OAZ2

Chr 15

ornithine decarboxylase antizyme 2

Also known as: AZ2

NCBI Gene: 4947 ENSG00000180304 UniProt: O95190

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. [provided by RefSeq, Dec 2014]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.76

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.76LOEUF

pLI 0.313

Z-score 2.03

OE 0.24 (0.10–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.27Z-score

OE missense 0.63 (0.52–0.79)

61 obs / 96.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.10–0.76)

0≤0.351.4

Missense OE?0.63 (0.52–0.79)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 2 / 8.3Missense obs/exp: 61 / 96.1Syn Z: 0.34

Background carrier burden — how many people carry a rare variant somewhere in OAZ2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 320

238 rare PASS variants

Rare truncating (LoF)

1 in 2,000

34 rare PASS variants

Rare synonymous (reference)

1 in 670

104 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for OAZ2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 420	1 in 1,700
South Asian	~43k	1 in 320	≈ 1 in 41,000
Remaining (unassigned)	~30k	1 in 310	≈ 1 in 9,100
European (Finnish)	~27k	1 in 1,500	≈ 1 in 7,900
Admixed American	~22k	1 in 450	≈ 1 in 19,000
African / African American	~21k	1 in 440	1 in 3,500
East Asian	~20k	1 in 350	none seen
Ashkenazi Jewish	~13k	≈ 1 in 6,300	≈ 1 in 13,000
Middle Eastern	~2,884	≈ 1 in 710	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 6 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 6.? see exons ↓