)
• Prorenin-induced stimulation of p38 MAPK/HSP27 pathway, resulting in alterations in actin filament dynamics, may underlie severe cardiac hypertrophy previously seen in rats with hepatic prorenin overexpression. (PMID:16940215)
• This study suggested that sequences other than the enhancer may be necessary for tissue-specific, cell-specific, and regulated expression of human RENIN. (PMID:16990260)
• Silent polymorphisms in the renin promoter and enhancer in hypertensive patients. (PMID:17158202)
• Angiotensinogen/renin transgenic rats develop hypertension. Remodeling in the heart conduction sytsem leads to ventricular tachycardia and sudden arrhythmic death. (PMID:17416596)
• the DR motif site of the renin gene functions as a negative regulatory element involved in a twofold repression of transcription; nucleic receptors bind the site and are important in renin gene expression; one of the binding proteins may be COUP-TFII. (PMID:17455195)
• Strong association of the renin TaqI polymorphism with essential hypertension in Chinese Han and Tibetan populations. (PMID:17476284)
• Ser84 of human renin contributes to the biphasic pH dependence of the renin-angiotensinogen reaction. (PMID:17485830)
• Investigation of the regulatory role of a conserved region of 800 bp in size, 14 kb upstream of the renin gene which is located upstream of a known 11 kb upstream regulatory region of the renin gene. (PMID:17660193)
• Plasma renin in the hypertensive subjects were lower in the Jordan Valley, but similar to normotensives in Irbid City. (PMID:17693975)
• Antagonists of renin in transgenic rats prevent renin-angiotensin system inhibition and prevent damage in an angiotensin ii model of hypertenion. (PMID:17703434)
• We found that PPARgamma targets a palindromic repeat with a 3-bp spacer (Pal3) in the proximal human renin promoter. Renin is the first gene described with a functional Pal3 sequence. PPARgamma agonists also stimulated renin gene expression. (PMID:17785633)
• While renin expressions increased in the local cord blood of pre-eclampsia in comparison to the normal cord blood, unpredictable decrements in the angiotensinogen and ACE expressions were observed within the same pre-eclamptic samples. (PMID:17851801)
• Chorionic enhancer is silent in vivo, at least in the transgenic mouse for human renin gene (PMID:18077515)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	ren	ENSDARG00000041858
mus_musculus	Ren1	ENSMUSG00000070645
rattus_norvegicus	Ren	ENSRNOG00000002937
drosophila_melanogaster	Bace	FBGN0032049
drosophila_melanogaster	CG6508	FBGN0032303
drosophila_melanogaster	CG17134	FBGN0032304
drosophila_melanogaster	CG33128	FBGN0053128
caenorhabditis_elegans		WBGENE00000214
caenorhabditis_elegans		WBGENE00000218
caenorhabditis_elegans		WBGENE00012681
caenorhabditis_elegans		WBGENE00012682
caenorhabditis_elegans		WBGENE00012683
caenorhabditis_elegans		WBGENE00013973
caenorhabditis_elegans		WBGENE00017678
caenorhabditis_elegans		WBGENE00019104
caenorhabditis_elegans		WBGENE00019105
caenorhabditis_elegans		WBGENE00077655

Paralogs (9): PGC (ENSG00000096088), CTSD (ENSG00000117984), NAPSA (ENSG00000131400), BACE2 (ENSG00000182240), BACE1 (ENSG00000186318), CTSE (ENSG00000196188), PGA4 (ENSG00000229183), PGA3 (ENSG00000229859), PGA5 (ENSG00000256713)

Protein

Protein identifiers

Renin — P00797 (reviewed: P00797)

Alternative names: Angiotensinogenase

All UniProt accessions (2): P00797, A0A1B0GUZ2

UniProt curated annotations — full annotation on UniProt →

Function. 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 retention by the kidney.

Subunit / interactions. Interacts with ATP6AP2.

Subcellular location. Secreted. Membrane.

Disease relevance. Renal tubular dysgenesis (RTD) [MIM:267430] Autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype). The disease is caused by variants affecting the gene represented in this entry. Tubulointerstitial kidney disease, autosomal dominant 4 (ADTKD4) [MIM:613092] A form of autosomal dominant tubulointerstitial kidney disease, a genetically heterogeneous disorder characterized by slowly progressive loss of kidney function, bland urinary sediment, hyperuricemia, absent or mildly increased albuminuria, lack of severe hypertension during the early stages, and normal or small kidneys on ultrasound. Renal histology shows variable abnormalities including interstitial fibrosis with tubular atrophy, microcystic dilatation of the tubules, thickening of tubular basement membranes, medullary cysts, and secondary glomerulosclerotic or glomerulocystic changes with abnormal glomerular tufting. There is significant variability, as well as incomplete penetrance. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Interaction with ATP6AP2 results in a 5-fold increased efficiency in angiotensinogen processing.

Similarity. Belongs to the peptidase A1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P00797-1	1	yes
P00797-2	2

RefSeq proteins (1): NP_000528* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001461	Aspartic_peptidase_A1	Family
IPR001969	Aspartic_peptidase_AS	Active_site
IPR012848	Aspartic_peptidase_N	Domain
IPR021109	Peptidase_aspartic_dom_sf	Homologous_superfamily
IPR033121	PEPTIDASE_A1	Domain
IPR034135	Renin-like_dom	Domain

Pfam: PF00026, PF07966

Enzyme classification (BRENDA):

• EC 3.4.23.15 — renin (BRENDA: 14 organisms, 40 substrates, 381 inhibitors, 19 Km, 8 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ANGIOTENSINOGEN	0.0003–0.0035	8
4-(4-DIMETHYLAMINOPHENYLAZO)BENZOIC ACID-IHPFHLV	0.0036	1
ACETYL-ASP-ARG-VAL-TYR-ILE-HIS-PRO-PHE-HIS-LEU-L	0.12	1
ARG-GLU(5-[(2-AMINOETHYL)AMINO]-NAPHTHALENE-1-SU	0.0064	1
ARG-GLU(EDANS)-ILE-HIS-PRO-PHE-HIS-LEU-VAL-ILE-H	0.0194	1
RECOMBINANT OVINE ANGIOTENSINOGEN FROM CHO CELLS	0.0001	1
RECOMBINANT OVINE ANGIOTENSINOGEN FROM ESCHERICH	0.0001	1

UniProt features (70 total): strand 29, helix 14, sequence variant 6, turn 5, sequence conflict 4, disulfide bond 3, active site 2, glycosylation site 2, signal peptide 1, propeptide 1, splice variant 1, chain 1, domain 1

Structure

Experimental structures (PDB)

91 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3K1W	X-RAY DIFFRACTION	1.5
1HRN	X-RAY DIFFRACTION	1.8
2G24	X-RAY DIFFRACTION	1.9
2IKO	X-RAY DIFFRACTION	1.9
3G72	X-RAY DIFFRACTION	1.9
3KM4	X-RAY DIFFRACTION	1.9
3G6Z	X-RAY DIFFRACTION	2
3G70	X-RAY DIFFRACTION	2
3GW5	X-RAY DIFFRACTION	2
3OWN	X-RAY DIFFRACTION	2
4Q1N	X-RAY DIFFRACTION	2.09
2G26	X-RAY DIFFRACTION	2.1
3SFC	X-RAY DIFFRACTION	2.1
4S1G	X-RAY DIFFRACTION	2.1
5KOT	X-RAY DIFFRACTION	2.1
5SXN	X-RAY DIFFRACTION	2.1
7XGO	X-RAY DIFFRACTION	2.1
3Q5H	X-RAY DIFFRACTION	2.16
3OAD	X-RAY DIFFRACTION	2.17
3Q4B	X-RAY DIFFRACTION	2.19
2BKS	X-RAY DIFFRACTION	2.2
2FS4	X-RAY DIFFRACTION	2.2
2G21	X-RAY DIFFRACTION	2.2
2V0Z	X-RAY DIFFRACTION	2.2
3D91	X-RAY DIFFRACTION	2.2
5TMG	X-RAY DIFFRACTION	2.2
2IL2	X-RAY DIFFRACTION	2.24
5SY2	X-RAY DIFFRACTION	2.25
2BKT	X-RAY DIFFRACTION	2.3
2I4Q	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00797-F1	85.36	0.65

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 104; 292

Disulfide bonds (3): 325–362, 117–124, 283–287

Glycosylation sites (2): 71, 141

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2022377	Metabolism of Angiotensinogen to Angiotensins

MSigDB gene sets: 0 (showing top):

GO Biological Process (23): kidney development (GO:0001822), mesonephros development (GO:0001823), angiotensin maturation (GO:0002003), renin-angiotensin regulation of aldosterone production (GO:0002018), proteolysis (GO:0006508), regulation of blood pressure (GO:0008217), male gonad development (GO:0008584), hormone-mediated signaling pathway (GO:0009755), response to lipopolysaccharide (GO:0032496), response to immobilization stress (GO:0035902), drinking behavior (GO:0042756), regulation of MAPK cascade (GO:0043408), cell maturation (GO:0048469), amyloid-beta metabolic process (GO:0050435), response to cAMP (GO:0051591), response to cGMP (GO:0070305), cellular response to xenobiotic stimulus (GO:0071466), juxtaglomerular apparatus development (GO:0072051), regulation of blood volume by renin-angiotensin (GO:0002016), maintenance of blood vessel diameter homeostasis by renin-angiotensin (GO:0002034), response to xenobiotic stimulus (GO:0009410), gene expression (GO:0010467), angiotensin-activated signaling pathway (GO:0038166)

GO Molecular Function (7): aspartic-type endopeptidase activity (GO:0004190), signaling receptor binding (GO:0005102), insulin-like growth factor receptor binding (GO:0005159), peptidase activity (GO:0008233), endopeptidase activity (GO:0004175), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), apical part of cell (GO:0045177), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Peptide hormone metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to oxygen-containing compound	3
cellular anatomical structure	3
kidney development	2
response to purine-containing compound	2
response to organophosphorus	2
regulation of systemic arterial blood pressure by renin-angiotensin	2
animal organ development	1
renal system development	1
regulation of angiotensin levels in blood	1
peptide hormone processing	1
regulation of blood volume by renin-angiotensin	1
renal system process involved in regulation of systemic arterial blood pressure	1
aldosterone secretion	1
regulation of aldosterone secretion	1
protein metabolic process	1
blood circulation	1
regulation of biological quality	1
gonad development	1
development of primary male sexual characteristics	1
signal transduction	1
cellular response to hormone stimulus	1
response to molecule of bacterial origin	1
response to lipid	1
response to stress	1
feeding behavior	1
MAPK cascade	1
regulation of intracellular signal transduction	1
cell development	1
cellular developmental process	1
anatomical structure maturation	1
metabolic process	1
response to xenobiotic stimulus	1
cellular response to chemical stimulus	1
anatomical structure development	1
blood vessel diameter maintenance	1
endopeptidase activity	1
aspartic-type peptidase activity	1
protein binding	1
signaling receptor binding	1
hydrolase activity	1

Protein interactions and networks

STRING

3214 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
REN	ATP6AP2	O75787	999
REN	AGT	P01019	989
REN	ACE	P12821	987
REN	AGTR1	P30556	969
REN	ACE2	Q9BYF1	960
REN	KNG1	P01042	951
REN	NR3C2	P08235	945
REN	NPPA	P01160	941
REN	AGTR2	P50052	934
REN	POMC	P01189	926
REN	EDN1	P05305	914
REN	CYP11B2	P19099	912
REN	RENBP	P51606	871
REN	ADM	P35318	861
REN	SCNN1G	P51170	850

IntAct

12 interactions, top by confidence:

A	B	Type	Score
REN	AGT	psi-mi:“MI:0570”(protein cleavage)	0.560
REN	AGT	psi-mi:“MI:0407”(direct interaction)	0.560
TMEM184B	INPPL1	psi-mi:“MI:0914”(association)	0.530
SAMTOR	PER1	psi-mi:“MI:0914”(association)	0.530
ZNF286A	HERC2	psi-mi:“MI:0914”(association)	0.530
CCDC24	REN	psi-mi:“MI:0915”(physical association)	0.490
REN	HSP90AB4P	psi-mi:“MI:0915”(physical association)	0.400
PHF23	SIN3B	psi-mi:“MI:0914”(association)	0.350
REN	FAT1	psi-mi:“MI:0914”(association)	0.350
KCTD15	REN	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): REN (Affinity Capture-MS), REN (Affinity Capture-MS), REN (Two-hybrid), REN (Two-hybrid), REN (Reconstituted Complex), REN (Affinity Capture-MS), FAT1 (Affinity Capture-MS), REN (Affinity Capture-MS), REN (Affinity Capture-MS), REN (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), HSP90AB4P (Affinity Capture-MS), ATP6AP2 (Reconstituted Complex), REN (Co-purification), AGT (Biochemical Activity)

ESM2 similar proteins: A2ZC67, C5FZ57, D4AIC4, D4AT39, D4DE18, D4DGR1, F5B8W7, O04057, O04496, O65390, P00797, P06281, P08424, P0DO21, P13917, P18242, P42210, P42211, P60016, P82952, Q0IU52, Q18DC8, Q18DC9, Q3EBM5, Q42369, Q42456, Q4V3D2, Q6DLS0, Q6DLW5, Q6IE75, Q8RVH5, Q8VYL3, Q8VYV9, Q9FEX1, Q9FSH9, Q9JL18, Q9LEW3, Q9LHE3, Q9LS40, Q9LTW4

Diamond homologs: A0A509AI82, A0A509AWX2, C5FS55, D4B385, D4DEN7, O09043, O42630, O76856, O93428, O96009, P00791, P00792, P00793, P00794, P00795, P00796, P00797, P03954, P03955, P04073, P06281, P07267, P07339, P08424, P0DJD7, P0DJD8, P0DJD9, P10977, P11489, P14091, P16228, P16476, P18242, P18276, P20142, P24268, P25796, P27677, P27678, P27821

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
“aliskiren fumarate”	down-regulates	REN	“chemical inhibition”
WT1	“down-regulates quantity by repression”	REN	“transcriptional regulation”
REN	“up-regulates activity”	AGT	cleavage
aliskiren	“down-regulates activity”	REN	“chemical inhibition”
AGT	“up-regulates activity”	REN	binding
REN	“up-regulates quantity”	Angiotensin-1	cleavage
REN	up-regulates	ATP6AP2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

230 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	6
Uncertain significance	124
Likely benign	43
Benign	26

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
1252080	NM_000537.4(REN):c.299_300del (p.Lys100fs)	Pathogenic
13122	NM_000537.4(REN):c.1159C>T (p.Arg387Ter)	Pathogenic
13124	NM_000537.4(REN):c.689G>A (p.Arg230Lys)	Pathogenic
2423261	NC_000001.10:g.(?204130400)(204135421_?)del	Pathogenic
3653918	NM_000537.4(REN):c.951dup (p.Leu318fs)	Pathogenic
3696631	NM_000537.4(REN):c.415A>T (p.Lys139Ter)	Pathogenic
50210	NM_000537.4(REN):c.127C>T (p.Arg43Ter)	Pathogenic
50211	NM_000537.4(REN):c.404C>A (p.Ser135Tyr)	Pathogenic
2131200	NM_000537.4(REN):c.249+1G>T	Likely pathogenic
3384161	NM_000537.4(REN):c.1079dup (p.Leu361fs)	Likely pathogenic
3577981	NM_000537.4(REN):c.1172_1173del (p.Thr391fs)	Likely pathogenic
3578102	NM_000537.4(REN):c.250-1del	Likely pathogenic
3899970	NM_000537.4(REN):c.799del (p.Trp267fs)	Likely pathogenic
562339	NM_000537.4(REN):c.116T>A (p.Met39Lys)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2655 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:204159514:C:A	G192W	0.996
1:204159518:A:C	F190L	0.995
1:204159518:A:T	F190L	0.995
1:204159520:A:G	F190L	0.995
1:204160571:C:G	D161H	0.994
1:204155032:A:G	F402S	0.993
1:204155872:A:G	F336S	0.993
1:204161315:C:G	C117S	0.993
1:204161316:A:T	C117S	0.993
1:204161334:A:G	W111R	0.993
1:204161334:A:T	W111R	0.993
1:204155058:A:C	F393L	0.992
1:204155058:A:T	F393L	0.992
1:204155060:A:G	F393L	0.992
1:204159513:C:T	G192E	0.992
1:204155070:G:C	F389L	0.991
1:204155070:G:T	F389L	0.991
1:204155072:A:G	F389L	0.991
1:204155102:A:G	W379R	0.991
1:204155102:A:T	W379R	0.991
1:204155041:C:G	R399P	0.990
1:204159415:A:G	S225P	0.989
1:204159516:T:A	D191V	0.989
1:204155083:A:G	F385S	0.988
1:204156696:A:G	W267R	0.988
1:204156696:A:T	W267R	0.988
1:204161332:C:A	W111C	0.988
1:204161332:C:G	W111C	0.988
1:204155035:C:T	G401D	0.987
1:204155100:C:A	W379C	0.987

dbSNP variants (sampled 300 via entrez): RS1000132641 (1:204154633 C>T), RS1000421260 (1:204160989 G>C), RS1000535659 (1:204166385 A>C), RS1000587853 (1:204166676 C>T), RS1000761342 (1:204160716 G>A,T), RS1001000285 (1:204160261 G>A,T), RS1001159312 (1:204166039 T>C), RS1001241802 (1:204154683 G>A,C), RS1001281567 (1:204159161 T>C), RS1001890169 (1:204164848 A>G), RS1002107243 (1:204167456 T>C,G), RS1002274717 (1:204161089 C>A,G,T), RS1002692154 (1:204156404 G>A), RS1002872818 (1:204162373 G>T), RS1002958343 (1:204157816 C>A,T)

Disease associations

OMIM: gene MIM:179820 | disease phenotypes: MIM:267430, MIM:613092, MIM:300978

GenCC curated gene-disease

Disease	Classification	Inheritance
familial juvenile hyperuricemic nephropathy type 2	Definitive	Autosomal dominant
renal tubular dysgenesis of genetic origin	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
renal tubular dysgenesis of genetic origin	Definitive	AR
familial juvenile hyperuricemic nephropathy type 2	Definitive	AD

Mondo (7): renal tubular dysgenesis of genetic origin (MONDO:0009970), familial juvenile hyperuricemic nephropathy type 2 (MONDO:0013128), renal tubular dysgenesis (MONDO:0017609), hepatoblastoma (MONDO:0018666), kidney disorder (MONDO:0005240), intellectual disability, X-linked 61 (MONDO:0010506), nephrotic syndrome (MONDO:0005377)

Orphanet (4): REN-related autosomal dominant tubulointerstitial kidney disease (Orphanet:217330), Renal tubular dysgenesis of genetic origin (Orphanet:97369), Renal tubular dysgenesis (Orphanet:3033), Hepatoblastoma (Orphanet:449)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D018197	Hepatoblastoma	C04.557.435.380
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643
C567760	Hyperuricemic Nephropathy, Familial Juvenile 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL286 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

13 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 102,065 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1560	CAPTOPRIL	4	66,415
CHEMBL1639	ALISKIREN	4	1,033
CHEMBL3545059	ALISKIREN FUMARATE	4	154
CHEMBL4110551	SITOKIREN	3	12
CHEMBL113841	ZANKIREN	2	1,247
CHEMBL1790497	DITEKIREN	2	1,503
CHEMBL296588	PEPSTATIN	2	26,094
CHEMBL300337	ENALKIREN	2	2,654
CHEMBL31601	REMIKIREN	2	1,234
CHEMBL3969876	IMARIKIREN HYDROCHLORIDE	2	66
CHEMBL3990145	IMARIKIREN	2	26
CHEMBL60550	TERLAKIREN	2	1,588
CHEMBL1276678	VTP-27999	1	39

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2368564	Toxicity	3	muraglitazar	Diabetes Mellitus;Edema;Hyperlipidemias

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2368564	REN	3	2.75	1	muraglitazar
rs11240688	REN		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — A1: Pepsin

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
sitokiren	Inhibition	9.4	pIC50
aliskiren	Inhibition	9.2	pIC50

Binding affinities (BindingDB)

418 measured of 443 human assays (453 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
trans,trans-4-arylpiperidine-based compound, 1	IC50	0.067 nM
piperidine-1-carboxamide, 21t	IC50	0.1 nM
piperidine-1-carboxamide, 21m	IC50	0.13 nM
piperidine-1-carboxamide, 21s	IC50	0.14 nM
Ketopiperazine-based inhibitor, 13	IC50	0.18 nM
(1R,5S)-7-{4-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-phenyl}-3,9-diaza-bicyclo[3.3.1]non-6-ene-6-carboxylic acid cyclopropyl-(2,3-dimethyl-benzyl)-amide	IC50	0.2 nM
N-[2-(7-{[(2R)-1-(4-{3-[(2-methoxyphenyl)methoxy]propoxy}phenyl)-6-oxopiperazin-2-yl]methoxy}-1,2,3,4-tetrahydroquinolin-1-yl)ethyl]acetamide	IC50	0.3 nM
(2R,4S,5S,7S)-5-amino-N-(2-acetamidoethyl)-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-2,8-dimethylnonanamide	IC50	0.3 nM
(3S,5R)-3-N-[(1S)-1-cyclohexyl-2-ethoxyethyl]-5-N-cyclopropyl-5-N-(4-methoxy-5-propan-2-yl-2-pyridinyl)piperidine-3,5-dicarboxamide	IC50	0.3 nM	US-8497286: Organic compounds
(3S,4R,5R)-3-N-cyclopropyl-3-N-(4-ethoxy-5-ethyl-2-pyridinyl)-5-N-[(2R)-1-ethoxy-4-methylpentan-2-yl]-4-hydroxypiperidine-3,5-dicarboxamide	IC50	0.3 nM	US-8497286: Organic compounds
(2R,4S,5S,7S)-5-amino-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-N-(3-methoxypropyl)-2,8-dimethylnonanamide	IC50	0.4 nM
(2S,4S,5S,7S)-5-amino-N-[2,2-dimethyl-2-(methylcarbamoyl)ethyl]-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide	IC50	0.4 nM
(2S,4S,5S,7S)-5-amino-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-N-[2-(morpholin-4-yl)ethyl]-2-(propan-2-yl)nonanamide	IC50	0.4 nM
(2R)-N-cyclopropyl-N-[(1R)-1-[1-(3-methoxypropyl)-3-methyl-4-(trifluoromethyl)indazol-6-yl]ethyl]morpholine-2-carboxamide	IC50	0.4 nM	US-9278944: Nitrogen-containing saturated heterocyclic compound
methyl N-[3-[3-[(1R)-1-[cyclopropyl-[(2R)-morpholine-2-carbonyl]amino]ethyl]-6-methylpyrazolo[5,4-b]pyridin-1-yl]propyl]carbamate	IC50	0.4 nM	US-9278944: Nitrogen-containing saturated heterocyclic compound
(3S,4R,5R)-3-N-cyclopropyl-5-N-[(2R)-1-ethoxy-4-methylpentan-2-yl]-4-hydroxy-3-N-[4-(3-methoxypropoxy)-5-propan-2-yl-2-pyridinyl]piperidine-3,5-dicarboxamide	IC50	0.4 nM	US-8497286: Organic compounds
2-(7-{[(2R)-1-(4-{3-[(2-methoxyphenyl)methoxy]propoxy}phenyl)-6-oxopiperazin-2-yl]methoxy}-1,2,3,4-tetrahydroquinolin-1-yl)ethyl acetate	IC50	0.42 nM
piperidine-1-carboxamide, 21l	IC50	0.47 nM
N-[2-(7-{[(2R)-1-(4-{3-[(2-methoxyphenyl)methoxy]propoxy}phenyl)piperazin-2-yl]methoxy}-1,2,3,4-tetrahydroquinolin-1-yl)ethyl]acetamide	IC50	0.5 nM
(2R)-N-cyclopropyl-N-[(1R)-1-[1-(4-methoxybutyl)-6-methylpyrrolo[2,3-b]pyridin-3-yl]ethyl]morpholine-2-carboxamide	IC50	0.5 nM	US-9278944: Nitrogen-containing saturated heterocyclic compound
methyl N-[3-[4-[(1R)-1-[cyclopropyl-[(2R)-morpholine-2-carbonyl]amino]ethyl]-6-methoxy-2-pyridinyl]propyl]carbamate	IC50	0.5 nM	US-9278944: Nitrogen-containing saturated heterocyclic compound
(rac)-(1RS,5SR)-3-(3-Carbamoyl-propionyl)-7-{4-[3-(2,3,6-trifluoro-phenoxy)-propyl]-phenyl}-3,9-diaza-bicyclo[3.3.1]non-6-ene-6-carboxylic acid(2-chloro-benzyl)-cyclopropyl-amide	IC50	0.55 nM
(2R,4S,5S,7S)-5-amino-7-{[3-(benzyloxy)-4-methoxyphenyl]methyl}-N-butyl-4-hydroxy-2,8-dimethylnonanamide	IC50	0.6 nM
(2S,4S,5S,7S)-5-amino-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-N-{[(2S)-5-oxopyrrolidin-2-yl]methyl}-2-(propan-2-yl)nonanamide	IC50	0.6 nM
(2S,4S,5S,7S)-5-amino-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-N-[2-methyl-2-(morpholin-4-yl)propyl]-2-(propan-2-yl)nonanamide	IC50	0.6 nM
(2R)-N-cyclopropyl-N-[(1R)-1-[4-fluoro-1-(3-methoxypropyl)-3-methylindazol-6-yl]ethyl]morpholine-2-carboxamide	IC50	0.6 nM	US-9278944: Nitrogen-containing saturated heterocyclic compound
(3S,5R)-3-N-[(2R)-1-ethoxy-4-methylpentan-2-yl]-5-N-[4-(3-methoxypropoxy)-5-propan-2-yl-2-pyridinyl]-5-N-(2-methylpropyl)piperidine-3,5-dicarboxamide	IC50	0.6 nM	US-8497286: Organic compounds
(3S,5R)-5-N-cyclopropyl-5-N-(4-ethoxy-5-ethyl-2-pyridinyl)-3-N-[(2R)-1-ethoxy-4-methylpentan-2-yl]piperidine-3,5-dicarboxamide	IC50	0.6 nM	US-8497286: Organic compounds
(3S,4R,5R)-3-N-cyclopropyl-3-N-(4-ethoxy-5-ethyl-2-pyridinyl)-5-N-[(2R)-1-ethoxy-3-methylbutan-2-yl]-4-hydroxypiperidine-3,5-dicarboxamide	IC50	0.6 nM	US-8497286: Organic compounds
Ketopiperazine-based inhibitor, 12	IC50	0.68 nM
(2S,4S,5S,7S)-5-amino-N-(3-carbamoylpropyl)-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide	IC50	0.7 nM
(2R)-N-cyclopropyl-N-[(1R)-1-[1-(4-methoxybutyl)indazol-3-yl]ethyl]morpholine-2-carboxamide	IC50	0.7 nM	US-9278944: Nitrogen-containing saturated heterocyclic compound
4-(4-(3-(2-chloro-3,6-difluorophenoxy)propyl)phenyl)-N-cyclopropyl-N-(3-methoxy-2-methylbenzyl)-2,4a,5,6,7,7a-hexahydro-1H-cyclopenta[b]pyridine-3-carboxamide	IC50	0.74 nM
N-{2-[(2S)-6-(2,4-diamino-6-ethylpyrimidin-5-yl)-2-methyl-3-oxo-2-phenyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethyl}acetamide	IC50	0.8 nM
(2R,4S,5S,7S)-5-amino-4-hydroxy-N-(4-hydroxybutyl)-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-2,8-dimethylnonanamide	IC50	0.8 nM
(2S,4S,5S,7S)-5-amino-N-[(1S)-1-carbamoylpropyl]-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide	IC50	0.8 nM
(2S,4S,5S,7S)-5-amino-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-N-[3-(methylcarbamoyl)propyl]-2-(propan-2-yl)nonanamide	IC50	0.8 nM
(3S,5R)-3-N-[(2R)-1-ethoxy-4-methylpentan-2-yl]-5-N-(4-methoxy-5-propan-2-yl-2-pyridinyl)-5-N-(2-methylpropyl)piperidine-3,5-dicarboxamide	IC50	0.8 nM	US-8497286: Organic compounds
(3S,4R,5R)-3-N-cyclopropyl-5-N-[(2R)-1-ethoxy-4-methylpentan-2-yl]-4-hydroxy-3-N-(4-methoxy-5-propan-2-yl-2-pyridinyl)piperidine-3,5-dicarboxamide	IC50	0.8 nM	US-8497286: Organic compounds
(2S,4S,5S,7S)-5-amino-N-[(2R)-2-carbamoyl-2-methylethyl]-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide	IC50	0.9 nM
(2S,4S,5S,7S)-5-amino-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-N-[(2R)-2-methyl-2-(methylcarbamoyl)ethyl]-2-(propan-2-yl)nonanamide	IC50	0.9 nM
(2R)-N-cyclopropyl-N-[(1R)-1-[1-(4-methoxybutyl)pyrrolo[2,3-b]pyridin-3-yl]ethyl]morpholine-2-carboxamide	IC50	0.9 nM	US-9278944: Nitrogen-containing saturated heterocyclic compound
methyl N-[3-[5-[(1R)-1-[cyclopropyl-[(2R)-morpholine-2-carbonyl]amino]ethyl]-2-methoxy-3-pyridinyl]propyl]carbamate	IC50	0.9 nM	US-9278944: Nitrogen-containing saturated heterocyclic compound
piperidine-1-carboxamide, 21v	IC50	0.9 nM
CHEMBL2152353	IC50	0.9 nM
CHEMBL2387567	IC50	0.9 nM
(3S,5R)-5-N-cyclopropyl-3-N-[(2R)-1-ethoxy-4-methylpentan-2-yl]-5-N-(5-propan-2-yl-2-pyridinyl)piperidine-3,5-dicarboxamide	IC50	0.9 nM	US-8497286: Organic compounds
(3S,5R)-5-N-cyclopropyl-3-N-[(2R)-1-ethoxy-3-methylbutan-2-yl]-5-N-(5-propan-2-yl-2-pyridinyl)piperidine-3,5-dicarboxamide	IC50	0.9 nM	US-8497286: Organic compounds
(3S,5R)-5-N-cyclopropyl-3-N-[(2R)-1-ethoxy-4-methylpentan-2-yl]-5-N-(4-methoxy-5-propan-2-yl-2-pyridinyl)piperidine-3,5-dicarboxamide	IC50	0.9 nM	US-8497286: Organic compounds
N-{2-[6-(2,4-diamino-6-ethylpyrimidin-5-yl)-2-(3,5-difluorophenyl)-2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethyl}acetamide	IC50	1 nM

ChEMBL bioactivities

4403 potent at pChembl≥5 of 4522 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL1761533
11.00	IC50	0.01	nM	CHEMBL1761535
11.00	IC50	0.01	nM	CHEMBL1761673
10.70	IC50	0.02	nM	CHEMBL1761532
10.70	IC50	0.02	nM	CHEMBL1761534
10.70	IC50	0.02	nM	CHEMBL1761519
10.70	IC50	0.02	nM	CHEMBL1796073
10.68	IC50	0.021	nM	CHEMBL1761519
10.66	IC50	0.022	nM	CHEMBL1761522
10.60	IC50	0.025	nM	REMIKIREN
10.59	Ki	0.026	nM	CHEMBL3144404
10.57	IC50	0.027	nM	CHEMBL1761525
10.55	IC50	0.028	nM	CHEMBL1761518
10.55	IC50	0.028	nM	CHEMBL1761521
10.52	IC50	0.03	nM	CHEMBL2052021
10.52	IC50	0.03	nM	CHEMBL1761674
10.52	IC50	0.03	nM	CHEMBL1910311
10.41	IC50	0.039	nM	CHEMBL3907708
10.41	IC50	0.039	nM	CHEMBL1276275
10.40	Ki	0.04	nM	DITEKIREN
10.40	IC50	0.04	nM	CHEMBL1256492
10.40	IC50	0.04	nM	CHEMBL1269698
10.40	IC50	0.04	nM	CHEMBL1761530
10.40	IC50	0.04	nM	CHEMBL1910302
10.40	IC50	0.04	nM	CHEMBL1910319
10.40	IC50	0.04	nM	CHEMBL1910546
10.40	Ki	0.04	nM	CHEMBL54411
10.37	Ki	0.043	nM	CHEMBL1790492
10.34	IC50	0.046	nM	CHEMBL1761520
10.30	IC50	0.05	nM	CHEMBL1269678
10.30	IC50	0.05	nM	CHEMBL1269746
10.30	IC50	0.05	nM	CHEMBL1269754
10.30	IC50	0.05	nM	CHEMBL1796075
10.30	IC50	0.05	nM	CHEMBL1910315
10.30	IC50	0.05	nM	CHEMBL1923131
10.30	IC50	0.05	nM	CHEMBL1957797
10.29	Ki	0.051	nM	CHEMBL264524
10.22	IC50	0.06	nM	CHEMBL2017100
10.22	IC50	0.06	nM	CHEMBL430539
10.22	IC50	0.06	nM	CHEMBL1276276
10.22	IC50	0.06	nM	CHEMBL1761531
10.22	IC50	0.06	nM	CHEMBL1761536
10.22	IC50	0.06	nM	CHEMBL1796074
10.22	IC50	0.06	nM	CHEMBL1910308
10.19	Ki	0.064	nM	CHEMBL3144405
10.19	IC50	0.064	nM	CHEMBL1761524
10.19	Ki	0.064	nM	CHEMBL54411
10.17	IC50	0.067	nM	CHEMBL390196
10.15	IC50	0.07	nM	CHEMBL1269743
10.15	IC50	0.07	nM	CHEMBL1796071

PubChem BioAssay actives

4180 with measured affinity, of 5120 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3R,4S)-N-[[3-[[1-(cyanomethyl)cyclopropyl]methoxy]-5-(3-methoxypropyl)phenyl]methyl]-N-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]piperidine-3-carboxamide	590895: Inhibition of human recombinant renin in PBS buffer using tetradecapeptide at pH 7.4	ic50	<0.0001	uM
(3R,4S)-N-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-N-[[3-[2-(dimethylamino)ethoxy]-5-(3-methoxypropyl)phenyl]methyl]piperidine-3-carboxamide	590895: Inhibition of human recombinant renin in PBS buffer using tetradecapeptide at pH 7.4	ic50	<0.0001	uM
4-[3-[[cyclopropyl-[(3R,4S)-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]piperidine-3-carbonyl]amino]methyl]-5-(3-methoxypropyl)phenoxy]-2,2-dimethylbutanoic acid	590895: Inhibition of human recombinant renin in PBS buffer using tetradecapeptide at pH 7.4	ic50	<0.0001	uM
4-[3-[[cyclopropyl-[(3R,4S)-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]piperidine-3-carbonyl]amino]methyl]-5-(3-methoxypropyl)phenoxy]-2,2-diethylbutanoic acid	590895: Inhibition of human recombinant renin in PBS buffer using tetradecapeptide at pH 7.4	ic50	<0.0001	uM
1-[2-[3-[[cyclopropyl-[(3R,4S)-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]piperidine-3-carbonyl]amino]methyl]-5-(3-methoxypropyl)phenoxy]ethyl]cyclopentane-1-carboxylic acid	590895: Inhibition of human recombinant renin in PBS buffer using tetradecapeptide at pH 7.4	ic50	<0.0001	uM
(3R,4S)-N-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-N-[[3-(3-methoxypropyl)-5-[[1-(2H-tetrazol-5-ylmethyl)cyclopropyl]methoxy]phenyl]methyl]piperidine-3-carboxamide	590895: Inhibition of human recombinant renin in PBS buffer using tetradecapeptide at pH 7.4	ic50	<0.0001	uM
2-[1-[[3-[[cyclopropyl-[(3R,4S)-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]piperidine-3-carbonyl]amino]methyl]-5-(3-methoxypropyl)phenoxy]methyl]cyclopropyl]acetic acid	590895: Inhibition of human recombinant renin in PBS buffer using tetradecapeptide at pH 7.4	ic50	<0.0001	uM
5-[3-[[cyclopropyl-[(3R,4S)-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]piperidine-3-carbonyl]amino]methyl]-5-(3-methoxypropyl)phenoxy]-2,2-dimethylpentanoic acid	590895: Inhibition of human recombinant renin in PBS buffer using tetradecapeptide at pH 7.4	ic50	<0.0001	uM
cis-(1S,2S)-2-[[3-[[cyclopropyl-[(3R,4S)-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]piperidine-3-carbonyl]amino]methyl]-5-(3-methoxypropyl)phenoxy]methyl]cyclopropane-1-carboxylic acid	590895: Inhibition of human recombinant renin in PBS buffer using tetradecapeptide at pH 7.4	ic50	<0.0001	uM
tert-butyl N-[(2S)-1-[[(2S)-1-[[1-[[(2S)-1-[(1-benzylpiperidin-4-yl)amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-6-methyl-1-oxoheptan-4-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate	198991: Inhibition of purified human kidney renin, radioimmunoassay using a synthetic tetradecapeptide renin substrate at 10e-9 M concentration	ki	<0.0001	uM
(3R,4S)-N-[(1-benzyl-4-fluoroindol-3-yl)methyl]-N-cyclopropyl-4-(1-methyl-2-oxo-4-pyridinyl)piperidine-3-carboxamide	603392: Inhibition of human recombinant renin using Q-FRET substrate after 3 hrs by fluorescence assay	ic50	<0.0001	uM
N-[2-[2-[4-[1-amino-3-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]propan-2-yl]-3-methylphenyl]phenyl]ethyl]acetamide	516476: Inhibition of human recombinant renin in phosphate buffer	ic50	<0.0001	uM
N-[[5-chloro-2-(3-methoxypropyl)-1-oxidopyridin-1-ium-4-yl]methyl]-N-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]piperidine-3-carboxamide	526063: Inhibition of renin in buffer	ic50	<0.0001	uM
(3S,4R)-N-cyclopropyl-4-(3,4-difluorophenyl)-4-(2,3-dihydroxypropoxy)-N-[[4-fluoro-1-[(3-fluorophenyl)methyl]indol-3-yl]methyl]piperidine-3-carboxamide	627051: Inhibition of human recombinant renin using DNP-Lys-His-Pro-Phe-His-Leu-Val-Ile-His-D,L-Amp as Q-FRET substrate after 3 hrs by fluorescence assay	ic50	<0.0001	uM
(3S,4R)-N-cyclopropyl-4-(3,4-difluorophenyl)-N-[[4-fluoro-1-[(3-fluorophenyl)methyl]indol-3-yl]methyl]-4-hydroxypiperidine-3-carboxamide	627051: Inhibition of human recombinant renin using DNP-Lys-His-Pro-Phe-His-Leu-Val-Ile-His-D,L-Amp as Q-FRET substrate after 3 hrs by fluorescence assay	ic50	<0.0001	uM
(3S,4R)-N-cyclopropyl-4-(3,4-difluorophenyl)-N-[[4-fluoro-1-[(3-methyl-1,2,4-oxadiazol-5-yl)methyl]indol-3-yl]methyl]-4-hydroxypiperidine-3-carboxamide	627051: Inhibition of human recombinant renin using DNP-Lys-His-Pro-Phe-His-Leu-Val-Ile-His-D,L-Amp as Q-FRET substrate after 3 hrs by fluorescence assay	ic50	<0.0001	uM
(3S,4R)-N-cyclopropyl-4-(3,4-difluorophenyl)-N-[[4-fluoro-1-[(2-methyl-4-pyridinyl)methyl]indol-3-yl]methyl]-4-hydroxypiperidine-3-carboxamide	627051: Inhibition of human recombinant renin using DNP-Lys-His-Pro-Phe-His-Leu-Val-Ile-His-D,L-Amp as Q-FRET substrate after 3 hrs by fluorescence assay	ic50	<0.0001	uM
(3R,4S)-N-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-N-[[3-(2-methoxyethoxy)-5-(3-methoxypropyl)phenyl]methyl]piperidine-3-carboxamide	590895: Inhibition of human recombinant renin in PBS buffer using tetradecapeptide at pH 7.4	ic50	<0.0001	uM
(3R,4S)-N-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-N-[[3-[3-(methanesulfonamido)propoxy]-5-(3-methoxypropyl)phenyl]methyl]piperidine-3-carboxamide	590895: Inhibition of human recombinant renin in PBS buffer using tetradecapeptide at pH 7.4	ic50	<0.0001	uM
(3R,4S)-N-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-N-[[3-(3-methoxypropyl)-5-[[(1S,2S)-2-(methylsulfonylcarbamoyl)cyclopropyl]methoxy]phenyl]methyl]piperidine-3-carboxamide	590895: Inhibition of human recombinant renin in PBS buffer using tetradecapeptide at pH 7.4	ic50	<0.0001	uM
(3R,4S)-N-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-N-[[3-[3-(ethylcarbamoylamino)propoxy]-5-(3-methoxypropyl)phenyl]methyl]piperidine-3-carboxamide	590895: Inhibition of human recombinant renin in PBS buffer using tetradecapeptide at pH 7.4	ic50	<0.0001	uM
tert-butyl (2S)-2-[[(2S)-1-[[(2S)-1-[[(4S,5S,7S)-5-hydroxy-2,8-dimethyl-7-[[(2S,3S)-3-methyl-1-oxo-1-(pyridin-2-ylmethylamino)pentan-2-yl]carbamoyl]nonan-4-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidine-1-carboxylate	198986: In vitro inhibition constants using recombinant human renin assay	ki	<0.0001	uM
(2S,4S,5S)-5-[[(2S)-2-[[(2R)-2-[[5-(dimethylamino)naphthalen-1-yl]sulfonylamino]-3-phenylpropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-hydroxy-7-methyl-N-[(2S,3S)-3-methyl-1-oxo-1-(pyridin-2-ylmethylamino)pentan-2-yl]-2-propan-2-yloctanamide	198986: In vitro inhibition constants using recombinant human renin assay	ki	<0.0001	uM
(3S,4R)-N-cyclopropyl-4-(3,4-difluorophenyl)-N-[[4-fluoro-1,7-bis(3-methoxypropyl)indol-3-yl]methyl]-4-hydroxypiperidine-3-carboxamide	627051: Inhibition of human recombinant renin using DNP-Lys-His-Pro-Phe-His-Leu-Val-Ile-His-D,L-Amp as Q-FRET substrate after 3 hrs by fluorescence assay	ic50	<0.0001	uM
(3R,3’S)-N-cyclopropyl-5,6-difluoro-N-[[8-(3-methoxypropyl)naphthalen-1-yl]methyl]spiro[1H-2-benzofuran-3,4’-piperidine]-3’-carboxamide	632373: Inhibition of recombinant human renin using 9 DNP-Lys-His-Pro-Phe-His-Leu-Val-Ile-His-D,L-Amp as substrate after 3 hrs by Q-FRET assay in presence of buffer at pH 7.4	ic50	<0.0001	uM
methyl (3R,5S)-5-[[2-tert-butyl-4-(furan-2-ylmethylamino)pyrimidine-5-carbonyl]-(2-methylpropyl)amino]piperidine-3-carboxylate	1320813: Inhibition of recombinant human preprorenin expressed in human 293F cells using angiotensinogen as substrate preincubated for 10 mins followed by substrate addition measured after 30 mins by ELISA	ic50	<0.0001	uM
(2S)-2-benzyl-3-tert-butylsulfonyl-N-[(2S)-1-[[(2S,3R,4S)-1-cyclohexyl-4-cyclopropyl-3,4-dihydroxybutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]propanamide	198513: In vitro inhibitory activity against purified recombinant human renin	ic50	<0.0001	uM
tert-butyl N-[(2S)-1-[[(2S)-1-[[(3S,4S)-1-[[(2S)-1-(benzylamino)-4-methylpentan-2-yl]amino]-3-hydroxy-6-methyl-1-oxoheptan-4-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate	198987: Compound was tested for inhibition of human kidney renin	ki	<0.0001	uM
N-[2-[7-[[(3R,4R)-4-[4-[3-[(2-methoxyphenyl)methoxy]propoxy]phenyl]piperidin-3-yl]oxymethyl]-3,4-dihydro-2H-quinolin-1-yl]ethyl]acetamide	353146: Inhibition of human recombinant rennin in buffer assessed as accumulation of angiotensin 1 using human tetradecapeptide by immunoassay	ic50	<0.0001	uM
(3R,4R)-3-[(1,4-dimethoxynaphthalen-2-yl)methoxy]-4-[4-[3-[(2-methoxyphenyl)methoxy]propoxy]phenyl]piperidine	198483: Inhibitory activity against purified recombinant human renin	ic50	0.0001	uM
(3R,4S)-N-[[2-chloro-5-(2-methoxyethyl)phenyl]methyl]-N-cyclopropyl-4-[6-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]-3-pyridinyl]piperidine-3-carboxamide	526107: Inhibition of renin in buffer	ic50	0.0001	uM
(3R,4S)-N-[[2-chloro-5-[(2-fluoroethylamino)methyl]phenyl]methyl]-N-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]piperidine-3-carboxamide	526063: Inhibition of renin in buffer	ic50	0.0001	uM
tert-butyl N-[(2S)-1-[[(2S)-1-[[(3S,4S)-1-[[(2S)-1-[(1-benzylpiperidin-4-yl)amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-6-methyl-1-oxoheptan-4-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate	198987: Compound was tested for inhibition of human kidney renin	ki	0.0001	uM
N-[(2S)-1-[[(2S)-1-[[(2S)-1-cyclohexyl-4,4-difluoro-5-(2-morpholin-4-ylethylamino)-3,5-dioxopentan-2-yl]amino]-1-oxopent-4-en-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]morpholine-4-carboxamide	195457: The concentration producing 50% inhibition of renin activity in monkey plasma was determined by radioimmunoassay.	ic50	0.0001	uM
(2S)-N-[2-[[(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6-methylheptan-2-yl]amino]-1-ethylsulfanyl-2-oxoethyl]-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanamide	199006: Inhibitory activity against monkey renin in vitro.	ic50	0.0001	uM
(2R)-4-(4-aminopiperidin-1-yl)-N-[(2S)-1-[[(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6-pyridin-2-ylhexan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]-2-(naphthalen-1-ylmethyl)-4-oxobutanamide	198701: In vitro inhibition of purified human kidney renin	ic50	0.0001	uM
(3R,4S)-N-[[2-chloro-5-(2-methoxyethyl)phenyl]methyl]-N-cyclopropyl-4-[6-[(3R)-3-(2,6-dichloro-4-methylphenoxy)pyrrolidin-1-yl]-3-pyridinyl]piperidine-3-carboxamide	526107: Inhibition of renin in buffer	ic50	0.0001	uM
(3R,4S)-N-[[5-(2-acetamidoethyl)-2-chlorophenyl]methyl]-4-[4-[[3-(2-chloro-3,6-difluorophenyl)-1,2-oxazol-5-yl]methoxy]phenyl]-N-cyclopropylpiperidine-3-carboxamide	526107: Inhibition of renin in buffer	ic50	0.0001	uM
(3S,4R)-N-[[2-chloro-5-(2-methoxyethyl)phenyl]methyl]-N-cyclopropyl-4-[6-[(3R)-3-(2,6-dichloro-4-methylphenoxy)pyrrolidin-1-yl]-3-pyridinyl]-4-hydroxypiperidine-3-carboxamide	526107: Inhibition of renin in buffer	ic50	0.0001	uM
(3R,4S)-N-cyclopropyl-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]-N-[[3-(2-hydroxy-2-methylpropoxy)-5-(3-methoxypropyl)phenyl]methyl]piperidine-3-carboxamide	590895: Inhibition of human recombinant renin in PBS buffer using tetradecapeptide at pH 7.4	ic50	0.0001	uM
3-[3-[[cyclopropyl-[(3R,4S)-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]piperidine-3-carbonyl]amino]methyl]-5-(3-methoxypropyl)phenoxy]-2,2-dimethylpropanoic acid	590895: Inhibition of human recombinant renin in PBS buffer using tetradecapeptide at pH 7.4	ic50	0.0001	uM
cis-ethyl (1S,2S)-2-[[3-[[cyclopropyl-[(3R,4S)-4-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]piperidine-3-carbonyl]amino]methyl]-5-(3-methoxypropyl)phenoxy]methyl]cyclopropane-1-carboxylate	590895: Inhibition of human recombinant renin in PBS buffer using tetradecapeptide at pH 7.4	ic50	0.0001	uM
methyl 3-[2-[4-[1-amino-3-[4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl]propan-2-yl]-3-methylphenyl]phenyl]propanoate	516476: Inhibition of human recombinant renin in phosphate buffer	ic50	0.0001	uM
(3R)-3-[(1S)-1-(3-bromophenyl)-1-hydroxy-5-methoxypentyl]-N-[(2S)-1-cyclohexyl-3-(methylamino)propan-2-yl]piperidine-1-carboxamide	1799047: Fluorescence Resonance Energy Transfer (FRET) Assay from Article 10.1016/j.bmcl.2009.04.140: “Design and optimization of renin inhibitors: Orally bioavailable alkyl amines.”	ic50	0.0001	uM
(3R)-N-[(2S)-1-cyclohexyl-3-(methylamino)propan-2-yl]-3-[(1S)-1-(2,3-difluorophenyl)-1-hydroxy-5-methoxypentyl]piperidine-1-carboxamide	1799047: Fluorescence Resonance Energy Transfer (FRET) Assay from Article 10.1016/j.bmcl.2009.04.140: “Design and optimization of renin inhibitors: Orally bioavailable alkyl amines.”	ic50	0.0001	uM
(3R)-3-[(1S)-1-(3-chloro-2-fluorophenyl)-1-hydroxy-5-methoxypentyl]-N-[(2S)-1-cyclohexyl-3-(methylamino)propan-2-yl]piperidine-1-carboxamide	1799047: Fluorescence Resonance Energy Transfer (FRET) Assay from Article 10.1016/j.bmcl.2009.04.140: “Design and optimization of renin inhibitors: Orally bioavailable alkyl amines.”	ic50	0.0001	uM
tert-butyl N-[(2S)-1-[[(2S)-1-[[3-hydroxy-1-[[(2S)-1-[(2-hydroxy-1,2-diphenylethyl)amino]-4-methyl-1-oxopentan-2-yl]amino]-6-methyl-1-oxoheptan-4-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate	198990: Inhibition of purified human kidney renin, fluorometric assay using a synthetic tetradecapeptide renin substrate at 10e-9 M concentration	ki	0.0001	uM
methyl 3-[[(2S,3R,4R)-1-cyclohexyl-3,4-dihydroxy-6-methylheptan-2-yl]amino]-2-[[(2S)-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanoyl]amino]-3-oxopropanoate	195613: Inhibition of monkey plasma renin	ic50	0.0001	uM
(2S)-1-N-[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]-2-N-[(2S)-1-[[(2S)-1-[[(4S,5S,7S)-5-hydroxy-2,8-dimethyl-7-[[(2S)-3-methyl-1-[(1-oxidopyridin-1-ium-2-yl)methylamino]-1-oxopentan-2-yl]carbamoyl]nonan-4-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]-methylamino]-1-oxo-3-phenylpropan-2-yl]pyrrolidine-1,2-dicarboxamide	198986: In vitro inhibition constants using recombinant human renin assay	ki	0.0001	uM
[(2S)-1-[[(2S)-1-[[(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6-pyridin-2-ylhexan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl] N-methyl-N-[2-[methyl(morpholine-4-carbonyl)amino]ethyl]carbamate	198702: In vitro inhibition of renin in human plasma	ic50	0.0001	uM

CTD chemical–gene interactions

123 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Angiotensin-Converting Enzyme Inhibitors	increases reaction, affects activity, increases expression, increases activity	12
Propranolol	increases activity, increases reaction, decreases reaction, increases expression, increases cleavage (+3 more)	11
Indomethacin	increases expression, decreases activity, affects cotreatment, decreases expression, decreases reaction (+1 more)	10
Nitroprusside	decreases reaction, increases activity, affects cotreatment, increases reaction, affects reaction	10
Clonidine	decreases activity, increases activity, affects cotreatment, decreases expression	8
Furosemide	increases activity, decreases reaction, increases expression	6
Nifedipine	increases secretion, increases expression, increases activity, increases reaction, affects cotreatment	5
Losartan	increases reaction, decreases activity, increases activity, decreases reaction, increases expression	5
Atenolol	decreases activity, decreases expression, increases secretion, affects cotreatment	4
Labetalol	increases expression, decreases activity, affects cotreatment	4
Oxprenolol	affects cotreatment, decreases activity	4
Spironolactone	increases expression, affects cotreatment, decreases expression, decreases response to substance	4
Bumetanide	affects cotreatment, increases expression, increases secretion, decreases reaction, increases activity	3
Chlorthalidone	increases activity, increases expression	3
Enalapril	decreases expression, affects cotreatment, decreases reaction, increases abundance, decreases activity (+1 more)	3
Hydralazine	increases expression, increases activity, decreases reaction	3
Hydrochlorothiazide	increases activity, increases expression, increases reaction, affects reaction	3
Isoflurane	affects cotreatment, decreases expression, affects activity, increases expression	3
Pindolol	decreases expression, decreases reaction, increases cleavage, decreases activity	3
Prazosin	decreases activity, increases activity	3
Sulindac	decreases reaction, increases expression, decreases activity	3
benazepril	affects cotreatment, increases activity, increases expression	2
soyasaponin I	decreases activity	2
Acetaminophen	increases activity, increases expression, decreases reaction	2
Aspirin	decreases activity	2
Contraceptives, Oral	increases activity	2
Dexamethasone	affects cotreatment, increases secretion, increases activity	2
Dobutamine	increases secretion, increases activity, increases expression, decreases reaction	2
Epinephrine	increases activity, decreases reaction	2
Fenoterol	increases activity, increases expression	2

ChEMBL screening assays

541 unique, capped per target: 472 binding, 68 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1032301	Binding	Inhibition of renin	Discovery and X-ray crystallographic analysis of a spiropiperidine iminohydantoin inhibitor of beta-secretase. — J Med Chem
CHEMBL4343420	ADMET	Inhibition of renin (unknown origin)	Discovery of AM-6494: A Potent and Orally Efficacious β-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitor with in Vivo Selectivity over BACE2. — J Med Chem
CHEMBL701248	Functional	Inhibitory activity against purified human renal renin at pH 6.5	Water-soluble renin inhibitors: design of a subnanomolar inhibitor with a prolonged duration of action. — J Med Chem

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	PHASE4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	PHASE4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	PHASE4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	PHASE4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	PHASE4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	PHASE4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	PHASE4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	PHASE4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	PHASE4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	PHASE4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	PHASE4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	PHASE4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	PHASE4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	PHASE4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	PHASE4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	PHASE4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	PHASE4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	PHASE4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	PHASE4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients
NCT01437943	PHASE4	TERMINATED	Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
NCT01545479	PHASE4	COMPLETED	Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition
NCT01614431	PHASE4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01631149	PHASE4	COMPLETED	Effect of Deep BLock on Intraoperative Surgical Conditions
NCT01722513	PHASE4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01985360	PHASE4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02311010	PHASE4	UNKNOWN	Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism
NCT02413073	PHASE4	COMPLETED	Whole Body Vibration in Kidney Disease
NCT02444013	PHASE4	UNKNOWN	Folic Acid for Prevention of Contrast Induced Nephropathy
NCT02663713	PHASE4	COMPLETED	A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor to Clopidogrel in Patients With Prior Myocardial Infarction
NCT02707809	PHASE4	COMPLETED	Effects of Dexmedetomidine on Microcirculation of Kidney Transplant Recipient
NCT02761577	PHASE4	COMPLETED	A Prospective Study on Incidence and Prevention of Contrast-induced Nephropathy in Croatia