OAZ3

Summary

OAZ3 (ornithine decarboxylase antizyme 3, HGNC:8097) is a protein-coding gene on chromosome 1q21.3, encoding Ornithine decarboxylase antizyme 3 (Q9UMX2). 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 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 3, the third member of the antizyme family. Like antizymes 1 and 2, antizyme 3 inhibits ODC activity and polyamine uptake; however, it does not stimulate ODC degradation. Also, while antizymes 1 and 2 have broad tissue distribution, expression of antizyme 3 is restricted to haploid germ cells in testis, suggesting a distinct role for this antizyme in spermiogenesis. Antizyme 3 gene knockout studies showed that homozygous mutant male mice were infertile, and indicated the likely role of this antizyme in the formation of a rigid connection between the sperm head and tail during spermatogenesis. Alternatively spliced transcript variants encoding different isoforms, including one resulting from the use of non-AUG (CUG) translation initiation codon, have been found for this gene.

Source: NCBI Gene 51686 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 5 total

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8097
Approved symbol	OAZ3
Name	ornithine decarboxylase antizyme 3
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000143450
Ensembl biotype	protein_coding
OMIM	605138
Entrez	51686

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000321531, ENST00000400999, ENST00000453029, ENST00000479764, ENST00000577465, ENST00000582415, ENST00000635179, ENST00000635322, ENST00000635374

RefSeq mRNA: 3 — MANE Select: None NM_001134939, NM_001301371, NM_016178

CCDS: CCDS58028, CCDS76216, CCDS81378

Canonical transcript exons

ENST00000321531 — 6 exons

Exon	Start	End
ENSE00001262574	151767225	151767299
ENSE00001448047	151767163	151767223
ENSE00001607818	151762969	151763167
ENSE00002705945	151771077	151771330
ENSE00003480895	151770172	151770257
ENSE00003534776	151768058	151768233

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 99.79.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8185 / max 343.7268, expressed in 303 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5246	0.3777	203
5247	0.3168	4
5245	0.1241	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.79	gold quality
left testis	UBERON:0004533	98.85	gold quality
right testis	UBERON:0004534	98.68	gold quality
male germ cell	CL:0000015	98.64	gold quality
adult organism	UBERON:0007023	97.95	gold quality
testis	UBERON:0000473	96.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.04	gold quality
prostate gland	UBERON:0002367	81.49	gold quality
right hemisphere of cerebellum	UBERON:0014890	79.41	gold quality
cerebellar hemisphere	UBERON:0002245	79.40	gold quality
cerebellar cortex	UBERON:0002129	79.13	gold quality
right lobe of thyroid gland	UBERON:0001119	76.70	gold quality
left lobe of thyroid gland	UBERON:0001120	76.13	gold quality
cerebellum	UBERON:0002037	76.11	gold quality
hindlimb stylopod muscle	UBERON:0004252	75.62	gold quality
cauda epididymis	UBERON:0004360	75.20	gold quality
thyroid gland	UBERON:0002046	75.05	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	74.49	gold quality
right frontal lobe	UBERON:0002810	73.53	gold quality
anterior cingulate cortex	UBERON:0009835	72.85	gold quality
cingulate cortex	UBERON:0003027	72.78	gold quality
prefrontal cortex	UBERON:0000451	72.53	gold quality
saliva-secreting gland	UBERON:0001044	72.40	gold quality
right uterine tube	UBERON:0001302	71.90	gold quality
minor salivary gland	UBERON:0001830	71.83	gold quality
islet of Langerhans	UBERON:0000006	71.74	gold quality
rectum	UBERON:0001052	71.60	gold quality
corpus epididymis	UBERON:0004359	71.55	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	71.55	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	3409.81
E-CURD-112	yes	8.78
E-MTAB-9543	yes	7.19
E-ANND-3	yes	2.91
E-GEOD-124858	no	69.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZNF423

miRNA regulators (miRDB)

8 targeting OAZ3, 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-4325	99.49	72.20	1342
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-1265	98.36	66.46	598
HSA-MIR-5571-3P	97.80	66.07	640
HSA-MIR-7703	97.64	67.00	965
HSA-MIR-4749-3P	96.40	66.24	798
HSA-MIR-7975	95.04	66.76	516

Literature-anchored findings (GeneRIF, showing 2)

• antizyme expression requires programmed, ribosomal frameshifting (PMID:10781085)
• Mutations in the OAZ3 gene are not a common cause of male infertility. (PMID:16542438)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	oaz1b	ENSDARG00000104782
mus_musculus	Oaz3	ENSMUSG00000028141
rattus_norvegicus	Oaz3	ENSRNOG00000020863

Paralogs (2): OAZ1 (ENSG00000104904), OAZ2 (ENSG00000180304)

Protein

Protein identifiers

Ornithine decarboxylase antizyme 3 — Q9UMX2 (reviewed: Q9UMX2)

All UniProt accessions (8): Q9UMX2, A0A0G2JH29, A0A0U1RR57, A0A0U1RRA2, A8MW57, H0Y7Y4, J3QLT2, Q5SZR7

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. Stabilizes AZIN2 by interfering with its ubiquitination. Involved in the translocation of AZNI2 from ER-Golgi intermediate compartment (ERGIC) to the cytosol. Probably plays a key role in spermatogenesis by regulating the intracellular concentration of polyamines in haploid germ cells.

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

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Testis specific.

Similarity. Belongs to the ODC antizyme family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UMX2-1	1	yes
Q9UMX2-2	2

RefSeq proteins (3): NP_001128411, NP_001288300, NP_057262 (*=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 (6 total): splice variant 3, modified residue 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UMX2-F1	65.22	0.08

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 (2): 9, 12

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: 147 (showing top): GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_TRANSPORT, GOBP_POLYAMINE_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, JAZAG_TGFB1_SIGNALING_DN

GO Biological Process (7): polyamine biosynthetic process (GO:0006596), spermatogenesis (GO:0007283), positive regulation of protein catabolic process (GO:0045732), negative regulation of stress fiber assembly (GO:0051497), viral translational frameshifting (GO:0075523), positive regulation of intracellular protein transport (GO:0090316), negative regulation of polyamine transmembrane transport (GO:1902268)

GO Molecular Function (3): ornithine decarboxylase inhibitor activity (GO:0008073), ankyrin repeat binding (GO:0071532), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), blood microparticle (GO:0072562), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), sperm flagellum (GO:0036126)

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	6
sperm flagellum	2
polyamine metabolic process	1
biogenic amine biosynthetic process	1
developmental process involved in reproduction	1
male gamete generation	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
negative regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	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
ornithine decarboxylase activity	1
enzyme inhibitor activity	1
ornithine decarboxylase regulator activity	1
protein domain specific binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
extracellular region	1
9+2 motile cilium	1

Protein interactions and networks

STRING

824 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OAZ3	AZIN2	Q96A70	966
OAZ3	AZIN1	O14977	943
OAZ3	ODC1	P11926	928
OAZ3	GGNBP2	Q9H3C7	779
OAZ3	ODF1	Q14990	744
OAZ3	SPATA6	Q9NWH7	678
OAZ3	SPATA19	Q7Z5L4	629
OAZ3	TSSK6	Q9BXA6	615
OAZ3	CNTROB	Q8N137	606
OAZ3	CCDC42	Q96M95	593
OAZ3	PRSS21	Q9Y6M0	578
OAZ3	TPPP2	P59282	566
OAZ3	GGN	Q86UU5	529
OAZ3	TEKT2	Q9UIF3	524
OAZ3	CLBA1	Q96F83	523

IntAct

34 interactions, top by confidence:

A	B	Type	Score
AZIN1	OAZ3	psi-mi:“MI:0915”(physical association)	0.800
ODC1	OAZ3	psi-mi:“MI:0915”(physical association)	0.800
OAZ3	ODC1	psi-mi:“MI:0915”(physical association)	0.800
OAZ3	AZIN1	psi-mi:“MI:0914”(association)	0.800
C1orf94	OAZ3	psi-mi:“MI:0915”(physical association)	0.670
OAZ3	BLZF1	psi-mi:“MI:0915”(physical association)	0.670
OAZ3	C1orf94	psi-mi:“MI:0915”(physical association)	0.670
BLZF1	OAZ3	psi-mi:“MI:0915”(physical association)	0.670
AZIN2	OAZ3	psi-mi:“MI:0915”(physical association)	0.560
OAZ3	REL	psi-mi:“MI:0915”(physical association)	0.560
L3MBTL3	OAZ3	psi-mi:“MI:0915”(physical association)	0.560
OAZ3	IKZF3	psi-mi:“MI:0915”(physical association)	0.560
OAZ3	AZIN2	psi-mi:“MI:0915”(physical association)	0.560
REL	OAZ3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (69): OAZ3 (Two-hybrid), OAZ3 (Two-hybrid), OAZ3 (Two-hybrid), OAZ3 (Two-hybrid), OAZ3 (Two-hybrid), L3MBTL3 (Two-hybrid), C1orf94 (Two-hybrid), AZIN2 (Two-hybrid), AZIN1 (Reconstituted Complex), ODC1 (Reconstituted Complex), AZIN1 (Affinity Capture-MS), ODC1 (Affinity Capture-MS), FABP4 (Affinity Capture-MS), TCHH (Affinity Capture-MS), LYPLA2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M9QN10, A1BPI0, A2ARM1, A2CI97, A2CI98, A2CJ06, C9JE40, O15055, O43147, O54943, O70173, O70303, O70361, O95238, P0C2N6, P0C6P5, P56645, P59025, P59729, P97433, Q0P4K8, Q3TD16, Q5EB20, Q5PQS0, Q5SSZ5, Q5VUB5, Q6IRN0, Q6P4K6, Q76I79, Q7TSI1, Q80TQ5, Q80UW3, Q810F8, Q8C8C1, Q8CCC3, Q8CJE2, Q8N1W1, Q8ND61, Q8TB24, Q8WWF5

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

5 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

1031 predictions. Top by Δscore:

Variant	Effect	Δscore
1:151762983:GCCTT:G	donor_loss	1.0000
1:151762984:CCTTA:C	donor_loss	1.0000
1:151762986:TTA:T	donor_loss	1.0000
1:151762987:TA:T	donor_loss	1.0000
1:151762988:A:AC	donor_gain	1.0000
1:151762988:A:AG	donor_loss	1.0000
1:151762988:ACTCT:A	donor_gain	1.0000
1:151762989:C:CA	donor_gain	1.0000
1:151762989:CT:C	donor_gain	1.0000
1:151762989:CTCTC:C	donor_gain	1.0000
1:151762992:T:A	donor_gain	1.0000
1:151762999:A:AC	donor_gain	1.0000
1:151763000:C:CC	donor_gain	1.0000
1:151763143:TGCC:T	acceptor_gain	1.0000
1:151763143:TGCCC:T	acceptor_loss	1.0000
1:151763145:CC:C	acceptor_gain	1.0000
1:151763146:CC:C	acceptor_gain	1.0000
1:151763146:CCTGG:C	acceptor_loss	1.0000
1:151763147:C:CC	acceptor_gain	1.0000
1:151763147:CTGGC:C	acceptor_loss	1.0000
1:151763148:T:A	acceptor_loss	1.0000
1:151763152:G:T	acceptor_gain	1.0000
1:151763155:C:CT	acceptor_gain	1.0000
1:151763156:A:T	acceptor_gain	1.0000
1:151763318:AGC:A	donor_gain	1.0000
1:151763324:CAC:C	donor_loss	1.0000
1:151763325:A:AT	donor_loss	1.0000
1:151763325:AC:A	donor_gain	1.0000
1:151763326:C:CG	donor_loss	1.0000
1:151763326:CC:C	donor_gain	1.0000

AlphaMissense

1241 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:151771109:T:C	F200L	0.996
1:151771111:T:A	F200L	0.996
1:151771111:T:G	F200L	0.996
1:151771110:T:C	F200S	0.993
1:151771094:T:C	F195L	0.992
1:151771096:C:A	F195L	0.992
1:151771096:C:G	F195L	0.992
1:151768121:T:C	F123L	0.986
1:151768122:T:C	F123S	0.986
1:151768123:T:A	F123L	0.986
1:151768123:T:G	F123L	0.986
1:151768157:T:A	W135R	0.985
1:151768157:T:C	W135R	0.985
1:151770174:T:C	L161S	0.983
1:151770222:T:A	V177E	0.981
1:151771095:T:C	F195S	0.981
1:151771110:T:G	F200C	0.979
1:151770234:T:C	F181S	0.978
1:151771106:G:C	G199R	0.978
1:151771109:T:A	F200I	0.977
1:151771109:T:G	F200V	0.977
1:151770228:T:A	V179E	0.975
1:151771163:T:C	F218L	0.975
1:151771165:T:A	F218L	0.975
1:151771165:T:G	F218L	0.975
1:151768164:G:A	G137D	0.974
1:151768187:T:C	F145L	0.974
1:151768189:C:A	F145L	0.974
1:151768189:C:G	F145L	0.974
1:151768068:T:C	L105S	0.971

dbSNP variants (sampled 300 via entrez): RS1000077895 (1:151771494 T>C,G), RS1000681460 (1:151761067 T>C), RS1001105807 (1:151765278 T>C), RS1001130916 (1:151764478 C>G,T), RS1001159552 (1:151764943 C>T), RS1001225777 (1:151764007 G>C), RS1001679728 (1:151771412 T>C,G), RS1001748100 (1:151770221 G>C), RS1002133291 (1:151765941 G>A), RS1002856014 (1:151769589 G>A,C,T), RS1003136332 (1:151767479 T>C), RS1003456080 (1:151761349 G>A,C), RS1003473428 (1:151769195 G>A), RS1003809841 (1:151761658 A>G), RS1004116666 (1:151766001 G>A)

Disease associations

OMIM: gene MIM:605138 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004162_38	Carotid plaque burden	6.000000e-06
GCST007387_26	Insomnia symptoms (never/rarely vs. sometimes/usually)	9.000000e-06
GCST007388_18	Insomnia symptoms (never/rarely vs. usually)	4.000000e-08
GCST008916_130	Asthma	1.000000e-12
GCST008916_88	Asthma	1.000000e-25

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006501	carotid plaque build
EFO:0007876	insomnia measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression	2
aristolochic acid I	increases expression	1
urushiol	decreases expression	1
bufotalin	increases expression	1
triphenyl phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
afimoxifene	increases expression	1
abrine	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	decreases expression	1
Methotrexate	increases expression	1
Niclosamide	increases expression	1
Aflatoxin B1	increases methylation	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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