ARG1

arginase 1

Basic information

Region (hg38): 6:131470832-131584332

Links

ENSG00000118520 ∙ NCBI:383 ∙ OMIM:608313 ∙ HGNC:663 ∙ Uniprot:P05089 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperargininemia (Definitive), mode of inheritance: AR
• hyperargininemia (Definitive), mode of inheritance: AR
• hyperargininemia (Strong), mode of inheritance: AR
• hyperargininemia (Definitive), mode of inheritance: AR
• hyperargininemia (Supportive), mode of inheritance: AR
• hyperargininemia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperargininemia	AR	Biochemical; Pharmacogenomic	Dietary and medical therapy (eg, with low-protein, arginine restricted diet, sodium benzoate, as well as with enzyme replacement), may be beneficial; Individuals with more severe and earlier presentations (similar to that of other urea cycle disorders) have been reported, and may benefit from similar care to prevent and acute sequelae; Individuals with urea cycle disorders may demonstrate sensitivity to certain agents, such as valproate	Biochemical; Neurologic	1124944; 839368; 624188; 6422160; 3104676; 2913054; 2311630; 2365823; 2246859; 2291040; 8474825; 7649538; 9762606; 12640389; 16963300; 19052914; 19381865; 21229317; 21802329; 21310339; 22959135; 22928720; 22633632; 25135652; 29726057; 36049366

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARG1 gene.

• Arginase deficiency (53 variants)
• not provided (6 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARG1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				139	2	141
missense	9	11	117	4		141
nonsense	6	8	1	1		16
start loss		2				2
frameshift	30	24	3			57
inframe indel	1		7			8
splice donor/acceptor (+/-2bp)	8	15				23
splice region			6	19	1	26
non coding			8	62	15	85
Total	54	60	136	206	17

Highest pathogenic variant AF is 0.0000197

Variants in ARG1

This is a list of pathogenic ClinVar variants found in the ARG1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-131572958-G-A			Likely benign (Jul 27, 2018)
6-131573213-A-G		Arginase deficiency	Uncertain significance (Jan 13, 2018)
6-131573218-C-T		Arginase deficiency	Benign (Jun 29, 2018)
6-131573262-A-C		Arginase deficiency	Uncertain significance (May 19, 2022)
6-131573284-T-C		Arginase deficiency	Pathogenic/Likely pathogenic (Feb 24, 2022)
6-131573285-G-A		Arginase deficiency	Pathogenic/Likely pathogenic (Oct 15, 2023)
6-131573286-A-G		Arginase deficiency	Uncertain significance (Dec 31, 2021)
6-131573287-G-T		Arginase deficiency	Uncertain significance (Nov 27, 2021)
6-131573288-C-T		Arginase deficiency	Likely benign (Nov 15, 2023)
6-131573289-G-A		Arginase deficiency	Uncertain significance (Jul 12, 2022)
6-131573289-G-C		Arginase deficiency	Uncertain significance (Oct 24, 2022)
6-131573291-C-G		Arginase deficiency	Likely benign (May 10, 2023)
6-131573296-C-G		Arginase deficiency	Uncertain significance (Jul 25, 2022)
6-131573297-C-G			Likely benign (Nov 27, 2018)
6-131573298-A-G		Arginase deficiency	Uncertain significance (Sep 06, 2022)
6-131573301-A-C		Arginase deficiency	Uncertain significance (Aug 19, 2022)
6-131573304-A-G		Arginase deficiency	Uncertain significance (Oct 03, 2023)
6-131573305-T-A		Arginase deficiency • not specified	Conflicting classifications of pathogenicity (May 14, 2024)
6-131573310-AT-A		Arginase deficiency	Likely pathogenic (Jun 16, 2020)
6-131573312-T-C		Arginase deficiency	Likely benign (Aug 04, 2023)
6-131573314-T-C		Arginase deficiency	Pathogenic/Likely pathogenic (Mar 03, 2024)
6-131573324-T-A		Arginase deficiency	Likely benign (Feb 01, 2024)
6-131573324-T-G		Arginase deficiency	Likely benign (Nov 27, 2023)
6-131573329-CA-C		Arginase deficiency	Pathogenic (Mar 21, 2022)
6-131573330-A-C		Arginase deficiency	Likely benign (Jul 26, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARG1	protein_coding	protein_coding	ENST00000356962	8	11189

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000359	0.957	125691	0	53	125744	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0560	176	178	0.988	0.00000862	2125
Missense in Polyphen		74	77.994	0.94879		913
Synonymous	0.0143	67	67.1	0.998	0.00000355	685
Loss of Function	1.81	8	15.7	0.508	8.27e-7	194

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00131	0.00131
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000109	0.000109
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. {ECO:0000305}.
• Disease: DISEASE: Argininemia (ARGIN) [MIM:207800]: A rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia and progressive spastic quadriplegia. {ECO:0000269|PubMed:1463019, ECO:0000269|PubMed:22959135, ECO:0000269|PubMed:23859858, ECO:0000269|PubMed:7649538}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Arginine and proline metabolism - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Arginine biosynthesis - Homo sapiens (human);Argininemia;Hyperornithinemia with gyrate atrophy (HOGA);Creatine deficiency, guanidinoacetate methyltransferase deficiency;L-arginine:glycine amidinotransferase deficiency;Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome];Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency);Citrullinemia Type I;Carbamoyl Phosphate Synthetase Deficiency;Argininosuccinic Aciduria;Urea Cycle;Prolinemia Type II;Prolidase Deficiency (PD);Ornithine Transcarbamylase Deficiency (OTC Deficiency);Arginine and Proline Metabolism;Hyperprolinemia Type I;Hyperprolinemia Type II;Ornithine Aminotransferase Deficiency (OAT Deficiency);Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency);Spinal Cord Injury;Amino Acid metabolism;Urea cycle and metabolism of amino groups;Neutrophil degranulation;Metabolism of polyamines;Metabolism of amino acids and derivatives;Innate Immune System;Immune System;Metabolism;ATF-2 transcription factor network;urea cycle;Arginine Proline metabolism;IL4-mediated signaling events;Urea cycle (Consensus)

Recessive Scores

• pRec: 0.431

Intolerance Scores

• loftool: 0.321
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.75

Haploinsufficiency Scores

• pHI: 0.656
• hipred: N
• hipred_score: 0.276
• ghis: 0.581

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.984

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Arg1
• Phenotype: homeostasis/metabolism phenotype; hematopoietic system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; immune system phenotype

Gene ontology

• Biological process: urea cycle;liver development;positive regulation of endothelial cell proliferation;adaptive immune response;arginine catabolic process;aging;response to herbicide;response to manganese ion;response to zinc ion;response to selenium ion;regulation of L-arginine import;response to amine;arginine catabolic process to ornithine;lung development;collagen biosynthetic process;response to vitamin A;response to vitamin E;negative regulation of T cell proliferation;defense response to protozoan;response to amino acid;neutrophil degranulation;innate immune response;negative regulation of activated T cell proliferation;response to cadmium ion;response to axon injury;response to methylmercury;mammary gland involution;maternal process involved in female pregnancy;negative regulation of interferon-gamma-mediated signaling pathway;protein homotrimerization;cellular response to hydrogen peroxide;positive regulation of neutrophil mediated killing of fungus;cellular response to lipopolysaccharide;cellular response to interleukin-4;cellular response to glucagon stimulus;cellular response to dexamethasone stimulus;cellular response to transforming growth factor beta stimulus;negative regulation of T-helper 2 cell cytokine production
• Cellular component: extracellular region;extracellular space;nucleus;cytoplasm;mitochondrial outer membrane;cytosol;azurophil granule lumen;specific granule lumen;neuron projection;neuronal cell body
• Molecular function: arginase activity;protein binding;manganese ion binding