ARG2

Summary

ARG2 (arginase 2, HGNC:664) is a protein-coding gene on chromosome 14q24.1, encoding Arginase-2, mitochondrial (P78540). May play a role in the regulation of extra-urea cycle arginine metabolism and also in down-regulation of nitric oxide synthesis.

Arginase catalyzes the hydrolysis of arginine to ornithine and urea. At least two isoforms of mammalian arginase exists (types I and II) which differ in their tissue distribution, subcellular localization, immunologic crossreactivity and physiologic function. The type II isoform encoded by this gene, is located in the mitochondria and expressed in extra-hepatic tissues, especially kidney. The physiologic role of this isoform is poorly understood; it is thought to play a role in nitric oxide and polyamine metabolism. Transcript variants of the type II gene resulting from the use of alternative polyadenylation sites have been described.

Source: NCBI Gene 384 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 73 total
• Phenotypes (HPO): 3
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001172

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:664
Approved symbol	ARG2
Name	arginase 2
Location	14q24.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000081181
Ensembl biotype	protein_coding
OMIM	107830
Entrez	384

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000261783, ENST00000556491, ENST00000557120, ENST00000557319, ENST00000927904

RefSeq mRNA: 1 — MANE Select: NM_001172 NM_001172

CCDS: CCDS9785

Canonical transcript exons

ENST00000261783 — 8 exons

Exon	Start	End
ENSE00000658652	67646644	67646738
ENSE00001168242	67650715	67651708
ENSE00001168252	67619920	67620088
ENSE00003501949	67620894	67620966
ENSE00003507352	67642186	67642363
ENSE00003508251	67646921	67647025
ENSE00003516515	67648047	67648183
ENSE00003667781	67645643	67645802

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 96.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.8396 / max 445.3931, expressed in 1507 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140238	11.5756	1440
140237	1.0510	663
140240	0.6774	301
140239	0.5124	231
140241	0.0202	4
140242	0.0030	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	96.77	gold quality
oocyte	CL:0000023	96.08	gold quality
cortical plate	UBERON:0005343	95.29	gold quality
renal medulla	UBERON:0000362	94.92	gold quality
metanephros cortex	UBERON:0010533	94.16	gold quality
adult mammalian kidney	UBERON:0000082	93.94	gold quality
secondary oocyte	CL:0000655	93.70	gold quality
islet of Langerhans	UBERON:0000006	93.41	gold quality
pituitary gland	UBERON:0000007	93.11	gold quality
type B pancreatic cell	CL:0000169	92.72	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.61	gold quality
adenohypophysis	UBERON:0002196	92.45	gold quality
prostate gland	UBERON:0002367	92.17	gold quality
nephron tubule	UBERON:0001231	92.10	gold quality
left lobe of thyroid gland	UBERON:0001120	91.83	gold quality
kidney	UBERON:0002113	91.29	gold quality
thyroid gland	UBERON:0002046	90.77	gold quality
right lobe of thyroid gland	UBERON:0001119	90.38	gold quality
lower esophagus mucosa	UBERON:0035834	89.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.42	gold quality
cortex of kidney	UBERON:0001225	88.18	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.03	gold quality
kidney epithelium	UBERON:0004819	87.87	gold quality
jejunal mucosa	UBERON:0000399	87.82	gold quality
medial globus pallidus	UBERON:0002477	87.31	gold quality
adrenal tissue	UBERON:0018303	87.19	gold quality
cerebellar hemisphere	UBERON:0002245	86.75	gold quality
cerebellar cortex	UBERON:0002129	86.71	gold quality
ganglionic eminence	UBERON:0004023	86.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	22.58
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

88 targeting ARG2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548AW	99.99	72.57	3559
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832

Literature-anchored findings (GeneRIF, showing 40)

• Plays a physiological role in male and female sexual arousal (PMID:12859189)
• Increased arginase II expression and activity in pulmonary arterial hypertension. (PMID:15364894)
• ArgII gene is an early IRF-3-regulated gene, which participates in the interferon-independent antiviral response through polyamine production and induction of apoptosis. (PMID:15955070)
• The Asn149–>Asp mutation is proposed to generate a conformational change responsible for the altered substrate specificity of arginase II. (PMID:16128822)
• Increasing L-Arg for NO synthesis by either arginase inhibition or direct L-Arg supplementation restores the age-related deficit in reflex cutaneous vasodilatation. (PMID:16675494)
• observed in both cytotrophoblasts and syncytiotrophoblasts (PMID:16720041)
• Increased arginase II expression & activity suggest a potential pathogenic role for platelet arginase and altered arginine and polyamine metabolism in sickle cell disease. (PMID:17353439)
• arginase II expression may play a role in prostate cancer progression (PMID:18202758)
• Cocoa flavonols lower ARG2 activity in endothelial cells in vitro and erythrocytes in vov. (PMID:18348861)
• ARG2 is expressed in lung cancer, but it does not induce tumor immune escape and does not affect disease progression, most probably due to the lack of concomitant NOS expression. (PMID:18528866)
• ARG1 and ARG2 loci are associated with childhood asthma. The association between ARG1 variation and asthma might depend on atopy and ambient ozone levels. (PMID:19281908)
• siRNA silencing of arginase-II but did not inhibit the up-regulation of endothelial VCAM-1, ICAM-1 and E-selectin by TNFalpha (PMID:19284655)
• [Review] Arginase is constitutively expressed in endothelial cells, but expression of the specific isoforms differs among mammalian species. Although some arginase I has been detected in human endothelial cells, the predominant isoform is arginase II. (PMID:19508396)
• Arginase AI activity and its mRNA level were significantly decreased in cirrhotic liver, whereas the activity and expression of arginase AII were concurrently raised, as compared to normal liver. (PMID:19636440)
• Increased arginase expression in preeclampsia can induce uncoupling of NOS as a source of superoxide in the maternal vasculature in preeclampsia. (PMID:19684035)
• These data support our hypothesis that hypoxia increases proliferation of human pulmonary artery smooth muscle cells through the induction of arginase II. (PMID:19801451)
• There was an overexpression of arginase II in anorexia nervosa patients. (PMID:20071203)
• Arginase contributes significantly to L-proline supply for collagen synthesis in rat fibroblasts, in which arginase I is the predominant isoenzyme, but not in human fibroblasts, in which arginase II is the only isoenzyme expressed (PMID:20107769)
• Association of ARG2 gene polymorphism is present in adult asthma, has lower reversibility specific with beta2 agonists. It is also associated with asthma severity, severe airway hyperresponsiveness, and less long-term response to inhaled corticosteroids. (PMID:20124949)
• gene silencing changed promotes apoptosis and reduced expression of cell proliferation markers in thyroid cancer cells (PMID:20542107)
• androgen-regulated immunosuppressive pathway in human PCa through the expression of ARG1, ARG2 and IL-8 (PMID:20711410)
• The alteration of arginase activity between colostrum and mature milk may be a consequence of the transfer of arginase from the blood of the breast mother mammary glands into the colostrum and mature milk (PMID:20853600)
• In human lung microvascular endothelial cells, hypoxia upregulates arginase activity as well as mRNA and protein levels of arginase II. Inhibition of arginase II by small interfering RNA or by the inhibitor BEC enhanced NO levels. (PMID:20861464)
• Sequence variations in the NOS2A and ARG2 loci were globally associated with exhaled nitric oxide (PMID:21039601)
• Delineate a clearer path from OxLDL through the endothelial cell LOX-1 receptor, RhoA, and ROCK, to the activation of arginase II, downregulation of NO, and vascular dysfunction in atherosclerosis. (PMID:21130456)
• This study demomistrated that H3K4me3 modification plays an important role in up regulation of ARG2 in prefrontal cortex. (PMID:22008221)
• DDIT3, STT3A, ARG2 and FAM129A immunohistochemistry does not appear to be useful in the diagnosis of thyroid follicular neoplasias, as they do not reliably distinguish follicular thyroid carcinoma from follicular thyroid adenoma. (PMID:22157935)
• has a vascular role in placental vessels counteracting the NOS-dependent relaxation (PMID:22391327)
• The inhibition of arginase II protein was found to be mediated by exchange protein directly activated by cAMP. (PMID:22447968)
• Data suggest that exposure to particulate matter (i.e., air pollutants) upregulates arginase II (but not arginase I) activity and expression in bronchial epithelial cells, in part, via epidermal growth factor-dependent signaling. (PMID:22712848)
• arginase-II (ARG2) was expressed by 60 percent of head and neck squamous cell carcinomas; the absence of ARG2 expression was significantly associated with prolonged overall survival (PMID:22815199)
• Endothelial eNOS/arginase imbalance contributes to vascular dysfunction in IUGR umbilical and placental vessels. (PMID:23122700)
• Gene expression studies have identified altered expression of arginase 2 in suicide completers with a history of mood disorders. (PMID:23260169)
• presence of ARG2-expressing CAFs is an indicator of poor prognosis, as well as hypoxia, in pancreatic ductal carcinoma (PMID:23424623)
• Enzymes that are directly involved in the formation of urea are expressed in ocular tissues. (PMID:23740519)
• Arg-II promotes mitochondrial dysfunction leading to VSMC senescence/apoptosis through complex positive crosstalk among S6K1-JNK, ERK, p66Shc, and p53, contributing to atherosclerotic vulnerability phenotype. (PMID:23832324)
• Maternal hypercholesterolemia in pregnancy alters umbilical vein reactivity because of fetal endothelial dysfunction associated with arginase and eNOS signaling imbalance. (PMID:23950140)
• Data indicate that arginase II (Arg II) expressions were higher in breast tumor tissues compared to the matched normal. (PMID:24223914)
• We speculate that cytomegalovirus may contribute to endothelial dysfunction via ARG II induction and reduced eNOS production. (PMID:24442486)
• HDAC2 is a critical regulator of Arg2 expression and thereby endothelial nitric oxide and endothelial function. (PMID:24833798)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	arg2	ENSDARG00000039269
mus_musculus	Arg2	ENSMUSG00000021125
rattus_norvegicus	Arg2	ENSRNOG00000053811
drosophila_melanogaster	arg	FBGN0023535

Paralogs (2): AGMAT (ENSG00000116771), ARG1 (ENSG00000118520)

Protein

Protein identifiers

Arginase-2, mitochondrial — P78540 (reviewed: P78540)

Alternative names: Arginase II, Kidney-type arginase, Non-hepatic arginase, Type II arginase

All UniProt accessions (1): P78540

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in the regulation of extra-urea cycle arginine metabolism and also in down-regulation of nitric oxide synthesis. Extrahepatic arginase functions to regulate L-arginine bioavailability to nitric oxid synthase (NOS). Arginine metabolism is a critical regulator of innate and adaptive immune responses. Seems to be involved in negative regulation of the survival capacity of activated CD4(+) and CD8(+) T cells. May suppress inflammation-related signaling in asthmatic airway epithelium. May contribute to the immune evasion of H.pylori by restricting M1 macrophage activation and polyamine metabolism. In fetal dendritic cells may play a role in promoting immune suppression and T cell TNF production during gestation. Regulates RPS6KB1 signaling, which promotes endothelial cell senescence and inflammation and implicates NOS3/eNOS dysfunction. Can inhibit endothelial autophagy independently of its enzymatic activity implicating mTORC2 signaling. Involved in vascular smooth muscle cell senescence and apoptosis independently of its enzymatic activity. Since NOS is found in the penile corpus cavernosum smooth muscle, the clitoral corpus cavernosum and the vagina, arginase-2 plays a role in both male and female sexual arousal.

Subunit / interactions. Homotrimer.

Subcellular location. Mitochondrion.

Tissue specificity. Expressed most strongly in kidney and prostate, much less strongly in the brain, skeletal muscle, placenta, lung, mammary gland, macrophage, uterus, testis and gut, but apparently not in the liver, heart and pancreas. Expressed in activated T cells.

Cofactor. Binds 2 manganese ions per subunit.

Pathway. Nitrogen metabolism; urea cycle; L-ornithine and urea from L-arginine: step 1/1.

Similarity. Belongs to the arginase family.

RefSeq proteins (1): NP_001163* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006035	Ureohydrolase	Family
IPR014033	Arginase	Family
IPR020855	Ureohydrolase_Mn_BS	Binding_site
IPR023696	Ureohydrolase_dom_sf	Homologous_superfamily

Pfam: PF00491

Enzyme classification (BRENDA):

• EC 3.5.3.1 — arginase (BRENDA: 62 organisms, 63 substrates, 320 inhibitors, 146 Km, 104 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-ARGININE	0.02–171.9	120
L-ARG	0.69–130	14
L-PHENYLALANINE	22.1–57.5	3
1-NITRO-3-GUANIDINOBENZENE	1.6	1
4-GUANIDINO-2-NITROPHENYLACETIC ACID	0.01	1
4-GUANIDINO-3-NITROBENZOIC ACID	0.007	1
AGMATINE	2.5	1
L-CANAVANINE	22.2	1
L-THIOARGININE	0.5	1
S-(4-AMINOBUTYL)ISOTHIOUREA	4	1
THIOGUANIDINO-VALERIC ACID	2.1	1

Catalyzed reactions (Rhea), 1 shown:

• L-arginine + H2O = urea + L-ornithine (RHEA:20569)

UniProt features (48 total): helix 17, binding site 13, strand 11, turn 3, transit peptide 1, chain 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
4HZE	X-RAY DIFFRACTION	1.6
8RG6	X-RAY DIFFRACTION	1.62
8RFA	X-RAY DIFFRACTION	1.76
4I06	X-RAY DIFFRACTION	1.8
8RGF	X-RAY DIFFRACTION	1.86
4IXU	X-RAY DIFFRACTION	1.9
8RGU	X-RAY DIFFRACTION	1.9
8RIM	X-RAY DIFFRACTION	1.9
9FRV	X-RAY DIFFRACTION	2.06
4IE2	X-RAY DIFFRACTION	2.21
6Q37	X-RAY DIFFRACTION	2.21
6Q39	X-RAY DIFFRACTION	2.21
4IXV	X-RAY DIFFRACTION	2.3
4IE3	X-RAY DIFFRACTION	2.35
6SS2	X-RAY DIFFRACTION	2.4
1PQ3	X-RAY DIFFRACTION	2.7
6SS4	X-RAY DIFFRACTION	2.9
6SS6	X-RAY DIFFRACTION	3.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78540-F1	92.55	0.86

Antibody-complex structures (SAbDab): 3 — 6SS2, 6SS4, 6SS6

Functional residue map

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

Ligand- & substrate-binding residues (13): 202; 251; 251; 253; 265; 296; 120; 143; 143; 145–149; 145; 147 …

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-70635	Urea cycle
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-1430728	Metabolism
R-HSA-392499	Metabolism of proteins
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 308 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_EPITHELIUM_DEVELOPMENT, WANG_CLIM2_TARGETS_UP, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, PEREZ_TP63_TARGETS, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOZGIT_ESR1_TARGETS_DN, GOBP_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_KIDNEY_EPITHELIUM_DEVELOPMENT, GOBP_CELLULAR_SENESCENCE

GO Biological Process (22): urea cycle (GO:0000050), ureteric bud development (GO:0001657), adaptive immune response (GO:0002250), negative regulation of type 2 immune response (GO:0002829), arginine metabolic process (GO:0006525), nitric oxide biosynthetic process (GO:0006809), striated muscle contraction (GO:0006941), regulation of interleukin-1 beta production (GO:0032651), negative regulation of interleukin-13 production (GO:0032696), negative regulation of interleukin-17 production (GO:0032700), negative regulation of tumor necrosis factor production (GO:0032720), innate immune response (GO:0045087), negative regulation of macrophage inflammatory protein 1 alpha production (GO:0071641), negative regulation of chemokine (C-C motif) ligand 4 production (GO:0071644), negative regulation of chemokine (C-C motif) ligand 5 production (GO:0071650), negative regulation of defense response to bacterium (GO:1900425), regulation of reactive oxygen species biosynthetic process (GO:1903426), negative regulation of activated CD8-positive, alpha-beta T cell apoptotic process (GO:1905403), negative regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000562), positive regulation of cellular senescence (GO:2000774), immune system process (GO:0002376), negative regulation of multicellular organismal process (GO:0051241)

GO Molecular Function (6): arginase activity (GO:0004053), manganese ion binding (GO:0030145), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines (GO:0016813), metal ion binding (GO:0046872)

GO Cellular Component (3): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Metabolism of proteins	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of chemokine production	3
biosynthetic process	2
immune response	2
negative regulation of cytokine production	2
urea metabolic process	1
mesonephric tubule development	1
regulation of type 2 immune response	1
type 2 immune response	1
negative regulation of immune response	1
amino acid metabolic process	1
carboxylic acid metabolic process	1
nitric oxide metabolic process	1
muscle contraction	1
interleukin-1 beta production	1
regulation of interleukin-1 production	1
interleukin-13 production	1
regulation of interleukin-13 production	1
interleukin-17 production	1
regulation of interleukin-17 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
defense response to symbiont	1
macrophage inflammatory protein-1 alpha production	1
regulation of macrophage inflammatory protein 1 alpha production	1
chemokine (C-C motif) ligand 4 production	1
regulation of chemokine (C-C motif) ligand 4 production	1
chemokine (C-C motif) ligand 5 production	1
regulation of chemokine (C-C motif) ligand 5 production	1
negative regulation of response to biotic stimulus	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
defense response to bacterium	1
regulation of defense response to bacterium	1
regulation of biosynthetic process	1
reactive oxygen species biosynthetic process	1
regulation of reactive oxygen species metabolic process	1
negative regulation of T cell apoptotic process	1
activated CD8-positive, alpha-beta T cell apoptotic process	1
regulation of activated CD8-positive, alpha-beta T cell apoptotic process	1

Protein interactions and networks

STRING

3718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARG2	OAT	P04181	876
ARG2	ASS1	P00966	874
ARG2	SLC7A2	P52569	825
ARG2	IL10	P22301	807
ARG2	ASL	P04424	797
ARG2	OTC	P00480	794
ARG2	ODC1	P11926	778
ARG2	H3C1	P02295	747
ARG2	H3-7	Q5TEC6	746
ARG2	H3-5	Q6NXT2	745
ARG2	H3C14	Q71DI3	743
ARG2	H3-4	Q16695	742
ARG2	H3-3A	P06351	738
ARG2	AZIN2	Q96A70	735
ARG2	SRM	P19623	709

IntAct

18 interactions, top by confidence:

A	B	Type	Score
ARG2	FOXD4L6	psi-mi:“MI:0915”(physical association)	0.560
PPP1R3C	STBD1	psi-mi:“MI:0914”(association)	0.530
ARG2	BAG5	psi-mi:“MI:0915”(physical association)	0.400
ARG1	ARG2	psi-mi:“MI:0915”(physical association)	0.400
DDX59	ARG2	psi-mi:“MI:0915”(physical association)	0.400
NT5E	ARG2	psi-mi:“MI:0915”(physical association)	0.400
ARG2	STK11	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
MATN4	MATN1	psi-mi:“MI:0914”(association)	0.350
MATN4	HSPA5	psi-mi:“MI:0914”(association)	0.350
DHX34	ARG2	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
	VWA8	psi-mi:“MI:2364”(proximity)	0.270
CLIC6	ARG2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): CPT2 (Affinity Capture-MS), ARG2 (Two-hybrid), ARG2 (Affinity Capture-MS), ARG2 (Affinity Capture-MS), BAG5 (Affinity Capture-MS), ARG2 (Affinity Capture-MS), ARG2 (Affinity Capture-MS), ARG2 (Proximity Label-MS), ARG2 (Proximity Label-MS), ARG2 (Affinity Capture-RNA), ARG2 (Proximity Label-MS), ARG2 (Affinity Capture-MS), ARG2 (Affinity Capture-MS), ARG2 (Affinity Capture-MS), ARG2 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R2JFW7, A9RBS1, B0X4N8, B8AU84, O08691, O08701, O42887, O59736, P00812, P05089, P07824, P0A2X9, P0A2Y0, P0A2Y1, P14012, P30759, P33280, P37818, P40906, P46637, P49079, P49900, P54889, P72703, P78540, Q10066, Q10088, Q12166, Q12611, Q1E180, Q2KJ64, Q4VK78, Q58DL1, Q61176, Q6CIB4, Q6CLS8, Q74ZW4, Q7X7N2, Q90XD2, Q91553

Diamond homologs: A0A2R2JFW7, A0A509AF89, C4LSS0, O08691, O08701, P00812, P05089, P07824, P0A2X9, P0A2Y0, P0A2Y1, P14012, P30759, P33280, P37818, P39138, P40906, P49900, P53608, P60086, P60087, P60088, P78540, Q10066, Q12611, Q1E180, Q2KJ64, Q4VK78, Q58DL1, Q61176, Q6CIB4, Q6CLS8, Q6G7E9, Q6GER3, Q74ZW4, Q7M0Z3, Q8I384, Q8NVE3, Q91553, Q91554

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
AR	“up-regulates quantity by expression”	ARG2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1323 predictions. Top by Δscore:

Variant	Effect	Δscore
14:67642183:CA:C	acceptor_loss	1.0000
14:67642184:A:AG	acceptor_gain	1.0000
14:67642184:A:AT	acceptor_loss	1.0000
14:67642184:AG:A	acceptor_gain	1.0000
14:67642184:AGGCT:A	acceptor_gain	1.0000
14:67642185:G:GT	acceptor_gain	1.0000
14:67642185:GG:G	acceptor_gain	1.0000
14:67642185:GGC:G	acceptor_gain	1.0000
14:67642185:GGCT:G	acceptor_gain	1.0000
14:67642185:GGCTG:G	acceptor_gain	1.0000
14:67642362:AGG:A	donor_loss	1.0000
14:67642363:GGTA:G	donor_loss	1.0000
14:67642364:G:GG	donor_gain	1.0000
14:67645641:A:AG	acceptor_gain	1.0000
14:67645642:G:GG	acceptor_gain	1.0000
14:67645642:GCCT:G	acceptor_gain	1.0000
14:67646640:A:AG	acceptor_gain	1.0000
14:67646641:TAGGT:T	acceptor_loss	1.0000
14:67646642:A:AG	acceptor_gain	1.0000
14:67646643:G:GC	acceptor_loss	1.0000
14:67646643:G:GG	acceptor_gain	1.0000
14:67646734:GAACA:G	donor_gain	1.0000
14:67646735:AACA:A	donor_gain	1.0000
14:67646736:ACA:A	donor_gain	1.0000
14:67646736:ACAGT:A	donor_loss	1.0000
14:67646737:CA:C	donor_gain	1.0000
14:67646737:CAGT:C	donor_loss	1.0000
14:67646738:AGT:A	donor_loss	1.0000
14:67646739:G:GG	donor_gain	1.0000
14:67646739:GTAA:G	donor_loss	1.0000

AlphaMissense

2283 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:67648069:A:C	S249R	0.998
14:67648071:T:A	S249R	0.998
14:67648071:T:G	S249R	0.998
14:67645701:T:A	W141R	0.997
14:67645701:T:C	W141R	0.997
14:67645720:A:T	D147V	0.997
14:67642362:A:C	S121R	0.996
14:67645643:C:A	S121R	0.996
14:67645643:C:G	S121R	0.996
14:67648076:A:T	D251V	0.996
14:67648083:T:A	D253E	0.996
14:67648083:T:G	D253E	0.996
14:67645708:A:T	D143V	0.995
14:67646718:A:C	R199S	0.995
14:67646718:A:T	R199S	0.995
14:67648077:T:A	D251E	0.995
14:67648077:T:G	D251E	0.995
14:67648082:A:T	D253V	0.995
14:67650742:A:T	E296V	0.995
14:67642356:G:C	D119H	0.994
14:67642357:A:T	D119V	0.994
14:67645654:G:A	G125D	0.994
14:67645721:C:A	D147E	0.994
14:67645721:C:G	D147E	0.994
14:67646717:G:C	R199T	0.994
14:67648063:C:G	H247D	0.994
14:67648150:G:C	G276R	0.994
14:67645666:G:A	G129D	0.993
14:67645696:T:A	V139D	0.993
14:67645705:T:A	V142D	0.993

dbSNP variants (sampled 300 via entrez): RS1000084856 (14:67634349 T>C), RS1000100341 (14:67624424 T>C), RS1000189711 (14:67639181 T>C,G), RS1000220904 (14:67638962 C>T), RS1000280745 (14:67618287 C>T), RS1000451393 (14:67632770 T>G), RS1000461378 (14:67631509 C>T), RS1000719272 (14:67618619 G>A), RS1000863820 (14:67645258 C>T), RS1000971957 (14:67651124 T>C), RS1001021747 (14:67619879 C>A), RS1001043321 (14:67643953 C>T), RS1001169827 (14:67644209 C>T), RS1001433549 (14:67643798 C>T), RS1001568146 (14:67644732 C>T)

Disease associations

OMIM: gene MIM:107830 | disease phenotypes:

GenCC curated gene-disease

Mondo (3): ptosis (MONDO:0000728), blepharophimosis (MONDO:0001008), hemangioma (MONDO:0006500)

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000508	Ptosis
HP:0000581	Blepharophimosis
HP:0001028	Hemangioma

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D016569	Blepharophimosis	C11.250.090; C11.338.190; C16.131.384.190
D001763	Blepharoptosis	C11.338.204
D006391	Hemangioma	C04.557.645.375

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795148 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 965 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL4218271	NUMIDARGISTAT	2	927
CHEMBL1234777	NOR-NOHA	1	38

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3742879	ARG2, VTI1B		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Arginase

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

Ligand	Action	Affinity	Parameter
2(S)-amino-6-boronohexanoic acid	Inhibition	8.07	pKi
compound 9 [PMID: 23472952]	Inhibition	6.29	pIC50

Binding affinities (BindingDB)

31 measured of 65 human assays (65 total across all organisms); most potent 31 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(1S,2S)-1-amino-2-(3-boronopropyl)cyclopentanecarboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-4-amino-3-(3-boronopropyl)piperidine-4-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3S,4S)-4-amino-3-(3-boronopropyl)piperidine-4-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)-1-isobutylpyrrolidine-3- carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-1-benzyl-4-(3-boronopropyl)pyrrolidine-3- carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)-1-(pyridin-3- ylmethyl)pyrrolidine-3-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)-1-(piperidin)-4- ylmethyl)pyrrolidine-3-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)-1-(quinolin-4- ylmethyl)pyrrolidine-3-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)-1-(3-(4- chlorophenyl)propyl)pyrrolidine-3-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)-1-(7H-purin-6-yl)pyrrolidine- 3-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
5-((3R,4S)-3-amino-4-(3-boronopropyl)-3-carboxypyrrolidin-1- yl)nicotinic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)-1-(piperidin-4-yl)pyrrolidine- 3-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)-1-(4- carboxycyclohexyl)pyrrolidine-3-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-4-(3-boronopropyl)-3-(methylamino)pyrrolidine-3- carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)-1-(4- chlorophenylcarbamoyl)pyrrolidine-3-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)-1-(2-(4- chlorophenyl)acetyl)pyrrolidine-3-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)-1-(4- fluorobenzoyl)pyrrolidine-3-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)-1-(4- methoxybenzoyl)pyrrolidine-3-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)-1-(4- fluorophenylcarbamoyl)pyrrolidine-3-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-1-(2-aminophenylsulfonyl)-4-(3- boronopropyl)pyrrolidine-3-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-1-(2-amino-3-(4- (trifluoromethyl)phenyl)propanoyl)-4-(3-boronopropyl)pyrrolidine- 3-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-1-(2-(benzylamino)acetyl)-4-(3- boronopropyl)pyrrolidine-3-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(1S,2S,4S)-1,4-diamino-2-(3-boronopropyl)cyclopentanecarboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(1S,2S,4S)-1-amino-4-(aminomethyl)-2-(3-boronopropyl)cyclopentane-1-carboxylic acid	IC50	625 nM	US-10098902: Arginase inhibitors as therapeutics
(2R,3S)-3-amino-2-(3-boronopropyl)tetrahydrofuran-3-carboxylic acid	IC50	1500 nM	US-10098902: Arginase inhibitors as therapeutics
3-amino-2-(3-boronopropyl)tetrahydrothiophene-3-carboxylic acid	IC50	1500 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4R)-3-amino-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid	IC50	1500 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)-1-(pyridin-2- ylmethyl)pyrrolidine-3-carboxylic acid	IC50	1500 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)-1-(4-methylpyridin-3- yl)pyrrolidine-3-carboxylic acid	IC50	1500 nM	US-10098902: Arginase inhibitors as therapeutics
(3R,4S)-3-amino-4-(3-boronopropyl)-1-(2-(methylamino)-3- phenylpropanoyl)pyrrolidine-3-carboxylic acid	IC50	1500 nM	US-10098902: Arginase inhibitors as therapeutics

ChEMBL bioactivities

243 potent at pChembl≥5 of 263 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL4764455
8.40	IC50	4	nM	CHEMBL4745275
8.15	IC50	7	nM	CHEMBL4749355
8.07	Ki	8.5	nM	CHEMBL1812661
8.07	IC50	8.5	nM	CHEMBL1812661
8.07	Ki	8.5	nM	CHEMBL5723327
8.00	IC50	10	nM	CHEMBL4749355
8.00	IC50	10	nM	CHEMBL5807059
7.82	IC50	15	nM	CHEMBL4757930
7.82	IC50	15	nM	CHEMBL4752307
7.70	IC50	20	nM	CHEMBL4752307
7.68	IC50	21	nM	CHEMBL4752391
7.68	IC50	21	nM	CHEMBL4753285
7.64	IC50	23	nM	CHEMBL2418831
7.64	IC50	23	nM	CHEMBL5798991
7.62	IC50	24	nM	CHEMBL4778086
7.62	IC50	24	nM	CHEMBL4750174
7.58	IC50	26	nM	CHEMBL6161542
7.52	IC50	30	nM	CHEMBL2418830
7.52	Ki	30	nM	CHEMBL4244287
7.52	IC50	30	nM	CHEMBL4244287
7.48	IC50	33	nM	CHEMBL2418991
7.41	IC50	39	nM	CHEMBL5572458
7.33	IC50	47	nM	CHEMBL2418829
7.30	IC50	50	nM	CHEMBL2418998
7.29	Ki	51	nM	NOR-NOHA
7.29	IC50	51	nM	NOR-NOHA
7.17	IC50	67	nM	CHEMBL2326090
7.16	IC50	70	nM	CHEMBL2418999
7.16	IC50	70	nM	CHEMBL4858437
7.09	IC50	81	nM	CHEMBL6082888
7.07	IC50	85	nM	CHEMBL2418828
7.05	Ki	89	nM	CHEMBL539140
7.00	IC50	100	nM	CHEMBL4793482
7.00	IC50	100	nM	CHEMBL5171566
6.82	IC50	150	nM	CHEMBL5853762
6.81	IC50	154	nM	CHEMBL6062097
6.72	IC50	190	nM	CHEMBL2326087
6.72	IC50	190	nM	CHEMBL5955172
6.70	IC50	200	nM	CHEMBL5192755
6.70	IC50	200	nM	CHEMBL5170454
6.70	IC50	200	nM	CHEMBL6012295
6.65	IC50	224	nM	CHEMBL6102647
6.64	IC50	230	nM	CHEMBL2418994
6.64	IC50	230	nM	CHEMBL2418993
6.64	IC50	230	nM	CHEMBL6014233
6.62	IC50	240	nM	CHEMBL2418995
6.60	Ki	250	nM	CHEMBL5723327
6.58	IC50	260	nM	CHEMBL5921659
6.57	IC50	270	nM	CHEMBL2326085

PubChem BioAssay actives

87 with measured affinity, of 107 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3R,4S)-3-amino-1-(2-aminoethylsulfamoyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid	1724062: Inhibition of human Arg2	ic50	0.0001	uM
(2R,4S)-4-amino-2-(4-boronobutyl)piperidine-2-carboxylic acid	1678561: Inhibition of human recombinant arginase 2 expressed in Escherichia coli using thioarginine by Ellman’s assay	ic50	0.0040	uM
(2S)-2-amino-6-boronohexanoic acid	1724057: Inhibition of human Arg2 at pH 7.5	ki	0.0085	uM
(2R,4R)-2-(4-boronobutyl)-4-(methylamino)pyrrolidine-2-carboxylic acid	1724065: Inhibition of human Arg2 by TOGA assay	ic50	0.0100	uM
2-amino-6-borono-2-[3-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]propyl]hexanoic acid	1724060: Inhibition of human Arg2 using L-arginine as substrate after 60 mins by spectrophotometric analysis	ki	0.0100	uM
2-amino-6-borono-2-[3-(2-phenylethylamino)propyl]hexanoic acid	1724060: Inhibition of human Arg2 using L-arginine as substrate after 60 mins by spectrophotometric analysis	ki	0.0100	uM
(2R,4S)-4-[[(2S)-2-amino-4-methylpentanoyl]amino]-2-(4-boronobutyl)piperidine-2-carboxylic acid	1678561: Inhibition of human recombinant arginase 2 expressed in Escherichia coli using thioarginine by Ellman’s assay	ic50	0.0150	uM
(2R,4R)-4-amino-2-(4-boronobutyl)pyrrolidine-2-carboxylic acid	1724065: Inhibition of human Arg2 by TOGA assay	ic50	0.0200	uM
(2R,4S)-4-[[(2S)-2-aminobutanoyl]amino]-2-(4-boronobutyl)piperidine-2-carboxylic acid	1678561: Inhibition of human recombinant arginase 2 expressed in Escherichia coli using thioarginine by Ellman’s assay	ic50	0.0210	uM
(2R,4S)-4-[[(2S,3S)-2-amino-3-methylpentanoyl]amino]-2-(4-boronobutyl)piperidine-2-carboxylic acid	1678561: Inhibition of human recombinant arginase 2 expressed in Escherichia coli using thioarginine by Ellman’s assay	ic50	0.0210	uM
2-amino-6-borono-2-[8-[(3,4-dichlorophenyl)methyl]-8-azabicyclo[3.2.1]octan-3-yl]hexanoic acid	765935: Inhibition of human arginase-2 assessed as L-arginine conversion to L-ornithine measured as urea level after 1 hr by colorimetric assay	ic50	0.0230	uM
(2R,4S)-4-[[(2S)-2-amino-3-methylbutanoyl]amino]-2-(4-boronobutyl)piperidine-2-carboxylic acid	1678561: Inhibition of human recombinant arginase 2 expressed in Escherichia coli using thioarginine by Ellman’s assay	ic50	0.0240	uM
(2R,4S)-4-[[(2S)-2-amino-3,3-dimethylbutanoyl]amino]-2-(4-boronobutyl)piperidine-2-carboxylic acid	1678561: Inhibition of human recombinant arginase 2 expressed in Escherichia coli using thioarginine by Ellman’s assay	ic50	0.0240	uM
2-amino-6-borono-2-[8-[(4-chlorophenyl)methyl]-8-azabicyclo[3.2.1]octan-3-yl]hexanoic acid	765935: Inhibition of human arginase-2 assessed as L-arginine conversion to L-ornithine measured as urea level after 1 hr by colorimetric assay	ic50	0.0300	uM
(2R)-2-amino-3-(2-boronoethylsulfanyl)propanoic acid	1724057: Inhibition of human Arg2 at pH 7.5	ki	0.0300	uM
2-amino-6-borono-2-[8-[(3,4-difluorophenyl)methyl]-8-azabicyclo[3.2.1]octan-3-yl]hexanoic acid	765935: Inhibition of human arginase-2 assessed as L-arginine conversion to L-ornithine measured as urea level after 1 hr by colorimetric assay	ic50	0.0330	uM
2-amino-2-(8-benzyl-8-azabicyclo[3.2.1]octan-3-yl)-6-boronohexanoic acid	765935: Inhibition of human arginase-2 assessed as L-arginine conversion to L-ornithine measured as urea level after 1 hr by colorimetric assay	ic50	0.0470	uM
2-amino-6-borono-2-[1-[3-(2,4-dichlorophenyl)propyl]piperidin-4-yl]hexanoic acid	765935: Inhibition of human arginase-2 assessed as L-arginine conversion to L-ornithine measured as urea level after 1 hr by colorimetric assay	ic50	0.0500	uM
(2S)-2-amino-4-[[amino-(hydroxyamino)methylidene]amino]butanoic acid	1370773: Inhibition of arginase 2 (unknown origin)	ki	0.0510	uM
(2R)-6-borono-2-(methylamino)-2-(2-piperidin-1-ylethyl)hexanoic acid	728412: Inhibition of human recombinant fully active truncated form of arginase 2 overexpressed in Escherichia coli BL21(DE3) assessed as inhibition of urea formation after 60 mins by spectrophotometric analysis	ic50	0.0670	uM
2-amino-6-borono-2-[1-[3-[4-(trifluoromethyl)phenyl]propyl]piperidin-4-yl]hexanoic acid	765935: Inhibition of human arginase-2 assessed as L-arginine conversion to L-ornithine measured as urea level after 1 hr by colorimetric assay	ic50	0.0700	uM
2-amino-2-(8-azabicyclo[3.2.1]octan-3-yl)-6-boronohexanoic acid	765935: Inhibition of human arginase-2 assessed as L-arginine conversion to L-ornithine measured as urea level after 1 hr by colorimetric assay	ic50	0.0850	uM
[(E)-3-phenylprop-1-enyl]boronic acid	1929548: Binding affinity to human Arg II	ki	0.0890	uM
(1R,2S,5R)-1-amino-5-(2-boronoethyl)-2-(piperidin-1-ylmethyl)cyclohexane-1-carboxylic acid	1724062: Inhibition of human Arg2	ic50	0.1000	uM
(1R,2S,5R)-1-amino-2-[[[(2S)-2-amino-4-methylpentanoyl]amino]methyl]-5-(2-boronoethyl)cyclohexane-1-carboxylic acid	1875447: Inhibition of recombinant human ARG2 expressed in Escherichia coli using L-arginine hydrochloride as substrate incubated for 1 hr by colorimetric assay	ic50	0.1000	uM
(2R)-2-amino-6-borono-2-[2-(propan-2-ylamino)ethyl]hexanoic acid	728412: Inhibition of human recombinant fully active truncated form of arginase 2 overexpressed in Escherichia coli BL21(DE3) assessed as inhibition of urea formation after 60 mins by spectrophotometric analysis	ic50	0.1900	uM
(1R,2S,5R)-1-amino-2-[[[(2S)-2-amino-3-methylbutanoyl]amino]methyl]-5-(2-boronoethyl)cyclohexane-1-carboxylic acid	1875447: Inhibition of recombinant human ARG2 expressed in Escherichia coli using L-arginine hydrochloride as substrate incubated for 1 hr by colorimetric assay	ic50	0.2000	uM
(1R,2S,5R)-1-amino-2-[[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]methyl]-5-(2-boronoethyl)cyclohexane-1-carboxylic acid	1875447: Inhibition of recombinant human ARG2 expressed in Escherichia coli using L-arginine hydrochloride as substrate incubated for 1 hr by colorimetric assay	ic50	0.2000	uM
2-amino-2-(1-benzylpiperidin-4-yl)-6-boronohexanoic acid	765935: Inhibition of human arginase-2 assessed as L-arginine conversion to L-ornithine measured as urea level after 1 hr by colorimetric assay	ic50	0.2300	uM
2-amino-6-borono-2-[1-(3-methylbutyl)piperidin-4-yl]hexanoic acid	765935: Inhibition of human arginase-2 assessed as L-arginine conversion to L-ornithine measured as urea level after 1 hr by colorimetric assay	ic50	0.2300	uM
2-amino-6-borono-2-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]hexanoic acid	765935: Inhibition of human arginase-2 assessed as L-arginine conversion to L-ornithine measured as urea level after 1 hr by colorimetric assay	ic50	0.2400	uM
(2R)-2-amino-6-borono-2-[2-(diethylamino)ethyl]hexanoic acid	728412: Inhibition of human recombinant fully active truncated form of arginase 2 overexpressed in Escherichia coli BL21(DE3) assessed as inhibition of urea formation after 60 mins by spectrophotometric analysis	ic50	0.2700	uM
2-amino-6-borono-2-[1-[(3,4-dichlorophenyl)methyl]piperidin-4-yl]hexanoic acid	765935: Inhibition of human arginase-2 assessed as L-arginine conversion to L-ornithine measured as urea level after 1 hr by colorimetric assay	ic50	0.2900	uM
(2R)-2-amino-6-borono-2-[1-[(3,4-dichlorophenyl)methyl]piperidin-4-yl]hexanoic acid	1937989: Inhibition of recombinant human ARG2 expressed in Escherichia coli using L-arginine hydrochloride as substrate incubated for 1 hr by colorimetric assay	ic50	0.2900	uM
(3R,4S)-3-amino-1-[(2S)-2-aminopropanoyl]-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid	1724062: Inhibition of human Arg2	ic50	0.2960	uM
2-amino-6-borono-2-[1-[(2,4-dichlorophenyl)methyl]piperidin-4-yl]hexanoic acid	1937989: Inhibition of recombinant human ARG2 expressed in Escherichia coli using L-arginine hydrochloride as substrate incubated for 1 hr by colorimetric assay	ic50	0.2960	uM
(2R)-2-amino-6-borono-2-(2-pyrrolidin-1-ylethyl)hexanoic acid	728412: Inhibition of human recombinant fully active truncated form of arginase 2 overexpressed in Escherichia coli BL21(DE3) assessed as inhibition of urea formation after 60 mins by spectrophotometric analysis	ic50	0.3100	uM
(2R)-2-amino-6-borono-2-[2-[methyl(propyl)amino]ethyl]hexanoic acid	728412: Inhibition of human recombinant fully active truncated form of arginase 2 overexpressed in Escherichia coli BL21(DE3) assessed as inhibition of urea formation after 60 mins by spectrophotometric analysis	ic50	0.3200	uM
(2R,4R)-4-[[(2S)-2-amino-3-methylbutanoyl]amino]-2-(4-boronobutyl)pyrrolidine-2-carboxylic acid	1724065: Inhibition of human Arg2 by TOGA assay	ic50	0.3300	uM
2-amino-6-borono-2-[1-[2-(2,4-dichlorophenyl)ethyl]piperidin-4-yl]hexanoic acid	765935: Inhibition of human arginase-2 assessed as L-arginine conversion to L-ornithine measured as urea level after 1 hr by colorimetric assay	ic50	0.3300	uM
(2R)-2-amino-6-borono-2-[2-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]ethyl]hexanoic acid	728412: Inhibition of human recombinant fully active truncated form of arginase 2 overexpressed in Escherichia coli BL21(DE3) assessed as inhibition of urea formation after 60 mins by spectrophotometric analysis	ic50	0.3400	uM
(2R)-2-amino-6-borono-2-[2-[ethyl(2-hydroxyethyl)amino]ethyl]hexanoic acid	728412: Inhibition of human recombinant fully active truncated form of arginase 2 overexpressed in Escherichia coli BL21(DE3) assessed as inhibition of urea formation after 60 mins by spectrophotometric analysis	ic50	0.3900	uM
(2R)-2-amino-6-borono-2-[2-(4-hydroxypiperidin-1-yl)ethyl]hexanoic acid	728412: Inhibition of human recombinant fully active truncated form of arginase 2 overexpressed in Escherichia coli BL21(DE3) assessed as inhibition of urea formation after 60 mins by spectrophotometric analysis	ic50	0.4200	uM
(2S,3R,5S)-3-amino-1-[(2S)-2-aminopropanoyl]-5-(2-boronoethyl)-2-methylpiperidine-3-carboxylic acid	1724062: Inhibition of human Arg2	ic50	0.5000	uM
(2S,3R,5S)-3-amino-1-[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]-5-(2-boronoethyl)-2-methylpiperidine-3-carboxylic acid	1724062: Inhibition of human Arg2	ic50	0.5000	uM
(2S,3R,5S)-3-amino-1-(2-aminoacetyl)-5-(2-boronoethyl)-2-methylpiperidine-3-carboxylic acid	1724062: Inhibition of human Arg2	ic50	0.5000	uM
(2R)-2-amino-6-borono-2-(2-piperidin-1-ylethyl)hexanoic acid	1937989: Inhibition of recombinant human ARG2 expressed in Escherichia coli using L-arginine hydrochloride as substrate incubated for 1 hr by colorimetric assay	ic50	0.5090	uM
(2R,4R)-4-[[(2S)-2-amino-3-hydroxy-3-methylbutanoyl]amino]-2-(4-boronobutyl)pyrrolidine-2-carboxylic acid	1724065: Inhibition of human Arg2 by TOGA assay	ic50	0.5200	uM
(2R)-2-amino-6-borono-2-[2-(1,3-dihydroisoindol-2-yl)ethyl]hexanoic acid	728412: Inhibition of human recombinant fully active truncated form of arginase 2 overexpressed in Escherichia coli BL21(DE3) assessed as inhibition of urea formation after 60 mins by spectrophotometric analysis	ic50	0.5500	uM
(2R)-2-amino-6-borono-2-[2-[(3R)-3-(hydroxymethyl)pyrrolidin-1-yl]ethyl]hexanoic acid	728412: Inhibition of human recombinant fully active truncated form of arginase 2 overexpressed in Escherichia coli BL21(DE3) assessed as inhibition of urea formation after 60 mins by spectrophotometric analysis	ic50	0.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	affects expression, affects cotreatment, increases expression	5
trichostatin A	increases expression, affects cotreatment, decreases expression	4
Valproic Acid	affects expression, decreases expression, increases expression	4
Cyclosporine	increases expression	4
bisphenol A	affects expression, increases expression	3
sodium arsenite	affects methylation, decreases expression, increases abundance	3
Benzo(a)pyrene	increases expression	3
Doxorubicin	decreases expression, increases expression	3
Estradiol	decreases expression, increases expression, affects cotreatment	3
Oxygen	decreases reaction, increases expression	3
Aflatoxin B1	affects expression, increases expression	3
perfluorooctanoic acid	increases expression	2
2-amino-6-boronohexanoic acid	affects binding, decreases activity	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	2
Cisplatin	decreases response to substance, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Particulate Matter	increases abundance, increases expression, affects reaction, increases activity	2
aristolochic acid I	decreases expression	1
N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine quinone	affects expression	1
dicrotophos	decreases expression	1
thymoquinone	increases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
deoxynivalenol	decreases expression	1
beta-lapachone	increases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc chloride	increases expression	1
butyraldehyde	increases expression	1

ChEMBL screening assays

37 unique, capped per target: 34 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1816206	Binding	Binding affinity to human arginase 2	Binding of α,α-disubstituted amino acids to arginase suggests new avenues for inhibitor design. — J Med Chem
CHEMBL4649958	Functional	in vitro enzyme assay to detect the production of urea directly proportional to the activity of Arginase II	University of Dundee, Small-Polar-MMV Screening Library

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1QR	HAP1 ARG2 (-) 1	Cancer cell line	Male
CVCL_E1QS	HAP1 ARG2 (-) 2	Cancer cell line	Male
CVCL_E1QT	HAP1 ARG2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00793988	PHASE4	COMPLETED	Vibration-Assisted Anaesthesia
NCT01239498	PHASE4	UNKNOWN	Saline Injection - Assisted Anesthesia in Eyelid Surgery
NCT02761083	PHASE4	WITHDRAWN	PMCF-study Using Novosyn® Quick Suture Material in Ophthalmic Surgery
NCT04007276	PHASE4	NOT_YET_RECRUITING	The Effect of Lumify™ on Ocular Redness, Intraocular Pressure, and Eyelid Position in Glaucoma Patients
NCT07390578	PHASE4	NOT_YET_RECRUITING	Upneeq vs. Lumify Ptosis
NCT01908972	PHASE4	COMPLETED	The Safety and Efficiency of Propranolol as an Initial Treatment for Pediatric Hemangioma
NCT04077515	PHASE4	COMPLETED	Safety and Efficacy of Low-dose Sirolimus to Kaposiform Hemangioendothelioma
NCT02436759	PHASE3	COMPLETED	Study of the Safety and Efficacy of RVL-1201 in the Treatment of Acquired Blepharoptosis
NCT03536949	PHASE3	COMPLETED	Study of Safety of RVL-1201 in Treatment of Blepharoptosis
NCT03565887	PHASE3	COMPLETED	Study of Safety and Efficacy of RVL-1201 in the Treatment of Blepharoptosis
NCT05945615	PHASE3	COMPLETED	Oxymetazoline Drops for Acquired Blepharoptosis From Synkinesis
NCT06683651	PHASE3	RECRUITING	A Study in Chinese Patients With Acquired Blepharoptosis
NCT06514612	PHASE3	RECRUITING	LIDRISE Study: A Phase 3 Study on the Efficacy and Safety of STN1013800 (Oxymetazoline HCl 0.1% Eye Drops, Single Dose) in the Treatment of Acquired Blepharoptosis.
NCT00312520	PHASE3	COMPLETED	Pulse Steroids Versus Oral Steroids in Problematic Hemangiomas of Infancy
NCT01685398	PHASE3	COMPLETED	Topical Timolol for Superficial Infantile Hemangioma
NCT01743885	PHASE3	TERMINATED	Efficacy and Safety of Propranolol Versus Acebutolol on the Proliferative Phase of Infantile Hemangioma
NCT02342275	PHASE3	COMPLETED	Efficacy and Safety of Propranolol Versus Atenolol on the Proliferative Phase of Infantile Hemangioma
NCT03266081	PHASE2	WITHDRAWN	Bupivacaine Epiphora Trial
NCT00555464	PHASE2	TERMINATED	Clinical Trial of Vincristine vs. Prednisolone for Treatment of Complicated Hemangiomas
NCT01072045	PHASE2	COMPLETED	Comparative Study of the Use of Beta Blocker and Oral Corticosteroid in the Treatment of Infantile Hemangioma
NCT01074437	PHASE2	TERMINATED	Corticosteroids With Placebo Versus Corticosteroids With Propranolol Treatment of Infantile Hemangiomas (IH)
NCT02145884	PHASE2	COMPLETED	Topical Timolol Gel for the Treatment of Infantile Hemangiomas
NCT02731287	PHASE2	COMPLETED	Topical Timolol for Infantile Hemangioma in Early Proliferative Phase
NCT07477548	PHASE2	NOT_YET_RECRUITING	A Study to Evaluate the Efficacy and Safety of Everolimus in Patients With Teratment-refractory Vascular Anomalies
NCT02496013	PHASE1	UNKNOWN	Clinical Translation of a Novel Albumin-Binding PET Radiotracer 68Ga-NEB
NCT02878694	PHASE2/PHASE3	TERMINATED	Treatment of Ptosis to Muscular Dystrophy Oculopharyngeal by Myoblast Autologous Graft
NCT05358977	PHASE2/PHASE3	UNKNOWN	Fibrin Sealant in Eyelid Surgery
NCT01848041	PHASE1/PHASE2	COMPLETED	Safety and Efficacy Study of RVL-1201 in Acquired Blepharoptosis
NCT05715346	PHASE1/PHASE2	COMPLETED	LEV102 Topical Gel in Acquired Blepharoptosis
NCT04807855	EARLY_PHASE1	COMPLETED	Custom Print Megnetic Levator Prosthesis Pilot Comparison
NCT06911216	EARLY_PHASE1	COMPLETED	A Pharmacokinetics (PK) Study in Healthy Adults
NCT00816270	Not specified	TERMINATED	Liquid Bandage (2-Octyl-Cyanoacrylate) in Upper Lid Blepharoplasty
NCT00864656	Not specified	COMPLETED	Eyelid Position Interdependence in Involutional Ptosis Patients Submitted to 10% Phenylephrine
NCT01350024	Not specified	COMPLETED	Comparison of Postoperative Pain With Two Different Types of Local Anesthesia in Surgery for a Drooping Eyelid
NCT01430247	Not specified	COMPLETED	Vision Screening for the Detection of Amblyopia
NCT01968174	Not specified	UNKNOWN	Astigmatic Changes Secondary to Eyelid Surgeries
NCT02201979	Not specified	COMPLETED	Laser Fluorescent Imaging of Nipple and Areola During Breast Lift
NCT02226016	Not specified	UNKNOWN	Levator Muscle Strength Evaluation
NCT02367677	Not specified	COMPLETED	Digital Photographs to Evaluate Blepharoptosis
NCT02376556	Not specified	COMPLETED	The Effect of Eyelid Surgery on Dry Eye - a Prospective Study