ACE2

Summary

ACE2 (angiotensin converting enzyme 2, HGNC:13557) is a protein-coding gene on chromosome Xp22.2, encoding Angiotensin-converting enzyme 2 (Q9BYF1). Essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis.

The protein encoded by this gene belongs to the angiotensin-converting enzyme family of dipeptidyl carboxydipeptidases and has considerable homology to human angiotensin 1 converting enzyme. This secreted protein catalyzes the cleavage of angiotensin I into angiotensin 1-9, and angiotensin II into the vasodilator angiotensin 1-7. ACE2 is known to be expressed in various human organs, and its organ- and cell-specific expression suggests that it may play a role in the regulation of cardiovascular and renal function, as well as fertility. In addition, the encoded protein is a functional receptor for the spike glycoprotein of the human coronavirus HCoV-NL63 and the human severe acute respiratory syndrome coronaviruses, SARS-CoV and SARS-CoV-2, the latter is the causative agent of coronavirus disease-2019 (COVID-19). Multiple splice variants have been found for this gene and the dACE2 (or MIRb-ACE2) splice variant has been found to be interferon inducible.

Source: NCBI Gene 59272 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 328 total — 49 pathogenic, 2 likely-pathogenic (top 10% of genes corpus-wide)
• GTEx eGene: eQTL in 15 tissues, sQTL in 1 (q < 0.05)
• ChEMBL bioactivity: 8 clinical-phase molecules tested; no curated mechanism-of-action drug
• MANE Select transcript: NM_001371415
• Interaction hub: 2,870 STRING partners (top 3% of genes corpus-wide)
• Notable: 328 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13557
Approved symbol	ACE2
Name	angiotensin converting enzyme 2
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Aliases	ACEH
Ensembl gene	ENSG00000130234
Ensembl biotype	protein_coding
OMIM	300335
Entrez	59272

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 16 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000252519

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

ENST00000252519, ENST00000427411, ENST00000471548, ENST00000473851, ENST00000677282, ENST00000678046, ENST00000678073, ENST00000679162, ENST00000679212, ENST00000679278, ENST00000680121, ENST00000871928, ENST00000871929, ENST00000871930, ENST00000871931, ENST00000954330, ENST00000954331, ENST00001016425, ENST00001016427

RefSeq mRNA: 6 — MANE Select: NM_001371415 NM_001371415, NM_001386259, NM_001386260, NM_001388452, NM_001389402, NM_021804

CCDS: CCDS14169, CCDS94556, CCDS94557

Canonical transcript exons

ENST00000252519 — 18 exons

Exon	Start	End
ENSE00000894057	15594845	15595003
ENSE00000894058	15592229	15592322
ENSE00000894059	15591713	15591856
ENSE00000894060	15589344	15589456
ENSE00000894061	15587753	15587858
ENSE00000894062	15585475	15585572
ENSE00000894063	15581221	15581390
ENSE00000894064	15578089	15578315
ENSE00000894065	15575666	15575810
ENSE00000894066	15573367	15573465
ENSE00000894067	15572201	15572323
ENSE00000894068	15571624	15571796
ENSE00000894069	15570295	15570353
ENSE00000894070	15567726	15567826
ENSE00000894071	15566253	15566369
ENSE00001334055	15561033	15562013
ENSE00003507229	15564024	15564218
ENSE00003897519	15600726	15600960

Expression profiles

Bgee: expression breadth ubiquitous, 152 present calls, max score 97.73.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8600 / max 428.0835, expressed in 83 samples.

Highest expression (Bgee): ileal mucosa, ileum, gall bladder, jejunal mucosa, duodenum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACE2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 15 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

16 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Nucleus accumbens basal ganglia	eqtl	4.4e-31	+0.67	X:15688707:C:A
Nerve Tibial	eqtl	3.3e-15	+0.25	X:15658294:G:A
Brain Hypothalamus	eqtl	1.1e-13	+0.52	X:15668176:C:A
Brain Cerebellar Hemisphere	eqtl	2.5e-11	+0.49	X:15625554:GA:G
Pituitary	eqtl	1.5e-08	+0.40	X:15679923:C:T
Brain Substantia nigra	eqtl	4.4e-08	+0.45	X:15661440:G:C
Brain Spinal cord cervical c-1	eqtl	6.9e-05	+0.42	X:15660010:C:T
Adipose Visceral Omentum	eqtl	4.9e-03	+0.42	X:14619826:C:T
Artery Tibial	eqtl	5.6e-03	+0.14	X:15661440:G:C
Heart Atrial Appendage	eqtl	1.1e-02	+0.17	X:15498851:A:G
Esophagus Muscularis	eqtl	1.2e-02	-0.40	X:14958906:T:TCATTTTTC
Pancreas	eqtl	1.5e-02	-0.72	X:15601694:T:C
Esophagus Mucosa	eqtl	2.0e-02	+0.10	X:15379783:T:C
Testis	eqtl	2.1e-02	+0.14	X:16526278:T:A
Artery Coronary	eqtl	3.2e-02	-0.49	X:16402310:A:G
Pancreas	sqtl	4.0e-02	-1.15	X:16182353:T:C

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
198534	0.4401	45
198535	0.3524	47
198536	0.0585	23
209610	0.0090	5

Top tissues by expression

showing 100 of 255 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	97.73	gold quality
ileum	UBERON:0002116	97.66	silver quality
gall bladder	UBERON:0002110	96.47	gold quality
jejunal mucosa	UBERON:0000399	95.23	gold quality
duodenum	UBERON:0002114	92.36	gold quality
right testis	UBERON:0004534	91.15	gold quality
left testis	UBERON:0004533	89.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.13	gold quality
testis	UBERON:0000473	85.60	gold quality
small intestine	UBERON:0002108	85.14	gold quality
heart left ventricle	UBERON:0002084	83.12	gold quality
adult mammalian kidney	UBERON:0000082	82.25	gold quality
cardiac ventricle	UBERON:0002082	81.69	gold quality
mucosa of transverse colon	UBERON:0004991	81.24	gold quality
apex of heart	UBERON:0002098	80.41	gold quality
right atrium auricular region	UBERON:0006631	78.93	gold quality
kidney epithelium	UBERON:0004819	78.37	silver quality
heart	UBERON:0000948	77.34	gold quality
cardiac atrium	UBERON:0002081	76.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.69	gold quality
pancreatic ductal cell	CL:0002079	76.58	gold quality
buccal mucosa cell	CL:0002336	76.51	gold quality
kidney	UBERON:0002113	76.33	gold quality
omental fat pad	UBERON:0010414	76.21	gold quality
rectum	UBERON:0001052	76.17	gold quality
peritoneum	UBERON:0002358	76.12	gold quality
adipose tissue of abdominal region	UBERON:0007808	74.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.45	gold quality
transverse colon	UBERON:0001157	72.33	gold quality
cortex of kidney	UBERON:0001225	71.90	gold quality
islet of Langerhans	UBERON:0000006	71.51	gold quality
jejunum	UBERON:0002115	70.75	gold quality
right lobe of thyroid gland	UBERON:0001119	70.13	gold quality
left lobe of thyroid gland	UBERON:0001120	70.13	gold quality
body of pancreas	UBERON:0001150	70.06	gold quality
pancreas	UBERON:0001264	69.39	gold quality
intestine	UBERON:0000160	68.34	gold quality
right lung	UBERON:0002167	68.32	gold quality
thyroid gland	UBERON:0002046	68.25	gold quality
metanephros cortex	UBERON:0010533	66.63	gold quality
esophagus mucosa	UBERON:0002469	65.24	gold quality
vermiform appendix	UBERON:0001154	64.33	gold quality
palpebral conjunctiva	UBERON:0001812	64.22	gold quality
left coronary artery	UBERON:0001626	64.20	gold quality
subcutaneous adipose tissue	UBERON:0002190	64.01	gold quality
left uterine tube	UBERON:0001303	63.54	gold quality
adipose tissue	UBERON:0001013	62.62	gold quality
colon	UBERON:0001155	62.48	gold quality
large intestine	UBERON:0000059	62.19	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	62.18	gold quality
coronary artery	UBERON:0001621	61.61	gold quality
minor salivary gland	UBERON:0001830	61.23	gold quality
esophagus	UBERON:0001043	61.15	gold quality
colonic epithelium	UBERON:0000397	60.94	silver quality
right lobe of liver	UBERON:0001114	60.64	gold quality
left ventricle myocardium	UBERON:0006566	60.17	gold quality
lower esophagus mucosa	UBERON:0035834	59.64	gold quality
smooth muscle tissue	UBERON:0001135	59.16	gold quality
caecum	UBERON:0001153	59.09	gold quality
bone marrow cell	CL:0002092	58.74	gold quality
epithelial cell of pancreas	CL:0000083	58.57	silver quality
mouth mucosa	UBERON:0003729	58.51	gold quality
saliva-secreting gland	UBERON:0001044	58.43	gold quality
metanephros	UBERON:0000081	58.42	gold quality
right adrenal gland cortex	UBERON:0035827	58.15	gold quality
vagina	UBERON:0000996	57.61	gold quality
upper lobe of left lung	UBERON:0008952	56.96	gold quality
liver	UBERON:0002107	56.82	gold quality
lower esophagus muscularis layer	UBERON:0035833	56.63	gold quality
lower esophagus	UBERON:0013473	56.56	gold quality
left adrenal gland	UBERON:0001234	55.65	gold quality
upper lobe of lung	UBERON:0008948	55.57	gold quality
left adrenal gland cortex	UBERON:0035825	55.54	gold quality
gastrocnemius	UBERON:0001388	55.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	55.34	gold quality
left ovary	UBERON:0002119	55.20	gold quality
adrenal cortex	UBERON:0001235	54.97	gold quality
adrenal gland	UBERON:0002369	54.63	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
right adrenal gland	UBERON:0001233	54.33	gold quality
muscle of leg	UBERON:0001383	54.08	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
right ovary	UBERON:0002118	53.46	gold quality
anatomical system	UBERON:0000467	53.41	gold quality
ovary	UBERON:0000992	53.33	gold quality
multicellular organism	UBERON:0000468	53.26	gold quality
material anatomical entity	UBERON:0000465	53.25	gold quality
descending thoracic aorta	UBERON:0002345	53.03	gold quality
skeletal muscle organ	UBERON:0014892	52.68	gold quality
muscle layer of sigmoid colon	UBERON:0035805	52.17	gold quality
thoracic aorta	UBERON:0001515	51.75	gold quality
lung	UBERON:0002048	51.75	gold quality
nasal cavity mucosa	UBERON:0001826	51.61	gold quality
ascending aorta	UBERON:0001496	51.47	gold quality
ventricular zone	UBERON:0003053	51.47	gold quality
fallopian tube	UBERON:0003889	51.12	gold quality
hindlimb stylopod muscle	UBERON:0004252	50.91	gold quality
female reproductive system	UBERON:0000474	50.88	gold quality
myocardium	UBERON:0002349	50.88	gold quality
muscle tissue	UBERON:0002385	50.88	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.10

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 66 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Small intestine	tissue	230.5	high
Duodenum	tissue	173.5	high
Kidney	tissue	82.4	high
Gallbladder	tissue	62.3	high
Testis	tissue	46.7	high
Heart muscle	tissue	40.1	not detected
Colon	tissue	9.4	high
Rectum	tissue	5.6	high
Liver	tissue	5.4	not detected
Choroid plexus	tissue	5.1
Seminal vesicle	tissue	3.9	medium
Adipose tissue	tissue	3.9	not detected
Thyroid gland	tissue	2.7	not detected
Stomach 1	tissue	2.5	not detected
Caudate putamen	tissue	2.1
Pancreas	tissue	1.8	medium
Frontal cortex	tissue	1.7
Parathyroid gland	tissue	1.4	not detected
Postcentral gyrus	tissue	1.3
Appendix	tissue	1.3	low
Vagina	tissue	1.1	not detected
Esophagus	tissue	1.1	not detected
Placenta	tissue	1.1	high
Nucleus accumbens	tissue	1.0
Locus coeruleus	tissue	1.0
Hippocampus	tissue	1.0	not detected
Urinary bladder	tissue	0.8	not detected
Salivary gland	tissue	0.7	not detected
Lung	tissue	0.7	not detected
Bone marrow	tissue	0.6	not detected
Cervix	tissue	0.5	not detected
Breast	tissue	0.5	not detected
Ovary	tissue	0.5	not detected
Smooth muscle	tissue	0.5	not detected
Epididymis	tissue	0.5	medium
Adrenal gland	tissue	0.5	not detected
Thymus	tissue	0.5
Fallopian tube	tissue	0.5	medium
Lymph node	tissue	0.4	not detected
Tongue	tissue	0.4
Retina	tissue	0.3
Endometrium 1	tissue	0.3	not detected
Corpus callosum	tissue	0.3
Skin 1	tissue	0.2	not detected
Medulla oblongata	tissue	0.2
Spinal cord	tissue	0.2
Prostate	tissue	0.2	not detected
Tonsil	tissue	0.2	not detected
Pituitary gland	tissue	0.1
Cerebral cortex	tissue	0.1	not detected
Pons	tissue	0.1
Skeletal muscle	tissue	0.1	not detected
Motor cortex	tissue	0.1
Putamen	tissue	0.1
Midbrain	tissue	0.1
Thalamus	tissue	0.1
Hypothalamus	tissue	0.1
Superior colliculi	tissue	0.1
Substantia nigra	tissue	0.1
Spleen	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 186; highest nTPM — Blood vessel (2.0), Flocculonodular lobe (1.7), Vermis (1.7), Cerebellar cortex (1.5), Nucleus tractus solitarii (1.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, HIF1A, HNF1A, HNF1B, MTF2, SRY

Functional genomics

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000252519 — one region, missense o/e 0.87.

Literature-anchored findings (GeneRIF, showing 40)

• role in hydrolyzing biological peptides (PMID:11815627)
• tissue distribution of ACE 2 mRNA by RT-PCR (PMID:12459472)
• We tested the hypothesis that cardiac ACE2 activity contributes to features of ventricular remodeling associated with the renin-angiotensin system (PMID:12967627)
• ACE2 is a functional receptor for the coronavirus that causes severe acute respiratory syndrome (SARS-CoV). (PMID:14647384)
• a metallopeptidase, angiotensin-converting enzyme 2 (ACE2), isolated from SARS coronavirus (SARS-CoV)-permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein; ACE2 is a functional receptor for SARS-CoV (PMID:14647384)
• ACE2 binds to a 193-amino acid fragment of the SARS coronavirus S protein (PMID:14670965)
• large hinge-bending motion is important for inhibitor binding and catalysis in ACE2 (PMID:14754895)
• ACE2 also serves as the cellular entry point for the severe acute respiratory syndrome virus and the enzyme is therefore a prime target for pharmacological intervention on several disease fronts–REVIEW (PMID:15165741)
• ACE2 is a constitutive product of adult-type Leydig cells and may participate in the control of testicular function by as yet unknown mechanisms. (PMID:15231706)
• Angiotensin-converting enzyme 2 gene (ACE2) is little associated in genetic predisposition to hypertension. (PMID:15233982)
• We have examined the kinetics of angiotensin peptide cleavage by full-length human ACE, the separate N- and C-domains of ACE, the homologue of ACE, ACE2, and NEP (neprilysin). (PMID:15283675)
• Failure of angiotensin-(1-9) to increase in response to increased angiotensin I indicated little role for ACE2 in angiotensin I metabolism. Levels of angiotensin-(1-7) were more linked to those of angiotensin I than angiotensin II. (PMID:15361769)
• cloning and characterization of a constitutively secreted form of ACE2 (PMID:15380922)
• This article will focus on angiotensin-converting enzyme 2 (ACE2) as a new, potential target of gene therapy for hypertensive disorders. (PMID:15640278)
• Upregulated in nonischemic but not ischemic cardiomyopathy. (PMID:15769906)
• Results identify the SARS coronavirus spike protein binding site on angiotensin-converting enzyme 2. (PMID:15791205)
• A molecular docking model of SARS-CoV S1 protein in complex with human ACE2 was constructed and the interacting residue pairs within this complex model and their contact types are described. (PMID:15979045)
• ADAM17 is the protease responsible for shedding of the SARS-CoV receptor, ACE2 (PMID:15983030)
• data identify a critical function for ACE2 in acute lung injury (PMID:16001071)
• report associates severe congenital uropathies and renal hypodysplasia with decreased renin-angiotensin system activity associated with the ACE II genotype and a possible functional imbalance among ATR1 receptors. (PMID:16006956)
• This paper reviews data regarding the biochemistry of angiotensin-(1-7)-forming enzymes and the elucidation of the regulatory mechanisms participating in the expression of ACE2 and angiotensin-(1-7) in the control of the circulation. (PMID:16055515)
• Aortic distensibility was increased by prolonged training in endurance athletes, particularly in those with the ACE II genotype. This effect represents an extracardiac adaptation to chronic prolonged training in athletes. (PMID:16088128)
• ACE2 and ACE are ectoenzymes that have distinct localization and secretion patterns that determine their role on the cell surface in kidney epithelium (PMID:16166094)
• crystal structure at 2.9 angstrom resolution of the receptor-binding domain(RBD)of SARS coronavirus spike protein bound to the peptidase domain of ACE2 shows that the RBD presents a gently concave surface which cradles the N-terminal lobe of the peptidase (PMID:16166518)
• In Finnish type 1 diabetic patients, ACE2 polymorphisms are not associated with diabetic nephropathy or any studied risk factor for this complication. (PMID:16211375)
• The G8790A polymorphism in angiotensin I converting enzyme 2 gene may be related to the essential hypertension with cardiac incompetence in Chinese population. (PMID:16215952)
• ACE2 might be involved in the progression of pulmonary sarcoidosis which may depend on gender. (PMID:16315782)
• ACE2 is expressed in the invading and intravascular trophoblast and in decidual cells during pregnancy. (PMID:16338465)
• ACE2 A/G polymorphism is associated with hypertension in patients with metabolic syndrome (PMID:16459167)
• charged amino acids between residues 22 and 57 were important (K26 and D30, in particular) as determinants on ACE2 critical for SARS-CoV infection (PMID:16510163)
• Telmisartan up-regulates the protein and gene expression of ACE2 in HUVECs in a concentration and time dependent manner. (PMID:16647014)
• shown to be localized on the apical plasma membrane of polarized respiratory epithelial cells and to mediate SARS-CoV infection from the apical side of these cells. (PMID:16690935)
• functions as a receptor for hCOV NL63 and 229E S proteins but is engaged diferentially by each strain. (PMID:16912312)
• There was higher angiotensin-converting enzyme (ACE) and chymase mRNA expression and mast cell density in failing than in control myocardium and no changes in ACE2 expression were detected. (PMID:16962475)
• analysis of SARS coronavirus interactions with ACE2 (PMID:17037534)
• analysis of spike protein of human coronavirus NL63 interaction with its cellular receptor ACE2 (PMID:17037543)
• ACE2 is a receptor for human respiratory coronavirus NL63 (PMID:17037544)
• SARS coronavirus airway epithelial infection is associated with ACE2 expression and localization (review) (PMID:17037581)
• Here we show that transgenic mice that express the SARS-CoV receptor (human angiotensin-converting enzyme 2 [hACE2]) in airway and other epithelia develop a rapidly lethal infection after intranasal inoculation with a human strain of the virus. (PMID:17079315)
• ACE2 might play an important role in maintaining a balanced status of local renin-angiotensin system synergistically with ACE by counterregulatory effects confounded by the presence of hypertension (PMID:17303661)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ace2	ENSDARG00000016918
mus_musculus	Ace2	ENSMUSG00000015405
rattus_norvegicus	Ace2	ENSRNOG00000031665
caenorhabditis_elegans		WBGENE00000039

Paralogs (1): ACE (ENSG00000159640)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1917258) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 82 distinct phenotype terms.

Mouse phenotype (MP)	Records
lung inflammation	4
increased susceptibility to weight loss	3
increased angiotensin II level	3
increased circulating angiotensin II level	3
dilated heart left ventricle	2
oxidative stress	2
pulmonary edema	2
decreased cardiac muscle contractility	2
congestive heart failure	2
increased susceptibility to induced colitis	2
increased susceptibility to pulmonary hyaline membrane formation	2
decreased colon length	2
increased neutrophil cell number	1
hypertension	1
abnormal heart morphology	1
enlarged heart	1
abnormal intestine morphology	1
abnormal spleen morphology	1
enlarged spleen	1
abnormal thymus morphology	1
enlarged thymus	1
abnormal uterus morphology	1
thick pulmonary interalveolar septum	1
lung hemorrhage	1
abnormal lens morphology	1

+57 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
Bos taurus	Q0VCT4	89.6%	Diamond
Mesocricetus auratus	Q50JE5	89.2%	Diamond
Sus scrofa	F1RRW5	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
ACE2-DT	ncRNA	104798195
ASB11	protein-coding	140456
VEGFD	protein-coding	2277
PIGA	protein-coding	5277
BMX	protein-coding	660
PIR	protein-coding	8544
PIR-FIGF	ncRNA	100532742
CA5BP1-CA5B	ncRNA	114004397
CLTRN	protein-coding	57393
CA5B	protein-coding	11238
ZRSR2	protein-coding	8233
INE2	ncRNA	8551
AP1S2	protein-coding	8905

Protein

Protein identifiers

Angiotensin-converting enzyme 2 — Q9BYF1 (reviewed: Q9BYF1)

Alternative names: Angiotensin-converting enzyme homolog, Angiotensin-converting enzyme-related carboxypeptidase, Metalloprotease MPROT15

All UniProt accessions (6): Q9BYF1, A0A7I2V2E9, A0A7I2V3N4, A0A7I2V3X6, A0A7I2V4H0, A0A7I2V5W5

UniProt curated annotations — full annotation on UniProt →

Function. Essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis. Converts angiotensin I to angiotensin 1-9, a nine-amino acid peptide with anti-hypertrophic effects in cardiomyocytes, and angiotensin II to angiotensin 1-7, which then acts as a beneficial vasodilator and anti-proliferation agent, counterbalancing the actions of the vasoconstrictor angiotensin II. Also removes the C-terminal residue from three other vasoactive peptides, neurotensin, kinetensin, and des-Arg bradykinin, but is not active on bradykinin. Also cleaves other biological peptides, such as apelins (apelin-13, [Pyr1]apelin-13, apelin-17, apelin-36), casomorphins (beta-casomorphin-7, neocasomorphin) and dynorphin A with high efficiency. In addition, ACE2 C-terminus is homologous to collectrin and is responsible for the trafficking of the neutral amino acid transporter SL6A19 to the plasma membrane of gut epithelial cells via direct interaction, regulating its expression on the cell surface and its catalytic activity. (Microbial infection) Acts as a receptor for human coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus NL63/HCoV-NL63. Non-functional as a carboxypeptidase. (Microbial infection) Non-functional as a receptor for human coronavirus SARS-CoV-2.

Subunit / interactions. Homodimer. Interacts with the catalytically active form of TMPRSS2. Interacts with SLC6A19; this interaction is essential for expression and function of SLC6A19 in intestine. Interacts with ITGA5:ITGB1. Probably interacts (via endocytic sorting signal motif) with AP2M1; the interaction is inhibited by phosphorylation of Tyr-781. Interacts (via PDZ-binding motif) with NHERF1 (via PDZ domains); the interaction may enhance ACE2 membrane residence. (Microbial infection) Interacts with SARS coronavirus/SARS-CoV spike protein. (Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 spike protein (via RBD domain). (Microbial infection) Interacts with human coronavirus NL63 spike protein. (Microbial infection) Interacts with human coronavirus NL63/HCoV-NL63 spike glycoprotein. (Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 spike protein; the interaction is increased by AVP/Arg-vasopressin with which they may form a complex.

Subcellular location. Secreted Cell membrane. Cytoplasm. Cell projection. Cilium. Apical cell membrane Apical cell membrane.

Tissue specificity. Expressed in endothelial cells from small and large arteries, and in arterial smooth muscle cells (at protein level). Expressed in enterocytes of the small intestine, Leydig cells and Sertoli cells (at protein level). Expressed in the renal proximal tubule and the small intestine (at protein level). Expressed in heart, kidney, testis, and gastrointestinal system (at protein level). In lung, expressed at low levels in some alveolar type 2 cells, the expression seems to be individual-specific (at protein level). Expressed in nasal epithelial cells (at protein level). Coexpressed with TMPRSS2 within some lung alveolar type 2 cells, ileal absorptive enterocytes, intestinal epithelial cells, cornea, gallbladder and nasal goblet secretory cells. Coexpressed with TMPRSS4 within mature enterocytes. Expressed in nasal and bronchial epithelial cells (at protein level).

Post-translational modifications. N-glycosylation on Asn-90 may limit SARS infectivity. Proteolytic cleavage by ADAM17 generates a secreted form. Also cleaved by serine proteases: TMPRSS2, TMPRSS11D and HPN/TMPRSS1. Phosphorylated. Phosphorylation at Tyr-781 probably inhibits interaction with AP2M1 and enables interactions with proteins containing SH2 domains. Ubiquitinated. Ubiquitinated on Lys-788 via ‘Lys-48’-linked ubiquitin. ‘Lys-48’-linked deubiquitinated by USP50 on the Lys-788; leading to its stabilization.

Activity regulation. Regulated by chloride and fluoride, but not bromide. Chloride increases angiotensin I and decreases angiotensin II cleavage. Inhibited by MLN-4760, cFP_Leu, and EDTA, but not by the ACE inhibitors lisinopril, captopril and enalaprilat. Highly potent and selective in vitro ACE2 inhibitors were identified.

Cofactor. Binds 1 zinc ion per subunit. Binds 1 Cl(-) ion per subunit.

Domain organisation. The extracellular region of the ACE2 enzyme is composed of two domains. The first is a zinc metallopeptidase domain (residues 19-611). The second domain is located at the C-terminus (residues 612-740) and is 48% identical to human collectrin. The cytoplasmic tail contains several linear motifs such as LIR, PDZ-binding, PTB and endocytic sorting signal motifs that would allow interaction with proteins that mediate endocytic trafficking and autophagy.

Induction. Up-regulated in failing heart. Expression is induced by IFNA and IFNG. Exposure to cigarette smoke increases expression in lungs. Expression is decreased in nasal and bronchial epithelium of individuals with allergy after allergen challenge. IL13 stimulation decreases expression in nasal and bronchial epithelium. Not induced by interferons such as IFNA, IFNB and IFNG. Expression is induced by interferons such as IFNA, IFNB and IFNG. It seems that isoform 2 is an interferon-stimulated gene (ISG) but not isoform 1. (Microbial infection) In airway epithelial cells, expression is increased upon influenza A virus infection. (Microbial infection) In airway epithelial cells, expression is induced by viruses such rhinoviruses and influenza virus. (Microbial infection) Induced by human coronavirus SARS-CoV-2.

Similarity. Belongs to the peptidase M2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BYF1-1	1, long	yes
Q9BYF1-3	2, delta, dACE2, short

RefSeq proteins (6): NP_001358344, NP_001373188, NP_001373189, NP_001375381, NP_001376331, NP_068576 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001548	Peptidase_M2	Family
IPR031588	Collectrin_dom	Domain

Pfam: PF01401, PF16959

Enzyme classification (BRENDA)

• EC 3.4.15.1 — peptidyl-dipeptidase A (BRENDA: 31 organisms, 224 substrates, 941 inhibitors, 246 Km, 169 kcat entries)
• EC 3.4.17.23 — angiotensin-converting enzyme 2 (BRENDA: 30 organisms, 124 substrates, 241 inhibitors, 10 Km, 8 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 II + H2O = angiotensin-(1-7) + L-phenylalanine (RHEA:26554)
• angiotensin I + H2O = angiotensin-(1-9) + L-leucine (RHEA:63532)
• bradykinin(1-8) + H2O = bradykinin(1-7) + L-phenylalanine (RHEA:63536)
• neurotensin + H2O = neurotensin-(1-12) + L-leucine (RHEA:63540)
• kinetensin + H2O = kinetensin-(1-8) + L-leucine (RHEA:63544)
• dynorphin A-(1-13) + H2O = dynorphin A-(1-12) + L-lysine (RHEA:63556)
• apelin-13 + H2O = apelin-12 + L-phenylalanine (RHEA:63564)
• beta-casomorphin-7 + H2O = beta-casomorphin-6 + L-isoleucine (RHEA:63568)
• neurotensin-(1-8) + H2O = neurotensin-(1-7) + L-arginine (RHEA:63572)
• neocasomorphin + H2O = neocasomorphin-(1-5) + L-isoleucine (RHEA:63600)
• [Pyr1]apelin-13 + H2O = [Pyr1]apelin-12 + L-phenylalanine (RHEA:63604)
• apelin-17 + H2O = apelin-16 + L-phenylalanine (RHEA:63608)

UniProt features (204 total): mutagenesis site 67, helix 49, strand 24, turn 12, binding site 9, glycosylation site 7, region of interest 6, short sequence motif 5, sequence variant 4, sequence conflict 3, disulfide bond 3, chain 2, active site 2, topological domain 2, modified residue 2, domain 2, signal peptide 1, compositionally biased region 1, transmembrane region 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

showing 30 of 328 structures by resolution:

PDB	Title	Method	Resolution (Å)
28KD	ACE2 extracellular domain in complex with the macrocyclic peptide GR3.1.2	X-RAY DIFFRACTION	2.02
8BYJ	The structures of Ace2 in complex with bicyclic peptide inhibitor	X-RAY DIFFRACTION	2.07
8B9P	ACE2 in complex with bicyclic peptide inhibitor	X-RAY DIFFRACTION	2.11
8XSF	SARS-CoV-2 RBD + IMCAS-364 + hACE2	ELECTRON MICROSCOPY	2.16
1R42	Native Human Angiotensin Converting Enzyme-Related Carboxypeptidase (ACE2)	X-RAY DIFFRACTION	2.2
7JVO	Importin alpha bound to the C-terminus of ACE2	X-RAY DIFFRACTION	2.2
8TOR	ACE2-peptide 2 complex	X-RAY DIFFRACTION	2.2
8TOQ	ACE2-peptide 1 complex	X-RAY DIFFRACTION	2.3
8BFW	The structures of Ace2 in complex with bicyclic peptide inhibitor	X-RAY DIFFRACTION	2.33
8TOS	ACE2-peptide 6 complex	X-RAY DIFFRACTION	2.35
7UFK	Crystal structure of chimeric omicron RBD (strain BA.2) complexed with human ACE2	X-RAY DIFFRACTION	2.38
7EKH	Structure of SARS-CoV-2 spike receptor-binding domain Y453F mutation complexed with human …	X-RAY DIFFRACTION	2.4
6M0J	Crystal structure of SARS-CoV-2 spike receptor-binding domain bound with ACE2	X-RAY DIFFRACTION	2.45
7T9K	Cryo-EM structure of SARS-CoV-2 Omicron spike protein in complex with human ACE2	ELECTRON MICROSCOPY	2.45
7LO4	SARS-CoV-2 spike receptor-binding domain with a G485R mutation in complex with human ACE2	X-RAY DIFFRACTION	2.46
8WE1	SARS-CoV-2 Omicron BF.7 RBD complexed with human ACE2	ELECTRON MICROSCOPY	2.47
7EFR	Structure of SARS-CoV-2 spike receptor-binding domain in complex with high affinity ACE2 …	X-RAY DIFFRACTION	2.49
6LZG	Structure of novel coronavirus spike receptor-binding domain complexed with its receptor …	X-RAY DIFFRACTION	2.5
9FMM	Structure of human ACE2 in complex with a fluorinated small molecule inhibitor	X-RAY DIFFRACTION	2.5
8DM5	Cryo-EM structure of SARS-CoV-2 Omicron BA.2 spike protein in complex with human ACE2	ELECTRON MICROSCOPY	2.51
8VQR	Crystal structure of chimeric SARS-CoV-2 RBD complexed with chimeric raccoon dog ACE2	X-RAY DIFFRACTION	2.56
7WPC	The second RBD of SARS-CoV-2 Omicron Variant in complexed with RBD-ACE2	ELECTRON MICROSCOPY	2.57
7SY5	Cryo-EM structure of the SARS-CoV-2 D614G,N501Y,E484K,K417N mutant spike protein …	ELECTRON MICROSCOPY	2.59
7WHH	Crystal structure of SARS-CoV-2 omicron RBD and human ACE2	X-RAY DIFFRACTION	2.6
7SXZ	Cryo-EM structure of the SARS-CoV-2 D614G,L452R mutant spike protein ectodomain bound to …	ELECTRON MICROSCOPY	2.61
7U0N	Crystal structure of chimeric omicron RBD (strain BA.1) complexed with human ACE2	X-RAY DIFFRACTION	2.61
8BN1	The structures of Ace2 in complex with bicyclic peptide inhibitor	X-RAY DIFFRACTION	2.61
8XSJ	SARS-CoV-2 Omicron BA.4 RBD + IMCAS-316 + ACE2	ELECTRON MICROSCOPY	2.61
22HG	SARS-CoV-2 BA.3.2.2(RE.2.2) RBD in complex with human ACE2 and monoclonal antibody S2H97	ELECTRON MICROSCOPY	2.61
7EKG	Structure of SARS-CoV-2 Beta variant spike receptor-binding domain complexed with human …	X-RAY DIFFRACTION	2.63

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYF1-F1	91.13	0.80

Antibody-complex structures (SAbDab)

20 antibodies co-crystallized with this protein: 7DX4, 7E7E, 7L0N, 7TN0, 7V61, 7XCP, 7YDI, 7YEG, 8DF5, 8E7M, 8FXB, 8FXC, 8S9G, 8WE4, 8XSF, 8XSJ, 8XXW, 8Y6A, 9R19, CIFURTILIMAB

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Metallopeptidases, Metabolic proteins, Transporters, Electrochemical Potential-driven transporters, Accessory Factors Involved in Transport, Predicted membrane proteins, Predicted secreted proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

Functional residue map

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

Catalytic / active sites (2)

Position	Role
375	proton acceptor
505	proton donor

Ligand- & substrate-binding residues (9)

Position	Role
169	chloride
273	substrate
345–346	substrate
374	Zn(2+)
378	Zn(2+)
402	Zn(2+)
477	chloride
481	chloride
515	substrate

Post-translational modifications (3)

Type	Positions
Phosphotyrosine	781
Phosphoserine	783
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)	788

Disulfide bonds (3)

Type	Positions
Disulfide bond	133–141, 344–361, 530–542

Glycosylation sites (7)

Type	Positions
N-linked (glcnac…) asparagine	53, 90, 103, 322, 432, 546, 690

Mutagenesis-validated functional residues (67)

Position	Phenotype
383	slightly inhibits interaction with sars-cov spike glycoprotein.
386	increases slightly the interaction with rbd domain of sars-cov-2 spike protein. in sace2.v2.2; increases interaction with rbd domain of …
389	slightly inhibits interaction with sars-cov spike glycoprotein.
389	increases very slightly the interaction with rbd domain of sars-cov-2 spike protein.
393	slightly inhibits interaction with sars-cov spike glycoprotein.
393	increases very slightly the interaction with rbd domain of sars-cov-2 spike protein.
425–427	slightly inhibits interaction with sars-cov spike glycoprotein.
465–467	no effect on interaction with sars-cov spike glycoprotein.
481	about 80% loss of angiotensin i cleavage.
505	complete loss of enzyme activity.
514	about 50% loss of angiotensin i cleavage but two-fold greater activity with angiotensin ii.
518	increases very slightly the interaction with rbd domain of sars-cov-2 spike protein.
559	slightly inhibits interaction with sars-cov spike glycoprotein.
603	no effect on interaction with sars-cov spike glycoprotein.
788	increases ace2 protein stability.
802–805	loss of interaction with nherf1.
19	increases slightly the interaction with rbd domain of sars-cov-2 spike protein.
24–26	slightly inhibits interaction with sars-cov spike glycoprotein.
24	increases slightly the interaction with rbd domain of sars-cov-2 spike protein.
25	increases slightly the interaction with rbd domain of sars-cov-2 spike protein.
27	increases slightly the interaction with rbd domain of sars-cov-2 spike protein. in sace2.v2.2; increases interaction with rbd domain of …
29	increases slightly the interaction with rbd domain of sars-cov-2 spike protein.
31	abolishes interaction with sars-cov spike glycoprotein.
31	increases slightly the interaction with rbd domain of sars-cov-2 spike protein.
33	increases slightly the interaction with rbd domain of sars-cov-2 spike protein.

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 15; 12 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

15 pathways:

ID	Pathway	Evidence
R-HSA-9678110	Attachment and Entry ⚕	curated
R-HSA-9733458	Induction of Cell-Cell Fusion ⚕	curated
R-HSA-9679191	Potential therapeutics for SARS ⚕	curated
R-HSA-2022377	Metabolism of Angiotensinogen to Angiotensins	curated
R-HSA-9694614	Attachment and Entry ⚕	electronic
R-HSA-1643685	Disease ⚕	—
R-HSA-9772572	Early SARS-CoV-2 Infection Events ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9772573	Late SARS-CoV-2 Infection Events ⚕	—
R-HSA-9679506	SARS-CoV Infections ⚕	—
R-HSA-9678108	SARS-CoV-1 Infection ⚕	—
R-HSA-9694516	SARS-CoV-2 Infection ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-2980736	Peptide hormone metabolism	—

MSigDB gene sets: 268 (showing top): GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE_BY_CIRCULATORY_RENIN_ANGIOTENSIN, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_INFLAMMATORY_RESPONSE, GOBP_MEMBRANE_FUSION, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_REGULATION_OF_HORMONE_LEVELS, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, TGACCTY_ERR1_Q2

GO Biological Process (27): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of cytokine production (GO:0001817), angiotensin maturation (GO:0002003), angiotensin-mediated drinking behavior (GO:0003051), regulation of systemic arterial blood pressure by renin-angiotensin (GO:0003081), tryptophan transport (GO:0015827), viral life cycle (GO:0019058), receptor-mediated endocytosis of virus by host cell (GO:0019065), regulation of vasoconstriction (GO:0019229), regulation of cell population proliferation (GO:0042127), symbiont entry into host cell (GO:0046718), receptor-mediated virion attachment to host cell (GO:0046813), negative regulation of smooth muscle cell proliferation (GO:0048662), regulation of inflammatory response (GO:0050727), positive regulation of amino acid transport (GO:0051957), maternal process involved in female pregnancy (GO:0060135), positive regulation of cardiac muscle contraction (GO:0060452), membrane fusion (GO:0061025), negative regulation of ERK1 and ERK2 cascade (GO:0070373), amino acid import across plasma membrane (GO:0089718), blood vessel diameter maintenance (GO:0097746), entry receptor-mediated virion attachment to host cell (GO:0098670), positive regulation of gap junction assembly (GO:1903598), regulation of cardiac conduction (GO:1903779), positive regulation of L-proline import across plasma membrane (GO:1905737), positive regulation of reactive oxygen species metabolic process (GO:2000379), proteolysis (GO:0006508)

GO Molecular Function (13): virus receptor activity (GO:0001618), endopeptidase activity (GO:0004175), carboxypeptidase activity (GO:0004180), metallocarboxypeptidase activity (GO:0004181), metallopeptidase activity (GO:0008237), peptidyl-dipeptidase activity (GO:0008241), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), transporter activator activity (GO:0141109), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (12): extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788), plasma membrane (GO:0005886), cilium (GO:0005929), cell surface (GO:0009986), membrane (GO:0016020), apical plasma membrane (GO:0016324), endocytic vesicle membrane (GO:0030666), brush border membrane (GO:0031526), membrane raft (GO:0045121), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

10 top-level categories:

Category	Pathways
SARS-CoV Infections	3
SARS-CoV-2 Infection	2
Peptide hormone metabolism	1
SARS-CoV-1 Infection	1
Early SARS-CoV-2 Infection Events	1
Late SARS-CoV-2 Infection Events	1
Metabolism of proteins	1
Disease	1
Viral Infection Pathways	1
Infectious disease	1

GO top-level categories

showing 60 of 80 GO namespaces:

Category	Terms
cellular anatomical structure	4
amino acid transport	2
symbiont entry into host cell	2
peptidase activity	2
exopeptidase activity	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
regulation of angiotensin levels in blood	1
peptide hormone processing	1
brain renin-angiotensin system	1
drinking behavior	1
regulation of systemic arterial blood pressure by hormone	1
aromatic amino acid transport	1
viral process	1
receptor-mediated endocytosis	1
endocytosis involved in viral entry into host cell	1
vasoconstriction	1
blood vessel diameter maintenance	1
regulation of blood circulation	1
cell population proliferation	1
regulation of cellular process	1
viral life cycle	1
symbiont entry into host	1
signaling receptor binding	1
virion attachment to host cell	1
negative regulation of cell population proliferation	1
smooth muscle cell proliferation	1
regulation of smooth muscle cell proliferation	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
positive regulation of amine transport	1
regulation of amino acid transport	1
female pregnancy	1
multicellular organismal reproductive process	1
positive regulation of heart contraction	1
positive regulation of striated muscle contraction	1
regulation of cardiac muscle contraction	1
cardiac muscle contraction	1
membrane organization	1
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
amino acid transmembrane transport	1
import across plasma membrane	1
exogenous protein binding	1
carboxypeptidase activity	1
metalloexopeptidase activity	1
transition metal ion binding	1
protein binding	1
transporter activity	1
molecular function activator activity	1
transporter regulator activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 25 of 53 annotations. The rest are phylogenetic / computational / electronic (IEA).

25 experimentally-supported GO terms:

GO term	NS	Evidence
amino acid import across plasma membrane	BP	direct assay
angiotensin-mediated drinking behavior	BP	mutant phenotype
entry receptor-mediated virion attachment to host cell	BP	direct assay
negative regulation of transcription by RNA polymerase II	BP	direct assay
positive regulation of L-proline import across plasma membrane	BP	genetic interaction
positive regulation of amino acid transport	BP	mutant phenotype
positive regulation of gap junction assembly	BP	mutant phenotype
receptor-mediated virion attachment to host cell	BP	direct assay
regulation of cardiac conduction	BP	mutant phenotype
regulation of inflammatory response	BP	direct assay
regulation of systemic arterial blood pressure by renin-angiotensin	BP	mutant phenotype
symbiont entry into host cell	BP	direct assay
apical plasma membrane	CC	direct assay
brush border membrane	CC	direct assay
cell surface	CC	direct assay
extracellular exosome	CC	high-throughput assay
extracellular region	CC	direct assay
plasma membrane	CC	direct assay
carboxypeptidase activity	MF	direct assay
endopeptidase activity	MF	direct assay
identical protein binding	MF	physical interaction
metallopeptidase activity	MF	direct assay
peptidyl-dipeptidase activity	MF	direct assay
transporter activator activity	MF	genetic interaction
virus receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,870 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACE2	REN	P00797	958
ACE2	TMPRSS2	O15393	949
ACE2	AGT	P01019	939
ACE2	AGTR2	P50052	917
ACE2	AGTR1	P30556	916
ACE2	CLEC4M	Q9H2X3	901
ACE2	FURIN	P09958	896
ACE2	KNG1	P01042	867
ACE2	IL6	P05231	858
ACE2	DPP4	P27487	853
ACE2	SWI5	Q1ZZU3	852
ACE2	ANPEP	P15144	845
ACE2	ADAM17	P78536	826
ACE2	CTSL	P07711	820
ACE2	TTR	P02766	799

IntAct

Human interaction partners of ACE2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 112 partners by confidence:

Partner	Interaction type	MIscore	Records
S	physical association	1.000	295
PDZK1	physical association	0.790	5
KNG1	protein cleavage	0.730	2
HSPA5	direct interaction	0.720	3
SHANK1	physical association	0.720	3
SNX27	physical association	0.720	3
SLC6A19	physical association	0.640	3
NHERF1	physical association	0.630	7
AGT	protein cleavage	0.620	3
NTS	protein cleavage	0.620	2
SCRIB	physical association	0.610	4
MAST1	physical association	0.610	2
MAST2	physical association	0.610	2
NHERF2	physical association	0.610	2
PARD3	physical association	0.610	2
PTPN3	physical association	0.610	2
TAMALIN	physical association	0.610	2
VIM	association	0.600	4
CLEC4M	physical association	0.590	3
ITGB1	physical association	0.570	4
KDM1A	colocalization	0.560	19
GRM2	physical association	0.520	2
APP	direct interaction	0.490	4
TMPRSS2	physical association	0.460	3
TGFBR2	physical association	0.460	2
PATJ	direct interaction	0.440	8
GRIP1	direct interaction	0.440	5
GRIP2	direct interaction	0.440	5
MAGI2	direct interaction	0.440	5
DLG4	direct interaction	0.440	3

BioGRID (2,594 interactions; top human partners by supporting records in a sample of 600 records): SLC6A19 (Co-crystal Structure; 4 records), VIM (Affinity Capture-MS; 4 records), AAMP (Affinity Capture-MS; 3 records), APOE (Co-localization; 3 records), TMPRSS2 (Biochemical Activity; 3 records), DLEU2 (Affinity Capture-RNA; 2 records), HSD17B12 (Affinity Capture-MS; 2 records), HSPA5 (Affinity Capture-Western; 2 records), LONP1 (Affinity Capture-MS; 2 records), MDM2 (Affinity Capture-Western; 2 records), PGRMC1 (Affinity Capture-MS; 2 records), RAB11A (Affinity Capture-MS; 2 records), RAB6A (Affinity Capture-MS; 2 records), SAFB (Affinity Capture-MS; 2 records), VDAC1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 12 of 17 signaling interactions:

A	Effect	B	Mechanism
S	“down-regulates activity”	ACE2	binding
Angiotensin-1	“up-regulates activity”	ACE2	binding
ACE2	“up-regulates quantity”	“Angiotensin 1-7”	cleavage
ACE2	up-regulates	“Receptor_mediated_ endocytosis”
ACE2	up-regulates	Membrane_fusion
ACE2	“up-regulates activity”	AGT	cleavage
ACE2	“up-regulates activity”	APLN	cleavage
ACE2	“up-regulates activity”	Angiotensin-1	cleavage
chloroquine	“down-regulates activity”	ACE2	“chemical inhibition”
ACE2	“form complex”	“Spike protein-ACE2”	binding
ACE2	“form complex”	“CoV2 Spike protein-ACE2”	binding
captopril	“down-regulates activity”	ACE2	“chemical inhibition”

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
★ ACE2-AGTR1 complex	2	ACE2, AGTR1
ACE2-TMPRSS2 complex	2	ACE2, TMPRSS2
ACE2-SLC6A19 complex	2	ACE2, SLC6A19

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 112 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	6	42.3×	5e-07
Unblocking of NMDA receptors, glutamate binding and activation	6	40.3×	5e-07
Negative regulation of NMDA receptor-mediated neuronal transmission	6	40.3×	5e-07
Long-term potentiation	6	35.2×	1e-06
Assembly and cell surface presentation of NMDA receptors	10	31.3×	1e-10
Dopamine Neurotransmitter Release Cycle	5	30.6×	3e-05
Neurexins and neuroligins	12	29.2×	3e-12
Protein-protein interactions at synapses	8	26.2×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	53.3×	2e-12
protein localization to synapse	6	42.2×	8e-07
receptor clustering	7	40.1×	1e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	7	31.8×	5e-07
learning	5	12.9×	3e-03
cell-cell adhesion	13	12.1×	3e-08
protein-containing complex assembly	11	11.5×	7e-07
negative regulation of ERK1 and ERK2 cascade	5	9.9×	7e-03

Disease & clinical

Genetic variants

Variant evidence for ACE2: 328 ClinVar records (51 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	49
Likely pathogenic	2
Uncertain significance	64
Likely benign	11
Benign	4

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 51 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
58559	GRCh38/hg38 Xp22.33-11.3(chrX:675360-46016699)x3	Pathogenic	criteria provided, single submitter	1
58589	GRCh38/hg38 Xp22.31-22.2(chrX:9038047-16646589)x2	Pathogenic	criteria provided, single submitter	1
59189	GRCh38/hg38 Xp22.33-22.11(chrX:253129-23023165)x1	Pathogenic	criteria provided, single submitter	1
59190	GRCh38/hg38 Xp22.33-11.1(chrX:253129-58271563)x1	Pathogenic	criteria provided, single submitter	1
253489	GRCh37/hg19 Xp22.33-21.1(chrX:71267-35809046)x1	Pathogenic	criteria provided, single submitter	1
253571	GRCh37/hg19 Xp22.33-11.21(chrX:70297-58066465)x1	Pathogenic	criteria provided, single submitter	1
625794	GRCh37/hg19 Xp22.33-22.11(chrX:801301-23768392)	Pathogenic	criteria provided, single submitter	1
635934	Single allele	Pathogenic	criteria provided, single submitter	1
638115	GRCh37/hg19 Xp22.33-11.22(chrX:60814-50519984)x1	Pathogenic	criteria provided, single submitter	1
2424508	NC_000023.10:g.(?14861689)(15870650_?)del	Pathogenic	criteria provided, single submitter	1
2685690	GRCh37/hg19 Xp22.33-11.22(chrX:2696762-53113314)x1	Pathogenic	criteria provided, single submitter	1
2685727	GRCh37/hg19 Xp22.33-21.2(chrX:168547-30774453)x2	Pathogenic	criteria provided, single submitter	1
3062471	GRCh37/hg19 Xp22.33-11.21(chrX:168546-55653170)x1	Pathogenic	criteria provided, single submitter	1
3391945	GRCh37/hg19 Xp22.33-21.3(chrX:2631638-25008584)x1	Pathogenic	criteria provided, single submitter	1
3391948	GRCh37/hg19 Xp22.2-11.23(chrX:15392463-48777470)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ACE2’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; 29 predictions of 1,367):

Position(s)	Effect	Δscore	Sites
X:15564022–15564023	donor_loss	1.0000	5
X:15564219–15564220	acceptor_loss	1.0000	5
X:15564223	acceptor_gain	1.0000
X:15564227	acceptor_gain	1.0000
X:15564233	acceptor_gain	1.0000
X:15578087–15578088	donor_loss	1.0000	6
X:15578316–15578317	acceptor_loss	1.0000	5
X:15578320	acceptor_gain	1.0000
X:15581280	donor_gain	1.0000
X:15589342–15589343	donor_loss	1.0000	3

AlphaMissense

1,333 missense substitutions predicted likely pathogenic (of 5,375 scored), across 386 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
F523	8	0.934	0.993
F452	8	0.913	0.993
F464	8	0.909	0.971
H505	8	0.908	0.959
F400	8	0.900	0.983
D499	8	0.894	0.952
F327	8	0.884	0.987
N188	8	0.878	0.946
H378	8	0.873	0.964
H241	8	0.845	0.976
F643	8	0.834	0.952
F715	8	0.827	0.924
W459	7	0.979	0.996
C530	7	0.979	0.989
W275	7	0.970	0.996
W165	7	0.963	0.987
W461	7	0.962	0.992
W566	7	0.962	0.994
R460	7	0.961	0.995
W477	7	0.948	0.992

HPA cancer prognostics

RNA cancer specificity: Group enriched (Colon Adenocarcinoma, Kidney Renal Clear Cell Carcinoma, Kidney Renal Papillary Cell Carcinoma, Rectum Adenocarcinoma)

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.88e-10

Disease associations

OMIM: gene MIM:300335 | disease phenotypes: MIM:300868

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
COVID-19 research	green

Mondo (2): multiple congenital anomalies-hypotonia-seizures syndrome 2 (MONDO:0010466), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Multiple congenital anomalies-hypotonia-seizures syndrome type 2 (Orphanet:300496)

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2096989 (PROTEIN FAMILY), CHEMBL3736 (SINGLE PROTEIN), CHEMBL4888460 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 513,163 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

8 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1560	CAPTOPRIL	4	66,788
CHEMBL76	CHLOROQUINE	4	59,347
CHEMBL1201284	CINACALCET	4	5,997
CHEMBL1057	FLUORESCEIN	4	332,497
CHEMBL1535	HYDROXYCHLOROQUINE	4	43,272
CHEMBL449782	CEPHARANTHINE	2	3,103
CHEMBL35241	DIMINAZENE	2	2,000
CHEMBL429844	ORE-1001	1	159

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

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

Variant	Association	Level	Drugs	Phenotypes
rs2106809	Efficacy	3	captopril	Hypertension

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2106809	ACE2	3	0.50	1	captopril

PharmGKB variant annotations

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

7 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs2285666		Other	Allele C is associated with increased severity of COVID-19 as compared to allele T.	PMID:34001841
rs2074192		Other	Allele T is associated with increased severity of COVID-19 in people with COVID-19 as compared to allele C.	PMID:34079337
rs2106809		Other	Allele A is associated with increased likelihood of COVID-19 in men with COVID-19 as compared to allele G.	PMID:34079337
rs4240157		Other	Allele C is associated with increased likelihood of COVID-19 in people with as compared to allele T.	PMID:34834450
rs4240157		Other	Genotype CC is associated with increased risk of Death in people with COVID-19 as compared to genotypes CT + TT.	PMID:34834450
rs2074192		Other	Allele T is associated with increased severity of COVID-19 as compared to allele C.	PMID:33386398
rs2106809	captopril	Efficacy	Genotype GG is associated with increased response to captopril in women with Hypertension as compared to genotypes AA + AG.	PMID:17473847

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 (8 total), top 8:

Ligand	Action	Affinity	Parameter
compound 28 [PMID: 18324760]	Inhibition	9.9	pKi
MLN-4760	Inhibition	9.36	pIC50
BCY15291	Inhibition	9.05	pKi
GR3.1.2	Inhibition	8.82	pKi
GR1.4	Inhibition	8.72	pKi
DX600	Inhibition	8.55	pKi
CPS4	Binding	6.2	pIC50
XNT [PMID: 18391097]	Activation	4.7	pEC50

Binding affinities (BindingDB)

349 measured of 409 human assays (415 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
The second fraction of the HPLC chromatogram.	KI	0.13 nM
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
MLN4760	IC50	0.44 nM
med.21724, Compound 13	IC50	0.44 nM
CHEMBL5430631	IC50	0.49 nM
CHEMBL5394399	IC50	0.64 nM
CHEMBL5406655	IC50	0.65 nM
The second fraction of the HPLC chromatogram.	KI	0.7 nM
CHEMBL5424883	IC50	0.78 nM
med.21724, Compound 10	IC50	1 nM
CHEMBL5281591	IC50	1 nM
3-{1-(2-acetamido-4-methylpentanoyl)pyrrolidin-2-ylphosphoryl}-2-[(3-phenyl-1,2-oxazol-5-yl)methyl]propanoic acid	KI	1.25 nM
CHEMBL5220314	IC50	1.3 nM
(2S)-2-{[(1S)-1-carboxy-2-{1-[(3,5-dimethylphenyl)methyl]-1H-imidazol-5-yl}ethyl]amino}-4-methylpentanoic acid	IC50	1.4 nM
1-[5-Benzoylamino-6-(3,4-dimethoxy-phenyl)-4-oxo-hexanoyl]-pyrrolidine-2-carboxylic acid	IC50	1.4 nM
1-{5-[(Furan-2-carbonyl)-amino]-4-oxo-6-phenyl-hexanoyl}-pyrrolidine-2-carboxylic acid	IC50	1.4 nM
CHEMBL257726	KI	1.4 nM
CHEMBL271225	KI	1.4 nM
CHEMBL252391	KI	1.5 nM
CHEMBL269997	KI	1.5 nM
CHEMBL5395954	IC50	1.5 nM
CHEMBL269996	KI	1.6 nM
CHEMBL257270	KI	1.8 nM
CHEMBL404117	KI	1.8 nM
CHEMBL5273921	IC50	1.9 nM
CHEMBL257229	KI	2.4 nM
CHEMBL5403774	IC50	2.6 nM
CHEMBL5429094	IC50	2.7 nM
CHEMBL1240682	KI	2.8 nM
1-(5-Benzoylamino-4-oxo-6-phenyl-hexanoyl)-pyrrolidine-2-carboxylic acid	IC50	3.2 nM
CHEMBL5220968	IC50	3.2 nM
CHEMBL5415414	IC50	3.2 nM
CHEMBL5424641	IC50	3.3 nM
(2S)-2-{[(1S)-1-carboxy-2-{1-[(3-methylphenyl)methyl]-1H-imidazol-5-yl}ethyl]amino}-4-methylpentanoic acid	IC50	4.2 nM
CHEMBL5277148	IC50	4.3 nM
1-[2-(3-Benzoylamino-2-oxo-4-phenyl-butoxy)-acetyl]-pyrrolidine-2-carboxylic acid	IC50	4.4 nM
CHEMBL5429562	IC50	4.5 nM
1-[5-Benzoylamino-6-(4-hydroxy-phenyl)-4-oxo-hexanoyl]-pyrrolidine-2-carboxylic acid	IC50	4.7 nM
CHEMBL5396932	IC50	4.9 nM
2-benzyl-3-({1-[2-acetamido-3-(4-hydroxyphenyl)propanoyl]pyrrolidin-2-yl}(hydroxy)phosphoryl)propanoic acid	KI	5.2 nM
2-benzyl-3-{1-(2-acetamido-3-phenylpropanoyl)pyrrolidin-2-ylphosphoryl}propanoic acid	KI	5.2 nM
1-(5-Benzoylamino-4-oxo-6-pyridin-3-yl-hexanoyl)-pyrrolidine-2-carboxylic acid	IC50	5.7 nM
CHEMBL5091821	IC50	6 nM
CHEMBL5591272	KD	6.1 nM
3-{1-(6-amino-2-acetamidohexanoyl)pyrrolidin-2-ylphosphoryl}-2-benzylpropanoic acid	KI	6.5 nM
2-benzyl-3-{1-(2-acetamido-3-methylbutanoyl)pyrrolidin-2-ylphosphoryl}propanoic acid	KI	6.6 nM
CHEMBL257727	KI	6.9 nM
5-{2-[(2-benzyl-2-carboxyethyl)(hydroxy)phosphoryl]pyrrolidin-1-yl}-4-acetamido-5-oxopentanoic acid	KI	7 nM
CHEMBL5281306	IC50	7 nM
CHEMBL5433480	IC50	7 nM

ChEMBL bioactivities

238 potent at pChembl≥5 of 269 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.31	Kd	0.049	nM	CHEMBL5430631
10.27	Kd	0.054	nM	CHEMBL5424883
10.24	Kd	0.057	nM	CHEMBL5406655
10.22	Kd	0.06	nM	CHEMBL5394399
9.89	Ki	0.13	nM	CHEMBL260273
9.66	Ki	0.22	nM	CHEMBL5430631
9.54	Ki	0.29	nM	CHEMBL5394399
9.52	Ki	0.3	nM	CHEMBL5406655
9.46	Ki	0.35	nM	CHEMBL260273
9.46	Ki	0.35	nM	CHEMBL5424883
9.40	Ki	0.4	nM	CHEMBL409105
9.36	IC50	0.44	nM	ORE-1001
9.36	IC50	0.44	nM	CHEMBL5279656
9.36	Kd	0.44	nM	CHEMBL5395954
9.31	IC50	0.49	nM	CHEMBL5430631
9.19	IC50	0.64	nM	CHEMBL5394399
9.19	IC50	0.65	nM	CHEMBL5406655
9.15	Ki	0.7	nM	CHEMBL261423
9.14	Kd	0.72	nM	CHEMBL5429094
9.11	IC50	0.78	nM	CHEMBL5424883
9.07	Ki	0.85	nM	CHEMBL251808
9.05	Ki	0.9	nM	CHEMBL251804
9.05	Ki	0.89	nM	CHEMBL5395954
9.00	IC50	1	nM	CHEMBL5281591
9.00	IC50	1	nM	CHEMBL95564
8.92	Ki	1.2	nM	CHEMBL5403774
8.92	Ki	1.2	nM	CHEMBL5429094
8.92	Kd	1.2	nM	CHEMBL5403774
8.90	Ki	1.25	nM	CHEMBL261121
8.90	IC50	1.259	nM	CHEMBL5220314
8.89	Ki	1.3	nM	CHEMBL253224
8.89	Kd	1.3	nM	CHEMBL5415414
8.85	Ki	1.4	nM	CHEMBL271225
8.85	Ki	1.4	nM	CHEMBL257726
8.82	Ki	1.5	nM	CHEMBL252391
8.82	Ki	1.5	nM	CHEMBL400526
8.82	Ki	1.5	nM	CHEMBL269997
8.82	Ki	1.5	nM	CHEMBL5424641
8.82	Ki	1.5	nM	CHEMBL5415414
8.82	IC50	1.5	nM	CHEMBL5395954
8.80	Ki	1.6	nM	CHEMBL269996
8.80	Kd	1.6	nM	CHEMBL5396932
8.77	Kd	1.7	nM	CHEMBL5433480
8.74	Ki	1.8	nM	CHEMBL404117
8.74	Ki	1.8	nM	CHEMBL257270
8.73	IC50	1.88	nM	CHEMBL5273921
8.72	Kd	1.9	nM	CHEMBL5424641
8.70	Ki	2	nM	CHEMBL398771
8.70	IC50	2	nM	CHEMBL5395954
8.70	Ki	2	nM	CHEMBL5429562

PubChem BioAssay actives

252 with measured affinity, of 492 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
(9R,12S,15S,18S,21S,27S,30S,33S,36S,40R,43S,46S,49S,52S,55R)-N-[(2S)-1-amino-1-oxopropan-2-yl]-55-[[(2S)-2-aminopropanoyl]amino]-15-[(2S)-butan-2-yl]-18,49-bis(3-carbamimidamidopropyl)-33,36,46-tris(hydroxymethyl)-12-(1H-imidazol-4-ylmethyl)-43-[(4-methylphenyl)methyl]-27,30-bis(2-methylpropyl)-4,11,14,17,20,26,29,32,35,39,42,45,48,51,54,60,63-heptadecaoxo-52-propan-2-yl-7,57,66-trithia-1,3,10,13,16,19,25,28,31,34,37,38,41,44,47,50,53,61-octadecazatetracyclo[38.22.5.13,61.021,25]octahexacontane-9-carboxamide	1997771: Binding affinity to human ACE2 assessed as binding constant by surface plasmon resonance analysis	kd	<0.0001	uM
(9R,12S,15S,18S,21S,27S,30S,33S,36S,40R,43S,46S,49S,52S,55R)-N-[(2S)-1-amino-1-oxopropan-2-yl]-55-[[(2S)-2-aminopropanoyl]amino]-43-benzyl-15-[(2S)-butan-2-yl]-18,49-bis(3-carbamimidamidopropyl)-33,36,46-tris(hydroxymethyl)-12-(1H-imidazol-4-ylmethyl)-27,30-bis(2-methylpropyl)-4,11,14,17,20,26,29,32,35,39,42,45,48,51,54,60,63-heptadecaoxo-52-propan-2-yl-7,57,66-trithia-1,3,10,13,16,19,25,28,31,34,37,38,41,44,47,50,53,61-octadecazatetracyclo[38.22.5.13,61.021,25]octahexacontane-9-carboxamide	1997771: Binding affinity to human ACE2 assessed as binding constant by surface plasmon resonance analysis	kd	0.0001	uM
(9R,12S,15S,18S,21S,27S,30S,33S,36S,40R,43S,46S,49S,52S,55R)-N-[(2S)-1-amino-1-oxopropan-2-yl]-55-[[(2S)-2-aminopropanoyl]amino]-15-[(2S)-butan-2-yl]-18,49-bis(3-carbamimidamidopropyl)-43-[(4-fluorophenyl)methyl]-33,36,46-tris(hydroxymethyl)-12-(1H-imidazol-4-ylmethyl)-27,30-bis(2-methylpropyl)-4,11,14,17,20,26,29,32,35,39,42,45,48,51,54,60,63-heptadecaoxo-52-propan-2-yl-7,57,66-trithia-1,3,10,13,16,19,25,28,31,34,37,38,41,44,47,50,53,61-octadecazatetracyclo[38.22.5.13,61.021,25]octahexacontane-9-carboxamide	1997771: Binding affinity to human ACE2 assessed as binding constant by surface plasmon resonance analysis	kd	0.0001	uM
(9R,12S,15S,18S,21S,27S,30S,33S,36S,40R,43S,46S,49S,52S,55R)-N-[(2S)-1-amino-1-oxopropan-2-yl]-55-[[(2S)-2-aminopropanoyl]amino]-15-[(2S)-butan-2-yl]-18,49-bis(3-carbamimidamidopropyl)-43-[(4-chlorophenyl)methyl]-33,36,46-tris(hydroxymethyl)-12-(1H-imidazol-4-ylmethyl)-27,30-bis(2-methylpropyl)-4,11,14,17,20,26,29,32,35,39,42,45,48,51,54,60,63-heptadecaoxo-52-propan-2-yl-7,57,66-trithia-1,3,10,13,16,19,25,28,31,34,37,38,41,44,47,50,53,61-octadecazatetracyclo[38.22.5.13,61.021,25]octahexacontane-9-carboxamide	1997771: Binding affinity to human ACE2 assessed as binding constant by surface plasmon resonance analysis	kd	0.0001	uM
(2S)-2-[[[(2S)-1-[(2S)-2-acetamido-4-methylpentanoyl]pyrrolidin-2-yl]-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	331168: Inhibition of ACE2	ki	0.0001	uM
[1-(2-acetamido-4-methylpentanoyl)-2,3-dihydropyrrol-5-yl]-(2-carboxy-3-phenylpropyl)-dihydroxyphosphanium	1798086: Enzyme Inhibition Assay from Article 10.1021/jm701275z: “Development of Potent and Selective Phosphinic Peptide Inhibitors of Angiotensin-Converting Enzyme 2.”	ki	0.0001	uM
(2S)-2-[[(9R,12S,15S,18S,21S,27S,30S,33S,36S,39R,42S,45S,48S,51S,54R)-54-[[(2S)-2-aminopropanoyl]amino]-15-[(2S)-butan-2-yl]-18,48-bis(3-carbamimidamidopropyl)-33,36,45-tris(hydroxymethyl)-12,42-bis(1H-imidazol-4-ylmethyl)-27,30-bis(2-methylpropyl)-4,11,14,17,20,26,29,32,35,38,41,44,47,50,53,59,62-heptadecaoxo-51-propan-2-yl-7,56,65-trithia-1,3,10,13,16,19,25,28,31,34,37,40,43,46,49,52,60-heptadecazatetracyclo[37.22.5.13,60.021,25]heptahexacontane-9-carbonyl]amino]propanoic acid	1997771: Binding affinity to human ACE2 assessed as binding constant by surface plasmon resonance analysis	kd	0.0004	uM
2-[[[(2S)-1-[(2S)-2-acetamido-3-(1H-imidazol-5-yl)propanoyl]pyrrolidin-2-yl]-hydroxyphosphoryl]methyl]-3-(3-phenyl-1,2-oxazol-5-yl)propanoic acid	331168: Inhibition of ACE2	ki	0.0004	uM
(2S)-2-[[(1S)-1-carboxy-2-[3-[(3,5-dichlorophenyl)methyl]imidazol-4-yl]ethyl]amino]-4-methylpentanoic acid	1560682: Inhibition of ACE2 (unknown origin)	ic50	0.0004	uM
[1-[2-acetamido-3-(1H-imidazol-5-yl)propanoyl]-2,3-dihydropyrrol-5-yl]-[2-carboxy-3-(3-phenyl-1,2-oxazol-5-yl)propyl]-dihydroxyphosphanium	1798086: Enzyme Inhibition Assay from Article 10.1021/jm701275z: “Development of Potent and Selective Phosphinic Peptide Inhibitors of Angiotensin-Converting Enzyme 2.”	ki	0.0004	uM
2-[[1-carboxy-2-[3-[(3,5-dichlorophenyl)methyl]imidazol-4-yl]ethyl]amino]-4-methylpentanoic acid	1804127: No assay is provided from Article 10.1002/med.21724: “The recent outbreaks of human coronaviruses: A medicinal chemistry perspective.”	ic50	0.0004	uM
(2S)-2-[[(9R,12S,15S,18S,21S,27S,30S,33S,36S,39R,42S,45S,48S,51S,54R)-54-[[(2S)-2-acetamidopropanoyl]amino]-15-[(2S)-butan-2-yl]-18,48-bis(3-carbamimidamidopropyl)-33,36,45-tris(hydroxymethyl)-12,42-bis(1H-imidazol-4-ylmethyl)-27,30-bis(2-methylpropyl)-4,11,14,17,20,26,29,32,35,38,41,44,47,50,53,59,62-heptadecaoxo-51-propan-2-yl-7,56,65-trithia-1,3,10,13,16,19,25,28,31,34,37,40,43,46,49,52,60-heptadecazatetracyclo[37.22.5.13,60.021,25]heptahexacontane-9-carbonyl]amino]propanoic acid	1997771: Binding affinity to human ACE2 assessed as binding constant by surface plasmon resonance analysis	kd	0.0007	uM
(2S)-2-[[[(2S)-1-[(2S)-2-acetamido-3-(1H-imidazol-5-yl)propanoyl]pyrrolidin-2-yl]-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	331168: Inhibition of ACE2	ki	0.0007	uM
[1-[2-acetamido-3-(1H-imidazol-5-yl)propanoyl]-2,3-dihydropyrrol-5-yl]-(2-carboxy-3-phenylpropyl)-dihydroxyphosphanium	1798086: Enzyme Inhibition Assay from Article 10.1021/jm701275z: “Development of Potent and Selective Phosphinic Peptide Inhibitors of Angiotensin-Converting Enzyme 2.”	ki	0.0007	uM
(2S)-3-[4-[(3,4-difluorophenyl)methoxy]phenyl]-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]propanoic acid	314424: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0008	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-(2-phenoxyphenyl)propanoic acid	314424: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0009	uM
benzyl N-[5-[[3-[formyl(hydroxy)amino]-2-(2-methylpropyl)hexanoyl]amino]-6-oxo-6-(1,3-thiazol-2-ylamino)hexyl]carbamate	1804127: No assay is provided from Article 10.1002/med.21724: “The recent outbreaks of human coronaviruses: A medicinal chemistry perspective.”	ic50	0.0010	uM
(2S)-1-[(2R,5S)-5-benzamido-2-methyl-4-oxo-6-phenylhexanoyl]pyrrolidine-2-carboxylic acid	39752: Inhibition of guinea pig serum Angiotensin I converting enzyme	ic50	0.0010	uM
benzyl N-[(5S)-5-[[(2R,3S)-3-[formyl(hydroxy)amino]-2-(2-methylpropyl)hexanoyl]amino]-6-oxo-6-(1,3-thiazol-2-ylamino)hexyl]carbamate	1927252: Inhibition of human recombinant ACE2 at 50 uM using (7Mca-Y-V-A- D -A-P- K(Knp) as a flurogenic substrate measured after 10 mins by fluorescence based analysis	ic50	0.0010	uM
(9R,12S,15S,18S,21S,27S,30S,33S,36S,39R,42S,45S,48S,54R)-N-[(2S)-1-amino-1-oxopropan-2-yl]-45-(3-amino-3-oxopropyl)-54-[[(2S)-2-aminopropanoyl]amino]-42-benzyl-18,48-bis(3-carbamimidamidopropyl)-33-[(1R)-1-hydroxyethyl]-15,36-bis(1H-imidazol-4-ylmethyl)-12,30-bis(2-methylpropyl)-27-(2-methylsulfanylethyl)-4,11,14,17,20,26,29,32,35,38,41,44,47,50,53,59,62-heptadecaoxo-7,56,65-trithia-1,3,10,13,16,19,25,28,31,34,37,40,43,46,49,52,60-heptadecazatetracyclo[37.22.5.13,60.021,25]heptahexacontane-9-carboxamide	1997770: Binding affinity to human ACE2 assessed as inhibition constant by surface plasmon resonance analysis	ki	0.0012	uM
(9R,12S,15S,18S,21S,23S,27S,30S,33S,36S,40R,43S,46S,49S,52S,55R)-N-[(2S)-1-amino-1-oxopropan-2-yl]-55-[[(2S)-2-aminopropanoyl]amino]-15-[(2S)-butan-2-yl]-18,49-bis(3-carbamimidamidopropyl)-23-hydroxy-33,36,46-tris(hydroxymethyl)-12,43-bis(1H-imidazol-4-ylmethyl)-27,30-bis(2-methylpropyl)-4,11,14,17,20,26,29,32,35,39,42,45,48,51,54,60,63-heptadecaoxo-52-propan-2-yl-7,57,66-trithia-1,3,10,13,16,19,25,28,31,34,37,38,41,44,47,50,53,61-octadecazatetracyclo[38.22.5.13,61.021,25]octahexacontane-9-carboxamide	1997771: Binding affinity to human ACE2 assessed as binding constant by surface plasmon resonance analysis	kd	0.0013	uM
(2S)-3-(4-hydroxyphenyl)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]propanoic acid	314424: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0013	uM
2-[[[(2S)-1-[(2S)-2-acetamido-4-methylpentanoyl]pyrrolidin-2-yl]-hydroxyphosphoryl]methyl]-3-(3-phenyl-1,2-oxazol-5-yl)propanoic acid	331168: Inhibition of ACE2	ki	0.0013	uM
(2R)-2-[[(1S)-1-carboxy-2-[3-[(3,5-dichlorophenyl)methyl]imidazol-4-yl]ethyl]amino]-4-methylpentanoic acid	1916554: Inhibition of recombinant human ACE2 using 7-Mca-YVADAPK (Dnp) as substrate by fluorescence plate reader assay	ic50	0.0013	uM
[1-(2-acetamido-4-methylpentanoyl)-2,3-dihydropyrrol-5-yl]-[2-carboxy-3-(3-phenyl-1,2-oxazol-5-yl)propyl]-dihydroxyphosphanium	1798086: Enzyme Inhibition Assay from Article 10.1021/jm701275z: “Development of Potent and Selective Phosphinic Peptide Inhibitors of Angiotensin-Converting Enzyme 2.”	ki	0.0013	uM
(2S)-2-[[(1S)-1-carboxy-2-[3-[(3,5-dimethylphenyl)methyl]imidazol-4-yl]ethyl]amino]-4-methylpentanoic acid	1798089: Enzyme Inhibition Assay from Article 10.1021/ja0277226: “Substrate-based design of the first class of angiotensin-converting enzyme-related carboxypeptidase (ACE2) inhibitors.”	ic50	0.0014	uM
(2S)-3-(4-phenylphenyl)-2-[[(2S)-2-sulfanylbutanoyl]amino]propanoic acid	317218: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0014	uM
(2S)-2-[[(2S)-4-methyl-2-sulfanylpentanoyl]amino]-3-(4-phenylphenyl)propanoic acid	317218: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0014	uM
2-[(9R,12S,15S,18S,21S,27S,30S,33R,36S,40R,43S,46S,49S,52S,55R)-9-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-55-[[(2S)-2-aminopropanoyl]amino]-15-[(2S)-butan-2-yl]-18,49-bis(3-carbamimidamidopropyl)-36,46-bis(hydroxymethyl)-12,43-bis(1H-imidazol-4-ylmethyl)-21-methyl-27,30-bis(2-methylpropyl)-4,11,14,17,20,26,29,32,35,39,42,45,48,51,54,60,63-heptadecaoxo-52-propan-2-yl-7,57,66-trithia-1,3,10,13,16,19,25,28,31,34,37,38,41,44,47,50,53,61-octadecazatetracyclo[38.22.5.13,61.021,25]octahexacontan-33-yl]acetic acid	1997770: Binding affinity to human ACE2 assessed as inhibition constant by surface plasmon resonance analysis	ki	0.0015	uM
(2S)-2-[[(2S)-3-methyl-2-sulfanylbutanoyl]amino]-3-(4-phenylphenyl)propanoic acid	317218: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0015	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-(4-phenylphenyl)propanoic acid	314424: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0015	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-phenylpropanoic acid	314424: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0015	uM
(9R,12S,15S,18S,21S,27S,30S,33S,36S,39R,42S,45S,51S,54S,57R)-N-[(2S)-1-amino-1-oxopropan-2-yl]-57-[[(2S)-2-aminopropanoyl]amino]-18,51-bis(3-carbamimidamidopropyl)-12,54-bis[(1R)-1-hydroxyethyl]-33-(hydroxymethyl)-36-(1H-imidazol-4-ylmethyl)-42-(1H-indol-3-ylmethyl)-15-methyl-27,30-bis(2-methylpropyl)-4,11,14,17,20,26,29,32,35,38,41,44,50,53,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,19,25,28,31,34,37,40,43,49,52,55,63-heptadecazapentacyclo[37.25.5.13,63.021,25.045,49]heptacontane-9-carboxamide	1997771: Binding affinity to human ACE2 assessed as binding constant by surface plasmon resonance analysis	kd	0.0016	uM
(2S)-2-[[(2S,3S)-3-methyl-2-sulfanylpentanoyl]amino]-3-(4-phenylphenyl)propanoic acid	317218: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0016	uM
(9R,12S,15S,18S,21S,27S,30S,33S,36S,40R,43S,46S,49S,52S,55R)-55-amino-15-[(2S)-butan-2-yl]-18,49-bis(3-carbamimidamidopropyl)-33,36,46-tris(hydroxymethyl)-12,43-bis(1H-imidazol-4-ylmethyl)-27,30-bis(2-methylpropyl)-4,11,14,17,20,26,29,32,35,39,42,45,48,51,54,60,63-heptadecaoxo-52-propan-2-yl-7,57,66-trithia-1,3,10,13,16,19,25,28,31,34,37,38,41,44,47,50,53,61-octadecazatetracyclo[38.22.5.13,61.021,25]octahexacontane-9-carboxamide	1997771: Binding affinity to human ACE2 assessed as binding constant by surface plasmon resonance analysis	kd	0.0017	uM
(2S)-2-[[(2S)-2-cyclopentyl-2-sulfanylacetyl]amino]-3-(4-phenylphenyl)propanoic acid	317218: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0018	uM
(2S)-3-(4-phenylphenyl)-2-[[(2S)-2-sulfanylhexanoyl]amino]propanoic acid	317218: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0018	uM
(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylsulfanylbutanoic acid	1927259: Inhibition of SARS-CoV S binding to human recombinant ACE2 expressed in Escherichia coli BL21(DE3) incubated for 2 hrs by ELISA method	ic50	0.0019	uM
(9R,12S,15S,18S,21S,27S,30S,33S,36S,40R,43S,46S,49S,52S,55R)-N-[(2S)-1-amino-1-oxopropan-2-yl]-55-[[(2S)-2-aminopropanoyl]amino]-15-[(2S)-butan-2-yl]-18,49-bis(3-carbamimidamidopropyl)-30-(2,2-dimethylpropyl)-33,36,46-tris(hydroxymethyl)-12,43-bis(1H-imidazol-4-ylmethyl)-27-(2-methylpropyl)-4,11,14,17,20,26,29,32,35,39,42,45,48,51,54,60,63-heptadecaoxo-52-propan-2-yl-7,57,66-trithia-1,3,10,13,16,19,25,28,31,34,37,38,41,44,47,50,53,61-octadecazatetracyclo[38.22.5.13,61.021,25]octahexacontane-9-carboxamide	1997770: Binding affinity to human ACE2 assessed as inhibition constant by surface plasmon resonance analysis	ki	0.0020	uM
(2S)-3-[4-[(2,4-difluorophenyl)methoxy]phenyl]-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]propanoic acid	314424: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0020	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-naphthalen-1-ylpropanoic acid	314424: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0022	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-(3-phenylphenyl)propanoic acid	314424: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0022	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-(4-phenoxyphenyl)propanoic acid	314424: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0022	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-naphthalen-2-ylpropanoic acid	314424: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0024	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-(3-phenylmethoxyphenyl)propanoic acid	314424: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0024	uM
(2S)-2-[[(2S)-2-cyclobutyl-2-sulfanylacetyl]amino]-3-(4-phenylphenyl)propanoic acid	317218: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0024	uM
(9R,12S,15S,18S,21S,27S,30S,33S,36S,39R,42S,45R,48S,51S,54R)-N-[(2S)-1-amino-1-oxopropan-2-yl]-54-[[(2S)-2-aminopropanoyl]amino]-15-[(2S)-butan-2-yl]-51-tert-butyl-18,48-bis(3-carbamimidamidopropyl)-33,36,45-tris(hydroxymethyl)-12,42-bis(1H-imidazol-4-ylmethyl)-29-methylidene-27,30-bis(2-methylpropyl)-4,11,14,17,20,26,32,35,38,41,44,47,50,53,59,62-hexadecaoxo-7,56,65-trithia-1,3,10,13,16,19,25,28,31,34,37,40,43,46,49,52,60-heptadecazatetracyclo[37.22.5.13,60.021,25]heptahexacontane-9-carboxamide	1997771: Binding affinity to human ACE2 assessed as binding constant by surface plasmon resonance analysis	kd	0.0025	uM
(2S)-3-[4-[(4-fluorophenyl)methoxy]phenyl]-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]propanoic acid	314424: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0025	uM
(9R,12S,15S,18S,21S,27S,30S,33S,36S,40R,43S,46S,49S,52S,55R)-55-acetamido-15-[(2S)-butan-2-yl]-18,49-bis(3-carbamimidamidopropyl)-33,36,46-tris(hydroxymethyl)-12,43-bis(1H-imidazol-4-ylmethyl)-27,30-bis(2-methylpropyl)-4,11,14,17,20,26,29,32,35,39,42,45,48,51,54,60,63-heptadecaoxo-52-propan-2-yl-7,57,66-trithia-1,3,10,13,16,19,25,28,31,34,37,38,41,44,47,50,53,61-octadecazatetracyclo[38.22.5.13,61.021,25]octahexacontane-9-carboxamide	1997771: Binding affinity to human ACE2 assessed as binding constant by surface plasmon resonance analysis	kd	0.0027	uM
(2S)-2-[[(2S,3R)-3-methyl-2-sulfanylpentanoyl]amino]-3-(4-phenylmethoxyphenyl)propanoic acid	314424: Inhibition of human recombinant ACE2 by fluorescence assay	ki	0.0027	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
benazepril	affects response to substance, increases response to substance, affects cotreatment	3
Doxorubicin	decreases expression, increases expression	3
DX600 peptide	decreases activity	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Etoposide	increases expression, decreases expression	2
Hydroxyzine	increases activity, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	affects expression	2
resorcinolnaphthalein	affects activity	1
tannic acid	decreases expression	1
diminazene aceturate	decreases reaction, increases expression, increases phosphorylation, increases reaction, affects cotreatment (+1 more)	1
pirinixic acid	affects binding, decreases expression, increases activity	1
potassium perchlorate	decreases reaction, increases expression	1
Lugol’s solution	decreases reaction, increases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
nimesulide	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	increases expression	1
hydroquinone	decreases expression	1
pentanal	increases expression	1
imidapril	increases response to substance	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases expression, affects reaction	1
nicotianamine	decreases activity	1
CGP 52608	affects binding, increases reaction	1
2,7-dihydroxynaphthalene	decreases expression	1
angiotensin I (1-7)	increases abundance, increases cleavage	1
desloratadine	affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2-(1-carboxy-2-(3-(3,5-dichlorobenzyl)-3H-imidazol-4-yl)ethylamino)-4-methylpentanoic acid	decreases activity	1

ChEMBL screening assays

107 unique, capped per target: 98 binding, 6 functional, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL644716	Binding	Inhibition of Angiotensin I converting enzyme	Dual inhibition of angiotensin-converting enzyme and neutral endopeptidase by tricyclic benzazepinone thiols — *Bioorg Med Chem Lett*
CHEMBL647713	Functional	Time to inhibit maximum Angiotensin I converting enzyme in Hog plasma	Angiotensin converting enzyme inhibitors. 10. Aryl sulfonamide substituted N-[1-carboxy-3-phenylpropyl]-L-alanyl-L-proline derivatives as novel antihypertensives. — *J Med Chem*
CHEMBL4374949	ADMET	Inhibition of human C-terminal His/FLAG-tagged ACE-2 expressed in HEK293 cells at 50 uM preincubated for 10 mins followed by Mca-Ala-Pro-Lys(Dnp)-OH substrate addition by fluorescence assay relative to control	Structure-Based Development of (1-(3’-Mercaptopropanamido)methyl)boronic Acid Derived Broad-Spectrum, Dual-Action Inhibitors of Metallo- and Serine-β-lactamases. — *J Med Chem*

Cellosaurus cell lines

40 cell lines: 18 cancer cell line, 14 transformed cell line, 6 spontaneously immortalized cell line, 1 induced pluripotent stem cell, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5KA	A549-hACE2 [Invivogen]	Cancer cell line	Male
CVCL_A5KB	A549-hACE2-TMPRSS2	Cancer cell line	Male
CVCL_A5TE	sciCHO:hACE2	Spontaneously immortalized cell line	Female
CVCL_A5TF	sciCHO:hACE2:hTMPRSS2	Spontaneously immortalized cell line	Female
CVCL_A7UK	HEK-293T-hACE2	Transformed cell line	Female
CVCL_A7UV	A549-hACE2 [BEI resources]	Cancer cell line	Male
CVCL_A7UW	A549-hACE2 (HA-FLAG)	Cancer cell line	Male
CVCL_A7YK	HEK-Blue hACE2	Transformed cell line	Female
CVCL_A7ZQ	A549-Dual hACE2-TMPRSS2	Cancer cell line	Male
CVCL_A7ZR	A549-Dual KO-MDA5 hACE2-TMPRSS2	Cancer cell line	Male

Clinical trials (associated diseases)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT06519786	Phase 3	UNKNOWN	Safety and Efficacy of Metformin for Treatment of Cytopenia in Children and Adolescents With Fanconi Anemia
NCT06719141	Phase 3	ACTIVE_NOT_RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	Phase 3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT07723976	Phase 3	NOT_YET_RECRUITING	A Study to Evaluate the Safety and Efficacy of CBD-OS in Participants With DEE
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00000603	Phase 2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00001749	Phase 2	COMPLETED	Medical Treatment for Diamond Blackfan Anemia
NCT00004787	Phase 2	COMPLETED	Phase II Pilot Study of Granulocyte Colony-Stimulating Factor for Inherited Bone Marrow Failure Syndromes
NCT00053989	Phase 2	COMPLETED	NMA Allogeneic Hematopoietic Cell Transplant in Hematologic Cancer/Disorders
NCT00084695	Phase 2	UNKNOWN	Umbilical Cord Blood for Stem Cell Transplantation in Treating Young Patients With Malignant or Nonmalignant Diseases
NCT00258427	Phase 2	COMPLETED	Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia
NCT00453388	Phase 2	COMPLETED	Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia
NCT01071239	Phase 2	COMPLETED	Hematopoietic Stem Cell Transplant for Fanconi Anemia
NCT02143830	Phase 2	RECRUITING	HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy
NCT02931071	Phase 2	COMPLETED	Clinical Phase II Trial to Evaluate CD34+ Cells Mobilization and Collection in Patients With Fanconi Anemia for Subsequent Transduction With a Lentiviral Vector Carring FANCA Gene. FANCOSTEM-1
NCT03206086	Phase 2	ACTIVE_NOT_RECRUITING	Eltrombopag for Fanconi Anemia
NCT03398824	Phase 2	COMPLETED	Pilot Study of Metformin for Patients With Fanconi Anemia
NCT03476330	Phase 2	COMPLETED	Quercetin Chemoprevention for Squamous Cell Carcinoma in Patients With Fanconi Anemia
NCT03579875	Phase 2	RECRUITING	Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
NCT03600909	Phase 2	TERMINATED	A Study of the Effect of Blood Stem Cell Transplant After Chemotherapy Alone in Patients With Fanconi Anemia
NCT04232085	Phase 2	RECRUITING	Regenerative Medicine to Restore Hematopoiesis and Immune Function in Immunodeficiencies and Inherited Bone Marrow Failures
NCT06045052	Phase 2	COMPLETED	Eltrombopag for Treatment of Fanconi Anemia
NCT05626634	Phase 2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00001399	Phase 1	COMPLETED	Gene Therapy for the Treatment of Fanconi’s Anemia Type C
NCT00005896	Phase 1	UNKNOWN	Phase I Pilot Study of CD34 Enriched, Fanconi’s Anemia Complementation Group C Gene Transduced Autologous Peripheral Blood Stem Cell Transplantation in Patients With Fanconi’s Anemia
NCT00006127	Phase 1	UNKNOWN	Phase I Study of Amifostine in Patients With Bone Marrow Failure Related to Fanconi’s Anemia
NCT00093743	Phase 1	COMPLETED	Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed by Unrelated Donor Stem Cell Transplant in Treating Patients With Fanconi Anemia
NCT00243399	Phase 1	COMPLETED	Oxandrolone for the Treatment of Bone Marrow Aplasia in Fanconi Anemia
NCT00272857	Phase 1	COMPLETED	Bone Marrow Cell Gene Transfer in Individuals With Fanconi Anemia
NCT00317876	Phase 1	COMPLETED	Cyclophosphamide in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant for Fanconi’s Anemia
NCT00586274	Phase 1	TERMINATED	Use of Rft5-Dga to Deplete Alloreactive Cells for Pts With Fanconi Anemia After Haploidentical SCT
NCT01331018	Phase 1	TERMINATED	Gene Therapy for Fanconi Anemia
NCT01720147	Phase 1	COMPLETED	Quercetin in Children With Fanconi Anemia; a Pilot Study
NCT01917708	Phase 1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT06700811	Phase 1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT00352976	Phase 2/3	COMPLETED	TBI Dose De-escalation for Fanconi Anemia
NCT01019876	Phase 2/3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT00005898	Phase 1/2	COMPLETED	Phase I/II Study of Total Body Irradiation, Cyclophosphamide, and Fludarabine Followed by Alternate Donor Hematopoietic Cell Transplantation in Patients With Fanconi’s Anemia
NCT00167206	Phase 1/2	TERMINATED	Stem Cell Transplantation for Fanconi Anemia
NCT00305708	Phase 1/2	COMPLETED	Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission
NCT00479115	Phase 1/2	COMPLETED	Mobilization and Collection of Peripheral Blood Stem Cells in Patients With Fanconi Anemia Using G-CSF and AMD3100
NCT00590460	Phase 1/2	TERMINATED	Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Fanconi Anemia
NCT00630253	Phase 1/2	COMPLETED	Cytoxan, Fludara, and Antithymocyte Globulin Conditioning Followed By Stem Cell Transplant in Treating Fanconi Anemia
NCT01001598	Phase 1/2	TERMINATED	Safety and Efficacy Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita
NCT02065869	Phase 1/2	TERMINATED	Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant
NCT02678533	Phase 1/2	COMPLETED	Mobilization and Collection of Peripheral Blood Stem Cells in Patients With Fanconi Anemia Using G-CSF and Plerixafor
NCT03157804	Phase 1/2	COMPLETED	Lentiviral-mediated Gene Therapy of Fanconi Anemia Patients Subtype A
NCT03733249	Phase 1/2	TERMINATED	Long Term Follow-up Study for Patients Enrolled on the BP-004 Clinical Study
NCT04522375	Phase 1/2	WITHDRAWN	A Dose Escalation Study of FP-045 in Patients With Fanconi Anemia

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ACE2 across ~30M SureChEMBL compounds — explore on Sugi Predict.