ARG2
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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): 75 total
- GTEx eGene: eQTL in 13 tissues, sQTL in 4 (q < 0.05)
- ChEMBL bioactivity: 2 clinical-phase molecules tested; no curated mechanism-of-action drug
- Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.78 (unconstrained)
- MANE Select transcript:
NM_001172 - Interaction hub: 2,546 STRING partners (top 4% of genes corpus-wide)
- Notable: 75 clinical variants but no curated precision-oncology (CIViC) evidence yet
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: 10 — 4 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined
MANE Select: ENST00000261783
Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 5: 1
ENST00000261783, ENST00000556491, ENST00000557120, ENST00000557319, ENST00000927904, ENST00001066861, ENST00001066863, ENST00001066866, ENST00001130715, ENST00001135688
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.
Highest expression (Bgee): tendon of biceps brachii, oocyte, cortical plate, renal medulla, metanephros cortex.
Genetic regulation across tissues (GTEx eQTL / sQTL)
ARG2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.
17 significant tissue × QTL associations:
| Tissue | QTL | q-value | Slope | Lead variant |
|---|---|---|---|---|
| Muscle Skeletal | sqtl | 1.7e-59 | -1.66 | 14:67720983:T:C |
| Muscle Skeletal | eqtl | 2.7e-50 | +0.50 | 14:67622713:G:A |
| Artery Tibial | eqtl | 5.5e-05 | +0.17 | 14:67622436:A:T |
| Adipose Subcutaneous | eqtl | 9.3e-03 | +0.45 | 14:67639045:TA:T |
| Cells EBV-transformed lymphocytes | eqtl | 1.0e-02 | +0.34 | 14:67605598:C:G |
| Nerve Tibial | eqtl | 1.4e-02 | -0.25 | 14:68506738:G:A |
| Skin Not Sun Exposed Suprapubic | eqtl | 1.7e-02 | +0.60 | 14:67607452:T:C |
| Breast Mammary Tissue | eqtl | 1.9e-02 | -0.91 | 14:66723982:T:TACACAC |
| Esophagus Mucosa | eqtl | 2.2e-02 | -0.10 | 14:67634170:T:C |
| Kidney Cortex | sqtl | 2.9e-02 | -3.51 | 14:68438468:C:T |
| Lung | eqtl | 3.1e-02 | -0.46 | 14:67652085:G:GTGGGT |
| Brain Hippocampus | eqtl | 3.2e-02 | -1.19 | 14:68533567:T:C |
| Spleen | eqtl | 3.5e-02 | +0.80 | 14:68310714:G:A |
| Esophagus Muscularis | eqtl | 4.4e-02 | +0.34 | 14:67683217:A:G |
| Thyroid | sqtl | 4.8e-02 | +0.87 | 14:68454120:G:C |
| Cells Cultured fibroblasts | sqtl | 4.9e-02 | +0.80 | 14:68002425:G:A |
| Skin Sun Exposed Lower leg | eqtl | 5.0e-02 | +0.34 | 14:67592075:CAG:C |
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
showing 100 of 296 tissues 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 |
| cerebellum | UBERON:0002037 | 85.41 | gold quality |
| gastrocnemius | UBERON:0001388 | 85.03 | gold quality |
| minor salivary gland | UBERON:0001830 | 84.52 | gold quality |
| muscle of leg | UBERON:0001383 | 84.39 | gold quality |
| esophagus mucosa | UBERON:0002469 | 84.22 | gold quality |
| hindlimb stylopod muscle | UBERON:0004252 | 84.12 | gold quality |
| sperm | CL:0000019 | 84.06 | gold quality |
| metanephros | UBERON:0000081 | 84.03 | gold quality |
| mouth mucosa | UBERON:0003729 | 83.90 | gold quality |
| embryo | UBERON:0000922 | 83.75 | gold quality |
| prefrontal cortex | UBERON:0000451 | 83.35 | gold quality |
| endothelial cell | CL:0000115 | 83.15 | gold quality |
| buccal mucosa cell | CL:0002336 | 82.97 | silver quality |
| saliva-secreting gland | UBERON:0001044 | 82.85 | gold quality |
| tendon | UBERON:0000043 | 82.80 | gold quality |
| endometrium | UBERON:0001295 | 82.75 | gold quality |
| renal glomerulus | UBERON:0000074 | 82.59 | gold quality |
| tibialis anterior | UBERON:0001385 | 82.52 | gold quality |
| metanephric glomerulus | UBERON:0004736 | 82.02 | gold quality |
| pancreatic ductal cell | CL:0002079 | 81.86 | silver quality |
| lateral nuclear group of thalamus | UBERON:0002736 | 81.85 | gold quality |
| cervix epithelium | UBERON:0004801 | 81.84 | gold quality |
| right frontal lobe | UBERON:0002810 | 81.77 | gold quality |
| nasal cavity mucosa | UBERON:0001826 | 81.70 | gold quality |
| epithelium of esophagus | UBERON:0001976 | 81.47 | gold quality |
| globus pallidus | UBERON:0001875 | 81.43 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 81.32 | gold quality |
| esophagus squamous epithelium | UBERON:0006920 | 81.24 | gold quality |
| male germ cell | CL:0000015 | 81.19 | gold quality |
| left ovary | UBERON:0002119 | 80.81 | gold quality |
| skeletal muscle organ | UBERON:0014892 | 80.81 | gold quality |
| muscle organ | UBERON:0001630 | 80.80 | gold quality |
| dorsolateral prefrontal cortex | UBERON:0009834 | 80.73 | gold quality |
| esophagus | UBERON:0001043 | 80.67 | gold quality |
| vagina | UBERON:0000996 | 80.48 | gold quality |
| small intestine Peyer’s patch | UBERON:0003454 | 80.36 | gold quality |
| nucleus accumbens | UBERON:0001882 | 80.23 | gold quality |
| pons | UBERON:0000988 | 79.99 | gold quality |
| squamous epithelium | UBERON:0006914 | 79.78 | gold quality |
| small intestine | UBERON:0002108 | 79.77 | gold quality |
| hypothalamus | UBERON:0001898 | 79.76 | gold quality |
| Brodmann (1909) area 9 | UBERON:0013540 | 79.74 | gold quality |
| cingulate cortex | UBERON:0003027 | 79.62 | gold quality |
| brain | UBERON:0000955 | 79.45 | gold quality |
| neocortex | UBERON:0001950 | 79.42 | gold quality |
| oral cavity | UBERON:0000167 | 79.35 | gold quality |
| oviduct epithelium | UBERON:0004804 | 79.34 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 79.31 | gold quality |
| central nervous system | UBERON:0001017 | 79.30 | gold quality |
| frontal cortex | UBERON:0001870 | 79.29 | gold quality |
| adult organism | UBERON:0007023 | 79.26 | gold quality |
| cervix squamous epithelium | UBERON:0006922 | 79.15 | silver quality |
| forebrain | UBERON:0001890 | 79.13 | gold quality |
| ileal mucosa | UBERON:0000331 | 79.10 | gold quality |
| nasal cavity epithelium | UBERON:0005384 | 78.90 | gold quality |
| pancreas | UBERON:0001264 | 78.63 | gold quality |
| cerebral cortex | UBERON:0000956 | 78.44 | gold quality |
| gall bladder | UBERON:0002110 | 78.23 | gold quality |
| caudate nucleus | UBERON:0001873 | 78.19 | gold quality |
| telencephalon | UBERON:0001893 | 77.89 | gold quality |
| monocyte | CL:0000576 | 77.49 | gold quality |
| C1 segment of cervical spinal cord | UBERON:0006469 | 77.26 | gold quality |
| mononuclear cell | CL:0000842 | 77.15 | gold quality |
| ventricular zone | UBERON:0003053 | 76.91 | gold quality |
| lower esophagus | UBERON:0013473 | 76.88 | gold quality |
| right ovary | UBERON:0002118 | 76.79 | gold quality |
| lower esophagus muscularis layer | UBERON:0035833 | 76.79 | gold quality |
| leukocyte | CL:0000738 | 76.78 | gold quality |
| ovary | UBERON:0000992 | 76.70 | gold quality |
| duodenum | UBERON:0002114 | 76.66 | 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 |
HPA expression
RNA tissue specificity: Tissue enhanced
showing 60 of 78 HPA tissues / cells by nTPM:
| Tissue / cell | Axis | nTPM | Protein (IHC) |
|---|---|---|---|
| Parathyroid gland | tissue | 206.5 | high |
| Prostate | tissue | 101.8 | high |
| Thyroid gland | tissue | 97.9 | low |
| Kidney | tissue | 59.7 | high |
| Tongue | tissue | 49.2 | |
| Pituitary gland | tissue | 47.4 | |
| Cerebral cortex | tissue | 21.1 | low |
| Somatosensory cortex | tissue | 21.1 | |
| Retina | tissue | 20.7 | |
| Skeletal muscle | tissue | 20.2 | low |
| Occipital cortex | tissue | 18.4 | |
| Temporal cortex | tissue | 18.1 | |
| Prefrontal cortex | tissue | 17.6 | |
| Hippocampal formation | tissue | 17.3 | |
| Entorhinal cortex | tissue | 17.3 | |
| Motor cortex | tissue | 17.1 | |
| Caudate putamen | tissue | 16.9 | |
| Basal ganglia | tissue | 16.8 | low |
| Retrosplenial and cingulate cortex | tissue | 16.8 | |
| Urinary bladder | tissue | 16.6 | not detected |
| Cervix | tissue | 16.0 | low |
| Retrosplenial cortex | tissue | 15.6 | |
| Septum | tissue | 15.5 | |
| Putamen | tissue | 14.5 | |
| Small intestine | tissue | 14.4 | high |
| Ventral forebrain | tissue | 14.4 | |
| Olfactory bulb | tissue | 14.3 | |
| Cerebellum | tissue | 14.2 | low |
| Insular cortex | tissue | 14.2 | |
| Thalamus | tissue | 14.0 | |
| Locus coeruleus | tissue | 13.8 | |
| Pons | tissue | 13.7 | |
| Amygdala | tissue | 13.2 | |
| Hypothalamus | tissue | 12.0 | |
| Superior colliculi | tissue | 11.8 | |
| Midbrain | tissue | 11.5 | |
| Salivary gland | tissue | 11.2 | not detected |
| Vagina | tissue | 11.0 | not detected |
| Choroid plexus | tissue | 10.4 | |
| Medulla oblongata | tissue | 10.2 | |
| Periaqueductal gray | tissue | 9.8 | |
| Substantia nigra | tissue | 9.5 | |
| Postcentral gyrus | tissue | 8.8 | |
| Gallbladder | tissue | 8.7 | low |
| Spinal cord | tissue | 8.6 | |
| Placenta | tissue | 8.3 | low |
| Esophagus | tissue | 7.3 | low |
| Adrenal gland | tissue | 6.9 | not detected |
| Nucleus accumbens | tissue | 6.8 | |
| Endometrium 1 | tissue | 6.5 | medium |
| Hippocampus | tissue | 5.5 | low |
| Seminal vesicle | tissue | 5.4 | low |
| Corpus callosum | tissue | 4.9 | |
| Pancreas | tissue | 4.8 | low |
| Breast | tissue | 4.5 | not detected |
| Smooth muscle | tissue | 3.5 | not detected |
| Duodenum | tissue | 3.5 | medium |
| Epididymis | tissue | 3.4 | low |
| Testis | tissue | 3.1 | not detected |
| Thymus | tissue | 2.8 |
Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Arcuate nucleus (19.8), Subiculum (16.8), Ventral hippocampus (14.8), Dorsal hippocampus (14.5), Lateral hypothalamic area (10.5).
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): AR
miRNA regulators (miRDB)
Targeting ARG2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).
showing 30 of 88 miRNAs:
| 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 |
Functional genomics
gnomAD constraint: pLI 0.00209, LOEUF 0.78, missense Z 1.29 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD
Regional missense constraint (gnomAD RMC): no regional variation along ENST00000261783 — one region, missense o/e 0.89.
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)
Mouse-model phenotypes
Observed phenotypes of the mouse ortholog (MGI:1330806) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 12 distinct phenotype terms.
| Mouse phenotype (MP) | Records |
|---|---|
| kyphosis | 1 |
| lordosis | 1 |
| abnormal heart morphology | 1 |
| enlarged heart | 1 |
| abnormal heart shape | 1 |
| abnormal spleen morphology | 1 |
| small spleen | 1 |
| abnormal thymus morphology | 1 |
| enlarged thymus | 1 |
| decreased exploration in new environment | 1 |
| abnormal spine curvature | 1 |
| increased circulating arginine level | 1 |
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 |
|---|---|---|---|
| Brucella melitensis bv. 1 str. 16M | P0A2X9 | 100.0% | Diamond |
| Brucella suis 1330 | P0A2Y0 | 100.0% | Diamond |
| Brucella abortus bv. 1 str. 9-941 | P0A2Y1 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus COL | P60086 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus Mu50 | P60087 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus N315 | P60088 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus MSSA476 | Q6G7E9 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus MW2 | Q8NVE3 | 100.0% | Diamond |
| Coccidioides posadasii C735 delta SOWgp | P40906 | 99.4% | Diamond |
| Coccidioides immitis RS | Q1E180 | 99.4% | Diamond |
| Xenopus laevis | Q91553 | 99.4% | Diamond |
| Staphylococcus aureus subsp. aureus MRSA252 | Q6GER3 | 94.0% | Diamond |
| Bos taurus | Q58DL1 | 92.4% | Diamond |
| Oryctolagus cuniculus | Q95KM0 | 91.3% | Diamond |
| Sus scrofa | Q95JC8 | 89.8% | Diamond |
| Schizosaccharomyces pombe 972h- | P37818 | 87.9% | Diamond |
| Aspergillus nidulans FGSC A4 | Q12611 | 75.3% | Diamond |
| Neurospora crassa OR74A | P33280 | 71.6% | Diamond |
| Aquarana catesbeiana | P49900 | 71.0% | Diamond |
| Kluyveromyces lactis NRRL Y-1140 | Q6CLS8 | 70.5% | Diamond |
| Eremothecium gossypii ATCC 10895 | Q74ZW4 | 70.5% | Diamond |
| Bacillus subtilis subsp. subtilis str. 168 | P39138 | 70.1% | Diamond |
| [Bacillus] caldovelox | P53608 | 70.1% | Diamond |
| Brevibacillus brevis | Q7M0Z3 | 65.8% | Diamond |
| Saccharomyces cerevisiae S288C | P00812 | 65.5% | Diamond |
| Plasmodium berghei ANKA | A0A509AF89 | 63.6% | Diamond |
| Agrobacterium fabrum str. C58 | P14012 | 63.3% | Diamond |
| Plasmodium falciparum 3D7 | Q8I384 | 63.1% | Diamond |
| Glaciozyma antarctica PI12 | A0A2R2JFW7 | 54.3% | Diamond |
| Entamoeba histolytica HM-1:IMSS | C4LSS0 | 36.6% | 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 |
|---|---|---|
| GPHN | protein-coding | 10243 |
| TMEM229B | protein-coding | 161145 |
| PIGH | protein-coding | 5283 |
| PLEKHH1 | protein-coding | 57475 |
| VTI1B | protein-coding | 10490 |
| RDH12 | protein-coding | 145226 |
| RDH11 | protein-coding | 51109 |
| MIR5694 | ncRNA | 100847064 |
| LINC02290 | ncRNA | 105370540 |
| GARIN2 | protein-coding | 161142 |
| EIF2S1 | protein-coding | 1965 |
| ZFYVE26 | protein-coding | 23503 |
| PLEK2 | protein-coding | 26499 |
| CCDC196 | protein-coding | 440184 |
| ATP6V1D | protein-coding | 51382 |
| PALS1 | protein-coding | 64398 |
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)
- L-arginine + H2O = urea + L-ornithine (RHEA:20569)
UniProt features (54 total): helix 21, binding site 13, strand 13, turn 3, transit peptide 1, chain 1, sequence variant 1, region of interest 1
Structure
Experimental structures (PDB)
18 structures by resolution:
| PDB | Title | Method | Resolution (Å) |
|---|---|---|---|
| 4HZE | Crystal structure of human Arginase-2 complexed with inhibitor 9 | X-RAY DIFFRACTION | 1.6 |
| 8RG6 | Arginase 2 in complex with inhibitor | X-RAY DIFFRACTION | 1.62 |
| 8RFA | Arginase 2 in complex with an inhibitor | X-RAY DIFFRACTION | 1.76 |
| 4I06 | Crystal structure of human Arginase-2 complexed with inhibitor 14 | X-RAY DIFFRACTION | 1.8 |
| 8RGF | Arginase 2 in complex with inhibitor | X-RAY DIFFRACTION | 1.86 |
| 4IXU | Crystal structure of human Arginase-2 complexed with inhibitor 11d: … | X-RAY DIFFRACTION | 1.9 |
| 8RGU | Arginase 2 in complex with inhibitor | X-RAY DIFFRACTION | 1.9 |
| 8RIM | Arginase 2 in complex with inhibitor | X-RAY DIFFRACTION | 1.9 |
| 9FRV | Arginase 2 in complex with inhibitor | X-RAY DIFFRACTION | 2.06 |
| 4IE2 | Crystal structure of human Arginase-2 complexed with inhibitor 1h | X-RAY DIFFRACTION | 2.21 |
| 6Q37 | Complex of Arginase 2 with Example 23 | X-RAY DIFFRACTION | 2.21 |
| 6Q39 | Complex of Arginase 2 with Example 49 | X-RAY DIFFRACTION | 2.21 |
| 4IXV | Crystal structure of human Arginase-2 complexed with inhibitor 2d: … | X-RAY DIFFRACTION | 2.3 |
| 4IE3 | Crystal structure of human Arginase-2 complexed with inhbitor 1o | X-RAY DIFFRACTION | 2.35 |
| 6SS2 | Structure of arginase-2 in complex with the inhibitory human antigen-binding fragment Fab … | X-RAY DIFFRACTION | 2.4 |
| 1PQ3 | Human Arginase II: Crystal Structure and Physiological Role in Male and Female Sexual … | X-RAY DIFFRACTION | 2.7 |
| 6SS4 | Structure of arginase-2 in complex with the inhibitory human antigen-binding fragment Fab … | X-RAY DIFFRACTION | 2.9 |
| 6SS6 | Structure of arginase-2 in complex with the inhibitory human antigen-binding fragment Fab … | 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 antibodies co-crystallized with this protein: 6SS2, 6SS4, 6SS6
Human Protein Atlas
Protein class: Enzymes, ENZYME proteins, Hydrolases, Metabolic proteins, Predicted intracellular proteins, Cancer-related genes, Candidate cancer biomarkers
Protein evidence: Evidence at protein level
Subcellular location (HPA, imaging): mitochondria
Antibody reliability (HPA): IH enhanced · IF supported
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)
| Position | Role |
|---|---|
| 202 | substrate |
| 251 | Mn(2+) |
| 253 | Mn(2+) |
| 265 | substrate |
| 296 | substrate |
| 120 | Mn(2+) |
| 143 | Mn(2+) |
| 145–149 | substrate |
| 145 | Mn(2+) |
| 147 | Mn(2+) |
| 156–158 | substrate |
Function
Pathways and Gene Ontology
Reactome pathways
2 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).
5 pathways:
| ID | Pathway | Evidence |
|---|---|---|
| R-HSA-9837999 | Mitochondrial protein degradation | curated |
| R-HSA-70635 | Urea cycle | curated |
| R-HSA-1430728 | Metabolism | — |
| R-HSA-71291 | Metabolism of amino acids and derivatives | — |
| R-HSA-392499 | Metabolism of proteins | — |
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 (21): 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), 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
3 top-level categories:
| Category | Pathways |
|---|---|
| Metabolism of amino acids and derivatives | 1 |
| Metabolism of proteins | 1 |
| Metabolism | 1 |
GO top-level categories
59 GO namespaces:
| 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 |
| 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 |
| CD4-positive, alpha-beta T cell proliferation | 1 |
| negative regulation of alpha-beta T cell proliferation | 1 |
| negative regulation of CD4-positive, alpha-beta T cell activation | 1 |
| regulation of CD4-positive, alpha-beta T cell proliferation | 1 |
| positive regulation of cellular process | 1 |
| cellular senescence | 1 |
| regulation of cellular senescence | 1 |
| biological_process | 1 |
| hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines | 1 |
| transition metal ion binding | 1 |
| binding | 1 |
| catalytic activity | 1 |
| hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds | 1 |
| cation binding | 1 |
| intracellular anatomical structure | 1 |
| cellular anatomical structure | 1 |
| cytoplasm | 1 |
| intracellular membrane-bounded organelle | 1 |
| mitochondrion | 1 |
| intracellular organelle lumen | 1 |
Experimentally-supported GO annotations
GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 30 annotations. The rest are phylogenetic / computational / electronic (IEA).
4 experimentally-supported GO terms:
| GO term | NS | Evidence |
|---|---|---|
| negative regulation of tumor necrosis factor production | BP | mutant phenotype |
| positive regulation of cellular senescence | BP | direct assay |
| mitochondrion | CC | direct assay |
| arginase activity | MF | mutant phenotype |
Protein interactions and networks
STRING
showing 15 of 2,546 interactions by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| ARG2 | OAT | P04181 | 965 |
| ARG2 | PYCR1 | P32322 | 821 |
| ARG2 | IL10 | P22301 | 815 |
| ARG2 | SLC7A2 | P52569 | 810 |
| ARG2 | ASS1 | P00966 | 792 |
| ARG2 | ASL | P04424 | 775 |
| ARG2 | ODC1 | P11926 | 764 |
| ARG2 | OTC | P00480 | 760 |
| ARG2 | IL4 | P05112 | 726 |
| ARG2 | AZIN2 | Q96A70 | 713 |
| ARG2 | IDO1 | P14902 | 700 |
| ARG2 | NOS2 | P35228 | 679 |
| ARG2 | IFNG | P01579 | 676 |
| ARG2 | SRM | P19623 | 676 |
| ARG2 | TGFB1 | P01137 | 675 |
IntAct
Human interaction partners of ARG2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).
8 partners by confidence:
| Partner | Interaction type | MIscore | Records |
|---|---|---|---|
| FOXD4L6 | physical association | 0.560 | 3 |
| ARG1 | physical association | 0.400 | 2 |
| BAG5 | physical association | 0.400 | 1 |
| DDX59 | physical association | 0.400 | 1 |
| NT5E | physical association | 0.400 | 1 |
| STK11 | physical association | 0.370 | 1 |
| DHX34 | association | 0.350 | 1 |
| CLIC6 | physical association | 0.000 | 1 |
BioGRID (22 interactions; top human partners by supporting records): ARG1 (Affinity Capture-MS; 2 records), CLPP (Proximity Label-MS; 2 records), MATN4 (Affinity Capture-MS; 2 records), BAG5 (Affinity Capture-MS), C1QBP (Proximity Label-MS), CAND1 (Affinity Capture-MS), CLIC1 (Affinity Capture-MS), CLIC6 (Two-hybrid), CPT2 (Affinity Capture-MS), DDX59 (Affinity Capture-MS), DHX34 (Affinity Capture-MS), GFM1 (Proximity Label-MS), HNRNPH1 (Affinity Capture-RNA), HSCB (Affinity Capture-MS), NT5E (Affinity Capture-MS)
SIGNOR signaling
1 signaling interactions:
| A | Effect | B | Mechanism |
|---|---|---|---|
| AR | “up-regulates quantity by expression” | ARG2 | “transcriptional regulation” |
Disease & clinical
Genetic variants
Variant evidence for ARG2: 75 ClinVar records (0 pathogenic / likely pathogenic).
ClinVar
75 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 60 |
| Likely benign | 3 |
| Benign | 1 |
SpliceAI
Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 703):
| Position(s) | Effect | Δscore | Sites |
|---|---|---|---|
| 14:67620089–67620090 | donor_loss | 1.0000 | 5 |
| 14:67642184–67642185 | acceptor_loss | 1.0000 | 3 |
| 14:67642364–67642365 | donor_loss | 1.0000 | 5 |
| 14:67646642–67646643 | acceptor_loss | 1.0000 | 4 |
| 14:67646739–67646740 | donor_loss | 1.0000 | 2 |
| 14:67647026–67647027 | donor_loss | 1.0000 | 5 |
| 14:67648045–67648046 | acceptor_loss | 1.0000 | 5 |
| 14:67648152 | donor_gain | 1.0000 | |
| 14:67648184–67648185 | donor_loss | 1.0000 | 5 |
| 14:67650714 | acceptor_loss | 1.0000 | 2 |
AlphaMissense
782 missense substitutions predicted likely pathogenic (of 2,283 scored), across 214 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 |
|---|---|---|---|
| D147 | 8 | 0.989 | 0.997 |
| D253 | 8 | 0.989 | 0.996 |
| D251 | 8 | 0.988 | 0.996 |
| D143 | 8 | 0.985 | 0.995 |
| D119 | 8 | 0.983 | 0.994 |
| H145 | 8 | 0.981 | 0.992 |
| H120 | 8 | 0.977 | 0.991 |
| H160 | 8 | 0.962 | 0.988 |
| D293 | 8 | 0.941 | 0.981 |
| H247 | 8 | 0.931 | 0.994 |
| D223 | 8 | 0.897 | 0.944 |
| D256 | 8 | 0.876 | 0.957 |
| D202 | 8 | 0.873 | 0.942 |
| M219 | 8 | 0.811 | 0.935 |
| D67 | 8 | 0.806 | 0.933 |
| E296 | 7 | 0.986 | 0.995 |
| W141 | 7 | 0.979 | 0.997 |
| E205 | 7 | 0.960 | 0.990 |
| W183 | 7 | 0.949 | 0.988 |
| E275 | 7 | 0.942 | 0.984 |
HPA cancer prognostics
RNA cancer specificity: Cancer enhanced (Prostate Adenocarcinoma)
Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.
3 prognostic cancer types:
| Cancer | Prognostic | p-value |
|---|---|---|
| Kidney Renal Clear Cell Carcinoma (validation) | favorable | 3.17e-06 |
| Lung Squamous Cell Carcinoma (validation) | favorable | 0.000403 |
| Skin Cutaneous Melanoma (TCGA) | unfavorable | 0.000533 |
Disease associations
OMIM: gene MIM:107830 | disease phenotypes:
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL1795148 (SINGLE PROTEIN)
Molecules with ChEMBL bioactivity
Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,010 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
2 molecules by phase:
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL4218271 | NUMIDARGISTAT | 2 | 972 |
| CHEMBL1234777 | NOR-NOHA | 1 | 38 |
PharmGKB: 1 entry (CPIC guideline: no)
PharmGKB variant annotations
Per-publication pharmacogenomic findings for this gene (significant associations).
1 published findings:
| Variant | Drug(s) | Category | Finding | PMID |
|---|---|---|---|---|
| rs3742879 | Methyldopa | Efficacy | Allele G is associated with increased response to Methyldopa in women with Pregnancy and Pre-Eclampsia as compared to allele A. | PMID:35971863 |
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)
197 measured of 206 human assays (215 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| CHEMBL4764455 | IC50 | 0.1 nM | |
| CHEMBL6161542 | IC50 | 0.1 nM | |
| CHEMBL4793482 | IC50 | 1 nM | |
| CHEMBL4749434 | IC50 | 1 nM | |
| CHEMBL4755855 | IC50 | 1 nM | |
| CHEMBL4750602 | IC50 | 1 nM | |
| CHEMBL5193387 | IC50 | 1 nM | |
| CHEMBL5184299 | IC50 | 1 nM | |
| CHEMBL5176739 | IC50 | 1 nM | |
| CHEMBL5171566 | IC50 | 1 nM | |
| CHEMBL5170454 | IC50 | 1 nM | |
| (+)-(R)-(5-amino-5-(1-(2-((2- fluorobenzyl)amino)-2-oxoethyl)-1H- tetrazol-5-yl)pentyl)boronic acid | IC50 | 3.4 nM | US-11845767: Arginase inhibitors |
| (5-amino-5-(1-(2-((2-fluorobenzyl)amino)- 2-oxoethyl)-1H-tetrazol-5- yl)pentyl)boronic acid | IC50 | 9.4 nM | US-11845767: Arginase inhibitors |
| (2R,4R)-4-amino-2-(4-boronobutyl)pyrrolidine-2-carboxylic acid | IC50 | 10 nM | US-11420984: Arginase inhibitors and methods of use thereof |
| (+)-(R)-(5-amino-5-(1-(2-oxo-2- (phenethylamino)ethyl)-1H-tetrazol-5- yl)pentyl)boronic acid | IC50 | 10.5 nM | US-11845767: Arginase inhibitors |
| (5-amino-5-(1-(2-((2,3- difluorobenzyl)amino)-2-oxoethyl)-1H- tetrazol-5-yl)pentyl)boronic acid | IC50 | 11.5 nM | US-11845767: Arginase inhibitors |
| (-)-(S)-(5-amino-5-(1-(2-((4- chlorobenzyl)amino)-2-oxoethyl)-1H- tetrazol-5-yl)pentyl)boronic acid | IC50 | 12 nM | US-11845767: Arginase inhibitors |
| (-)-(S)-(5-amino-5-(1-(2-oxo-2- (phenethylamino)ethyl)-1H-tetrazol-5- yl)pentyl)boronic acid | IC50 | 13.2 nM | US-11845767: Arginase inhibitors |
| (1S,2S)-1-amino-2-(3-boronopropyl)cyclopentanecarboxylic acid | IC50 | 14 nM | |
| (5-amino-5-(1-(2-((4-chlorobenzyl) amino)-2-oxoethyl)-1H-tetrazol-5- yl)pentyl)boronic acid | IC50 | 14 nM | US-11845767: Arginase inhibitors |
| (5-Amino-5-(1-(2-oxo-2- (phenethylamino)ethyl)-1H-tetrazol-5- yl)pentyl)boronic acid | IC50 | 15 nM | US-11845767: Arginase inhibitors |
| (+)-(R)-(5-amino-5-(1-(2-oxo-2-(prop-2- yn-1-ylamino)ethyl)-1H-tetrazol-5- yl)pentyl)boronic acid | IC50 | 15 nM | US-11845767: Arginase inhibitors |
| (5-amino-5-(1-(2-((4-chloro-2- fluorobenzyl)amino)-2-oxoethyl)-1H- tetrazol-5-yl)pentyl)boronic acid | IC50 | 15.5 nM | US-11845767: Arginase inhibitors |
| CHEMBL2418830 | IC50 | 17 nM | |
| (5-amino-5-(1-(2-oxo-2-(prop-2-yn-1- ylamino)ethyl)-1H-tetrazol-5- yl)pentyl)boronic acid | IC50 | 17 nM | US-11845767: Arginase inhibitors |
| CHEMBL4757930 | IC50 | 18 nM | |
| CHEMBL5572458 | IC50 | 20 nM | |
| CHEMBL2418831 | IC50 | 21 nM | |
| CHEMBL2418991 | IC50 | 22 nM | |
| CHEMBL4753285 | IC50 | 23 nM | |
| CHEMBL2418829 | IC50 | 24 nM | |
| CHEMBL4752391 | IC50 | 25 nM | |
| (-)-(S)-(5-amino-5-(1-(2-oxo-2-(prop-2- yn-1-ylamino)ethyl)-1H-tetrazol-5- yl)pentyl)boronic acid | IC50 | 28 nM | US-11845767: Arginase inhibitors |
| CHEMBL4778086 | IC50 | 29 nM | |
| CHEMBL4745275 | IC50 | 30 nM | |
| CHEMBL4750174 | IC50 | 31 nM | |
| (-)-(S)-(5-amino-5-(1-(2-((2- fluorobenzyl)amino)-2-oxoethyl)-1H- tetrazol-5-yl)pentyl)boronic acid | IC50 | 36.4 nM | US-11845767: Arginase inhibitors |
| CHEMBL6082888 | IC50 | 39 nM | |
| (+)-(R)-(5-amino-5-(1-(2-((4- chlorobenzyl)amino)-2-oxoethyl)-1H- tetrazol-5-yl)pentyl)boronic acid | IC50 | 55 nM | US-11845767: Arginase inhibitors |
| CHEMBL2326090 | IC50 | 60 nM | |
| (2S,4R)-2-(4-boronobutyl)-4-(dimethylamino)pyrrolidine-2-carboxylic acid | IC50 | 60 nM | US-11420984: Arginase inhibitors and methods of use thereof |
| CHEMBL2418828 | IC50 | 80 nM | |
| CHEMBL5276302 | IC50 | 86 nM | |
| 3-phenylprop-1-enylboronic acid | KI | 89 nM | |
| CHEMBL6102647 | IC50 | 90 nM | |
| (2S,4R)-4-(2-aminoethylamino)-2-(4-boronobutyl)pyrrolidine-2-carboxylic acid | IC50 | 90 nM | US-11420984: Arginase inhibitors and methods of use thereof |
| (3R,4S)-3-amino-4-(3-boronopropyl)-1-((1-methyl-1H-imidazol-2- yl)methyl)pyrrolidine-3-carboxylic acid | IC50 | 100 nM | |
| CHEMBL2326087 | IC50 | 100 nM | |
| CHEMBL2418998 | IC50 | 100 nM | |
| CHEMBL5197405 | IC50 | 100 nM |
ChEMBL bioactivities
243 potent at pChembl≥5 of 263 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
PubChem BioAssay actives
116 with measured affinity, of 149 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 |
| (2R,4R)-2-(4-boronobutyl)-4-(methylamino)pyrrolidine-2-carboxylic acid | 2207511: Inhibition of Arg2 (unknown origin) | ic50 | 0.0070 | uM |
| (2S)-2-amino-6-boronohexanoic acid | 1724057: Inhibition of human Arg2 at pH 7.5 | ki | 0.0085 | 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,4R)-4-amino-2-(4-boronobutyl)pyrrolidine-2-carboxylic acid | 2207511: Inhibition of Arg2 (unknown origin) | ic50 | 0.0150 | 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,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 |
| (2R)-2-(4-boronobutyl)pyrrolidine-2-carboxylic acid | 2218724: Inhibition of ARG2 (unknown origin) | ic50 | 0.0230 | 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 |
| (2R)-2-amino-6-borono-2-[3-(3-phenylpropylamino)cyclobutyl]hexanoic acid | 2218724: Inhibition of ARG2 (unknown origin) | ic50 | 0.0260 | 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 |
| (1R,2S,5R)-1-amino-5-(2-boronoethyl)-2-[(dimethylamino)methyl]cyclohexane-1-carboxylic acid | 2218728: Inhibition of human recombinant ARG2 extracted from Escherichia coli | ic50 | 0.0390 | 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 |
| (2S,3R)-3-(3-boronopropyl)pyrrolidine-2-carboxylic acid | 2207511: Inhibition of Arg2 (unknown origin) | ic50 | 0.0700 | 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 |
| (2S,3R)-2-amino-3-(aminomethyl)-6-boronohexanoic acid | 2207401: Inhibition of recombinant human Arg2 extracted from Escherichia coli incubated for 30 mins by Ellman’s method | ic50 | 0.0810 | 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,4R)-2-(4-boronobutyl)-4-(dimethylamino)pyrrolidine-2-carboxylic acid | 2207511: Inhibition of Arg2 (unknown origin) | ic50 | 0.1540 | 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 |
| (2S,3S)-2-amino-3-(aminomethyl)-6-boronohexanoic acid | 2207401: Inhibition of recombinant human Arg2 extracted from Escherichia coli incubated for 30 mins by Ellman’s method | ic50 | 0.2240 | 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 |
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 | affects cotreatment, decreases expression, increases expression | 4 |
| Valproic Acid | decreases expression, increases expression, affects 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 | affects cotreatment, decreases expression | 2 |
| Cisplatin | increases expression, decreases response to substance | 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)
Via MONDO — disease-level, not drug-specific.
showing 60 of 82 trials:
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00793988 | Phase 4 | COMPLETED | Vibration-Assisted Anaesthesia |
| NCT01239498 | Phase 4 | UNKNOWN | Saline Injection - Assisted Anesthesia in Eyelid Surgery |
| NCT02761083 | Phase 4 | WITHDRAWN | PMCF-study Using Novosyn® Quick Suture Material in Ophthalmic Surgery |
| NCT04007276 | Phase 4 | NOT_YET_RECRUITING | The Effect of Lumify™ on Ocular Redness, Intraocular Pressure, and Eyelid Position in Glaucoma Patients |
| NCT07390578 | Phase 4 | NOT_YET_RECRUITING | Upneeq vs. Lumify Ptosis |
| NCT01908972 | Phase 4 | COMPLETED | The Safety and Efficiency of Propranolol as an Initial Treatment for Pediatric Hemangioma |
| NCT04077515 | Phase 4 | COMPLETED | Safety and Efficacy of Low-dose Sirolimus to Kaposiform Hemangioendothelioma |
| NCT02436759 | Phase 3 | COMPLETED | Study of the Safety and Efficacy of RVL-1201 in the Treatment of Acquired Blepharoptosis |
| NCT03536949 | Phase 3 | COMPLETED | Study of Safety of RVL-1201 in Treatment of Blepharoptosis |
| NCT03565887 | Phase 3 | COMPLETED | Study of Safety and Efficacy of RVL-1201 in the Treatment of Blepharoptosis |
| NCT05945615 | Phase 3 | COMPLETED | Oxymetazoline Drops for Acquired Blepharoptosis From Synkinesis |
| NCT06683651 | Phase 3 | RECRUITING | A Study in Chinese Patients With Acquired Blepharoptosis |
| NCT06514612 | Phase 3 | 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 | Phase 3 | COMPLETED | Pulse Steroids Versus Oral Steroids in Problematic Hemangiomas of Infancy |
| NCT01685398 | Phase 3 | COMPLETED | Topical Timolol for Superficial Infantile Hemangioma |
| NCT01743885 | Phase 3 | TERMINATED | Efficacy and Safety of Propranolol Versus Acebutolol on the Proliferative Phase of Infantile Hemangioma |
| NCT02342275 | Phase 3 | COMPLETED | Efficacy and Safety of Propranolol Versus Atenolol on the Proliferative Phase of Infantile Hemangioma |
| NCT03266081 | Phase 2 | WITHDRAWN | Bupivacaine Epiphora Trial |
| NCT00555464 | Phase 2 | TERMINATED | Clinical Trial of Vincristine vs. Prednisolone for Treatment of Complicated Hemangiomas |
| NCT01072045 | Phase 2 | COMPLETED | Comparative Study of the Use of Beta Blocker and Oral Corticosteroid in the Treatment of Infantile Hemangioma |
| NCT01074437 | Phase 2 | TERMINATED | Corticosteroids With Placebo Versus Corticosteroids With Propranolol Treatment of Infantile Hemangiomas (IH) |
| NCT02145884 | Phase 2 | COMPLETED | Topical Timolol Gel for the Treatment of Infantile Hemangiomas |
| NCT02731287 | Phase 2 | COMPLETED | Topical Timolol for Infantile Hemangioma in Early Proliferative Phase |
| NCT07477548 | Phase 2 | NOT_YET_RECRUITING | A Study to Evaluate the Efficacy and Safety of Everolimus in Patients With Teratment-refractory Vascular Anomalies |
| NCT02496013 | Phase 1 | UNKNOWN | Clinical Translation of a Novel Albumin-Binding PET Radiotracer 68Ga-NEB |
| NCT02878694 | Phase 2/3 | TERMINATED | Treatment of Ptosis to Muscular Dystrophy Oculopharyngeal by Myoblast Autologous Graft |
| NCT05358977 | Phase 2/3 | UNKNOWN | Fibrin Sealant in Eyelid Surgery |
| NCT01848041 | Phase 1/2 | COMPLETED | Safety and Efficacy Study of RVL-1201 in Acquired Blepharoptosis |
| NCT05715346 | Phase 1/2 | COMPLETED | LEV102 Topical Gel in Acquired Blepharoptosis |
| NCT04807855 | Early Phase 1 | COMPLETED | Custom Print Megnetic Levator Prosthesis Pilot Comparison |
| NCT06911216 | Early Phase 1 | 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 |
| NCT02501187 | Not specified | UNKNOWN | Risk of Dry Eye Post Different Surgeries for Blepharoptosis Repair |
| NCT02638610 | Not specified | UNKNOWN | Assessment of Changes of Periocular Skin Sensation Following Eyelid and Ocular Surface Surgeries |
| NCT02959697 | Not specified | UNKNOWN | Subconjunctival Injection of Local Anesthetic in Anterior Blepharoptosis Repair |
| NCT02988856 | Not specified | COMPLETED | Magnetic Correction of Eye Lid Paralysis |
| NCT03149367 | Not specified | UNKNOWN | Surgical Management of Blepharoptosis |
| NCT03239418 | Not specified | TERMINATED | NMES to Improve Eyelid Functions in Cranial Nerve (CN) III and VII Palsy |
| NCT03375879 | Not specified | UNKNOWN | Bandage Contact Lens in Post Operative Ptosis Patients |
| NCT03812016 | Not specified | RECRUITING | A Feedback-enabled Magnetic Device for Temporary Management of Blepharoptosis |
| NCT03818204 | Not specified | COMPLETED | Clinical Trial to Improve the Magnetic Levator Prosthesis |
| NCT04214379 | Not specified | COMPLETED | Management of Severe Congenital Blepharoptosis |
| NCT04235803 | Not specified | COMPLETED | Telemedicine Follow-up for Routine, Low-Risk Oculoplastic Surgery |
| NCT04678115 | Not specified | COMPLETED | Clinical Trial Comparing Two Non-Surgical Treatments for Severe Blepharoptosis |
| NCT04714424 | Not specified | COMPLETED | Comparing Vision Tests in a Virtual Reality Headset to Existing Analogues |
| NCT04883853 | Not specified | COMPLETED | A Newly Modified Technique for Levator Muscle Tucking in Blepharoptosis Surgery: An Egyptian Tertiary Center Study |
| NCT05746078 | Not specified | RECRUITING | Performance and Safety Assessment of SPRING THREAD® Elastic Tensor Thread in Patients with Mild to Moderate Facial Ptosis. |
| NCT06047418 | Not specified | COMPLETED | Blepharoptosis in Indonesia: A 5-Year Multicenter Study on Characteristics and Surgical Evaluation |
| NCT06292182 | Not specified | UNKNOWN | Red Light Ptosis Proof-of-Concept |
| NCT07534436 | Not specified | RECRUITING | A Prospective Cohort Study on Visual Function and Psychological Conditions Before and After Surgery for Congenital Ptosis |
| NCT07821450 | Not specified | NOT_YET_RECRUITING | Blepharoptosis After Repeated Intravitreal Anti-VEGF Injections: A Prospective Study |
| NCT01147601 | Early Phase 1 | TERMINATED | Topical Timolol 0.5% Solution for Proliferating Infantile Hemangiomas |
Predicted chemistry — Sugi Predict
The predicted patent-compound landscape for ARG2 across ~30M SureChEMBL compounds — explore on Sugi Predict.
Related Atlas pages
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): blepharophimosis, hemangioma, ptosis