ODC1

Chr 2AD

ornithine decarboxylase 1

Also known as: BABS, NEDBA, NEDBIA, ODC

NCBI Gene: 4953ENSG00000115758UniProt: P11926

This gene encodes the rate-limiting enzyme of the polyamine biosynthesis pathway which catalyzes ornithine to putrescine. The activity level for the enzyme varies in response to growth-promoting stimuli and exhibits a high turnover rate in comparison to other mammalian proteins. Originally localized to both chromosomes 2 and 7, the gene encoding this enzyme has been determined to be located on 2p25, with a pseudogene located on 7q31-qter. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Dec 2013]

Primary Disease Associations & Inheritance

Bachmann-Bupp syndromeMIM #619075
AD
127
ClinVar variants
28
Pathogenic / LP
0.17
pLI score
1
Active trials
Clinical Summary— ODC1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 62 VUS of 127 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.54LOEUF
pLI 0.170
Z-score 3.02
OE 0.26 (0.13–0.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.47Z-score
OE missense 0.75 (0.67–0.84)
209 obs / 277.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.26 (0.13–0.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.67–0.84)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.12
0≤1.21.6
LoF obs/exp: 5 / 19.4Missense obs/exp: 209 / 277.8Syn Z: -0.95

ClinVar Variant Classifications

127 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic4
VUS62
Likely Benign32
Benign4
Conflicting1
24
Pathogenic
4
Likely Pathogenic
62
VUS
32
Likely Benign
4
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
21
0
24
Likely Pathogenic
2
0
2
0
4
VUS
7
46
9
0
62
Likely Benign
0
24
0
8
32
Benign
0
1
2
1
4
Conflicting
—1
Total1271349127

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ODC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ODC1-related neurodevelopmental disorder

strong
ADGain Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗
stop gained NMD escapingframeshift variant NMD escaping

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Bachmann-Bupp syndrome

MIM #619075

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — ODC1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A clinical-stage Nrf2 activator suppresses osteoclast differentiation via the iron-ornithine axis.
Dong Y et al.·Cell Metab
2024
A surge in endogenous spermidine is essential for rapamycin-induced autophagy and longevity.
Hofer SJ et al.·Autophagy
2024
Eflornithine for treatment of high-risk neuroblastoma.
Jiang J et al.·Trends Pharmacol Sci
2024
ODC1 loss upon KLF6 upregulation promotes macrophage pyroptosis and acute kidney injury in sepsis.
Ding J et al.·Hum Cell
2025
Emerging Role of ODC1 in Neurodevelopmental Disorders and Brain Development.
Prokop JW et al.·Genes (Basel)
2021
Polyamine depletion limits progression of acute leukaemia.
Gao W et al.·Int J Cancer
2025
Androgen Receptor Drives Polyamine Synthesis, Creating a Vulnerability for Prostate Cancer.
Kumar R et al.·Cancer Res
2026
IP-SNPs-seq links noncoding risk alleles to lineage transcription factor programs in prostate cancer.
Xu W et al.·Cell Mol Life Sci
2025
Novel de novo pathogenic variant in the ODC1 gene in a girl with developmental delay, alopecia, and dysmorphic features.
Bupp CP et al.·Am J Med Genet A
2018Case report
A gain-of-function PIK3CD variant, R512W, impairs T cell function through polyamine-dependent metabolic dysregulation.
Kiyota K et al.·Biochem Biophys Res Commun
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Recurrent Ovarian High Grade Serous AdenocarcinomaRecurrent Platinum-Resistant Ovarian Carcinoma

Testing the Addition of Abemaciclib to Olaparib for Women With Recurrent Ovarian Cancer

RECRUITING
NCT04633239Phase PHASE1National Cancer Institute (NCI)Started 2021-07-02
AbemaciclibBiopsy ProcedureBiospecimen Collection

External Resources

Links to major genomics databases and tools