ARG2
protein-codingarginase 2
Gene summary
Arginase catalyzes the hydrolysis of arginine to ornithine and urea. At least two isoforms of mammalian arginase exists (types I and II) which differ in their tissue distribution, subcellular localization, immunologic crossreactivity and physiologic function. The type II isoform encoded by this gene, is located in the mitochondria and expressed in extra-hepatic tissues, especially kidney. The physiologic role of this isoform is poorly understood; it is thought to play a role in nitric oxide and polyamine metabolism. Transcript variants of the type II gene resulting from the use of alternative polyadenylation sites have been described. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~31.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ARG2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001172.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 1 | 4 | ||
| missense | 49 | 2 | 51 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 50 | 4 | 1 | 55 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001163.1 | 8 | MANE Select | |
| Ensembl | ENSP00000261783.3 | 8 | MANE Select | |
| Ensembl | ENSP00000597963.1 | 7 | Standard | |
| Ensembl | ENSP00000597963.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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
Biological Process
- urea cycle
- ureteric bud development
- adaptive immune response
- negative regulation of type 2 immune response
- nitric oxide biosynthetic process
Molecular Function
- arginase activity
- manganese ion binding
Cellular Component
- cytoplasm
- mitochondrion
- mitochondrial matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261783
- Coding exons
- 8
- Length
- 31923
- Individuals with no LoFs
- 125658
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 90
- Defined
- 125748
- p
- 0.000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.344 | 176 | 189 | 0.930 | 0.00000918 | 2270 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00075 | 0.00074 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0.00069 | 0.00069 | rare |
| East Asian | 0.0017 | 0.0017 | notable |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.487
Intolerance Scores
- LoFtool
- 0.378
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 50.22
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.965
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |