Key element of the urea cycle converting L-arginine to urea and L-ornithine, which is further metabolized into metabolites proline and polyamides that drive collagen synthesis and bioenergetic pathways critical for cell proliferation, respectively; the urea cycle takes place primarily in the liver and, to a lesser extent, in the kidneys

OMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.921 OMIM phenotype
VCEP Guidelines: Urea Cycle DisordersReleased
ClinGen Panel
Clinical SummaryARG1
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Gene-Disease Validity (ClinGen)
arginase deficiency · 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.
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.92LOEUF
pLI 0.000
Z-score 1.81
OE 0.51 (0.300.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.06Z-score
OE missense 0.99 (0.871.12)
176 obs / 178.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.51 (0.300.92)
00.351.4
Missense OE?0.99 (0.871.12)
00.61.4
Synonymous OE?1.00
01.21.6
LoF obs/exp: 8 / 15.7Missense obs/exp: 176 / 178.1Syn Z: 0.01
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveARG1-related argininemiaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.75top 25%
GOF
0.4874th %ile
LOF
0.3260th %ile

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

0 submitted variants 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.