ARG1
Chr 6ARarginase 1
The protein catalyzes the final step of the urea cycle, converting L-arginine to urea and L-ornithine, with ornithine serving as a precursor for proline and polyamines essential for collagen synthesis and cell proliferation. Mutations cause argininemia, an autosomal recessive urea cycle disorder characterized by hyperargininemia and progressive neurological deterioration. The pathogenic mechanism involves loss of enzyme function leading to toxic accumulation of arginine and impaired urea production.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
499 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 39 | 11 | 14 | 0 | 64 |
Likely Pathogenic | 48 | 11 | 7 | 0 | 66 |
VUS | 6 | 109 | 29 | 0 | 144 |
Likely Benign | 2 | 4 | 82 | 112 | 200 |
Benign | 0 | 0 | 13 | 1 | 14 |
Conflicting | — | 9 | |||
| Total | 95 | 135 | 145 | 113 | 497 |
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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
RECRUITINGArginine Replacement Therapy in COVID-19
RECRUITINGHost 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 RECRUITINGHost Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools