HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
ARG1
arginase 1
Chromosome 6 Β· 6q23.2
NCBI Gene: 383Ensembl: ENSG00000118520.16HGNC: HGNC:663UniProt: A0A5F9ZH78
279PubMed Papers
21Diseases
0Drugs
139Pathogenic Variants
RESEARCH IMPACT
TrendingVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
L-arginine catabolic processprotein bindingneutrophil-mediated killing of fungusGO:0005615Argininemiaarginase deficiencytype 2 diabetes mellitusgenetic disorder
✦AI Summary

ARG1 (arginase 1) catalyzes hydrolysis of L-arginine into L-ornithine and urea, functioning primarily in nitrogen detoxification within the urea cycle 1. Beyond its hepatic metabolic role, ARG1 plays critical immunoregulatory functions by competing with nitric oxide synthase for arginine substrate, thereby controlling arginine bioavailability and modulating immune responses 2. In myeloid cells, ARG1 expression defines alternatively activated macrophages and suppresses T cell proliferation through arginine depletion 23. In pancreatic cancer, ARG1 drives immune suppression by depleting arginine and inhibiting CD8+ T cell activation; genetic deletion or pharmacological inhibition with CB-1158 increases T cell infiltration and sensitizes tumors to checkpoint blockade 3. In stroke, STAT6-mediated ARG1 expression promotes microglia/macrophage-mediated efferocytosis of dying neurons, accelerating inflammation resolution and improving functional outcomes 4. Conversely, in ischemia/hypoxia-induced vascular dysfunction, elevated ARG1 drives pathological mitochondrial cristae remodeling and vascular smooth muscle cell PANoptosis via the cGAS-STING pathway 5. In pancreatic ductal adenocarcinoma, NET-associated human ARG1 is cleaved by cathepsin S into catalytically enhanced forms; anti-ARG1 monoclonal antibodies restore CD8+ T cell function and enhance immunotherapy efficacy 6. ARG1 deficiency causes hyperargininemia with neurological impairment, highlighting its essential metabolic role 7.

Sources cited
1
ARG1 catalyzes hydrolysis of L-arginine to L-ornithine and urea; crucial for nitrogen detoxification in urea cycle and arginine bioavailability control
PMID: 39952693
2
ARG1 expression defines alternatively activated M2 macrophages; iNOS/ARG1 dichotomy involved in macrophage polarization and arginine metabolism
PMID: 33460504
3
ARG1 in tumor-associated macrophages suppresses T cell activation by depleting arginine; arginase inhibitor CB-1158 enhances anti-PD1 efficacy in pancreatic cancer
PMID: 36727849
4
STAT6/ARG1 axis in microglia/macrophages promotes efferocytosis of dead neurons in stroke; ARG1 deficiency impairs inflammation resolution and worsens outcomes
PMID: 31619589
5
ARG1 upregulation in ischemic vascular smooth muscle cells drives mitochondrial cristae remodeling and PANoptosis via Mic10 interaction and mtDNA release
PMID: 40425583
6
NET-associated human ARG1 is cleaved by cathepsin S into enhanced forms; anti-ARG1 monoclonal antibodies restore CD8+ T cells and improve immunotherapy in PDAC
PMID: 36921034
7
ARG1 deficiency causes autosomal recessive hyperargininemia with spastic paraparesis, neurological impairment, and growth retardation
PMID: 26467175
Disease Associationsβ“˜21
ArgininemiaOpen Targets
0.80Strong
arginase deficiencyOpen Targets
0.78Strong
type 2 diabetes mellitusOpen Targets
0.47Moderate
genetic disorderOpen Targets
0.41Moderate
Abnormality of the skeletal systemOpen Targets
0.41Moderate
obesityOpen Targets
0.36Weak
metabolic syndromeOpen Targets
0.35Weak
cervical carcinomaOpen Targets
0.28Weak
neoplasmOpen Targets
0.12Weak
diabetes mellitusOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.12Weak
SepsisOpen Targets
0.11Weak
infectionOpen Targets
0.10Weak
sign or symptomOpen Targets
0.10Suggestive
strokeOpen Targets
0.10Suggestive
COVID-19Open Targets
0.09Suggestive
psoriasisOpen Targets
0.09Suggestive
Townes-Brocks syndromeOpen Targets
0.08Suggestive
influenzaOpen Targets
0.08Suggestive
Patent ductus arteriosusOpen Targets
0.08Suggestive
ArgininemiaUniProt
Pathogenic Variants139
NM_000045.4(ARG1):c.61C>T (p.Arg21Ter)Pathogenic
Arginase deficiency|not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2026β†’ Residue 21
NM_000045.4(ARG1):c.466-1G>CPathogenic
not provided|Arginase deficiency|ARG1-related disorder
β˜…β˜…β˜†β˜†2026
NM_000045.4(ARG1):c.923G>A (p.Arg308Gln)Pathogenic
Arginase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 308
NM_000045.4(ARG1):c.892G>C (p.Ala298Pro)Pathogenic
not provided|Arginase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 298
NM_000045.4(ARG1):c.938del (p.Lys313fs)Pathogenic
Arginase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 313
NM_000045.4(ARG1):c.679dup (p.Ile227fs)Pathogenic
Arginase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 227
NM_000045.4(ARG1):c.703G>A (p.Gly235Arg)Pathogenic
not provided|Arginase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 235
NM_000045.4(ARG1):c.860AAG[1] (p.Glu288del)Likely pathogenic
Arginase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 288
NM_000045.4(ARG1):c.295G>A (p.Gly99Arg)Pathogenic
Arginase deficiency|not provided|ARG1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 99
NM_000045.4(ARG1):c.871C>T (p.Arg291Ter)Pathogenic
Arginase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 291
NM_000045.4(ARG1):c.3G>A (p.Met1Ile)Pathogenic
Arginase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 1
NM_000045.4(ARG1):c.434T>A (p.Val145Glu)Pathogenic
Arginase deficiency|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 145
NM_000045.4(ARG1):c.370G>T (p.Asp124Tyr)Pathogenic
Arginase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 124
NM_000045.4(ARG1):c.365G>A (p.Trp122Ter)Pathogenic
Arginase deficiency|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 122
NM_000045.4(ARG1):c.80G>A (p.Gly27Asp)Pathogenic
Arginase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 27
NM_000045.4(ARG1):c.23T>A (p.Ile8Lys)Pathogenic
Arginase deficiency|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 8
NM_000045.4(ARG1):c.272dup (p.Arg92fs)Pathogenic
not provided|Arginase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 92
NM_000045.4(ARG1):c.404C>T (p.Thr135Ile)Pathogenic
Arginase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 135
NM_000045.4(ARG1):c.124G>T (p.Glu42Ter)Pathogenic
Arginase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 42
NM_000045.4(ARG1):c.425G>A (p.Gly142Glu)Pathogenic
Arginase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 142
View on ClinVar β†—
Related Genes
CD8AProtein interaction100%ASS1Protein interaction100%SRMProtein interaction100%CPS1Protein interaction100%ACY1Protein interaction99%OTCProtein interaction99%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
12%
Lung
1%
Ovary
0%
Brain
0%
Heart
0%
Gene Interaction Network
Click a node to explore
ARG1CD8AASS1SRMCPS1ACY1OTC
PROTEIN STRUCTURE
Preparing viewer…
PDB2AEB Β· 1.29 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.83LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.58 [0.41–0.83]
RankingsWhere ARG1 stands among ~20K protein-coding genes
  • #1,293of 20,598
    Most Researched279 Β· top 10%
  • #549of 5,498
    Most Pathogenic Variants139 Β· top 10%
  • #7,118of 17,882
    Most Constrained (LOEUF)0.83
Genes detectedARG1
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
STAT6/Arg1 promotes microglia/macrophage efferocytosis and inflammation resolution in stroke mice.
PMID: 31619589
JCI Insight Β· 2019
1.00
2
Arginase 1 drives mitochondrial cristae remodeling and PANoptosis in ischemia/hypoxia-induced vascular dysfunction.
PMID: 40425583
Signal Transduct Target Ther Β· 2025
0.90
3
Neutralization of NET-associated human ARG1 enhances cancer immunotherapy.
PMID: 36921034
Sci Transl Med Β· 2023
0.80
4
Targeting OXCT1-mediated ketone metabolism reprograms macrophages to promote antitumor immunity via CD8
PMID: 38759889
J Hepatol Β· 2024
0.70
5
Arginase-1-specific T cells target and modulate tumor-associated macrophages.
PMID: 39880485
J Immunother Cancer Β· 2025
0.60