ARG1

Chr 6

arginase 1

NCBI Gene: 383 ENSG00000118520 UniProt: P05089

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.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtArgininemia

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · arginase deficiency · AR · ClinGen 2020

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

700

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.92

LOEUF

LOF

Mechanism· G2P

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?

0.92LOEUF

pLI 0.000

Z-score 1.81

OE 0.51 (0.30–0.92)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.06Z-score

OE missense 0.99 (0.87–1.12)

176 obs / 178.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.30–0.92)

0≤0.351.4

Missense OE?0.99 (0.87–1.12)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 8 / 15.7Missense obs/exp: 176 / 178.1Syn Z: 0.01

Background carrier burden — how many people carry a rare variant somewhere in ARG1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

424 rare PASS variants

Rare truncating (LoF)

1 in 1,100

85 rare PASS variants

Rare synonymous (reference)

1 in 320

155 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ARG1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 240	1 in 840
South Asian	~43k	1 in 140	1 in 3,300
Remaining (unassigned)	~30k	1 in 180	1 in 450
European (Finnish)	~27k	1 in 400	≈ 1 in 6,700
Admixed American	~22k	1 in 110	1 in 450
African / African American	~21k	1 in 130	1 in 1,100
East Asian	~20k	1 in 160	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 220	1 in 2,200
Middle Eastern	~2,884	1 in 360	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓