ARG1

Chr 6

arginase 1

NCBI Gene: 383ENSG00000118520UniProt: P05089

Arginase catalyzes the hydrolysis of arginine to ornithine and urea. At least two isoforms of mammalian arginase exist (types I and II) which differ in their tissue distribution, subcellular localization, immunologic crossreactivity and physiologic function. The type I isoform encoded by this gene, is a cytosolic enzyme and expressed predominantly in the liver as a component of the urea cycle. Inherited deficiency of this enzyme results in argininemia, an autosomal recessive disorder characterized by hyperammonemia. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

Primary Disease Associations & Inheritance

UniProtArgininemia
411
ClinVar variants
107
Pathogenic / LP
0.00
pLI score
4
Active trials
Clinical Summary— ARG1
🧬
Gene-Disease Validity (ClinGen)
hyperargininemia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
107 Pathogenic / Likely Pathogenic· 120 VUS of 411 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.92LOEUF
pLI 0.000
Z-score 1.81
OE 0.51 (0.30–0.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.06Z-score
OE missense 0.99 (0.87–1.12)
176 obs / 178.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.51 (0.30–0.92)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.87–1.12)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 8 / 15.7Missense obs/exp: 176 / 178.1Syn Z: 0.01

ClinVar Variant Classifications

411 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic47
VUS120
Likely Benign156
Benign16
Conflicting12
60
Pathogenic
47
Likely Pathogenic
120
VUS
156
Likely Benign
16
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
29
10
21
0
60
Likely Pathogenic
20
15
12
0
47
VUS
3
93
24
0
120
Likely Benign
1
1
65
89
156
Benign
0
0
14
2
16
Conflicting
—12
Total5311913691411

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ARG1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ARG1-related argininemia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — ARG1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Single-cell tumor heterogeneity landscape of hepatocellular carcinoma: unraveling the pro-metastatic subtype and its interaction loop with fibroblasts.
Guo DZ et al.·Mol Cancer
2024
STAT6/Arg1 promotes microglia/macrophage efferocytosis and inflammation resolution in stroke mice.
Cai W et al.·JCI Insight
2019Case report
Ultrasound reduces inflammation by modulating M1/M2 polarization of microglia through STAT1/STAT6/PPARγ signaling pathways.
Hsu CH et al.·CNS Neurosci Ther
2023
Neutralization of NET-associated human ARG1 enhances cancer immunotherapy.
Canè S et al.·Sci Transl Med
2023
Targeting OXCT1-mediated ketone metabolism reprograms macrophages to promote antitumor immunity via CD8(+) T cells in hepatocellular carcinoma.
Zhu CX et al.·J Hepatol
2024
Targeting CXCR2 inhibits the progression of lung cancer and promotes therapeutic effect of cisplatin.
Cheng Y et al.·Mol Cancer
2021
Twist1 regulates macrophage plasticity to promote renal fibrosis through galectin-3.
Wu Q et al.·Cell Mol Life Sci
2022
FFAR2 expressing myeloid-derived suppressor cells drive cancer immunoevasion.
Zhao Z et al.·J Hematol Oncol
2024
Arginase-1 deficiency.
Sin YY et al.·J Mol Med (Berl)
2015Review
Mesenchymal stem cells reciprocally regulate the M1/M2 balance in mouse bone marrow-derived macrophages.
Cho DI et al.·Exp Mol Med
2014Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
ARG1 inhibition after Neonatal Hypoxic-Ischemic Brain Injury.
Natarajan E et al.·Dev Neurosci
2026
Unraveling the matrix stiffness landscape in idiopathic pulmonary fibrosis: GSN and ARG1 as novel diagnostic biomarkers and potential therapeutic targets.
Chen J et al.·Int Immunopharmacol
2026
Fenchone alleviates 7-ketocholesterol-induced oxiapoptophagy through activation of KLF4-PPARγ-Arg1-mediated M2 macrophage signalling.
Ravi S et al.·J Steroid Biochem Mol Biol
2026
Histone lactylation-derived TET2 enhanced Arg1-mediated MDSC immunosuppression.
Da W et al.·Front Immunol
2025🔓 Open Access
NOS2/ARG1 axis and immune cell ratios as promising prognostic and predictive biomarkers for Cetuximab combined with chemotherapy in wt-KRAS human colorectal cancer.
Mataam DH et al.·Front Immunol
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
COVID-19

Arginine Replacement Therapy in COVID-19

RECRUITING
NCT05855330Phase PHASE2Emory UniversityStarted 2024-01-08
Arginine Hydrochloride
Single Cell Sequencing TechnologyGene Expression ProfilingGene Expression

Host Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA. a Prospective Study Will Evaluate the Performance of Direct LS-TA in Triage Febrile Patients Into Major Categories of Infections: Viral, Bacterial or Active Tuberculosis.

NOT YET RECRUITING
NCT06846645Chinese University of Hong KongStarted 2025-02
No intervention
Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING
NCT01793168Sanford HealthStarted 2010-07
Gene ExpressionGene Expression ProfilingInfection

Host Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA

ACTIVE NOT RECRUITING
NCT06838780Chinese University of Hong KongStarted 2018-01-01
No intervention

External Resources

Links to major genomics databases and tools