OAZ1
protein-codingornithine decarboxylase antizyme 1
Gene summary
The protein encoded by this gene belongs to the ornithine decarboxylase antizyme family, which plays a role in cell growth and proliferation by regulating intracellular polyamine levels. Expression of antizymes requires +1 ribosomal frameshifting, which is enhanced by high levels of polyamines. Antizymes in turn bind to and inhibit ornithine decarboxylase (ODC), the key enzyme in polyamine biosynthesis; thus, completing the auto-regulatory circuit. This gene encodes antizyme 1, the first member of the antizyme family, that has broad tissue distribution, and negatively regulates intracellular polyamine levels by binding to and targeting ODC for degradation, as well as inhibiting polyamine uptake. Antizyme 1 mRNA contains two potential in-frame AUGs; and studies in rat suggest that alternative use of the two translation initiation sites results in N-terminally distinct protein isoforms with different subcellular localization. Alternatively spliced transcript variants have also been noted for this gene. [provided by RefSeq, Dec 2014]
- OAZ
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.0 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 OAZ1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript . 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 | 0 | |||||
| missense | 1 | 1 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 0 | 1 | 0 | 1 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001287949.1 | 6 | Standard | |
| RefSeq | NP_004143.1 | 6 | Standard | |
| Ensembl | ENSP00000463955.3 | 6 | Standard | |
| Ensembl | ENSP00000463955.3 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Nucleotide Metabolism
- Regulation of ornithine decarboxylase (ODC)
- Metabolism of polyamines
- Metabolism of amino acids and derivatives
- Metabolism
Biological Process
- regulation of cellular amino acid metabolic process
- polyamine biosynthetic process
- negative regulation of catalytic activity
- positive regulation of protein catabolic process
- positive regulation of intracellular protein transport
Molecular Function
- protein binding
- ornithine decarboxylase inhibitor activity
Cellular Component
- nucleus
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000602676
- Coding exons
- 6
- Length
- 4003
- Individuals with no LoFs
- 124111
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 124121
- p
- 0.0000403
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.875 | 160 | 132 | 1.21 | 0.00000767 | 1462 |
| Missense (PolyPhen) | 41 | 42.201 | 0.97154 | 482 | ||
| Synonymous | -3.50 | 95 | 60.4 | 1.57 | 0.00000416 | 443 |
| Loss of Function | 2.19 | 3 | 10.7 | 0.280 | 8.09e-7 | 94 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00014 | 0.00011 | rare |
| Finnish | 0.000049 | 0.000046 | rare |
| European (Non-Finnish) | 0.000064 | 0.000053 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Ornithine decarboxylase (ODC) antizyme protein that negatively regulates ODC activity and intracellular polyamine biosynthesis and uptake in response to increased intracellular polyamine levels. Binds to ODC monomers, inhibiting the assembly of the functional ODC homodimer, and targets the monomers for ubiquitin-independent proteolytic destruction by the 26S proteasome (PubMed:17900240, PubMed:26305948, PubMed:26443277). Triggers ODC degradation by inducing the exposure of a cryptic proteasome-interacting surface of ODC (PubMed:26305948). Stabilizes AZIN2 by interfering with its ubiquitination (PubMed:17900240). Also inhibits cellular uptake of polyamines by inactivating the polyamine uptake transporter. SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1. Involved in the translocation of AZIN2 from ER-Golgi intermediate compartment (ERGIC) to the cytosol (PubMed:12097147). {ECO:0000269|PubMed:12097147, ECO:0000269|PubMed:17900240, ECO:0000269|PubMed:26305948, ECO:0000269|PubMed:26443277}.;
Recessive Scores
- pRec
- 0.176
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Indispensability pred.
- E
- Indispensability score
- 0.914
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |