ODC1

Chr 2AD

ornithine decarboxylase 1

Also known as: BABS, NEDBA, NEDBIA, ODC

NCBI Gene: 4953 ENSG00000115758 OMIM: 165640

This protein catalyzes the rate-limiting step in polyamine biosynthesis, converting ornithine to putrescine, which is essential for cell proliferation and DNA replication. Mutations cause Bachmann-Bupp syndrome, an autosomal dominant condition affecting neurodevelopment and growth. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.543), and detailed clinical information is available in GeneReviews.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

GOFmechanismADLOEUF 0.541 OMIM phenotype

Clinical Summary— ODC1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.47Z-score

OE missense 0.75 (0.67–0.84)

209 obs / 277.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.26 (0.13–0.54)

0≤0.351.4

Missense OE?0.75 (0.67–0.84)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 5 / 19.4Missense obs/exp: 209 / 277.8Syn Z: -0.95

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongODC1-related neurodevelopmental disorderGOFAD

This gene — mechanism propensity

0.7034th %ile

GOF

0.4875th %ile

LOF

0.3067th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOF1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

GOFGain-of-function variants in the ODC1 gene cause a syndromic neurodevelopmental disorder associated with macrocephaly, alopecia, dysmorphic features, and neuroimaging abnormalities.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References