ACE

Summary

ACE (angiotensin I converting enzyme, HGNC:2707) is a protein-coding gene on chromosome 17q23.3, encoding Angiotensin-converting enzyme (P12821). Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regulation of blood pressure, electrolyte homeostasis or synaptic plasticity.

This gene encodes an enzyme involved in blood pressure regulation and electrolyte balance. It catalyzes the conversion of angiotensin I into a physiologically active peptide angiotensin II. Angiotensin II is a potent vasopressor and aldosterone-stimulating peptide that controls blood pressure and fluid-electrolyte balance. This angiotensin converting enzyme (ACE) also inactivates the vasodilator protein, bradykinin. Accordingly, the encoded enzyme increases blood pressure and is a drug target of ACE inhibitors, which are often prescribed to reduce blood pressure. This enzyme additionally plays a role in fertility through its ability to cleave and release GPI-anchored membrane proteins in spermatozoa. Many studies have associated the presence or absence of a 287 bp Alu repeat element in this gene with the levels of circulating enzyme. This polymorphism, as well as mutations in this gene, have been implicated in a wide variety of diseases including cardiovascular pathophysiologies, psoriasis, renal disease, stroke, and Alzheimer’s disease. Regulation of the homologous ACE2 gene may be involved in progression of disease caused by several human coronaviruses, including SARS-CoV and SARS-CoV-2. Alternative splicing results in multiple transcript variants encoding both somatic (sACE) and male-specific testicular (tACE) isoforms.

Source: NCBI Gene 1636 — RefSeq curated summary.

At a glance

• Gene–disease (curated): renal tubular dysgenesis - ACE (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 40 (top 3% of genes corpus-wide)
• Clinical variants (ClinVar): 884 total — 30 pathogenic, 32 likely-pathogenic (top 4% of genes corpus-wide)
• GTEx eGene: eQTL in 30 tissues, sQTL in 6 (q < 0.05)
• Phenotypes (HPO): 11
• Drug target: yes — 17 curated mechanism-of-action drugs; 31 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 15 — Benazepril Hydrochloride, Captopril, Cilazapril, +12 more
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.88 (unconstrained)
• MANE Select transcript: NM_000789
• Interaction hub: 3,428 STRING partners (top 2% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2707
Approved symbol	ACE
Name	angiotensin I converting enzyme
Location	17q23.3
Locus type	gene with protein product
Status	Approved
Aliases	ACE1, CD143
Ensembl gene	ENSG00000159640
Ensembl biotype	protein_coding
OMIM	106180
Entrez	1636

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 17 protein_coding, 7 nonsense_mediated_decay, 6 retained_intron, 3 protein_coding_CDS_not_defined

MANE Select: ENST00000290866

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 11, TSL 3: 4, TSL 4: 1, TSL 5: 3

ENST00000290866, ENST00000290863, ENST00000413513, ENST00000428043, ENST00000577418, ENST00000578679, ENST00000578839, ENST00000579204, ENST00000579314, ENST00000579462, ENST00000579726, ENST00000580318, ENST00000582005, ENST00000582244, ENST00000582627, ENST00000582678, ENST00000582761, ENST00000583336, ENST00000583645, ENST00000584529, ENST00000584865, ENST00000884274, ENST00000884275, ENST00000884276, ENST00000884277, ENST00000884278, ENST00000884279, ENST00000884280, ENST00000884281, ENST00000953328, ENST00001038909, ENST00001108863, ENST00001135621

RefSeq mRNA: 6 — MANE Select: NM_000789 NM_000789, NM_001178057, NM_001382700, NM_001382701, NM_001382702, NM_152830

CCDS: CCDS11637, CCDS45755, CCDS54155

Canonical transcript exons

ENST00000290866 — 25 exons

Exon	Start	End
ENSE00002259849	63497137	63498373
ENSE00003460790	63488941	63489132
ENSE00003484452	63479007	63479100
ENSE00003485879	63490954	63491051
ENSE00003498519	63482466	63482689
ENSE00003545829	63493922	63494066
ENSE00003546645	63485236	63485372
ENSE00003548315	63483029	63483173
ENSE00003557946	63496798	63496985
ENSE00003561256	63486986	63487073
ENSE00003566846	63484330	63484541
ENSE00003574324	63493436	63493659
ENSE00003583833	63483849	63483971
ENSE00003606637	63488648	63488791
ENSE00003629718	63477061	63477343
ENSE00003644850	63491209	63491381
ENSE00003655430	63479769	63479912
ENSE00003657193	63480337	63480528
ENSE00003659350	63486557	63486715
ENSE00003661262	63477931	63478098
ENSE00003665301	63483460	63483558
ENSE00003666007	63481566	63481738
ENSE00003673106	63481091	63481188
ENSE00003683947	63494372	63494470
ENSE00003685583	63496394	63496516

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 98.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.6907 / max 1168.7492, expressed in 923 samples.

Highest expression (Bgee): ileal mucosa, testis, jejunal mucosa, small intestine Peyer’s patch, small intestine.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACE is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 30 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 36 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	1.9e-34	-0.29	17:63478937:C:G
Testis	sqtl	2.6e-34	+0.65	17:63486691:A:G
Lung	eqtl	6.6e-26	+0.34	17:63485839:C:A
Colon Transverse	eqtl	2.9e-22	+0.44	17:63476980:C:T
Skin Sun Exposed Lower leg	eqtl	2.7e-15	-0.18	17:63476980:C:T
Muscle Skeletal	eqtl	7.7e-15	-0.63	17:63468728:T:C
Brain Frontal Cortex BA9	eqtl	3.0e-13	-0.40	17:63468418:C:T
Brain Anterior cingulate cortex BA24	eqtl	1.5e-11	-0.41	17:63468418:C:T
Brain Cerebellum	eqtl	4.3e-11	-0.42	17:63478937:C:G
Brain Cerebellar Hemisphere	eqtl	1.5e-10	-0.40	17:63476833:T:A
Adipose Subcutaneous	eqtl	9.2e-10	-0.16	17:63482264:A:G
Heart Left Ventricle	eqtl	5.1e-09	-0.61	17:63468728:T:C
Thyroid	eqtl	1.5e-07	+0.17	17:63498888:G:A
Brain Cortex	eqtl	1.9e-07	-0.32	17:63473368:C:A
Spleen	eqtl	5.1e-07	+0.47	17:63460695:C:G
Kidney Cortex	eqtl	6.1e-06	+0.58	17:63468418:C:T
Skin Not Sun Exposed Suprapubic	eqtl	1.1e-05	-0.14	17:63483402:T:C
Nerve Tibial	eqtl	2.2e-05	-0.16	17:63476980:C:T
Esophagus Muscularis	eqtl	6.2e-05	-0.44	17:63491783:C:T
Adrenal Gland	eqtl	3.9e-04	-0.24	17:63476980:C:T

FANTOM5 promoters

showing 10 of 12 alternative TSS:

Promoter ID	TPM avg	Samples expressed
162181	4.9983	854
162182	0.1968	81
162189	0.1637	4
162180	0.1434	59
162195	0.0425	4
208311	0.0361	10
162190	0.0283	3
162184	0.0200	6
162191	0.0197	3
162192	0.0168	4

Top tissues by expression

showing 100 of 260 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	98.92	gold quality
right testis	UBERON:0004534	97.07	gold quality
left testis	UBERON:0004533	96.93	gold quality
jejunal mucosa	UBERON:0000399	95.08	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.19	gold quality
small intestine	UBERON:0002108	93.01	gold quality
mucosa of transverse colon	UBERON:0004991	92.80	gold quality
testis	UBERON:0000473	92.13	gold quality
duodenum	UBERON:0002114	91.96	gold quality
upper lobe of left lung	UBERON:0008952	90.70	gold quality
apex of heart	UBERON:0002098	90.34	gold quality
right uterine tube	UBERON:0001302	89.84	gold quality
upper lobe of lung	UBERON:0008948	88.82	gold quality
right lung	UBERON:0002167	88.22	gold quality
adenohypophysis	UBERON:0002196	85.78	gold quality
gall bladder	UBERON:0002110	84.64	gold quality
right lobe of thyroid gland	UBERON:0001119	84.53	gold quality
left lobe of thyroid gland	UBERON:0001120	84.18	gold quality
thyroid gland	UBERON:0002046	84.00	gold quality
lung	UBERON:0002048	83.90	gold quality
transverse colon	UBERON:0001157	83.23	gold quality
putamen	UBERON:0001874	83.17	gold quality
caudate nucleus	UBERON:0001873	82.72	gold quality
pituitary gland	UBERON:0000007	82.68	gold quality
smooth muscle tissue	UBERON:0001135	82.42	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.28	gold quality
ectocervix	UBERON:0012249	82.25	gold quality
omental fat pad	UBERON:0010414	81.43	gold quality
peritoneum	UBERON:0002358	81.32	gold quality
intestine	UBERON:0000160	81.07	gold quality
minor salivary gland	UBERON:0001830	80.96	gold quality
adipose tissue of abdominal region	UBERON:0007808	80.81	gold quality
islet of Langerhans	UBERON:0000006	80.77	gold quality
rectum	UBERON:0001052	80.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.59	gold quality
colonic epithelium	UBERON:0000397	80.49	gold quality
endocervix	UBERON:0000458	79.98	gold quality
nucleus accumbens	UBERON:0001882	79.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.92	gold quality
granulocyte	CL:0000094	78.88	gold quality
vermiform appendix	UBERON:0001154	78.65	gold quality
decidua	UBERON:0002450	78.54	gold quality
heart left ventricle	UBERON:0002084	78.11	gold quality
right frontal lobe	UBERON:0002810	77.82	gold quality
saliva-secreting gland	UBERON:0001044	77.76	gold quality
mouth mucosa	UBERON:0003729	77.64	gold quality
cardiac ventricle	UBERON:0002082	77.56	gold quality
colon	UBERON:0001155	77.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.48	gold quality
visceral pleura	UBERON:0002401	77.40	gold quality
right atrium auricular region	UBERON:0006631	77.38	gold quality
adipose tissue	UBERON:0001013	77.16	gold quality
large intestine	UBERON:0000059	77.14	gold quality
right adrenal gland	UBERON:0001233	77.04	gold quality
muscle of leg	UBERON:0001383	76.92	gold quality
lower esophagus	UBERON:0013473	76.80	gold quality
right adrenal gland cortex	UBERON:0035827	76.77	gold quality
lower esophagus muscularis layer	UBERON:0035833	76.77	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.75	gold quality
left adrenal gland	UBERON:0001234	76.53	gold quality
cardiac atrium	UBERON:0002081	76.53	gold quality
adult mammalian kidney	UBERON:0000082	76.50	gold quality
body of stomach	UBERON:0001161	76.44	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	76.41	gold quality
pancreatic ductal cell	CL:0002079	76.19	silver quality
right coronary artery	UBERON:0001625	76.19	gold quality
prostate gland	UBERON:0002367	76.18	gold quality
heart	UBERON:0000948	75.98	gold quality
pancreas	UBERON:0001264	75.98	gold quality
left adrenal gland cortex	UBERON:0035825	75.66	gold quality
caecum	UBERON:0001153	75.62	gold quality
cortex of kidney	UBERON:0001225	75.50	gold quality
gastrocnemius	UBERON:0001388	75.46	gold quality
stomach	UBERON:0000945	75.25	gold quality
esophagus	UBERON:0001043	75.15	gold quality
left ventricle myocardium	UBERON:0006566	75.05	gold quality
body of uterus	UBERON:0009853	74.54	gold quality
cardiac muscle of right atrium	UBERON:0003379	74.49	gold quality
body of pancreas	UBERON:0001150	74.48	gold quality
uterine cervix	UBERON:0000002	74.46	gold quality
prefrontal cortex	UBERON:0000451	74.46	gold quality
Brodmann (1909) area 9	UBERON:0013540	74.30	gold quality
muscle layer of sigmoid colon	UBERON:0035805	74.13	gold quality
skin of leg	UBERON:0001511	73.92	gold quality
esophagus mucosa	UBERON:0002469	73.82	gold quality
kidney	UBERON:0002113	73.69	gold quality
cortical plate	UBERON:0005343	73.66	gold quality
adrenal gland	UBERON:0002369	73.56	gold quality
tibial nerve	UBERON:0001323	73.49	gold quality
adrenal cortex	UBERON:0001235	73.42	gold quality
jejunum	UBERON:0002115	73.31	gold quality
anatomical system	UBERON:0000467	73.06	gold quality
fundus of stomach	UBERON:0001160	72.88	gold quality
multicellular organism	UBERON:0000468	72.87	gold quality
material anatomical entity	UBERON:0000465	72.84	gold quality
seminal vesicle	UBERON:0000998	72.80	gold quality
skin of abdomen	UBERON:0001416	72.74	gold quality
lymph node	UBERON:0000029	72.70	gold quality
ganglionic eminence	UBERON:0004023	72.54	gold quality
mucosa of stomach	UBERON:0001199	72.45	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	725.04
E-ANND-3	yes	7.80
E-GEOD-111727	no	50.83
E-MTAB-6142	no	34.43

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Small intestine	tissue	249.7	high
Duodenum	tissue	166.0	high
Lung	tissue	46.3	medium
Testis	tissue	42.2	high
Seminal vesicle	tissue	22.4	medium
Putamen	tissue	21.9
Caudate putamen	tissue	20.9
Spinal cord	tissue	17.7
Parathyroid gland	tissue	17.6	not detected
Cervix	tissue	17.0	not detected
Substantia nigra	tissue	16.3
Basal ganglia	tissue	15.9	not detected
Pons	tissue	15.7
Thalamus	tissue	15.6
Superior colliculi	tissue	15.4
Skeletal muscle	tissue	15.1	not detected
Midbrain	tissue	15.0
Thyroid gland	tissue	14.8	not detected
Medulla oblongata	tissue	14.4
Hypothalamus	tissue	12.1
Adipose tissue	tissue	11.8	not detected
Cerebral cortex	tissue	11.2	not detected
Motor cortex	tissue	11.2
Nucleus accumbens	tissue	11.2
Insular cortex	tissue	11.2
Ventral forebrain	tissue	11.1
Somatosensory cortex	tissue	11.0
Placenta	tissue	10.9	not detected
Colon	tissue	10.5	not detected
Kidney	tissue	10.1	high
Retrosplenial and cingulate cortex	tissue	10.1
Temporal cortex	tissue	10.1
Occipital cortex	tissue	10.1
Hippocampal formation	tissue	10.0
Entorhinal cortex	tissue	10.0
Prefrontal cortex	tissue	9.9
Septum	tissue	9.9
Corpus callosum	tissue	9.8
Periaqueductal gray	tissue	9.8
Heart muscle	tissue	9.7	not detected
Tongue	tissue	9.3
Retrosplenial cortex	tissue	9.1
Pituitary gland	tissue	9.0
Smooth muscle	tissue	9.0	not detected
Amygdala	tissue	8.6
Prostate	tissue	8.4	medium
Stomach 1	tissue	7.8	not detected
Gallbladder	tissue	7.7	low
Endometrium 1	tissue	7.6	high
Frontal cortex	tissue	6.8
Olfactory bulb	tissue	6.8
Fallopian tube	tissue	6.0	medium
Cerebellum	tissue	5.9	not detected
Pancreas	tissue	5.8	not detected
Rectum	tissue	5.7	not detected
Postcentral gyrus	tissue	5.7
Urinary bladder	tissue	5.2	not detected
Lymph node	tissue	4.6	not detected
Adrenal gland	tissue	4.6	not detected
Appendix	tissue	4.6	not detected

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Dorsal spinal cord (17.7), Caudate nucleus (16.2), Ventral spinal cord (16.1), Nucleus basalis of Meynert (11.3), White matter (9.8).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets:

Target	Regulation
GJA1	Repression

Upstream regulators (CollecTRI, top): AP1, ATF2, CEBPA, CREM, EGR1, ETS1, FOXC1, HIF1A, JUN, KLF2, MYC, NR3C2, POU4F2, PPARA, PPARG, SP3, SRY

miRNA regulators (miRDB)

Targeting ACE by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 49 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628

Functional genomics

gnomAD constraint: pLI 6.24e-32, LOEUF 0.88, missense Z -0.503 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000290866 — one region, missense o/e 1.04.

Literature-anchored findings (GeneRIF, showing 16)

• The DD genotype of ACE polymorphism is a risk factor for coronary artery disease and coronary stent restenosis in Japanese patients. (PMID:11665795)
• During shedding of the ectodomain of ACE, a minimum requirement is an exposed or unhindered sequence of minimum length between the extracellular domain and the membrane, within or adjacent to otherwise compact, folded domains. (PMID:11747437)
• association between left ventricular hypertrophy and the C825T allele of the G-protein beta3 subunit gene in Arabs. (G PROTEIN BETA3) (PMID:11768721)
• It appears that the DD genotype (of ACE gene) is associated with progression of Japanese type 2 diabetic nephropathy. (PMID:11770799)
• vasomotor properties are influenced by the I/D polymorphism of the ACE gene. (PMID:11818755)
• ACE insertion/deletion polymorphism and submaximal exercise cardiovascular hemodynamics in postmenopausal women. (PMID:11842043)
• Homozygosity for the insertion allele of the I/D polymorphism is associated with adaptation to high altitude. (PMID:11851983)
• ACE polymorphism is not a risk factor for the development of cerebral infarction in a Korean population. (PMID:11859923)
• effects of monoclonal antibodies (mAbs) to eight different epitopes on the N-terminal domain of ACE on shedding (PMID:11879185)
• alleles of the ACE gene may be a predisposing factor for developing white matter lesions in essential hypertensive patients. (PMID:11882570)
• Angiotensin I-converting enzyme and metabolism of the haematological peptide N-acetyl-seryl-aspartyl-lysyl-proline. (PMID:11903317)
• Different aortic reflection wave responses following long-term angiotensin-converting enzyme inhibition and beta-blocker in essential hypertension (PMID:11903319)
• A prospective evaluation of the angiotensin-converting enzyme D/I polymorphism and left ventricular remodeling in the ‘Healing and Early Afterload Reducing Therapy’ study. (PMID:11903350)
• Toward an optimal joint recognition of the S1’ subsites of endothelin converting enzyme-1 (ECE-1), angiotensin converting enzyme (ACE), and neutral endopeptidase (NEP). (PMID:11906289)
• Polymorphisms of genes encoding kininase II as risk factors for orthostatic hypotension. (PMID:11910300)
• Enhanced responses of blood pressure, renal function, and aldosterone to angiotensin I in the DD genotype are blunted by low sodium intake. MAP, renal hemodynamic parameters, and aldosterone concentrations to AngI are enhanced for DD genotype. (PMID:11912262)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ace	ENSMUSG00000020681
rattus_norvegicus	Ace	ENSRNOG00000062101

Paralogs (1): ACE2 (ENSG00000130234)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:87874) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 72 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased urine osmolality	6
decreased systemic arterial systolic blood pressure	5
abnormal kidney vasculature morphology	4
kidney inflammation	4
polyuria	3
reduced male fertility	3
decreased litter size	3
decreased angiotensin I-converting enzyme activity	3
abnormal kidney pelvis morphology	3
postnatal lethality, incomplete penetrance	3
abnormal systemic arterial blood pressure	2
abnormal kidney morphology	2
increased heart rate	2
abnormal kidney medulla morphology	2
decreased kidney weight	2
increased renin activity	2
dilated kidney calyx	2
abnormal kidney arterial blood vessel morphology	2
abnormal renal artery morphology	2
kidney cortex atrophy	2
decreased circulating angiotensin II level	2
decreased hematocrit	1
impaired fertilization	1
hydronephrosis	1
increased body weight	1

+47 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pan troglodytes	Q9GLN7	99.2%	Diamond
Pongo abelii	Q5RFN1	98.1%	Diamond
Felis catus	Q56H28	93.0%	Diamond
Paguma larvata	Q56NL1	93.0%	Diamond
Mesocricetus auratus	Q50JE5	89.2%	Diamond
Sus scrofa	F1RRW5	88.9%	Diamond
Bos taurus	P12820	88.9%	Diamond
Oryctolagus cuniculus	P12822	87.2%	Diamond
Drosophila melanogaster	Q10714	80.3%	Diamond
Haematobia irritans exigua	Q10715	80.3%	Diamond
Gallus gallus	Q10751	68.2%	Diamond
Theromyzon tessulatum	Q6Q4G4	53.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
DCAF7	protein-coding	10238
KCNH6	protein-coding	81033
CYB561	protein-coding	1534
TANC2	protein-coding	26115
TACO1	protein-coding	51204

Protein

Protein identifiers

Angiotensin-converting enzyme — P12821 (reviewed: P12821)

Alternative names: Dipeptidyl carboxypeptidase I, Kininase II

All UniProt accessions (9): P12821, A0A0A0MSN4, J3KRH5, J3KS28, J3KSQ5, J3KTB8, J3KTH9, J3QLR4, J3QSC7

UniProt curated annotations — full annotation on UniProt →

Function. Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regulation of blood pressure, electrolyte homeostasis or synaptic plasticity. Composed of two similar catalytic domains, each possessing a functional active site, with different selectivity for substrates. Plays a major role in the angiotensin-renin system that regulates blood pressure and sodium retention by the kidney by converting angiotensin I to angiotensin II, resulting in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent vasodilator, and therefore enhance the blood pressure response. Acts as a regulator of synaptic transmission by mediating cleavage of neuropeptide hormones, such as substance P, neurotensin or enkephalins. Catalyzes degradation of different enkephalin neuropeptides (Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Phe and possibly Met-enkephalin-Arg-Gly-Leu). Acts as a regulator of synaptic plasticity in the nucleus accumbens of the brain by mediating cleavage of Met-enkephalin-Arg-Phe, a strong ligand of Mu-type opioid receptor OPRM1, into Met-enkephalin. Met-enkephalin-Arg-Phe cleavage by ACE decreases activation of OPRM1, leading to long-term synaptic potentiation of glutamate release. Also acts as a regulator of hematopoietic stem cell differentiation by mediating degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP). Acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1. Involved in amyloid-beta metabolism by catalyzing degradation of Amyloid-beta protein 40 and Amyloid-beta protein 42 peptides, thereby preventing plaque formation. Catalyzes cleavage of cholecystokinin (maturation of Cholecystokinin-8 and Cholecystokinin-5) and Gonadoliberin-1 (both maturation and degradation) hormones. Degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) and amyloid-beta proteins is mediated by the N-terminal catalytic domain, while angiotensin I and cholecystokinin cleavage is mediated by the C-terminal catalytic region. Soluble form that is released in blood plasma and other body fluids following proteolytic cleavage in the juxtamembrane stalk region. Isoform produced by alternative promoter usage that is specifically expressed in spermatocytes and adult testis, and which is required for male fertility. In contrast to somatic isoforms, only contains one catalytic domain. Acts as a dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of substrates. The identity of substrates that are needed for male fertility is unknown. May also have a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety. The GPIase activity was reported to be essential for the egg-binding ability of the sperm. This activity is however unclear and has been challenged by other groups, suggesting that it may be indirect.

Subunit / interactions. Monomer and homodimer; homodimerizes following binding to an inhibitor. Interacts with calmodulin (CALM1, CALM2 or CALM3); interaction takes place in the cytoplasmic region and regulates phosphorylation and proteolytic cleavage.

Subcellular location. Cell membrane. Cytoplasm Secreted Cell membrane. Secreted.

Tissue specificity. Ubiquitously expressed, with highest levels in lung, kidney, heart, gastrointestinal system and prostate. Specifically expressed in spermatocytes and adult testis.

Post-translational modifications. Produced following proteolytic cleavage by secretase enzymes that cleave the transmembrane form in the juxtamembrane stalk region upstream of the transmembrane region. Cleavage can take place at different sites of the juxtamembrane stalk region. Phosphorylated by CK2 on Ser-1299; which allows membrane retention. Phosphorylated on tyrosine residues on its extracellular part, promoting cleavage by secretase enzymes and formation of the soluble form (Angiotensin-converting enzyme, soluble form).

Disease relevance. Ischemic stroke (ISCHSTR) [MIM:601367] A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. Disease susceptibility is associated with variants affecting the gene represented in this entry. 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. Microvascular complications of diabetes 3 (MVCD3) [MIM:612624] Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Disease susceptibility is associated with variants affecting the gene represented in this entry. Intracerebral hemorrhage (ICH) [MIM:614519] A pathological condition characterized by bleeding into one or both cerebral hemispheres including the basal ganglia and the cerebral cortex. It is often associated with hypertension and craniocerebral trauma. Intracerebral bleeding is a common cause of stroke. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Activity regulation. The dipeptidyl carboxypeptidase activity is strongly activated by chloride. The dipeptidyl carboxypeptidase activity is specifically inhibited by lisinopril, captopril and enalaprilat. Strongly inhibited by lisinopril and captopril.

Cofactor. Binds 2 Zn(2+) ions per subunit. Isoform Testis-specific only binds 1 Zn(2+) ion per subunit. Binds 3 chloride ions per subunit.

Induction. Up-regulated in failing heart.

Polymorphism. Genetic variants in ACE are associated with interindividual variability of angiotensin I-converting enzyme plasma levels [MIM:621420].

Miscellaneous. Inhibitors of ACE are commonly used to treat hypertension and some types of renal and cardiac dysfunction. Incomplete sequence.

Similarity. Belongs to the peptidase M2 family.

Isoforms (4)

UniProt ID	Names	Canonical?
P12821-1	Somatic-1	yes
P12821-2	Somatic-2, Soluble
P12821-3	Testis-specific, ACE-T, ACEt, tACE, hTACE
P12821-4	4

RefSeq proteins (6): NP_000780, NP_001171528, NP_001369629, NP_001369630, NP_001369631, NP_690043 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001548	Peptidase_M2	Family

Pfam: PF01401

Enzyme classification (BRENDA)

• EC 3.4.15.1 — peptidyl-dipeptidase A (BRENDA: 31 organisms, 224 substrates, 941 inhibitors, 246 Km, 169 kcat entries)

Substrate kinetics (BRENDA)

95 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
HIPPURYL-HIS-LEU	0.0308–20	30
ANGIOTENSIN I	0.009–2.7	25
BENZYLOXYCARBONYL-PHE-HIS-LEU	0.13–2.8	8
BENZOYL-GLY-HIS-LEU	0.56–18.2	4
LEQIYHL	0.0157–0.4125	4
LVVYPWTQRY	0.014–0.033	4
N-(3-(2-FURYL)ACRYLOYL)-PHE-PHE-ARG	0.05–0.12	4
NKLKPSQWI	0.0147–0.5237	4
NKLKPSQWISL	0.0027–0.1505	4
NKLKPSQWISLSD	0.1367–0.6738	4
[PHE9,ARG10]ANGIOTENSIN I	0.011–0.025	4
2-FURANACRYLOYL-PHE-GLY-GLY	0.08–0.174	3
HIPPURYL-PHE-ARG	0.5–1.8	3
N-(3-(2-FURYL)ACRYLOYL)-PHE-ALA-LYS	0.14–0.17	3
N-(3-(2-FURYL)ACRYLOYL)-PHE-ALA-PRO	0.005–0.008	3

Catalyzed reactions (Rhea)

• angiotensin I + H2O = L-histidyl-L-leucine + angiotensin II (RHEA:63560)
• Met-enkephalin-Arg-Phe + H2O = L-arginyl-L-phenylalanine + Met-enkephalin (RHEA:70675)
• bradykinin + H2O = L-Phe-L-Arg + bradykinin(1-7) (RHEA:71451)
• goralatide + H2O = N-acetyl-L-seryl-L-aspartate + L-lysyl-L-proline (RHEA:71455)
• substance P + H2O = substance P(1-9) + L-Leu-L-Met-NH2 (RHEA:71459)
• substance P + H2O = substance P(1-8) + Gly-L-Leu-L-Met-NH2 (RHEA:71463)
• substance P + H2O = L-Phe-L-Phe-Gly-L-Leu-L-Met-NH2 + substance P(1-6) (RHEA:71471)
• neurotensin + H2O = neurotensin(1-11) + L-isoleucyl-L-leucine (RHEA:71475)
• Met-enkephalin + H2O = L-phenylalanyl-L-methionine + L-tyrosylglycylglycine (RHEA:71483)
• Leu-enkephalin + H2O = L-tyrosylglycylglycine + L-phenylalanyl-L-leucine (RHEA:71487)

UniProt features (223 total): helix 77, sequence variant 24, mutagenesis site 23, strand 21, glycosylation site 20, binding site 16, turn 10, disulfide bond 6, splice variant 6, active site 4, site 4, chain 2, topological domain 2, domain 2, sequence conflict 2, signal peptide 1, modified residue 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

showing 30 of 97 structures by resolution:

PDB	Title	Method	Resolution (Å)
6H5W	Crystal structure of human Angiotensin-1 converting enzyme C-domain in complex with …	X-RAY DIFFRACTION	1.37
9H1E	Crystal structure of Angiotensin-1 converting enzyme C-domain in complex with dual …	X-RAY DIFFRACTION	1.45
7Q27	Crystal structure of Angiotensin-1 converting enzyme C-domain in complex with dual …	X-RAY DIFFRACTION	1.5
9QAN	Human angiotensin-1 converting enzyme C-domain in complex with ramiprilat	X-RAY DIFFRACTION	1.5
9QAP	Human angiotensin-1 converting enzyme C-domain in complex with quinaprilat	X-RAY DIFFRACTION	1.5
5AMB	Crystal structure of the Angiotensin-1 converting enzyme N-domain in complex with …	X-RAY DIFFRACTION	1.55
6F9T	Crystal structure of human testis Angiotensin-1 converting enzyme in complex with …	X-RAY DIFFRACTION	1.6
7Q25	Crystal structure of Angiotensin-1 converting enzyme N-domain in complex with dual …	X-RAY DIFFRACTION	1.6
7Q29	Crystal structure of Angiotensin-1 converting enzyme C-domain in complex with dual …	X-RAY DIFFRACTION	1.6
8QFX	Human Angiotensin-1 converting enzyme N-domain in complex with the lactotripeptide IPP	X-RAY DIFFRACTION	1.6
5AMC	Crystal structure of the Angiotensin-1 converting enzyme N-domain in complex with …	X-RAY DIFFRACTION	1.65
7Q28	Crystal structure of Angiotensin-1 converting enzyme C-domain in complex with dual …	X-RAY DIFFRACTION	1.65
6F9V	Crystal structure of human Angiotensin-1 converting enzyme N-domain in complex with …	X-RAY DIFFRACTION	1.69
6TT3	Crystal structure of ‘Res_S2 mutant human Angiotensin-1 converting enzyme N-domain in …	X-RAY DIFFRACTION	1.7
7Q26	Crystal structure of Angiotensin-1 converting enzyme N-domain in complex with dual …	X-RAY DIFFRACTION	1.7
9H1B	Crystal structure of Angiotensin-1 converting enzyme N-domain in complex with dual …	X-RAY DIFFRACTION	1.7
6EN5	Crystal structure A of the Angiotensin-1 converting enzyme N-domain in complex with a …	X-RAY DIFFRACTION	1.75
7Z6Z	Crystal structure of Angiotensin-1 converting enzyme N-domain in complex with fosinoprilat	X-RAY DIFFRACTION	1.75
4C2O	Crystal structure of human testis angiotensin-I converting enzyme mutant D465T	X-RAY DIFFRACTION	1.8
4UFA	Crystal structure of the Angiotensin-1 converting enzyme N-domain in complex with Ac-SD	X-RAY DIFFRACTION	1.8
4UFB	Crystal structure of the Angiotensin-1 converting enzyme N-domain in complex with Lys-Pro	X-RAY DIFFRACTION	1.8
5AM9	Crystal structure of the Angiotensin-1 converting enzyme N-domain in complex with …	X-RAY DIFFRACTION	1.8
5AMA	Crystal structure of the Angiotensin-1 converting enzyme N-domain in complex with …	X-RAY DIFFRACTION	1.8
6EN6	Crystal structure B of the Angiotensin-1 converting enzyme N-domain in complex with a …	X-RAY DIFFRACTION	1.8
6H5X	Crystal structure of human Angiotensin-1 converting enzyme N-domain in complex with …	X-RAY DIFFRACTION	1.8
6QS1	Crystal structure of human Angiotensin-1 converting enzyme N-domain in complex with BPPb	X-RAY DIFFRACTION	1.8
6TT1	Crystal structure of ‘Res_S2 mutant human Angiotensin-1 converting enzyme N-domain in …	X-RAY DIFFRACTION	1.8
6TT4	Crystal structure of ‘Res_S2 mutant human Angiotensin-1 converting enzyme N-domain in …	X-RAY DIFFRACTION	1.8
9H1C	Crystal structure of Angiotensin-1 converting enzyme C-domain in complex with dual …	X-RAY DIFFRACTION	1.8
9H1D	Crystal structure of Angiotensin-1 converting enzyme C-domain in complex with dual …	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P12821-F1	91.38	0.82

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Metallopeptidases, Metabolic proteins, CD markers, Predicted membrane proteins, Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, Candidate cardiovascular disease genes, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Congenital malformations, Congenital malformations of the urinary system, Diabetes, Eye disease

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH enhanced · IF approved

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 (8)

Position	Role
520	proton donor 1
989	proton acceptor 2
1118	proton donor 2
523	not glycosylated
1166–1167	cleavage
1225	not glycosylated
1232–1233	cleavage
391	proton acceptor 1

Ligand- & substrate-binding residues (16)

Position	Role
231	chloride
390	Zn(2+)
394	Zn(2+)
418	Zn(2+)
529	chloride
791	chloride
829	chloride
988	Zn(2+)
414	Zn(2+)
442	Zn(2+)
992	Zn(2+)
1016	Zn(2+)
1090	chloride
1094	chloride
1127	chloride

Post-translational modifications (1)

Type	Positions
Phosphoserine	1299

Disulfide bonds (6)

Type	Positions
Disulfide bond	157–165, 359–377, 545–557, 757–763, 957–975, 1143–1155

Glycosylation sites (20)

Type	Positions
N-linked (glcnac…) asparagine	103, 121, 140, 368, 617, 38, 54, 74, 111, 146, 160, 318, 445, 509, 677, 760, 942, 1191
N-linked (glcnac…) (complex) asparagine	695, 714

Mutagenesis-validated functional residues (23)

Position	Phenotype
103	in ace(t)g0 mutant; abolished n-glycosylation leading to impaired stability and degradation; when associated with d-121, d-140, d-368 and …
121	in ace(t)g0 mutant; abolished n-glycosylation leading to impaired stability and degradation; when associated with d-103, d-140, d-368 and …
140	in ace(t)g0 mutant; abolished n-glycosylation leading to impaired stability and degradation; when associated with d-103, d-121, d-368 and …
368	in ace(t)g0 mutant; abolished n-glycosylation leading to impaired stability and degradation; when associated with d-103, d-121, d-140 and …
553	abolished binding to chloride ion.
617	in ace(t)g0 mutant; abolished n-glycosylation leading to impaired stability and degradation; when associated with d-103, d-121, d-140 and …
318	in ndom123456 mutant; abolished dipeptidyl carboxypeptidase activity; when associated with d-445 and d-509. in ndom1234569 mutant; does not …
390–394	abolished dipeptidyl carboxypeptidase activity; when associated with 988-k–k-992. abolished n-terminal active sites, leading to impaired …
391	abolished peptidase activity, leading to increased levels of amyloid-beta; when associated with d-989.
445	in ndom123456 mutant; abolished dipeptidyl carboxypeptidase activity; when associated with d-318 and d-445. in ndom1234569 mutant; does not …
509	in ndom123456 mutant; abolished dipeptidyl carboxypeptidase activity; when associated with d-318 and d-445.
529	abolished dependence to chloride, leading to reduced peptidyl dipeptidase activity.
988–992	abolished dipeptidyl carboxypeptidase activity; when associated with 390-k–k-394. abolishes the second active site, preventing maturation …
989	abolished peptidase activity, leading to increased levels of amyloid-beta; when associated with d-391.
1016	strongly decreased dipeptidyl carboxypeptidase activity; when associated with 390-k–k-394.
1016	abolished dipeptidyl carboxypeptidase activity; when associated with 390-k–k-394.
1020	decreased dipeptidyl carboxypeptidase activity; when associated with 390-k–k-394.
1116	decreased ability to cleave substance p and bradykinin. reduced binding to captopril inhibitor.
1125	decreased ability to cleave substance p and captopril inhibitor.
1127	abolished dependence to chloride, leading to reduced peptidyl dipeptidase activity.
1166	does not prevent cleavage and secretion of the soluble form, suggesting that processing can take place at different sites.
1229	increased cleavage and secretion of the soluble form by generating a new cleavage site.
1299	abolishes phosphorylation and decreases membrane retention.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-2022377	Metabolism of Angiotensinogen to Angiotensins	curated
R-HSA-392499	Metabolism of proteins	—
R-HSA-2980736	Peptide hormone metabolism	—

MSigDB gene sets: 318 (showing top): MODULE_172, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE_BY_CIRCULATORY_RENIN_ANGIOTENSIN, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOMF_METALLOPEPTIDASE_ACTIVITY, MODULE_255, GOBP_RESPONSE_TO_ANGIOTENSIN, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, MODULE_317, GOBP_REGULATION_OF_HORMONE_LEVELS, GOCC_CELL_SURFACE, KYNG_DNA_DAMAGE_DN, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY

GO Biological Process (34): kidney development (GO:0001822), blood vessel remodeling (GO:0001974), angiotensin maturation (GO:0002003), regulation of renal output by angiotensin (GO:0002019), neutrophil mediated immunity (GO:0002446), antigen processing and presentation of peptide antigen via MHC class I (GO:0002474), regulation of systemic arterial blood pressure by renin-angiotensin (GO:0003081), positive regulation of systemic arterial blood pressure (GO:0003084), proteolysis (GO:0006508), spermatogenesis (GO:0007283), regulation of blood pressure (GO:0008217), male gonad development (GO:0008584), post-transcriptional regulation of gene expression (GO:0010608), negative regulation of gene expression (GO:0010629), substance P catabolic process (GO:0010814), bradykinin catabolic process (GO:0010815), regulation of smooth muscle cell migration (GO:0014910), regulation of vasoconstriction (GO:0019229), mononuclear cell proliferation (GO:0032943), angiotensin-activated signaling pathway (GO:0038166), hormone metabolic process (GO:0042445), hormone catabolic process (GO:0042447), peptide catabolic process (GO:0043171), regulation of synaptic plasticity (GO:0048167), amyloid-beta metabolic process (GO:0050435), arachidonate secretion (GO:0050482), heart contraction (GO:0060047), regulation of angiotensin metabolic process (GO:0060177), hematopoietic stem cell differentiation (GO:0060218), cell proliferation in bone marrow (GO:0071838), regulation of heart rate by cardiac conduction (GO:0086091), blood vessel diameter maintenance (GO:0097746), regulation of hematopoietic stem cell proliferation (GO:1902033), negative regulation of gap junction assembly (GO:1903597)

GO Molecular Function (20): actin binding (GO:0003779), endopeptidase activity (GO:0004175), metallocarboxypeptidase activity (GO:0004181), metalloendopeptidase activity (GO:0004222), calmodulin binding (GO:0005516), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), exopeptidase activity (GO:0008238), tripeptidyl-peptidase activity (GO:0008240), peptidyl-dipeptidase activity (GO:0008241), zinc ion binding (GO:0008270), chloride ion binding (GO:0031404), mitogen-activated protein kinase kinase binding (GO:0031434), bradykinin receptor binding (GO:0031711), mitogen-activated protein kinase binding (GO:0051019), metallodipeptidase activity (GO:0070573), carboxypeptidase activity (GO:0004180), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (8): extracellular region (GO:0005576), lysosome (GO:0005764), endosome (GO:0005768), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Peptide hormone metabolism	1
Metabolism of proteins	1

GO top-level categories

showing 60 of 61 GO namespaces:

Category	Terms
peptidase activity	3
cellular anatomical structure	3
regulation of gene expression	2
metalloexopeptidase activity	2
exopeptidase activity	2
protein kinase binding	2
animal organ development	1
renal system development	1
tissue remodeling	1
regulation of angiotensin levels in blood	1
peptide hormone processing	1
regulation of blood volume by renin-angiotensin	1
myeloid leukocyte mediated immunity	1
antigen processing and presentation of peptide antigen	1
regulation of systemic arterial blood pressure by hormone	1
regulation of systemic arterial blood pressure	1
positive regulation of blood pressure	1
protein metabolic process	1
developmental process involved in reproduction	1
male gamete generation	1
blood circulation	1
regulation of biological quality	1
gonad development	1
development of primary male sexual characteristics	1
gene expression	1
negative regulation of macromolecule biosynthetic process	1
neuropeptide catabolic process	1
catabolic process	1
smooth muscle cell migration	1
regulation of cell migration	1
vasoconstriction	1
blood vessel diameter maintenance	1
regulation of blood circulation	1
leukocyte proliferation	1
G protein-coupled receptor signaling pathway	1
cellular response to angiotensin	1
cytoskeletal protein binding	1
carboxypeptidase activity	1
endopeptidase activity	1
metallopeptidase activity	1
protein binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
serine-type exopeptidase activity	1
transition metal ion binding	1
anion binding	1
G protein-coupled receptor binding	1
dipeptidase activity	1
binding	1
catalytic activity	1
cation binding	1
lytic vacuole	1
endomembrane system	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 30 of 63 annotations. The rest are phylogenetic / computational / electronic (IEA).

30 experimentally-supported GO terms:

GO term	NS	Evidence
amyloid-beta metabolic process	BP	direct assay
angiotensin maturation	BP	direct assay
arachidonate secretion	BP	direct assay
bradykinin catabolic process	BP	direct assay
hormone catabolic process	BP	direct assay
hormone metabolic process	BP	direct assay
kidney development	BP	mutant phenotype
peptide catabolic process	BP	direct assay
regulation of angiotensin metabolic process	BP	direct assay
regulation of systemic arterial blood pressure by renin-angiotensin	BP	mutant phenotype
substance P catabolic process	BP	direct assay
endosome	CC	direct assay
external side of plasma membrane	CC	direct assay
extracellular exosome	CC	direct assay
lysosome	CC	direct assay
plasma membrane	CC	direct assay
actin binding	MF	direct assay
bradykinin receptor binding	MF	physical interaction
chloride ion binding	MF	direct assay
endopeptidase activity	MF	direct assay
exopeptidase activity	MF	direct assay
metallodipeptidase activity	MF	direct assay
metalloendopeptidase activity	MF	direct assay
metallopeptidase activity	MF	direct assay
mitogen-activated protein kinase binding	MF	physical interaction
mitogen-activated protein kinase kinase binding	MF	physical interaction
peptidase activity	MF	direct assay
peptidyl-dipeptidase activity	MF	direct assay
tripeptidyl-peptidase activity	MF	direct assay
zinc ion binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,428 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACE	AGT	P01019	984
ACE	REN	P00797	979
ACE	AGTR1	P30556	968
ACE	KNG1	P01042	952
ACE	AGTR2	P50052	906
ACE	ALB	P02768	903
ACE	NR3C2	P08235	891
ACE	MME	P08473	882
ACE	MMEL1	Q495T6	882
ACE	CRP	P02741	881
ACE	INS	P01308	856
ACE	CMA1	P23946	826
ACE	NPPA	P01160	815
ACE	BDKRB2	P30411	814
ACE	MTHFR	P42898	807

IntAct

Human interaction partners of ACE in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
TEX101	association	0.350	1

BioGRID (28 interactions; top human partners by supporting records): AGT (Biochemical Activity; 3 records), BDKRB2 (Affinity Capture-Western; 3 records), MYH9 (Affinity Capture-Western; 3 records), CSNK2A1 (Affinity Capture-Western; 2 records), ACTB (Affinity Capture-Western), AGR2 (Proximity Label-MS), AIMP2 (Affinity Capture-MS), ALMS1 (Co-fractionation), CLCN3 (Co-fractionation), DBI (Cross-Linking-MS (XL-MS)), EWSR1 (Proximity Label-MS), HOOK1 (Proximity Label-MS), ITGB7 (Co-fractionation), LGALS1 (Affinity Capture-MS), LMNA (Proximity Label-MS)

SIGNOR signaling

showing 13 of 14 signaling interactions:

A	Effect	B	Mechanism
ACE	“up-regulates activity”	AGT	cleavage
ACE	“down-regulates quantity by destabilization”	bradykinin	binding
benazepril	“down-regulates activity”	ACE	“chemical inhibition”
Angiotensin-1	“up-regulates activity”	ACE	binding
ACE	“up-regulates quantity”	Angiotensin-2	cleavage
trandolapril	“down-regulates activity”	ACE	“chemical inhibition”
enalapril	“down-regulates activity”	ACE	“chemical inhibition”
“enalaprilat (anhydrous)”	“down-regulates activity”	ACE	“chemical inhibition”
ramipril	“down-regulates activity”	ACE	“chemical inhibition”
lisinopril	“down-regulates activity”	ACE	“chemical inhibition”
captopril	“down-regulates activity”	ACE	“chemical inhibition”
fosinoprilat	“down-regulates activity”	ACE	“chemical inhibition”
CSNK2A1	“up-regulates activity”	ACE	phosphorylation

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
★ ACE-HSPA2-PDIA6 complex	3	ACE, HSPA2, PDIA6
★ ACE-BDKRB2 complex	2	ACE, BDKRB2
★ ACE homodimer, inhibitor-induced	1	ACE

Disease & clinical

Genetic variants

Variant evidence for ACE: 884 ClinVar records (62 pathogenic / likely pathogenic); 27 PharmGKB clinical annotations; 40 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	32
Uncertain significance	426
Likely benign	211
Benign	66

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 62 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
235336	NM_000789.4(ACE):c.1522C>T (p.Arg508Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
50209	NM_000789.4(ACE):c.2371C>T (p.Arg791Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
2712424	NM_000789.4(ACE):c.444_445insTTAGC (p.Arg149fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
827586	NM_000789.4(ACE):c.1473_1475delinsA (p.Asp491fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
2573840	NM_000789.4(ACE):c.793C>T (p.Arg265Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
424035	NM_000789.4(ACE):c.1487G>A (p.Arg496Gln)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
559878	NM_000789.4(ACE):c.3503+1G>C	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1723253	NM_000789.4(ACE):c.1511del (p.Pro504fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1930250	NM_000789.4(ACE):c.945+2T>G	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3234989	NM_000789.4(ACE):c.1342+1G>T	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1285224	NM_000789.4(ACE):c.2673_2674dup (p.Tyr892fs)	Pathogenic	criteria provided, single submitter	3
2631754	NM_000789.4(ACE):c.3503+1G>A	Pathogenic	criteria provided, single submitter	2
424033	NM_000789.4(ACE):c.412C>T (p.Gln138Ter)	Pathogenic	criteria provided, single submitter	1
632285	NM_000789.4(ACE):c.2149_2150del (p.Ile717fs)	Pathogenic	criteria provided, single submitter	1
974372	NM_000789.4(ACE):c.1361del (p.Leu454fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ACE’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 20 predictions of 2,331):

Position(s)	Effect	Δscore	Sites
17:63477344–63477345	donor_loss	1.0000	5
17:63477918	acceptor_gain	1.0000
17:63478085	donor_gain	1.0000
17:63480529–63480530	donor_loss	1.0000	5
17:63481086	acceptor_gain	1.0000
17:63481189	donor_loss	1.0000	2
17:63481686	donor_gain	1.0000
17:63481728	donor_gain	1.0000
17:63481751	donor_gain	1.0000
17:63482691	donor_loss	1.0000	2

AlphaMissense

2,984 missense substitutions predicted likely pathogenic (of 8,613 scored), across 772 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H992	8	0.983	0.993
D1112	8	0.983	0.992
H988	8	0.970	0.995
D1070	8	0.967	0.993
F1014	8	0.956	0.995
H1118	8	0.956	0.987
H394	8	0.955	0.982
F1111	8	0.954	0.989
F1136	8	0.954	0.996
D365	8	0.952	0.981
D514	8	0.949	0.968
D963	8	0.949	0.985
H853	8	0.946	0.989
H1015	8	0.945	0.978
D472	8	0.936	0.983
F538	8	0.936	0.995
F940	8	0.933	0.992
D1020	8	0.931	0.977
H255	8	0.928	0.982
H390	8	0.928	0.985

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.65e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000201

Disease associations

OMIM: gene MIM:106180 | disease phenotypes: MIM:267430, MIM:612624, MIM:614519, MIM:610805

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
renal tubular dysgenesis of genetic origin	Strong	Autosomal recessive	5
intracerebral hemorrhage	Limited	Unknown

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
renal tubular dysgenesis - ACE	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 7 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
CAKUT	green
Fetal anomalies	green
Paediatric disorders	green
Paediatric disorders - additional genes	green
Unexplained kidney failure in young people	green
Unexplained young onset end-stage renal disease	green
Unexplained young onset end-stage renal disease - additional genes	green

Mondo (7): renal tubular dysgenesis (MONDO:0017609), renal tubular dysgenesis of genetic origin (MONDO:0009970), microvascular complications of diabetes, susceptibility to, 3 (MONDO:0012963), hemorrhage, intracerebral, susceptibility to (MONDO:0100533), hereditary angioedema with normal C1Inh (MONDO:0100567), congenital anomaly of kidney and urinary tract (MONDO:0019719), intracerebral hemorrhage (MONDO:0013792)

Orphanet (4): Renal tubular dysgenesis (Orphanet:3033), Renal tubular dysgenesis of genetic origin (Orphanet:97369), Hereditary angioedema with normal C1Inh (Orphanet:528647), Renal or urinary tract malformation (Orphanet:93545)

HPO phenotypes

11 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000079	Abnormality of the urinary system
HP:0000252	Microcephaly
HP:0001562	Oligohydramnios
HP:0002009	Potter facies
HP:0002089	Pulmonary hypoplasia
HP:0002093	Respiratory insufficiency
HP:0002615	Hypotension
HP:0004492	Widely patent fontanelles and sutures
HP:0008660	Renotubular dysgenesis
HP:0100519	Anuria

GWAS associations

showing 30 of 40 associations:

Study	Trait	p-value
GCST006585_2934	Blood protein levels	9e-136
GCST012020_139	Serum metabolite levels	2e-41
GCST000565_2	Angiotensin-converting enzyme activity	3e-25
GCST002388_1	Serum metabolite levels	9e-25
GCST007930_15	Medication use (agents acting on the renin-angiotensin system)	7e-20
GCST001217_23	Metabolic traits	8e-20
GCST002388_3	Serum metabolite levels	1e-18
GCST006249_106	Serum metabolite levels	1e-16
GCST006193_61	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3e-16
GCST006190_5	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	7e-16
GCST006249_108	Serum metabolite levels	5e-15
GCST006195_94	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	8e-15
GCST004777_19	Diastolic blood pressure	2e-14
GCST006193_39	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3e-14
GCST006249_107	Serum metabolite levels	4e-14
GCST006192_80	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	6e-14
GCST004280_38	Diastolic blood pressure	7e-14
GCST002388_4	Serum metabolite levels	8e-14
GCST006195_88	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2e-13
GCST007929_39	Medication use (calcium channel blockers)	3e-13
GCST006190_80	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	4e-13
GCST001882_9	Metabolite levels	9e-13
GCST006166_106	Diastolic blood pressure x alcohol consumption interaction (2df test)	1e-12
GCST006434_53	Systolic blood pressure x alcohol consumption interaction (2df test)	2e-12
GCST006192_45	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	3e-12
GCST006249_109	Serum metabolite levels	3e-12
GCST002665_1	Cerebrospinal fluid levels of Alzheimer’s disease-related proteins	4e-12
GCST006249_15	Serum metabolite levels	1e-11
GCST012335_4	Hodgkin’s lymphoma	7e-11
GCST007324_122	Adventurousness	8e-10

EFO canonical traits (from GWAS)

12 canonical traits:

EFO ID	Trait name
EFO:0004725	metabolite measurement
EFO:0006514	Alzheimer’s disease biomarker measurement
EFO:0006515	angiotensin-converting enzyme measurement
EFO:0006336	diastolic blood pressure
EFO:0004329	alcohol drinking
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0008579	risk-taking behaviour
EFO:1001870	late-onset Alzheimers disease
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009268	family history of Alzheimer’s disease

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D002543	Cerebral Hemorrhage	C10.228.140.300.535.200; C14.907.253.573.200; C23.550.414.913.100
C566906	Cakut *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1808 (SINGLE PROTEIN), CHEMBL2096989 (PROTEIN FAMILY), CHEMBL6066541 (PROTEIN COMPLEX), CHEMBL6066554 (PROTEIN COMPLEX)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the ACE protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

17 curated-mechanism drugs:

Drug	Modality	Max phase
BENAZEPRIL HYDROCHLORIDE	Small molecule	4
CAPTOPRIL	Small molecule	4
CILAZAPRIL	Small molecule	4
ENALAPRIL MALEATE	Small molecule	4
ENALAPRILAT	Small molecule	4
FOSINOPRIL SODIUM	Small molecule	4
IMIDAPRIL	Small molecule	4
LISINOPRIL	Small molecule	4
MOEXIPRIL HYDROCHLORIDE	Small molecule	4
PERINDOPRIL ARGININE	Small molecule	4
PERINDOPRIL ERBUMINE	Small molecule	4
QUINAPRIL HYDROCHLORIDE	Small molecule	4
RAMIPRIL	Small molecule	4
SPIRAPRIL HYDROCHLORIDE	Small molecule	4
TRANDOLAPRIL	Small molecule	4
DELAPRIL	Small molecule	3
ILEPATRIL	Small molecule	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,761,629 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

31 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL838	BENAZEPRIL	4	28,311
CHEMBL1560	CAPTOPRIL	4	66,788
CHEMBL578	ENALAPRIL	4	53,113
CHEMBL577	ENALAPRILAT ANHYDROUS	4	10,299
CHEMBL3039598	FOSINOPRIL	4	62
CHEMBL317094	IMIDAPRIL	4	9,650
CHEMBL1237	LISINOPRIL ANHYDROUS	4	56,436
CHEMBL1165	MOEXIPRIL	4	14,992
CHEMBL1592	QUINAPRIL	4	31,233
CHEMBL1168	RAMIPRIL	4	47,237
CHEMBL1519	TRANDOLAPRIL	4	20,665
CHEMBL191	LOSARTAN	4	89,650
CHEMBL1581	PERINDOPRIL	4	23,173
CHEMBL1422	SITAGLIPTIN	4	26,952
CHEMBL1017	TELMISARTAN	4	27,686
CHEMBL858	EDETIC ACID	3	1,241,876
CHEMBL1192519	BENAZEPRILAT	2	2,677
CHEMBL36503	CERONAPRIL	2	8,898
CHEMBL581	FOSINOPRILAT	2	1,821
CHEMBL99701	IMIDAPRILAT	2	110
CHEMBL430554	LIBENZAPRIL	2
CHEMBL1201405	MOEXIPRILAT	2
CHEMBL289556	OMAPATRILAT	2
CHEMBL54922	PROLINE	2
CHEMBL1733	QUINAPRILAT	2
CHEMBL309962	RENTIAPRIL	2
CHEMBL42583	SAMPATRILAT	2
CHEMBL579	SPIRAPRILAT	2
CHEMBL408983	TEPROTIDE	2
CHEMBL331378	ZOFENOPRIL	2
CHEMBL429844	ORE-1001	1

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

27 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs1799752	Efficacy	2A	captopril	Chronic Obstructive Pulmonary Disease;Diabetes Mellitus;Type 2;Heart Failure
rs1799752	Efficacy	3	fluoxetine;sertraline	Depressive Disorder
rs1799752	Efficacy	3	bumetanide;furosemide;torasemide
rs1799752	Efficacy	3	benazepril;perindopril	Diabetes Mellitus
rs1799752	Efficacy	3	hydrochlorothiazide	Essential hypertension
rs1799752	Efficacy	3	irbesartan	Hypertension;Hypertrophy;Left Ventricular
rs1799752	Efficacy	3	enalapril	Arteriosclerosis;Coronary Disease;Essential hypertension;Glomerulonephritis;IGA;Kidney Disorder
rs1799752	Efficacy	3	nitroprusside
rs1799752	Efficacy	3	acetylcholine
rs1799752	Efficacy	3	spironolactone	Heart Failure
rs1799752	Efficacy	3	pravastatin
rs1799752	Efficacy	3	fluvastatin	Coronary Artery Disease
rs1799752	Efficacy	3	atorvastatin;quinapril	Coronary Artery Disease
rs1799752	Other	3	antidepressants;antiepileptics;Beta Blocking Agents;Calcium channel blockers	Headache Disorders;Migraine with Aura;Migraine without Aura
rs1799752	Toxicity	3	Ace Inhibitors;Plain
rs4291	Efficacy	3	amlodipine;chlorthalidone;lisinopril	Hypertension
rs4291	Toxicity	3	aspirin	Asthma
rs4291	Efficacy	3	captopril	Alzheimer Disease
rs4292	Toxicity	3	aspirin	Asthma
rs4341	Efficacy	3	pravastatin
rs4341	Toxicity	3	Thiazides;plain	Diabetes Mellitus
rs4343	Efficacy	3	sildenafil	Erectile Dysfunction
rs4343	Efficacy	3	spironolactone
rs4344	Efficacy	3	ramipril	Hypertension
rs4359	Efficacy	3	ramipril	Hypertension
rs8075924	Efficacy	3	bupropion	Major Depressive Disorder
rs1799752	Efficacy	4	lisinopril	Diabetes Mellitus;Type 1;Heart Failure

PharmGKB variants

7 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4291	ACE	3	2.75	3	captopril;amlodipine;chlorthalidone;lisinopril;aspirin
rs4292	ACE	3	2.25	1	aspirin
rs4341	ACE	3	2.75	2	Thiazides;plain;pravastatin
rs4343	ACE	3	2.50	2	sildenafil;spironolactone
rs4344	ACE	3	2.25	1	ramipril
rs4359	ACE	3	2.75	1	ramipril
rs1799752	ACE	2A	13.00	16	spironolactone;atorvastatin;quinapril;enalapril;lisinopril;acetylcholine;nitroprusside;hydrochlorothiazide;fluvastatin;pravastatin;bumetanide;furosemide;torasemide

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

showing 59 of 64 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs1799752	quinapril	Efficacy	Genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del + del/del are associated with increased response to quinapril in people with Coronary Artery Disease as compared to genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC.	PMID:11954942
rs1799752	quinapril	Efficacy	Genotype del/del is associated with increased response to quinapril as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:15526248
rs4291	aspirin	Toxicity	Genotypes AT + TT are associated with increased risk of aspirin intolerance when exposed to aspirin in people with Asthma as compared to genotype AA.	PMID:18727619
rs4292	aspirin	Toxicity	Genotypes CC + CT are associated with increased risk of aspirin intolerance when exposed to aspirin in people with Asthma as compared to genotype TT.	PMID:18727619
rs1799752	perindopril	Toxicity	Genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC is associated with increased likelihood of ACEI-related cough due to perindopril in people with Diabetes Mellitus, Type 2 as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del + del/del.	PMID:11699055
rs1799752	losartan	Efficacy	Genotype del/del is associated with increased response to losartan in people with Diabetes Mellitus, Type 2 as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:20830509
rs1799752	captopril	Efficacy	Genotype del/del is associated with increased response to captopril in people with Diabetes Mellitus, Type 2 as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:20830509
rs1799752	irbesartan	Efficacy	Genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC is associated with increased response to irbesartan in people with Hypertension as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del + del/del.	PMID:11593098
rs1799752	antidepressants, antiepileptics, Beta Blocking Agents, Calcium channel blockers	Other	Genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC is associated with decreased use of antidepressants, antiepileptics, Beta Blocking Agents or calcium channel blockers in people with Migraine with Aura as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del + del/del.	PMID:24444405
rs1799752	antidepressants, antiepileptics, Beta Blocking Agents, Calcium channel blockers	Other	Genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC is associated with decreased use of antidepressants, antiepileptics, Beta Blocking Agents or calcium channel blockers in people with chronic migraine as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del + del/del.	PMID:24444405
rs1799752	sertraline	Efficacy	Genotype del/del is associated with increased response to sertraline in people with Depressive Disorder.	PMID:27262302
rs4291	captopril	Efficacy	Genotype AA is associated with decreased severity of Kidney Failure when treated with captopril in people with Alzheimer Disease as compared to genotypes AT + TT.	PMID:27546928
rs1799752	interferon beta-1a	Efficacy	Genotype del/del is associated with decreased response to interferon beta-1a in men Multiple Sclerosis.	PMID:28430710
rs1799752	Ace Inhibitors, Plain	Toxicity	Allele ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC is associated with increased likelihood of Cough when treated with Ace Inhibitors, Plain as compared to allele del.	PMID:30672376
rs8075924	bupropion	Efficacy	Genotype TT is associated with decreased response to bupropion in people with Depressive Disorder, Major as compared to genotypes CC + CT.	PMID:22947179
rs1799752	salvianolic acid b	Efficacy	Genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC is associated with increased response to salvianolic acid b in people with Coronary Disease as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del + del/del.	PMID:24827774
rs1799752	enalapril, lisinopril	Efficacy	Genotype del/del is associated with increased clinical benefit to enalapril or lisinopril in men with Hypertension as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:25002132
rs1799752		Other	Allele ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC is associated with decreased likelihood of COVID-19 as compared to allele del.	PMID:34805533
rs1799752		Other	Genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC is associated with decreased severity of COVID-19 in people with COVID-19.	PMID:34079337
rs1799752		Other	Allele del is associated with increased likelihood of COVID-19 in people with as compared to allele ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC.	PMID:34834450
rs1799752		Other	Genotype del/del is associated with increased risk of Death in people with COVID-19 as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:34834450
rs1799752		Other	Genotype del/del is associated with increased severity of COVID-19 in people with COVID-19 as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:33676010
rs4291	losartan	Efficacy	Genotypes AT + TT is associated with increased clinical benefit to losartan in people with Hypertension as compared to genotype AA.	PMID:38551694
rs1799752	hydrochlorothiazide, valsartan	Efficacy	Genotype del/del is associated with decreased clinical benefit to hydrochlorothiazide and valsartan in people with Hypertension as compared to genotype TTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCATACAGTCACTTTT/TTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCATACAGTCACTTTT.	PMID:41794841
rs1799752	hydrochlorothiazide, valsartan	Efficacy	Genotype TTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCATACAGTCACTTTT/del is associated with decreased clinical benefit to hydrochlorothiazide and valsartan in people with Hypertension as compared to genotype TTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCATACAGTCACTTTT/TTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCATACAGTCACTTTT.	PMID:42535691
rs1799752	“““Ace Inhibitors, Plain””, ““Beta Blocking Agents””, ““Calcium channel blockers””, ““digoxin””, ““diuretics”””	Efficacy	Allele del is associated with increased mortality when treated with Ace Inhibitors, Plain, Beta Blocking Agents, calcium channel blockers, digoxin or diuretics in people with Heart Failure as compared to allele ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC.	PMID:19752885
rs4343		Metabolism/PK	Allele G is associated with increased ACE activity in people with Hypertension as compared to allele A.	PMID:20066004
rs4343	spironolactone	Efficacy	Genotypes AA + AG are associated with improvement in left ventricular ejection fraction, end-systolic and end-diastolic volume when treated with spironolactone in people with chronic heart failure as compared to genotype GG.	PMID:15121491
rs4341	Thiazides, plain	Toxicity	Genotype GG is associated with increased risk of Diabetes Mellitus when treated with Thiazides, plain as compared to genotypes CC + CG.	PMID:19247266
rs1799752	enalapril	Efficacy	Genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC is associated with increased likelihood of Kidney Failure, Chronic when treated with enalapril in people with Glomerulonephritis, IGA as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del + del/del.	PMID:19319668
rs1799752	hydrochlorothiazide	Efficacy	Genotype del/del is associated with increased reduction in blood pressure when treated with hydrochlorothiazide in men with Essential hypertension as compared to genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC.	PMID:12371972
rs1799752	hydrochlorothiazide	Efficacy	Genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC is associated with increased reduction in blood pressure when treated with hydrochlorothiazide in women with Essential hypertension as compared to genotype del/del.	PMID:12371972
rs1799752			Allele del is associated with increased enzyme activity of ACE.	PMID:12371972
rs1799752	hydrochlorothiazide	Efficacy	Genotype del/del is associated with increased reduction in systolic blood pressure when treated with hydrochlorothiazide in people with Essential hypertension as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:21269061
rs4341	furosemide, spironolactone	Efficacy	Genotypes CG + GG are associated with increased likelihood of diuretic unresponsiveness when treated with furosemide and spironolactone in people with Liver Cirrhosis as compared to genotype CC.	PMID:21692745
rs1799752	Ace Inhibitors, Plain	Toxicity	Allele del is associated with increased major cardiovascular events (MACE) rate when treated with Ace Inhibitors, Plain in people with Coronary Artery Disease as compared to allele ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC.	PMID:23407050
rs1799752	atenolol, enalapril	Efficacy	Genotype del/del is associated with increased resistance to atenolol and enalapril in people with Kidney Diseases as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:8538349
rs1799752	captopril	Efficacy	Genotype del/del is associated with increased resistance to captopril in people with Diabetes Mellitus as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:8806248
rs1799752	enalapril	Efficacy	Genotype del/del is associated with increased response to enalapril in people with Essential hypertension as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:8986921
rs1799752	captopril	Efficacy	Genotype del/del is associated with decreased response to captopril in healthy individuals as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:9069453
rs1799752	captopril	Efficacy	Genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC is associated with increased response to captopril in people with Diabetes Mellitus as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del + del/del.	PMID:9551410
rs1799752	captopril	Efficacy	Genotype del/del is associated with decreased response to captopril in people with Heart Failure as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:9869506
rs1799752	acetylcholine, nitroprusside	Efficacy	Allele ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC is associated with increased response to acetylcholine or nitroprusside in healthy individuals as compared to allele del.	PMID:10334805
rs1799752	spironolactone	Efficacy	Genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del are associated with improvement in left ventricular ejection fraction, end-systolic and end-diastolic volume when treated with spironolactone in people with chronic heart failure as compared to genotype del/del.	PMID:15121491
rs1799752	fluvastatin	Efficacy	Genotype del/del is associated with increased response to fluvastatin in people with Coronary Artery Disease as compared to genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC.	PMID:10636265
rs1799752	pravastatin	Efficacy	Genotype del/del is associated with response to pravastatin in people with non-hypercholesterolaemic patients scheduled for angioplasty as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:12695469
rs1799752	atorvastatin, quinapril	Efficacy	Genotype del/del is associated with decreased reduction in D-dimer levels when treated with atorvastatin and quinapril in men with Coronary Artery Disease as compared to allele ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC.	PMID:16116691
rs1799752	atorvastatin, quinapril	Efficacy	Genotype del/del is associated with increased reduction in CRP levels when treated with atorvastatin and quinapril in men with Coronary Artery Disease as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:16116691
rs1799752	atorvastatin, quinapril	Efficacy	Genotype del/del is associated with decreased reduction in IL-6 levels when treated with atorvastatin and quinapril in men with Coronary Artery Disease as compared to allele ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC.	PMID:16116691
rs1799752	enalapril	Efficacy	Genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del + del/del are associated with increased response to enalapril in people with Arteriosclerosis as compared to genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC.	PMID:10880412
rs1799752	benazepril, perindopril	Efficacy	Genotype del/del is associated with increased response to benazepril or perindopril in people with Diabetes Mellitus as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:11007831
rs1799752	captopril	Efficacy	Genotype del/del is associated with decreased response to captopril in men with Pulmonary Disease, Chronic Obstructive as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:12832683
rs1799752	captopril	Efficacy	Genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC is associated with increased response to captopril in men with Pulmonary Disease, Chronic Obstructive as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del + del/del.	PMID:12832683
rs1799752	benazepril	Efficacy	Genotype del/del is associated with increased response to benazepril in people with Essential hypertension as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:15788353
rs1799752	enalapril, losartan	Efficacy	Genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC is associated with increased response to enalapril and losartan in men with Coronary Disease as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del + del/del.	PMID:16020596
rs1799752	captopril	Efficacy	Genotype del/del is associated with decreased response to captopril in people with Diabetes Mellitus, Type 2 as compared to genotypes ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC + ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/del.	PMID:19286758
rs4291	amlodipine, chlorthalidone, lisinopril	Other	Genotypes AA + AT are associated with decreased fasting glucose when treated with amlodipine, chlorthalidone or lisinopril in people with Hypertension as compared to genotype TT.	PMID:20577119
rs1799752	bumetanide, furosemide, torasemide	Efficacy	Genotype del/del is associated with increased response to bumetanide, furosemide and torasemide in healthy individuals as compared to genotype ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC/ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC.	PMID:20877298
rs4341	pravastatin	Efficacy	Genotypes CG + GG are associated with increased response to pravastatin as compared to genotype CC.	PMID:16103896

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M2: Angiotensin-converting enzymes (ACE and ACE2)

Most potent curated ligand interactions (24 total), top 24:

Ligand	Action	Affinity	Parameter
lisinopril	Inhibition	9.4	pKi
zofenoprilat	Inhibition	9.4	pKi
spiraprilat	Inhibition	9.1	pIC50
perindoprilat	Inhibition	9.0	pIC50
benazepril	Inhibition	8.8	pIC50
imidaprilat	Inhibition	8.7	pIC50
cilazaprilat	Inhibition	8.7	pIC50
quinaprilat	Inhibition	8.5	pIC50
trandolaprilat	Inhibition	8.5	pIC50
temocaprilat	Inhibition	8.44	pIC50
captopril	Inhibition	8.4	pKi
ramiprilat	Inhibition	8.4	pIC50
moexiprilat	Inhibition	8.2	pIC50
lisinopril-tryptophan	Inhibition	8.18	pIC50
RXP-407	Inhibition	8.15	pIC50
quinapril	Inhibition	8.1	pIC50
fosinoprilat	Inhibition	8.0	pIC50
fasidotrilat	Inhibition	8.0	pKi
trandolapril	Inhibition	7.8	pIC50
AD015	Inhibition	7.72	pIC50
ramipril	Inhibition	7.6	pIC50
enalaprilat	Inhibition	7.5	pIC50
benazeprilat	Inhibition	6.6	pIC50
enalapril	Inhibition	4.3	pIC50

Binding affinities (BindingDB)

900 measured of 1004 human assays (1011 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL5272537	KI	0.004 nM
(2S,5S)-1-((S)-3-mercapto-2-methylpropanoyl)-5-(3-phenylpropylthio)pyrrolidine-2-carboxylic acid	IC50	0.029 nM
(3R,7S)-7-((R)-2-Mercapto-3-phenyl-propionylamino)-6-oxo-1,2,3,4,6,7,8,12b-octahydro-benzo[c]pyrido[1,2-a]azepine-4-carboxylic acid	IC50	0.11 nM
Name not given	IC50	0.115 nM
The second fraction of the HPLC chromatogram.	KI	0.13 nM
Name not given	IC50	0.132 nM
CHEMBL1788109	KI	0.16 nM
(2S,5S)-1-((S)-3-mercapto-2-methylpropanoyl)-5-(phenethylthio)pyrrolidine-2-carboxylic acid	IC50	0.18 nM
(2R,4R)-5-[4-(3-chlorophenyl)phenyl]-2-hydroxy-4-(oxaloamino)pentanoic acid	KI	0.2 nM	US-20230285340: NEPRILYSIN INHIBITORS
CHEMBL80665	IC50	0.229 nM
CHEMBL78629	IC50	0.251 nM
CHEMBL35682	IC50	0.288 nM
CHEMBL284734	IC50	0.295 nM
Name not given	IC50	0.295 nM
(2R,4R)-4-[(2-carboxyacetyl)amino]-5-[4-(3-chlorophenyl)phenyl]-2-hydroxypentanoic acid	KI	0.316 nM	US-20230285340: NEPRILYSIN INHIBITORS
3-({1-[2-acetamido-3-(1H-imidazol-4-yl)propanoyl]pyrrolidin-2-yl}(hydroxy)phosphoryl)-2-[(3-phenyl-1,2-oxazol-5-yl)methyl]propanoic acid	KI	0.4 nM
1-(3-Benzoylsulfanyl-2-methyl-propionyl)-4-phenylsulfanyl-pyrrolidine-2-carboxylic acid(zofenopril)	IC50	0.4 nM
(2S)-2-({3-[Hydroxyl(2-phenyl-(1R)-1-{[(benzyloxy)carbonyl]-amino}ethyl)phosphinyl]-(2S)-2-[(3-phenylisoxazol-5-yl)methyl]-1-oxopropyl}amino)-3-phenyl Propanoic Acid	KI	0.4 nM
(S)-2-[(S)-3-[((R)-1-Benzyloxycarbonylamino-2-phenyl-ethyl)-hydroxy-phosphinoyl]-2-(3-phenyl-isoxazol-5-ylmethyl)-propionylamino]-3-(4-hydroxy-phenyl)-propionic acid	KI	0.41 nM
MLN4760	IC50	0.44 nM
Name not given	IC50	0.49 nM
CHEMBL5430631	IC50	0.49 nM
1-[6-Amino-2-(1-carboxy-3-phenyl-propylamino)-hexanoyl]-pyrrolidine-2-carboxylic acid; hydrate ( Lisinopril)	IC50	0.5 nM
(2R,4R)-4-(3-carboxypropanoylamino)-5-[4-(3-chlorophenyl)phenyl]-2-hydroxypentanoic acid	KI	0.501 nM	US-20230285340: NEPRILYSIN INHIBITORS
(2R,4R)-4-(4-carboxybutanoylamino)-5-[4-(3-chlorophenyl)phenyl]-2-hydroxypentanoic acid	KI	0.501 nM	US-11547687: Neprilysin inhibitors
CHEMBL289022	IC50	0.525 nM
CHEMBL34832	IC50	0.525 nM
6-(1-Carboxy-3-phenyl-propylamino)-5-oxo-octahydro-thiazolo[3,2-a]azepine-3-carboxylic acid	IC50	0.6 nM
CHEMBL4476621	IC50	0.6 nM
CHEMBL34650	IC50	0.631 nM
CHEMBL5394399	IC50	0.64 nM
(S)-2-[(R)-3-[((R)-1-Benzyloxycarbonylamino-2-phenyl-ethyl)-hydroxy-phosphinoyl]-2-(3-phenyl-isoxazol-5-ylmethyl)-propionylamino]-3-(4-hydroxy-phenyl)-propionic acid	KI	0.65 nM
CHEMBL5406655	IC50	0.65 nM
The second fraction of the HPLC chromatogram.	KI	0.7 nM
CHEMBL431707	IC50	0.776 nM
CHEMBL5424883	IC50	0.78 nM
7-[2-(1-Carboxy-3-phenyl-propylamino)-propionyl]-1,4-dithia-7-aza-spiro[4.4]nonane-8-carboxylic acid	IC50	0.8 nM
CHEMBL33025	IC50	0.871 nM
CHEMBL284843	IC50	0.891 nM
(R)-2-[4-(4-Bromo-benzoylamino)-benzenesulfonylamino]-3-(1H-indol-3-yl)-propionic acid	IC50	0.9 nM
(2S,5S)-1-((S)-3-Mercapto-2-methyl-propionyl)-5-(3-methyl-benzylsulfanyl)-pyrrolidine-2-carboxylic acid	IC50	0.9 nM
(2S,5R)-1-[2-((S)-2-Mercapto-3-phenyl-propionylamino)-acetyl]-5-p-tolyl-pyrrolidine-2-carboxylic acid	IC50	1 nM
(4S)-4-cyclohexyl-1-({2-methyl-1-(propanoyloxy)propoxyphosphoryl}acetyl)-L-proline	IC50	1 nM
1-(3-Mercapto-propionyl)-6-methyl-piperidine-2-carboxylic acid	IC50	1 nM
(S)-1-((1R,5S)-5-Benzoylamino-2-methyl-4-oxo-6-phenyl-hexanoyl)-pyrrolidine-2-carboxylic acid	IC50	1 nM
CHEMBL310750	IC50	1 nM
(2S,4S)-4-(3-carboxypropanoylamino)-2-(hydroxymethyl)-5-(4-phenylphenyl)pentanoic acid	KI	1 nM	US-20230285340: NEPRILYSIN INHIBITORS
Name not given	IC50	1.1 nM
CHEMBL80779	IC50	1.1 nM
MDL-27088	KI	1.2 nM

ChEMBL bioactivities

853 potent at pChembl≥5 of 966 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.82	Ki	0.015	nM	OMAPATRILAT
10.80	Ki	0.016	nM	OMAPATRILAT
10.54	IC50	0.029	nM	CHEMBL443353
10.00	IC50	0.1	nM	LISINOPRIL ANHYDROUS
10.00	IC50	0.1	nM	OMAPATRILAT
9.96	IC50	0.11	nM	CHEMBL198316
9.94	IC50	0.1148	nM	CHEMBL35561
9.92	IC50	0.12	nM	CAPTOPRIL
9.88	IC50	0.1318	nM	CHEMBL35309
9.80	Ki	0.16	nM	CHEMBL1788109
9.74	IC50	0.18	nM	CHEMBL526298
9.70	Ki	0.2	nM	CHEMBL5931110
9.64	IC50	0.2291	nM	CHEMBL80665
9.60	IC50	0.2512	nM	CHEMBL78629
9.54	IC50	0.2884	nM	CHEMBL35682
9.53	IC50	0.2951	nM	CHEMBL284734
9.53	IC50	0.2951	nM	CHEMBL285935
9.50	Ki	0.316	nM	CHEMBL5848092
9.40	Ki	0.4	nM	CHEMBL570718
9.40	IC50	0.4	nM	ZOFENOPRIL
9.39	Ki	0.41	nM	CHEMBL570732
9.31	IC50	0.4898	nM	CHEMBL286339
9.30	Ki	0.5	nM	CHEMBL309601
9.30	Ki	0.501	nM	CHEMBL5872996
9.30	IC50	0.5	nM	CHEMBL295690
9.28	IC50	0.5248	nM	CHEMBL34832
9.28	IC50	0.5248	nM	CHEMBL289022
9.22	IC50	0.6	nM	CHEMBL340528
9.22	IC50	0.6026	nM	CHEMBL312224
9.22	IC50	0.6	nM	CHEMBL347755
9.20	IC50	0.63	nM	CAPTOPRIL
9.20	Ki	0.631	nM	CHEMBL5842509
9.20	IC50	0.631	nM	CHEMBL34650
9.19	Ki	0.65	nM	CHEMBL570953
9.17	Ki	0.68	nM	CHEMBL570953
9.15	IC50	0.7	nM	CHEMBL4476621
9.11	IC50	0.7762	nM	CHEMBL431707
9.10	IC50	0.8	nM	SPIRAPRILAT
9.10	IC50	0.7943	nM	CHEMBL110925
9.06	IC50	0.871	nM	CHEMBL33025
9.05	IC50	0.9	nM	CHEMBL499612
9.05	IC50	0.8913	nM	CHEMBL284843
9.03	IC50	0.93	nM	TRANDOLAPRIL
9.00	IC50	1	nM	CHEMBL95564
9.00	IC50	1	nM	OMAPATRILAT
9.00	Ki	1	nM	CHEMBL5750525
9.00	IC50	1	nM	CHEMBL315037
9.00	IC50	1	nM	FOSINOPRIL
9.00	IC50	1	nM	CHEMBL310750
9.00	IC50	1	nM	CHEMBL331575

PubChem BioAssay actives

709 with measured affinity, of 1529 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
(2S,5S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-5-(3-phenylpropylsulfanyl)pyrrolidine-2-carboxylic acid	362193: Inhibition of ACE	ic50	<0.0001	uM
(4S,7S,12bR)-7-[[(1S)-1-carboxy-3-phenylpropyl]amino]-6-oxo-2,3,4,7,8,12b-hexahydro-1H-pyrido[2,1-a][2]benzazepine-4-carboxylic acid	1954028: Binding affinity to angiotensin-converting enzyme (unknown origin) assessed as inhibition constant	ki	<0.0001	uM
(4S,7S,10aS)-5-oxo-4-[[(2S)-3-phenyl-2-sulfanylpropanoyl]amino]-2,3,4,7,8,9,10,10a-octahydropyrido[2,1-b][1,3]thiazepine-7-carboxylic acid	1423287: Inhibition of human fully glycosylated ACE N-terminal domain expressed in CHO cells using Cbz-Phe-His-Leu as substrate preincubated for 15 mins followed by substrate addition measured after 10 mins by Morrison’s plot analysis	ki	<0.0001	uM
(2S,4R)-1-[(2S)-6-amino-2-[hydroxy(4-phenylbutyl)phosphoryl]oxyhexanoyl]-4-phenylpyrrolidine-2-carboxylic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0001	uM
2-[[(2S)-6-amino-2-[hydroxy(4-phenylbutyl)phosphoryl]oxyhexanoyl]-(1,3-benzodioxol-5-yl)amino]acetic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0001	uM
Captopril	433785: Inhibition of human recombinant ACE by fluorimetry	ic50	0.0001	uM
(4R,7S)-6-oxo-7-[[(2R)-3-phenyl-2-sulfanylpropanoyl]amino]-2,3,4,7,8,12b-hexahydro-1H-pyrido[2,1-a][2]benzazepine-4-carboxylic acid	254756: Inhibitory concentration against angiotensin I converting enzyme	ic50	0.0001	uM
lisinopril anhydrous	1895844: Inhibition of angiotensin converting enzyme (unknown origin)	ic50	0.0001	uM
(2S)-1-[(2S)-2-[[1-carboxy-4-(4-iodoanilino)-4-oxobutyl]amino]propanoyl]pyrrolidine-2-carboxylic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0002	uM
(2S,5S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-5-(2-phenylethylsulfanyl)pyrrolidine-2-carboxylic acid	362193: Inhibition of ACE	ic50	0.0002	uM
(2S,4S,5R)-1-[(2R)-2-acetylsulfanylpropanoyl]-5-phenylpyrrolidine-2,4-dicarboxylic acid	38874: Enzyme inhibitory activity towards Angiotensin I converting enzyme	ki	0.0002	uM
2-[[(2S)-6-amino-2-[hydroxy(4-phenylbutyl)phosphoryl]oxyhexanoyl]-cyclohexylamino]acetic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0003	uM
2-(N-[(2S)-6-amino-2-[hydroxy(4-phenylbutyl)phosphoryl]oxyhexanoyl]-3,4-dimethoxyanilino)acetic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0003	uM
(2S)-1-[(2S)-6-amino-2-[hydroxy(4-phenylbutyl)phosphoryl]oxyhexanoyl]-2,3-dihydroindole-2-carboxylic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0003	uM
(2S)-1-[(4R)-4-carboxy-4-[[3-phenyl-2-(phenylmethoxycarbonylamino)propanoyl]amino]butanoyl]-2,3-dihydroindole-2-carboxylic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0003	uM
(2S)-2-[[(2S)-2-[[hydroxy-[(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]methyl]-3-(3-phenyl-1,2-oxazol-5-yl)propanoyl]amino]-3-phenylpropanoic acid	444546: Inhibition of human somatic ACE C-terminal domain	ki	0.0004	uM
(2S)-3-(4-hydroxyphenyl)-2-[[(2S)-2-[[hydroxy-[(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]methyl]-3-(3-phenyl-1,2-oxazol-5-yl)propanoyl]amino]propanoic acid	444546: Inhibition of human somatic ACE C-terminal domain	ki	0.0004	uM
(2S,4S)-1-[(2S)-3-benzoylsulfanyl-2-methylpropanoyl]-4-phenylsulfanylpyrrolidine-2-carboxylic acid	39767: Inhibitory activity against angiotensin I converting enzyme (ACE)	ic50	0.0004	uM
(2S)-1-[(2S)-2-[[hydroxy(2-phenylethyl)phosphoryl]amino]propanoyl]pyrrolidine-2-carboxylic acid	38871: Compound was evaluated for the inhibition of Angiotensin I converting enzyme	ki	0.0005	uM
(8S)-7-[(2S)-6-amino-2-[[(1S)-1-carboxy-3-phenylpropyl]amino]hexanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid	38853: Compound tested in vitro for inhibition of Angiotensin I converting enzyme	ic50	0.0005	uM
(2S,4R)-1-[(2S)-6-amino-2-[hydroxy(4-phenylbutyl)phosphoryl]oxyhexanoyl]-4-cyclohexylpyrrolidine-2-carboxylic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0005	uM
(2S,4S)-1-[(2S)-6-amino-2-[hydroxy(4-phenylbutyl)phosphoryl]oxyhexanoyl]-4-phenylsulfanylpyrrolidine-2-carboxylic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0005	uM
(2S,4R)-1-[(2S)-6-amino-2-[hydroxy(4-phenylbutyl)phosphoryl]oxyhexanoyl]-4-methylsulfanylpyrrolidine-2-carboxylic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0005	uM
(2S)-3-(4-hydroxyphenyl)-2-[[(2R)-2-[[hydroxy-[(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]methyl]-3-(3-phenyl-1,2-oxazol-5-yl)propanoyl]amino]propanoic acid	444546: Inhibition of human somatic ACE C-terminal domain	ki	0.0006	uM
(8S)-7-[(2S)-6-amino-2-[hydroxy(4-phenylbutyl)phosphoryl]oxyhexanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0006	uM
(3R,9aR)-6-[(1-carboxy-3-phenylpropyl)amino]-5-oxo-3,6,7,8,9,9a-hexahydro-2H-[1,3]thiazolo[3,2-a]azepine-3-carboxylic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0006	uM
(3R,6S)-6-[(1-carboxy-3-phenylpropyl)amino]-5-oxo-3,6,7,8,9,9a-hexahydro-2H-[1,3]thiazolo[3,2-a]azepine-3-carboxylic acid	38850: Inhibition of Angiotensin I converting enzyme	ic50	0.0006	uM
(3R,6S,9aR)-6-[(1-carboxy-3-phenylpropyl)amino]-5-oxo-3,6,7,8,9,9a-hexahydro-2H-[1,3]thiazolo[3,2-a]azepine-3-carboxylic acid	39622: Inhibition of Angiotensin I converting enzyme (ACE) in Bothrops jararaca venom	ic50	0.0006	uM
1-(3,4-dichlorophenyl)-3-[(2-hydroxybenzoyl)amino]thiourea	1584848: Inhibition of human recombinant ACE using Abz-FRK(Dnp)-P-OH as substrate after 30 mins by fluorimetric analysis	ic50	0.0007	uM
(2S,4R)-1-[(2S)-6-amino-2-[hydroxy(4-phenylbutyl)phosphoryl]oxyhexanoyl]-4-phenylsulfanylpyrrolidine-2-carboxylic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0008	uM
(8S)-7-[(2S)-2-[[(1S)-1-carboxy-3-phenylpropyl]amino]propanoyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid	38853: Compound tested in vitro for inhibition of Angiotensin I converting enzyme	ic50	0.0008	uM
1-[2-[[1-carboxy-4-(4-iodoanilino)-4-oxobutyl]amino]propanoyl]pyrrolidine-2-carboxylic acid	38849: Inhibition of angiotensin I converting enzyme in silico	ic50	0.0008	uM
(2S,4S)-1-[(2S)-6-amino-2-[hydroxy(4-phenylbutyl)phosphoryl]oxyhexanoyl]-4-benzylpyrrolidine-2-carboxylic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0009	uM
(2S,4R)-1-[(2S)-6-amino-2-[hydroxy(4-phenylbutyl)phosphoryl]oxyhexanoyl]-4-hydroxypyrrolidine-2-carboxylic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0009	uM
(2S,5S)-5-[(3-methylphenyl)methylsulfanyl]-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid	362193: Inhibition of ACE	ic50	0.0009	uM
Trandolapril	39767: Inhibitory activity against angiotensin I converting enzyme (ACE)	ic50	0.0009	uM
(5S)-2-(2-carboxyethyl)-1,3-dioxo-5,8-dihydro-[1,2,4]triazolo[1,2-a]pyridazine-5-carboxylic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0010	uM
(2S)-1-[(2R,5S)-5-benzamido-2-methyl-4-oxo-6-phenylhexanoyl]pyrrolidine-2-carboxylic acid	2272421: Inhibition of ACE (unknown origin)	ic50	0.0010	uM
6-methyl-1-(3-sulfanylpropanoyl)piperidine-2-carboxylic acid	39625: Inhibitory activity against Angiotensin I converting enzyme (ACE) from bovine kidney	ic50	0.0010	uM
(2S,5R)-5-(4-methylphenyl)-1-[2-[[(2S)-3-phenyl-2-sulfanylpropanoyl]amino]acetyl]pyrrolidine-2-carboxylic acid	2246724: Inhibition of human glycosylated C-terminal catalytic ACE domain using Cbz-Phe-His-Leu substrate by fluorogenic end point activity assay	ic50	0.0010	uM
Fosinopril	39767: Inhibitory activity against angiotensin I converting enzyme (ACE)	ic50	0.0010	uM
2-(N-[(2S)-6-amino-2-[hydroxy(4-phenylbutyl)phosphoryl]oxyhexanoyl]anilino)acetic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0011	uM
(2S)-1-[(2S)-2-[(1-carboxy-3-naphthalen-1-ylpropyl)amino]propanoyl]pyrrolidine-2-carboxylic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0011	uM
(2S)-1-[(2S)-2-[(1-carboxy-3-phenylpropyl)amino]propanoyl]pyrrolidine-2-carboxylic acid	39018: Inhibitory activity against angiotensin converting enzyme (ACE)	ic50	0.0012	uM
(4S,12bR)-7-[(1-carboxy-3-phenylpropyl)amino]-6-oxo-2,3,4,7,8,12b-hexahydro-1H-pyrido[2,1-a][2]benzazepine-4-carboxylic acid	38873: Compound was tested for its inhibitory potency against angiotensin I converting enzyme.	ki	0.0012	uM
enalaprilat dihydrate	1954024: Inhibition of angiotensin-converting enzyme (unknown origin)	ic50	0.0012	uM
(2S)-1-[(2S)-2-[[(2R)-2-carboxy-4-phenylbutan-2-yl]amino]propanoyl]pyrrolidine-2-carboxylic acid	38850: Inhibition of Angiotensin I converting enzyme	ic50	0.0012	uM
(2S)-3-(1H-indol-3-yl)-2-[[(2R)-2-[(1S)-5-methoxy-2,3-dihydro-1H-inden-1-yl]-3-sulfanylpropanoyl]amino]propanoic acid	254288: Inhibition constant against angiotensin I converting enzyme	ki	0.0013	uM
(2S)-1-[5-benzamido-6-(3,4-dimethoxyphenyl)-4-oxohexanoyl]pyrrolidine-2-carboxylic acid	39754: Concentration required to inhibit the activity of Angiotensin I converting enzyme by 50%	ic50	0.0014	uM
(2S)-1-[5-(furan-2-carbonylamino)-4-oxo-6-phenylhexanoyl]pyrrolidine-2-carboxylic acid	39754: Concentration required to inhibit the activity of Angiotensin I converting enzyme by 50%	ic50	0.0014	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
benazepril	affects response to substance, decreases activity	8
sodium arsenite	decreases expression, increases methylation, affects reaction, increases expression, affects binding (+1 more)	3
Enalapril	decreases activity, affects cotreatment, affects response to substance, decreases reaction, increases response to substance	3
Benzo(a)pyrene	decreases expression, increases methylation	2
Glucose	decreases reaction, increases expression, decreases expression	2
Tetradecanoylphorbol Acetate	increases expression, decreases reaction	2
Ramipril	decreases activity	2
Particulate Matter	decreases methylation, increases abundance, increases expression	2
ethylbenzene	affects cotreatment, decreases methylation, increases expression	1
lasiocarpine	decreases expression	1
bisphenol A	increases expression	1
zaprinast	increases expression, increases reaction	1
steviol	decreases expression	1
stevioside	decreases expression	1
bioallethrin	decreases activity	1
herbimycin	decreases reaction, increases expression	1
1,10-phenanthroline	decreases expression	1
rebaudioside A	decreases expression	1
boric acid	decreases activity, decreases reaction	1
epigallocatechin gallate	decreases activity, decreases reaction, affects binding	1
bisindolylmaleimide I	decreases reaction, increases expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	affects cotreatment, affects localization, increases activity	1
idrapril	decreases activity	1
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide	increases expression, increases reaction	1
nicotianamine	decreases activity	1
omapatrilat	decreases activity	1
2-(1-carboxy-2-(3-(3,5-dichlorobenzyl)-3H-imidazol-4-yl)ethylamino)-4-methylpentanoic acid	decreases activity	1
ICG 001	decreases reaction, increases expression	1
Bortezomib	affects cotreatment, increases activity	1
Sunitinib	decreases expression	1

ChEMBL screening assays

304 unique, capped per target: 288 binding, 8 functional, 5 admet, 3 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1002956	Binding	Inhibition of ACE	Specific targeting of metzincin family members with small-molecule inhibitors: progress toward a multifarious challenge. — *Bioorg Med Chem*
CHEMBL4269905	ADMET	Inhibition of human fully glycosylated ACE N-terminal domain expressed in CHO cells using Cbz-Phe-His-Leu as substrate preincubated for 15 mins followed by substrate addition measured after 10 mins by fluorescence spectrophotometric analysi	Molecular Basis for Multiple Omapatrilat Binding Sites within the ACE C-Domain: Implications for Drug Design. — *J Med Chem*
CHEMBL4406515	Unclassified	Selectivity index, ratio of Ki for human ACE N-domain soluble form (1 to 629 residues) expressed in CHO cells to Ki for human testis ACE C-domain lacking unique O-glycosylated region, transmembrane anchor and cytoplasmic tail expressed in C	Molecular Basis for Omapatrilat and Sampatrilat Binding to Neprilysin-Implications for Dual Inhibitor Design with Angiotensin-Converting Enzyme. — *J Med Chem*

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C7SN	SK-N-FI ACE KO	Cancer cell line	Male
CVCL_F1RL	HyCyte MDA-MB-231 KO-hACE	Cancer cell line	Female
CVCL_SB19	HAP1 ACE (-) 1	Cancer cell line	Male
CVCL_SB20	HAP1 ACE (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 299 trials:

NCT	Phase	Status	Title
NCT00699465	Phase 4	UNKNOWN	Prevention of Venous Thromboembolism in Patients With Acute Primary Intracerebral Hemorrhage
NCT01918722	Phase 4	UNKNOWN	Clinical Re-evaluation of Removing Blood Stasis Therapy in Treating Acute Cerebral Hemorrhage Safety and Efficacy
NCT05095857	Phase 4	RECRUITING	The Anaesthetic Ketamine as Treatment for Patients With Severe Acute Brain Injury
NCT06429332	Phase 4	RECRUITING	International Care Bundle Evaluation in Cerebral Hemorrhage Research
NCT06673602	Phase 4	RECRUITING	Fufang Congrong Yizhi Capsules (FCYC) of Cognitive Impairment After Intracerebral Hemorrhage
NCT06899464	Phase 4	NOT_YET_RECRUITING	Safety and Feasibility of Using Cerebrolysin in the Treatment of Primary Intracerebral Hemorrhage - a Prospective Randomized Open Blinded End-point Trial
NCT07044232	Phase 4	RECRUITING	NICardipine for Fast Achievement of Systolic BP Targets in ICH
NCT07609654	Phase 4	NOT_YET_RECRUITING	Oral Anticoagulation After Stroke With Prior ICH in Subjects With AF
NCT00127283	Phase 3	COMPLETED	Recombinant Factor VIIa in Acute Intracerebral Haemorrhage
NCT01176565	Phase 3	TERMINATED	Antihypertensive Treatment of Acute Cerebral Hemorrhage-II
NCT01221142	Phase 3	UNKNOWN	Pilot Study of Hypothermia for Intracerebral Hemorrhage in Croatia
NCT01737541	Phase 3	TERMINATED	Fluoxetine for Motor Recovery After Acute Intracerebral Hemorrhage
NCT01827046	Phase 3	COMPLETED	Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III
NCT03044184	Phase 3	UNKNOWN	Tranexamic Acid for Spontaneous Acute Cerebral Hemorrhage Trial
NCT03243175	Phase 3	RECRUITING	Avoiding Anticoagulation After IntraCerebral Haemorrhage
NCT03496883	Phase 3	ACTIVE_NOT_RECRUITING	Recombinant Factor VIIa (rFVIIa) for Hemorrhagic Stroke Trial
NCT03546283	Phase 3	UNKNOWN	Neuroprotectant for Hypertensive Intracerebral Hemorrhage
NCT03785067	Phase 3	TERMINATED	Triple Therapy Prevention of Recurrent Intracerebral Disease EveNts Trial (TRIDENT) Cognitive Sub-Study
NCT03907046	Phase 3	RECRUITING	Anticoagulation in ICH Survivors for Stroke Prevention and Recovery
NCT03936361	Phase 3	RECRUITING	Statins In Intracerbral Hemorrhage
NCT03996772	Phase 3	COMPLETED	PREvention of STroke in Intracerebral haemorrhaGE Survivors With Atrial Fibrillation
NCT04522102	Phase 3	COMPLETED	Antiplatelet Secondary Prevention International Randomised Trial After INtracerebral HaemorrhaGe (ASPIRING)-Pilot Phase
NCT04604587	Phase 3	UNKNOWN	MRI-visible Enlarged Perivascular Spaces and the Alteration of Lymphatic Drainage System in CAA
NCT04657133	Phase 3	UNKNOWN	Remote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage
NCT05066620	Phase 3	UNKNOWN	Chinese Herbal Medicine in Acute INtracerebral Haemorrhage (CHAIN) Trial
NCT05679024	Phase 3	RECRUITING	Stroke Prophylaxis With Apixaban in Chronic Kidney Disease Stage 5 Patients With Atrial Fibrillation
NCT06763055	Phase 3	RECRUITING	The Fifth INTEnsive pReventing Secondary Injury in Acute Cerebral Haemorrhage Trial Within ACT-GLOBAL
NCT06863558	Phase 3	NOT_YET_RECRUITING	Reduction of Edema With a Specialized Cocktail for Ultra-early Management in Intracerebral Hemorrhage
NCT07227246	Phase 3	RECRUITING	Recombinant Factor VIIa (rFVIIa) for Hemorrhagic Stroke Trial - Part 2
NCT07243704	Phase 3	NOT_YET_RECRUITING	Reducing the Burden of Cardiovascular Events With Antiplatelet Therapy in Patients With IntraCerebral Haemorrhage
NCT07338175	Phase 3	RECRUITING	Efficacy and Safety of Minocycline in Acute Spontaneous Intracerebral Hemorrhage
NCT07752719	Phase 3	NOT_YET_RECRUITING	APEX-STROKE CALM-ICH Domain
NCT07801599	Phase 3	NOT_YET_RECRUITING	Huayu Jiedu Formula (FTFY-919) Granules Versus Traditional Decoction for Acute Hypertensive Intracerebral Hemorrhage
NCT00075959	Phase 2	COMPLETED	Safety of NXY-059 for the Treatment of Patients Who Have Suffered From a Stroke
NCT00128050	Phase 2	COMPLETED	Efficacy and Safety of Factor VIIa on Rebleeding After Surgery for Spontaneous Intracerebral Hemorrhage (ICH)
NCT00222625	Phase 2	UNKNOWN	rFVIIa in ICH in Patients Treated With Anticoagulants or Anti-Platelets
NCT00224770	Phase 2	COMPLETED	Minimally Invasive Surgery and rtPA for Intracerebral Hemorrhage Evacuation
NCT00266006	Phase 2	COMPLETED	Factor VIIa in Acute Intracerebral Haemorrhage
NCT00364559	Phase 2	COMPLETED	Effect of Rosuvastatin in Intracerebral Hemorrhage
NCT00426803	Phase 2	COMPLETED	Recombinant Factor VIIa in Acute Intracerebral Haemorrhage
NCT00566709	Phase 2	COMPLETED	Near Infrared Spectroscopy (NIRS) as Transfusion Indicator in Neurocritical Patients
NCT00718328	Phase 2	TERMINATED	Simvastatin For Intracerebral Hemorrhage Study
NCT00810888	Phase 2	COMPLETED	The Spot Sign for Predicting and Treating ICH Growth Study
NCT00827892	Phase 2	COMPLETED	Safety of Pioglitazone for Hematoma Resolution In Intracerebral Hemorrhage
NCT00961532	Phase 2	COMPLETED	Improving Platelet Activity for Cerebral Hemorrhage Treatment - DDAVP Proof of Concept
NCT00963976	Phase 2	COMPLETED	Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial
NCT00990509	Phase 2	TERMINATED	Albumin for Intracerebral Hemorrhage Intervention
NCT01176214	Phase 2	TERMINATED	WEANING-Study: Weaning by Early Versus lAte Tracheostomy iN supratentorIal iNtracerebral Bleedings
NCT01563445	Phase 2	COMPLETED	Safety and Preliminary Efficacy of Activated Recombinant Human Factor VII for Preventing Early Hematoma Growth in Acute Intracerebral Haemorrhage
NCT01566786	Phase 2	COMPLETED	Safety and Preliminary Efficacy of Activated Recombinant Human Factor VII in Acute Intracerebral Haemorrhage
NCT01662895	Phase 2	TERMINATED	High-Dose Deferoxamine in Intracerebral Hemorrhage
NCT01702636	Phase 2	COMPLETED	STOP-AUST: The Spot Sign and Tranexamic Acid On Preventing ICH Growth - AUStralasia Trial
NCT01811693	Phase 2	TERMINATED	Field Administration of Stroke Therapy-Blood Pressure Lowering
NCT02175225	Phase 2	COMPLETED	Intracerebral Hemorrhage Deferoxamine Trial - iDEF Ttrial
NCT02281838	Phase 2	TERMINATED	The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial II
NCT02625948	Phase 2	UNKNOWN	Tranexamic Acid for Acute ICH Growth prEdicted by Spot Sign
NCT02998905	Phase 2	COMPLETED	NOACs for Stroke Prevention in Patients With Atrial Fibrillation and Previous ICH
NCT03168581	Phase 2	COMPLETED	A Proof of Concept Study to Evaluate CN-105 in ICH Patients
NCT03338998	Phase 2	COMPLETED	Efficacy, Safety and Tolerability of BAF312 Compared to Placebo in Patients With Intracerebral Hemorrhage (ICH).
NCT03385928	Phase 2	COMPLETED	STOP-MSU: Stopping Haemorrhage With Tranexamic Acid for Hyperacute Onset Presentation Including Mobile Stroke Units

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ACE across ~30M SureChEMBL compounds — explore on Sugi Predict.