AZIN2
protein-codingantizyme inhibitor 2
Gene summary
The protein encoded by this gene belongs to the antizyme inhibitor family, which plays a role in cell growth and proliferation by maintaining polyamine homeostasis within the cell. Antizyme inhibitors are homologs of ornithine decarboxylase (ODC, the key enzyme in polyamine biosynthesis) that have lost the ability to decarboxylase ornithine; however, retain the ability to bind to antizymes. Antizymes negatively regulate intracellular polyamine levels by binding to ODC and targeting it for degradation, as well as by inhibiting polyamine uptake. Antizyme inhibitors function as positive regulators of polyamine levels by sequestering antizymes and neutralizing their effect. This gene encodes antizyme inhibitor 2, the second member of this gene family. Like antizyme inhibitor 1, antizyme inhibitor 2 interacts with all 3 antizymes and stimulates ODC activity and polyamine uptake. However, unlike antizyme inhibitor 1, which is ubiquitously expressed and localized in the nucleus and cytoplasm, antizyme inhibitor 2 is predominantly expressed in the brain and testis and localized in the endoplasmic reticulum-golgi intermediate compartment. Recent studies indicate that antizyme inhibitor 2 is also expressed in specific cell types in ovaries, adrenal glands and pancreas, and in mast cells. The exact function of this gene is not known, however, available data suggest its role in cell growth, spermiogenesis, vesicular trafficking and secretion. Accumulation of antizyme inhibitor 2 has also been observed in brains of patients with Alzheimer's disease. There has been confusion in literature and databases over the nomenclature of this gene, stemming from an earlier report that a human cDNA clone (identical to ODCp/AZIN2) had arginine decarboxylase (ADC) activity (PMID:14738999). Subsequent studies in human and mouse showed that antizyme inhibitor 2 was devoid of arginine decarboxylase activity (PMID:19956990). Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2014]
- ADC
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~42.4 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 AZIN2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_052998.4. 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 | 1 | 2 | |||
| missense | 53 | 4 | 2 | 59 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 57 | 4 | 3 | 64 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_443724.1 | 9 | MANE Select | |
| Ensembl | ENSP00000294517.6 | 9 | MANE Select | |
| RefSeq | NP_001280491.1 | 9 | Standard | |
| RefSeq | NP_001288752.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Arginine and proline metabolism - Homo sapiens (human)
- putrescine biosynthesis II
- Agmatine biosynthesis
- Metabolism of polyamines
- Metabolism of amino acids and derivatives
Biological Process
- spermatogenesis
- putrescine transport
- putrescine biosynthetic process from ornithine
- negative regulation of protein catabolic process
- positive regulation of catalytic activity
Molecular Function
- ornithine decarboxylase activity
- protein binding
- arginine decarboxylase activity
- putrescine transmembrane transporter activity
- ornithine decarboxylase activator activity
Cellular Component
- nucleus
- cytoplasm
- mitochondrion
- cis-Golgi network
- trans-Golgi network
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000294517
- Coding exons
- 9
- Length
- 39427
- Individuals with no LoFs
- 125709
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 39
- Defined
- 125748
- p
- 0.000155
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.467 | 246 | 267 | 0.920 | 0.0000147 | 3000 |
| Missense (PolyPhen) | 69 | 91.555 | 0.75365 | 1068 | ||
| Synonymous | 0.290 | 113 | 117 | 0.966 | 0.00000726 | 936 |
| Loss of Function | 1.75 | 13 | 21.8 | 0.596 | 0.00000112 | 238 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.00043 | 0.00042 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Antizyme inhibitor (AZI) protein that positively regulates ornithine decarboxylase (ODC) activity and polyamine uptake. AZI is an enzymatically inactive ODC homolog that counteracts the negative effect of ODC antizymes (AZs) OAZ1, OAZ2 and OAZ3 on ODC activity by competing with ODC for antizyme- binding (PubMed:17900240). Inhibits antizyme-dependent ODC degradation and releases ODC monomers from their inactive complex with antizymes, leading to formation of the catalytically active ODC homodimer and restoring polyamine production (PubMed:17900240). Participates in the morphological integrity of the trans-Golgi network (TGN) and functions as a regulator of intracellular secretory vesicle trafficking (PubMed:20188728). {ECO:0000269|PubMed:17900240, ECO:0000269|PubMed:20188728}.;
Recessive Scores
- pRec
- 0.324
Intolerance Scores
- RVIS EVS
- 0.0000761
- RVIS percentile EVS
- 53.98
Essentials
- Essential (gene trap)
- N