ARG2

arginase 2

Basic information

Region (hg38): 14:67619919-67651708

Links

ENSG00000081181 ∙ NCBI:384 ∙ OMIM:107830 ∙ HGNC:664 ∙ Uniprot:P78540 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARG2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARG2 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				2	1	3
missense			26	1		27
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			3			3
Total	0	0	29	3	1

Variants in ARG2

This is a list of pathogenic ClinVar variants found in the ARG2 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-67619982-C-A		not specified	Uncertain significance (Aug 14, 2023)
14-67619987-A-T			Likely benign (Jun 04, 2018)
14-67619995-C-G		not specified	Uncertain significance (Mar 02, 2023)
14-67620085-G-A			Benign (Feb 01, 2018)
14-67620953-G-C		not specified	Uncertain significance (Jan 03, 2024)
14-67620954-C-G		not specified	Uncertain significance (Jun 05, 2024)
14-67642210-A-G		not specified	Uncertain significance (Dec 16, 2023)
14-67642305-G-A		not specified	Uncertain significance (Jul 25, 2023)
14-67642316-A-T		not specified	Uncertain significance (Mar 14, 2023)
14-67642317-G-C		not specified	Uncertain significance (May 04, 2022)
14-67645647-G-A		not specified	Uncertain significance (Jan 04, 2024)
14-67645675-G-A		not specified	Uncertain significance (Aug 17, 2021)
14-67645740-A-C		not specified	Uncertain significance (Nov 17, 2023)
14-67645767-C-A		not specified	Uncertain significance (Jul 05, 2022)
14-67645788-G-C		not specified	Uncertain significance (Apr 03, 2023)
14-67646644-G-A		not specified	Uncertain significance (Aug 10, 2023)
14-67646649-A-G			Likely benign (Jul 09, 2018)
14-67646662-T-C		not specified	Uncertain significance (Sep 20, 2023)
14-67646681-G-A		not specified	Uncertain significance (Jul 28, 2021)
14-67646692-G-T		not specified	Uncertain significance (Aug 21, 2023)
14-67646976-C-G		not specified	Uncertain significance (May 01, 2022)
14-67646979-G-T		not specified	Uncertain significance (Oct 02, 2023)
14-67648051-C-A		not specified	Uncertain significance (Jan 10, 2022)
14-67650779-G-A			Benign/Likely benign (Oct 01, 2022)
14-67650811-T-C		not specified	Uncertain significance (May 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARG2	protein_coding	protein_coding	ENST00000261783	8	31923

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000182	0.976	125658	0	90	125748	0.000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.344	176	189	0.930	0.00000918	2270
Missense in Polyphen		59	72.207	0.8171		842
Synonymous	0.153	69	70.6	0.977	0.00000337	739
Loss of Function	2.01	9	18.3	0.492	0.00000109	202

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00101	0.000999
Ashkenazi Jewish	0.000695	0.000695
East Asian	0.00174	0.00174
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000160	0.000158
Middle Eastern	0.00174	0.00174
South Asian	0.000196	0.000196
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in the regulation of extra-urea cycle arginine metabolism and also in down-regulation of nitric oxide synthesis. Extrahepatic arginase functions to regulate L-arginine bioavailability to nitric oxid synthase (NOS). Arginine metabolism is a critical regulator of innate and adaptive immune responses. Seems to be involved in negative regulation of the survival capacity of activated CD4(+) and CD8(+) T cells (PubMed:27745970). May suppress inflammation-related signaling in asthmatic airway epithelium (PubMed:27214549). May contribute to the immune evasion of H.pylori by restricting M1 macrophage activation and polyamine metabolism (By similarity). In fetal dendritic cells may play a role in promoting immune suppression and T cell TNF-alpha production during gestation (PubMed:28614294). Regulates RPS6KB1 signaling, which promotes endothelial cell senescence and inflammation and implicates NOS3/eNOS dysfunction (PubMed:22928666). Can inhibit endothelial autophagy independently of its enzymatic activity implicating mTORC2 signaling (PubMed:25484082). Involved in vascular smooth muscle cell senescence and apoptosis independently of its enzymatic activity (PubMed:23832324). Since NOS is found in the penile corpus cavernosum smooth muscle, the clitoral corpus cavernosum and the vagina, arginase-2 plays a role in both male and female sexual arousal (PubMed:12859189). {ECO:0000250|UniProtKB:O08691, ECO:0000269|PubMed:12859189, ECO:0000269|PubMed:22928666, ECO:0000269|PubMed:23832324, ECO:0000269|PubMed:25484082, ECO:0000269|PubMed:27214549, ECO:0000269|PubMed:27745970}.
• Pathway: Arginine and proline metabolism - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Arginine biosynthesis - Homo sapiens (human);Amino Acid metabolism;Urea cycle and metabolism of amino groups;Metabolism of polyamines;Metabolism of amino acids and derivatives;Metabolism;urea cycle;Arginine Proline metabolism;Urea cycle (Consensus)

Recessive Scores

• pRec: 0.487

Intolerance Scores

• loftool: 0.378
• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.22

Haploinsufficiency Scores

• pHI: 0.119
• hipred: Y
• hipred_score: 0.570
• ghis: 0.509

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.965

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arg2
• Phenotype: homeostasis/metabolism phenotype

Gene ontology

• Biological process: urea cycle;ureteric bud development;adaptive immune response;negative regulation of type 2 immune response;nitric oxide biosynthetic process;striated muscle contraction;arginine catabolic process to ornithine;negative regulation of tumor necrosis factor production;innate immune response;regulation of interleukin-1 beta secretion;negative regulation of macrophage inflammatory protein 1 alpha production;negative regulation of chemokine (C-C motif) ligand 4 production;negative regulation of chemokine (C-C motif) ligand 5 production;negative regulation of defense response to bacterium;regulation of reactive oxygen species biosynthetic process;negative regulation of tumor necrosis factor secretion;negative regulation of interleukin-17 secretion;negative regulation of activated CD8-positive, alpha-beta T cell apoptotic process;negative regulation of CD4-positive, alpha-beta T cell proliferation;negative regulation of interleukin-13 secretion;positive regulation of cellular senescence
• Cellular component: cytoplasm;mitochondrion;mitochondrial matrix
• Molecular function: arginase activity;manganese ion binding