OAZ2

Summary

OAZ2 (ornithine decarboxylase antizyme 2, HGNC:8096) is a protein-coding gene on chromosome 15q22.31, encoding Ornithine decarboxylase antizyme 2 (O95190). Ornithine decarboxylase (ODC) antizyme protein that negatively regulates ODC activity and intracellular polyamine biosynthesis and uptake in response to increased intracellular polyamine levels.

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 polyamines. 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 2, the second member of the antizyme family. Like antizyme 1, antizyme 2 has broad tissue distribution, inhibits ODC activity and polyamine uptake, and stimulates ODC degradation in vivo; however, it fails to promote ODC degradation in vitro. Antizyme 2 is expressed at lower levels than antizyme 1, but is evolutionary more conserved, suggesting it likely has an important biological role. Studies also show different subcellular localization of antizymes 1 and 2, indicating specific function for each antizyme in discrete compartments of the cell. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 4947 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 7 total

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8096
Approved symbol	OAZ2
Name	ornithine decarboxylase antizyme 2
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000180304
Ensembl biotype	protein_coding
OMIM	604152
Entrez	4947

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding_CDS_not_defined, 3 protein_coding, 2 retained_intron

ENST00000326005, ENST00000558194, ENST00000559555, ENST00000559665, ENST00000559753, ENST00000559912, ENST00000560258, ENST00000560781, ENST00000560837

RefSeq mRNA: 2 — MANE Select: None NM_001301302, NM_002537

CCDS: CCDS58372

Canonical transcript exons

ENST00000326005 — 6 exons

Exon	Start	End
ENSE00001300985	64691434	64691514
ENSE00002315371	64691516	64691591
ENSE00002564418	64690374	64690549
ENSE00002714089	64703029	64703281
ENSE00004035055	64687573	64688834
ENSE00004035056	64689084	64689169

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 72.4188 / max 805.3284, expressed in 1823 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150483	72.4188	1823

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.01	gold quality
monocyte	CL:0000576	97.96	gold quality
right testis	UBERON:0004534	97.96	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.88	gold quality
prefrontal cortex	UBERON:0000451	97.87	gold quality
amygdala	UBERON:0001876	97.82	gold quality
leukocyte	CL:0000738	97.76	gold quality
mononuclear cell	CL:0000842	97.76	gold quality
nucleus accumbens	UBERON:0001882	97.73	gold quality
gastrocnemius	UBERON:0001388	97.71	gold quality
cingulate cortex	UBERON:0003027	97.61	gold quality
right frontal lobe	UBERON:0002810	97.60	gold quality
spinal cord	UBERON:0002240	97.56	gold quality
anterior cingulate cortex	UBERON:0009835	97.56	gold quality
caudate nucleus	UBERON:0001873	97.55	gold quality
muscle of leg	UBERON:0001383	97.53	gold quality
hypothalamus	UBERON:0001898	97.52	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.51	gold quality
putamen	UBERON:0001874	97.48	gold quality
smooth muscle tissue	UBERON:0001135	97.47	gold quality
adenohypophysis	UBERON:0002196	97.44	gold quality
apex of heart	UBERON:0002098	97.41	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.41	gold quality
gall bladder	UBERON:0002110	97.33	gold quality
ganglionic eminence	UBERON:0004023	97.31	gold quality
right coronary artery	UBERON:0001625	97.30	gold quality
body of uterus	UBERON:0009853	97.22	gold quality
adrenal tissue	UBERON:0018303	97.13	gold quality
stromal cell of endometrium	CL:0002255	97.10	gold quality
granulocyte	CL:0000094	97.05	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	48.09
E-HCAD-11	yes	22.81
E-MTAB-9388	yes	11.84
E-GEOD-134144	yes	9.48
E-GEOD-93593	yes	9.30
E-GEOD-125970	no	3.64
E-HCAD-5	no	2.14
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

84 targeting OAZ2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-452-5P	99.65	69.63	1762

Literature-anchored findings (GeneRIF, showing 5)

• elevated ODC and low OAZ2 mRNA expression levels correlate with several unfavorable genetic and clinical features in neuroblastoma. (PMID:19960435)
• This study demomistrated that H3K4me3 modification plays an important role in up regulation of OAZ2 in prefrontal cortex. (PMID:22008221)
• Gene expression studies have identified altered expression of ornithine decarboxylase antizyme 2 in suicide completers with a history of mood disorders. (PMID:23260169)
• this study reveals a critical role of miR-34a/OAZ2 cascade in conferring a proper cellular response to colon cancer chemotherapy (PMID:30175154)
• The protein product is generated using polyamine-regulated programmed ribosomal frameshifting. (PMID:9782076)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	oaz2a	ENSDARG00000045929
danio_rerio	oaz2b	ENSDARG00000059815
mus_musculus	Oaz2	ENSMUSG00000040652
rattus_norvegicus	Oaz2	ENSRNOG00000015953

Paralogs (2): OAZ1 (ENSG00000104904), OAZ3 (ENSG00000143450)

Protein

Protein identifiers

Ornithine decarboxylase antizyme 2 — O95190 (reviewed: O95190)

All UniProt accessions (3): O95190, J3KRW5, J3KS80

UniProt curated annotations — full annotation on UniProt →

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 homodimers. Does not target the ODC monomers for degradation, which allows a protein synthesis-independent restoration of ODC activity. Involved in the translocation of AZIN2 from ER-Golgi intermediate compartment (ERGIC) to the cytosol.

Subunit / interactions. Interacts with ODC1 and thereby sterically blocks ODC homodimerization. Interacts with AZIN2; this interaction disrupts the interaction between the antizyme and ODC1.

Subcellular location. Nucleus.

Similarity. Belongs to the ODC antizyme family.

Isoforms (1)

UniProt ID	Names	Canonical?
O95190-1	1	yes

RefSeq proteins (1): NP_002528 (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002993	ODC_AZ	Family
IPR016181	Acyl_CoA_acyltransferase	Homologous_superfamily
IPR038581	ODC_AZ_sf	Homologous_superfamily

Pfam: PF02100

UniProt features (3 total): chain 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95190-F1	78.09	0.53

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 186

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-350562	Regulation of ornithine decarboxylase (ODC)
R-HSA-351202	Metabolism of polyamines

MSigDB gene sets: 273 (showing top): GCM_MAP4K4, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, PAX4_01, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, CMYB_01, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GGGTGGRR_PAX4_03, SP1_Q2_01, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_TRANSPORT, GOBP_POLYAMINE_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT

GO Biological Process (8): polyamine metabolic process (GO:0006595), polyamine biosynthetic process (GO:0006596), positive regulation of protein catabolic process (GO:0045732), viral translational frameshifting (GO:0075523), positive regulation of intracellular protein transport (GO:0090316), negative regulation of polyamine transmembrane transport (GO:1902268), translational frameshifting (GO:0006452), biogenic amine metabolic process (GO:0006576)

GO Molecular Function (2): ornithine decarboxylase inhibitor activity (GO:0008073), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of polyamines	1
Metabolism of amino acids and derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
biogenic amine metabolic process	1
polyamine metabolic process	1
biogenic amine biosynthetic process	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
viral process	1
viral translation	1
intracellular protein transport	1
positive regulation of intracellular transport	1
regulation of intracellular protein transport	1
positive regulation of protein transport	1
negative regulation of transmembrane transport	1
polyamine transmembrane transport	1
regulation of polyamine transmembrane transport	1
translational elongation	1
amine metabolic process	1
ornithine decarboxylase activity	1
enzyme inhibitor activity	1
ornithine decarboxylase regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

450 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OAZ2	AZIN1	O14977	941
OAZ2	ODC1	P11926	919
OAZ2	AZIN2	Q96A70	919
OAZ2	SMOX	Q9NWM0	613
OAZ2	PAOX	Q6QHF9	570
OAZ2	SMS	P52788	570
OAZ2	SAT1	P21673	437
OAZ2	IGSF8	Q969P0	424
OAZ2	ATG16L2	Q8NAA4	421
OAZ2	OR2D3	Q8NGH3	418
OAZ2	PIF1	Q9H611	407
OAZ2	UBE2L5	A0A1B0GUS4	400
OAZ2	THNSL1	Q8IYQ7	388
OAZ2	SRM	P19623	385
OAZ2	OR51A7	Q8NH64	376

IntAct

14 interactions, top by confidence:

A	B	Type	Score
AZIN1	OAZ2	psi-mi:“MI:0914”(association)	0.670
OAZ2	SYTL3	psi-mi:“MI:0915”(physical association)	0.560
OAZ2	CDR2	psi-mi:“MI:0915”(physical association)	0.560
AZIN2	OAZ2	psi-mi:“MI:0914”(association)	0.530
OAZ2	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
AZIN1	KIF5C	psi-mi:“MI:0914”(association)	0.350
ODC1	OAZ2	psi-mi:“MI:0915”(physical association)	0.000
OAZ2	AZIN1	psi-mi:“MI:0915”(physical association)	0.000
OAZ2	CDR2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): OAZ2 (Affinity Capture-RNA), OAZ2 (Affinity Capture-RNA), OAZ2 (Affinity Capture-MS), OAZ2 (Reconstituted Complex), OAZ2 (Affinity Capture-MS), OAZ2 (Affinity Capture-MS), OAZ2 (Affinity Capture-RNA), AZIN1 (Affinity Capture-MS), MYC (Affinity Capture-Western), OAZ2 (Affinity Capture-Western), MYC (Co-localization), OAZ2 (Two-hybrid), OAZ2 (Two-hybrid), OAZ2 (Two-hybrid), OAZ2 (Affinity Capture-MS)

ESM2 similar proteins: A4VCH4, B4F7E8, G3V7Q0, O08608, O14795, O42148, O70585, O95190, P0C7A6, P42225, P50747, P54368, P55814, Q05AA6, Q0VGY8, Q13474, Q1LVW0, Q2KIM1, Q2KJ58, Q3TLI0, Q3UHE1, Q4KM45, Q56K12, Q5JSJ4, Q5R680, Q5VZK9, Q5XII8, Q62768, Q62769, Q6EDY6, Q6IQ26, Q6NYU2, Q6PAL8, Q6WKZ8, Q7SYD9, Q7ZXK3, Q80YV4, Q8BND4, Q8IWV8, Q8K2I9

Diamond homologs: A1BPI0, O08608, O42148, O95190, P54368, P54369, P54370, P55814, P70112, Q56K12, Q5R680, Q9R109, Q9UMX2, Q9YI97, Q9YI98, P54361, Q95P51, O44535, Q9NHZ5, Q9NHZ6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

7 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

832 predictions. Top by Δscore:

Variant	Effect	Δscore
15:64688835:C:CC	acceptor_gain	1.0000
15:64689079:CTCAC:C	donor_loss	1.0000
15:64689081:CACC:C	donor_loss	1.0000
15:64689083:C:CT	donor_loss	1.0000
15:64689083:CCT:C	donor_gain	1.0000
15:64689102:T:TA	donor_gain	1.0000
15:64689165:ACAAT:A	acceptor_gain	1.0000
15:64689166:CAAT:C	acceptor_gain	1.0000
15:64689166:CAATC:C	acceptor_gain	1.0000
15:64689167:AAT:A	acceptor_gain	1.0000
15:64689167:AATC:A	acceptor_gain	1.0000
15:64689168:AT:A	acceptor_gain	1.0000
15:64689168:ATCT:A	acceptor_gain	1.0000
15:64689169:TC:T	acceptor_loss	1.0000
15:64689169:TCTGC:T	acceptor_gain	1.0000
15:64689170:C:CA	acceptor_loss	1.0000
15:64689170:C:CC	acceptor_gain	1.0000
15:64689174:A:T	acceptor_gain	1.0000
15:64689180:C:CT	acceptor_gain	1.0000
15:64690372:AC:A	donor_gain	1.0000
15:64690373:CC:C	donor_gain	1.0000
15:64690373:CCCTT:C	donor_gain	1.0000
15:64690385:C:CA	donor_gain	1.0000
15:64690421:CAGG:C	donor_gain	1.0000
15:64690480:A:AC	donor_gain	1.0000
15:64690481:C:CC	donor_gain	1.0000
15:64690545:TCGTC:T	acceptor_gain	1.0000
15:64690546:CGTC:C	acceptor_gain	1.0000
15:64690546:CGTCC:C	acceptor_gain	1.0000
15:64690547:GTC:G	acceptor_gain	1.0000

AlphaMissense

1242 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:64688801:A:G	F158S	1.000
15:64688805:C:G	G157R	1.000
15:64689119:A:T	V135D	1.000
15:64690450:A:G	W93R	1.000
15:64690450:A:T	W93R	1.000
15:64688746:G:C	F176L	0.999
15:64688746:G:T	F176L	0.999
15:64688748:A:G	F176L	0.999
15:64688771:A:T	V168D	0.999
15:64688800:A:C	F158L	0.999
15:64688800:A:T	F158L	0.999
15:64688802:A:G	F158L	0.999
15:64688802:A:T	F158I	0.999
15:64688804:C:A	G157V	0.999
15:64688804:C:T	G157D	0.999
15:64688809:G:C	F155L	0.999
15:64688809:G:T	F155L	0.999
15:64688811:A:G	F155L	0.999
15:64688816:A:G	F153S	0.999
15:64689146:G:T	A126D	0.999
15:64689147:C:G	A126P	0.999
15:64689155:A:G	L123P	0.999
15:64689158:A:G	L122P	0.999
15:64690379:T:A	K116N	0.999
15:64690379:T:G	K116N	0.999
15:64690422:A:G	L102P	0.999
15:64690444:C:G	A95P	0.999
15:64690485:A:G	F81S	0.999
15:64690533:A:T	V65E	0.999
15:64691524:A:G	W30R	0.999

dbSNP variants (sampled 300 via entrez): RS1000244034 (15:64703233 A>C,G), RS1000345984 (15:64703234 C>G), RS1000390714 (15:64691720 C>G,T), RS1000393660 (15:64696976 C>T), RS1000827899 (15:64697138 G>A), RS1000841723 (15:64699487 G>A), RS1001243268 (15:64702248 G>A,C), RS1001410425 (15:64689038 G>C), RS1001432514 (15:64695848 C>G), RS1001523243 (15:64689417 A>G), RS1001705585 (15:64698450 C>T), RS1001779178 (15:64698681 AC>A), RS1001800133 (15:64695597 C>T), RS1001952099 (15:64703626 A>G), RS1002235539 (15:64700575 C>T)

Disease associations

OMIM: gene MIM:604152 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002931_16	Aluminium levels	6.000000e-06
GCST005232_36	Neuroticism	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	3
Estradiol	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Valproic Acid	affects expression, decreases expression	2
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases expression	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Coumestrol	affects cotreatment, increases expression	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Selenium	increases expression	1
Dronabinol	decreases methylation	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Vitamin E	increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.