ODC1

Summary

ODC1 (ornithine decarboxylase 1, HGNC:8109) is a protein-coding gene on chromosome 2p25.1, encoding Ornithine decarboxylase (P11926). Catalyzes the first and rate-limiting step of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine.

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.

Source: NCBI Gene 4953 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with alopecia and brain abnormalities (Strong, GenCC)
• Clinical variants (ClinVar): 122 total — 6 pathogenic, 5 likely-pathogenic
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002539

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8109
Approved symbol	ODC1
Name	ornithine decarboxylase 1
Location	2p25.1
Locus type	gene with protein product
Status	Approved
Aliases	ODC
Ensembl gene	ENSG00000115758
Ensembl biotype	protein_coding
OMIM	165640
Entrez	4953

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 20 protein_coding, 1 nonsense_mediated_decay

ENST00000234111, ENST00000405333, ENST00000443218, ENST00000446285, ENST00000699835, ENST00000699836, ENST00000887501, ENST00000887502, ENST00000887503, ENST00000887504, ENST00000887505, ENST00000887506, ENST00000887507, ENST00000887508, ENST00000926727, ENST00000926728, ENST00000926729, ENST00000953421, ENST00000953422, ENST00000953423, ENST00000953424

RefSeq mRNA: 4 — MANE Select: NM_002539 NM_001287188, NM_001287189, NM_001287190, NM_002539

CCDS: CCDS1672

Canonical transcript exons

ENST00000234111 — 12 exons

Exon	Start	End
ENSE00000710599	10441509	10441723
ENSE00000710600	10441817	10441929
ENSE00000710601	10442012	10442174
ENSE00000710602	10443230	10443313
ENSE00000710603	10443490	10443571
ENSE00000710605	10443702	10443836
ENSE00000710607	10444474	10444647
ENSE00001001268	10439968	10440868
ENSE00001349711	10445155	10445264
ENSE00001349715	10448121	10448327
ENSE00003477426	10444095	10444267
ENSE00003607498	10444931	10445049

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 100.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 87.2011 / max 959.3081, expressed in 1818 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26869	78.1676	1812
26871	2.8287	1440
26870	2.5344	1379
26873	0.9936	663
26872	0.9726	635
26874	0.4407	235
26863	0.3840	139
26867	0.3192	156
26868	0.2445	77
26862	0.2332	87

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	100.00	gold quality
oocyte	CL:0000023	99.93	gold quality
embryo	UBERON:0000922	99.27	gold quality
ventricular zone	UBERON:0003053	99.23	gold quality
ganglionic eminence	UBERON:0004023	99.23	gold quality
sperm	CL:0000019	99.20	gold quality
male germ cell	CL:0000015	99.04	gold quality
cortical plate	UBERON:0005343	98.72	gold quality
amniotic fluid	UBERON:0000173	98.59	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.34	gold quality
cartilage tissue	UBERON:0002418	98.29	gold quality
islet of Langerhans	UBERON:0000006	98.12	gold quality
left testis	UBERON:0004533	97.95	gold quality
right testis	UBERON:0004534	97.89	gold quality
trabecular bone tissue	UBERON:0002483	97.85	gold quality
germinal epithelium of ovary	UBERON:0001304	97.56	gold quality
gastrocnemius	UBERON:0001388	97.45	gold quality
tibialis anterior	UBERON:0001385	97.43	gold quality
colonic mucosa	UBERON:0000317	97.37	gold quality
adult organism	UBERON:0007023	97.28	gold quality
muscle of leg	UBERON:0001383	97.12	gold quality
smooth muscle tissue	UBERON:0001135	96.97	gold quality
testis	UBERON:0000473	96.86	gold quality
pigmented layer of retina	UBERON:0001782	96.86	gold quality
right coronary artery	UBERON:0001625	96.85	gold quality
retina	UBERON:0000966	96.84	gold quality
monocyte	CL:0000576	96.82	gold quality
mononuclear cell	CL:0000842	96.79	gold quality
deltoid	UBERON:0001476	96.77	gold quality
rectum	UBERON:0001052	96.75	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-HCAD-8	yes	718.06
E-HCAD-6	yes	469.16
E-MTAB-8221	yes	305.96
E-HCAD-10	yes	28.00
E-MTAB-9221	yes	16.39
E-MTAB-9388	yes	12.93
E-MTAB-8271	yes	11.96
E-GEOD-135922	yes	9.98
E-GEOD-93593	yes	7.96
E-GEOD-125970	yes	6.78
E-MTAB-9689	no	1197.26
E-HCAD-5	no	704.15
E-HCAD-29	no	689.41
E-MTAB-8559	no	638.78
E-MTAB-6524	no	192.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting ODC1, 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-4668-3P	100.00	68.74	2635
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-4272	98.76	68.74	1810

Literature-anchored findings (GeneRIF, showing 40)

• Overexpression of ornithine decarboxylase enhances endothelial proliferation by suppressing endostatin expression. (PMID:11830503)
• ODC activity reflects aggressive growth and malignization in meningiomas. (PMID:15015770)
• MTAP activity is frequently lost, and ODC activity is frequently elevated in both pancreatic adenocarcinoma and neuroendocrine tumors (PMID:15534104)
• Data show that expressing whole proteins, protein domains, or peptide ligands fused to the N terminus of ornithine decarboxylase promotes proteasome-dependent degradation of these chimeric fusion proteins and their interacting cellular target proteins. (PMID:16219697)
• review of key factors that contribute to the regulation of ornithine decarboxylase levels, which can occur at the levels of transcription, translation, and protein turnover [review] (PMID:16459331)
• findings show that antibody-bound amyloid precursor protein induces expression of ornithine decarboxylase (PMID:16469300)
• Data suggest that prolaction-mediated induction of ornithine decarboxylase activity enhances expression of Bcl-2 strongly enough to bring about prolactin’s anti-apoptotic function. (PMID:16520895)
• This is the first report showing the existence of a causal relationship between ornithine decarboxylase expression, Erk and p38 MAP kinase activation, and MMP-2 expression. (PMID:17088079)
• no association observed between the ODC ploymorphism and H. pylori seropositivity; results did not support the hypothesis that the different genetic traits in the ODC-polyamine pathway are associated with susceptibility to persistent H. pylori infection (PMID:17378176)
• The expression of ornithine decarboxylase is positively correlated with the degree of malignity of gastric mucosa and development of gastric lesions. (PMID:17569126)
• tumor ornithine decarboxylase level heterogeneity increased with increasing tumor malignancy (PMID:17582600)
• Among colorectal cancer patients, ODC activity in cancer tissue was correlated with T factors, lymph node metastasis and stages. (PMID:17957960)
• The results suggested that the ODC gene might act as a prognostic factor for breast cancer and it could be a promising therapeutic target. (PMID:18330478)
• Antisense RNA specifically inhibited the expression of ODC and AdoMetDC and the synthesis of polyamine, while it induced p21 expression, resulting in cell growth arrest in the G1 phase in prostate cancer cells. (PMID:18548481)
• Elevated ODC1 (independent of MYCN amplification) was associated with reduced survival in a large independent neuroblastoma cohort. (PMID:19047152)
• sporadic breast cancer, the presence of at least one A allele in ornithine decarboxylase is protective against the disease. (PMID:19225907)
• The ODC1 SNP may be protective for colon adenoma recurrence and detrimental for survival after colon cancer diagnosis. (PMID:19789310)
• ODC activity, which AZIN2 is assumed to regulate, is strongly associated with cell growth and transformation. (PMID:19832840)
• elevated ODC and low OAZ2 mRNA expression levels correlate with several unfavorable genetic and clinical features in neuroblastoma. (PMID:19960435)
• Low Ornithine decarboxylase mRNA expression is associated with more aggressive non-small-cell lung cancer. (PMID:20199977)
• There was no significant association between ODC G316A and risk of colorectal cancer for either heterozygotes or rare allele homozygotes. (PMID:20456464)
• Up-regulation of ODC in gastric macrophages impairs host defense against H pylori by suppressing iNOS-derived NO production. (PMID:20600019)
• Overexpression of ODC suppresses thapsigargin-induced apoptosis, blocks caspase-4 activation and PERK phosphorylation,and attenuates CHOP expression. It inhibits Bak increase and maintains Bcl-2 expression, blocking the intrinsic pathway of apoptosis. (PMID:20814750)
• Gingival ornithine decarboxylase levels were higher in the gingivitis group compared to the periodontitis and healthy groups at baseline. (PMID:20831369)
• Ornithine decarboxylase induces hypomethylation of genome DNA and histone H3 lysine 9 dimethylation in human oral cancer cell line. (PMID:20838441)
• Studies provide lead compounds for inhibitors of ornithine decarboxylase and human histidine decarboxylase. (PMID:21454364)
• the differences in residues 125 and 140 in ODC and AZI are responsible for the differential antizyme-binding affinities (PMID:21552531)
• the mechanism of formation of the internal aldimine, a common intermediate to most pyridoxal 5’-phosphate (PLP)-dependent enzymes (PMID:21854048)
• Variants of the ornithine decarboxylase gene influence risk of colorectal adenoma and aspirin chemoprevention. (PMID:21930798)
• AZ_95-176 is the minimal AZ peptide that is fully functioning in the binding of ODC and AZI and inhibition of their function. (PMID:21931692)
• Introduction of a fluorine atom at C3 of 3-deazauridine shifts its antimetabolic activity from inhibition of CTP synthetase to inhibition of orotidylate decarboxylase, an early event in the de novo pyrimidine nucleotide biosynthesis pathway. (PMID:22730407)
• The results of this study suggest that specific genetic variants in a subset of glutamatergic (GRIN2B) and polyaminergic (ODC1) neurosystem genes may be of importance in certain suicidal subjects. (PMID:22850629)
• Overexpression of antizyme (AZ), an ornithine decarboxylase (ODC) inhibitory protein, suppressed ERalpha expression, suggesting that ODC plays an important role in regulation of ERalpha expression. (PMID:22976807)
• There are five conserved residues in ODC. (PMID:23872168)
• Based on the investigation of the polyamine metabolite pathway, these data establish that the downstream metabolites of ornithine are increased, potentially implicating ornithine decarboxylase activity in AD pathology. (PMID:23917584)
• ODC overexpression suppresses the expression of tumstatin, which may provide fundamental evidence for the combination of anti-angiogenic therapy and conventional therapy for cancer treatment. (PMID:24002681)
• Authors identified SPR as a novel regulator of ODC enzyme activity and, based on clinical evidence, present a model in which SPR drives ODC-mediated malignant progression in neuroblastoma. (PMID:24096079)
• Akt activation by ODC+COX-2 over-expression. (PMID:24260338)
• BTF3, HINT1, NDRG1 and ODC1 protein over-expression in human prostate cancer tissue (PMID:24386364)
• We earlier presented evidence for a physical interaction between ODC and SPR and we showed that RNAi-mediated knockdown of SPR expression significantly reduced native ODC enzyme activity and impeded Neuroblastoma cell proliferation. (PMID:26093909)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	odc1	ENSDARG00000007377
mus_musculus	Odc1	ENSMUSG00000011179
rattus_norvegicus	Odc1	ENSRNOG00000005424
drosophila_melanogaster	Odc1	FBGN0013307
drosophila_melanogaster	Odc2	FBGN0013308
caenorhabditis_elegans	F53F10.2	WBGENE00018764

Paralogs (2): AZIN2 (ENSG00000142920), AZIN1 (ENSG00000155096)

Protein

Protein identifiers

Ornithine decarboxylase — P11926 (reviewed: P11926)

All UniProt accessions (3): A0A8V8TQA2, C9JG30, P11926

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the first and rate-limiting step of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine. Polyamines are essential for cell proliferation and are implicated in cellular processes, ranging from DNA replication to apoptosis.

Subunit / interactions. Homodimer. Only the dimer is catalytically active, as the active sites are constructed of residues from both monomers. Does not form a heterodimer with AZIN2.

Post-translational modifications. S-Nitrosylation inhibits the enzyme. S-Nitrosylated in vitro on 4 cysteine residues.

Disease relevance. Bachmann-Bupp syndrome (BABS) [MIM:619075] An autosomal dominant disorder characterized by global developmental delay, alopecia, absolute or relative macrocephaly, and facial dysmorphism. Neuroimaging shows white matter abnormalities, prominent Virchow-Robin spaces, periventricular cysts, and abnormalities of the corpus callosum. The disease is caused by variants affecting the gene represented in this entry. BABS is due to truncating variants that lead to a gain of function. This phenomenon apparently results from truncation proximal to or involving the C-terminal region of ODC1 protein, distal enough to allow escape from nonsense-mediated decay. A gain of function is corroborated by elevated plasma levels of N-acetylputrescine, with otherwise normal polyamine levels, in affected individuals.

Activity regulation. Inhibited by S-nitrosylation. Inhibited by antizymes (AZs) OAZ1, OAZ2 and OAZ3 in response to polyamine levels. AZs inhibit the assembly of the functional homodimer by binding to ODC monomers. Additionally, OAZ1 targets ODC monomers for ubiquitin-independent proteolytic destruction by the 26S proteasome. Inhibited by 1-amino-oxy-3-aminopropane (APA, an isosteric analog of putrescine). Irreversibly inhibited by alpha-difluoromethylornithine (DFMO).

Induction. Down-regulated in response to enterovirus 71 (EV71) infection (at protein level).

Pathway. Amine and polyamine biosynthesis; putrescine biosynthesis via L-ornithine pathway; putrescine from L-ornithine: step 1/1.

Similarity. Belongs to the Orn/Lys/Arg decarboxylase class-II family.

RefSeq proteins (4): NP_001274117, NP_001274118, NP_001274119, NP_002530* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000183	Orn/DAP/Arg_de-COase	Family
IPR002433	Orn_de-COase	Family
IPR009006	Ala_racemase/Decarboxylase_C	Homologous_superfamily
IPR022643	De-COase2_C	Domain
IPR022644	De-COase2_N	Domain
IPR022653	De-COase2_pyr-phos_BS	Binding_site
IPR022657	De-COase2_CS	Conserved_site
IPR029066	PLP-binding_barrel	Homologous_superfamily

Pfam: PF00278, PF02784

Enzyme classification (BRENDA):

• EC 4.1.1.17 — ornithine decarboxylase (BRENDA: 114 organisms, 141 substrates, 237 inhibitors, 107 Km, 57 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-ORNITHINE	0.023–1660	54
L-ORN	0.0027–5.6	31
L-LYSINE	1.06–30.1	11
L-2,4-DIAMINOBUTANOATE	3.9–4.9	2
L-ARGININE	0.18–1.4	2
ALPHA-METHYLORNITHINE	0.092	1
ARG	0.1	1
L-LYS	0.5	1
LYS	0.091	1

Catalyzed reactions (Rhea), 1 shown:

• L-ornithine + H(+) = putrescine + CO2 (RHEA:22964)

UniProt features (60 total): strand 22, helix 20, binding site 6, modified residue 3, turn 3, sequence variant 2, chain 1, active site 1, mutagenesis site 1, site 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
7S3G	X-RAY DIFFRACTION	1.66
7U6U	X-RAY DIFFRACTION	1.85
2OO0	X-RAY DIFFRACTION	1.9
9B8N	X-RAY DIFFRACTION	2
1D7K	X-RAY DIFFRACTION	2.1
7U6P	X-RAY DIFFRACTION	2.35
7S3F	X-RAY DIFFRACTION	2.49
4ZGY	X-RAY DIFFRACTION	2.63
9B8M	X-RAY DIFFRACTION	2.9
2ON3	X-RAY DIFFRACTION	3
5BWA	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11926-F1	88.30	0.78

Functional residue map

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

Catalytic / active sites (2): 360 (proton donor; shared with dimeric partner); 197 (stacks against the aromatic ring of pyridoxal phosphate and stabilizes reaction intermediates)

Ligand- & substrate-binding residues (6): 200; 237; 274–277; 331–332 (in other chain); 361; 389

Post-translational modifications (3): 303, 360, 69

Mutagenesis-validated functional residues (1):

Position	Phenotype
360	25% decrease of in vitro nitrosylation level.

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: 548 (showing top): ELVIDGE_HYPOXIA_DN, chr2p25, HORIUCHI_WTAP_TARGETS_DN, PAL_PRMT5_TARGETS_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCANCTGNY_MYOD_Q6, TTTGTAG_MIR520D, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, YANG_BREAST_CANCER_ESR1_LASER_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_METABOLIC_PROCESS, GOLDRATH_ANTIGEN_RESPONSE, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, PUJANA_CHEK2_PCC_NETWORK

GO Biological Process (8): kidney development (GO:0001822), polyamine metabolic process (GO:0006595), cell population proliferation (GO:0008283), positive regulation of cell population proliferation (GO:0008284), response to virus (GO:0009615), obsolete putrescine biosynthetic process from arginine, via ornithine (GO:0033387), regulation of protein catabolic process (GO:0042176), polyamine biosynthetic process (GO:0006596)

GO Molecular Function (6): ornithine decarboxylase activity (GO:0004586), protein homodimerization activity (GO:0042803), catalytic activity (GO:0003824), protein binding (GO:0005515), lyase activity (GO:0016829), carboxy-lyase activity (GO:0016831)

GO Cellular Component (2): 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
animal organ development	1
renal system development	1
biogenic amine metabolic process	1
cellular process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to other organism	1
regulation of catabolic process	1
protein catabolic process	1
regulation of protein metabolic process	1
polyamine metabolic process	1
biogenic amine biosynthetic process	1
carboxy-lyase activity	1
identical protein binding	1
protein dimerization activity	1
molecular_function	1
binding	1
catalytic activity	1
carbon-carbon lyase activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

2572 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ODC1	SRM	P19623	983
ODC1	OAZ1	P54368	970
ODC1	SMS	P52788	968
ODC1	OAZ3	Q9UMX2	928
ODC1	OAZ2	O95190	919
ODC1	SAT1	P21673	856
ODC1	PAOX	Q6QHF9	810
ODC1	ZNF148	Q9UQR1	788
ODC1	OAT	P04181	783
ODC1	AGMAT	Q9BSE5	779
ODC1	ARG2	P78540	778
ODC1	SMOX	Q9NWM0	755
ODC1	MYC	P01106	747
ODC1	ARG1	P05089	738
ODC1	RRM2	P31350	721

IntAct

43 interactions, top by confidence:

A	B	Type	Score
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
ODC1	GORASP2	psi-mi:“MI:0915”(physical association)	0.780
KAT5	ODC1	psi-mi:“MI:0915”(physical association)	0.720
ODC1	KAT5	psi-mi:“MI:0915”(physical association)	0.720
OAZ1	AZIN1	psi-mi:“MI:0914”(association)	0.640
ODC1	OAZ3	psi-mi:“MI:0915”(physical association)	0.560
ODC1	SSR1	psi-mi:“MI:0915”(physical association)	0.370
ODC1	CSNK2B	psi-mi:“MI:0915”(physical association)	0.370
TK1	ODC1	psi-mi:“MI:0915”(physical association)	0.370
ODC1	BAAT	psi-mi:“MI:0915”(physical association)	0.370
ODC1	TSTD2	psi-mi:“MI:0915”(physical association)	0.370
ODC1	HEMGN	psi-mi:“MI:0915”(physical association)	0.370
MAP2K1	ODC1	psi-mi:“MI:0915”(physical association)	0.370
ODC1	NANS	psi-mi:“MI:0915”(physical association)	0.370
STX17	ODC1	psi-mi:“MI:0915”(physical association)	0.370
ODC1	TDRD7	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (37): KAT5 (Two-hybrid), GORASP2 (Two-hybrid), OAZ3 (Two-hybrid), ODC1 (Reconstituted Complex), ODC1 (Reconstituted Complex), OAZ1 (Reconstituted Complex), OAZ2 (Reconstituted Complex), ODC1 (Affinity Capture-MS), ODC1 (Affinity Capture-MS), ODC1 (Affinity Capture-MS), ODC1 (Affinity Capture-Western), RSC1A1 (Affinity Capture-Western), RSC1A1 (Reconstituted Complex), ODC1 (Co-localization), ODC1 (Synthetic Lethality)

ESM2 similar proteins: A1Z6E0, A2BHJ4, A8IU92, B0X9V1, B3MDR0, B3NRP1, B4F739, B4GBN7, B4HQ29, B4J6Q0, B4KNC5, B4LMQ3, B4MR59, B4P4K8, B4QE02, P00860, P0C2W1, P0CH38, P11926, P27117, P27119, P27120, P48455, P53041, P53042, Q0G819, Q16XV7, Q290L5, Q5BJ41, Q5E9X6, Q5VST6, Q5XH73, Q60676, Q68FK8, Q6AXU9, Q6AY17, Q6IR85, Q6NZ03, Q7M759, Q7QGL9

Diamond homologs: A0A1S4AUX8, B8NHE2, D4A693, E0WN94, O14977, O22616, O35484, O50657, P00860, P07805, P08432, P09057, P11926, P14019, P27116, P27117, P27118, P27119, P27120, P27121, P40807, P40808, P41931, P49725, P50134, P78599, P93351, Q54UF3, Q5MNH7, Q5MNI5, Q5R7K3, Q63764, Q8BVM4, Q8S3N2, Q96A70, Q9FPK5, Q9I8S4, Q9UQW9, Q2G1M6, Q92445

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
APC	“down-regulates quantity by repression”	ODC1	“transcriptional regulation”
ODC1	“up-regulates quantity”	putrescine	“chemical modification”
ODC1	“up-regulates quantity”	spermine	“chemical modification”
ODC1	“down-regulates quantity”	L-ornithine	“chemical modification”
ODC1	“up-regulates quantity”	spermidine	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	5
Uncertain significance	57
Likely benign	33
Benign	2

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1074405	NM_002539.3(ODC1):c.1242-2A>G	Pathogenic
983285	NM_002539.3(ODC1):c.1241+1G>T	Pathogenic
983286	NM_002539.3(ODC1):c.1240_1241dup (p.Trp414fs)	Pathogenic
983287	NM_002539.3(ODC1):c.1255C>T (p.Gln419Ter)	Pathogenic
983288	NC_000002.12:g.10440850_10440871del	Pathogenic
983289	NM_002539.3(ODC1):c.1342A>T (p.Lys448Ter)	Pathogenic
3342607	NM_002539.3(ODC1):c.1252C>T (p.Gln418Ter)	Likely pathogenic
3767967	NM_002539.3(ODC1):c.1064dup (p.Trp356fs)	Likely pathogenic
3776026	NM_002539.3(ODC1):c.1329G>A (p.Trp443Ter)	Likely pathogenic
4820063	NM_002539.3(ODC1):c.499_500del (p.Ser167fs)	Likely pathogenic
978044	NM_002539.3(ODC1):c.1313_1316del (p.Pro438fs)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3073 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:10441554:C:A	G399V	1.000
2:10441554:C:T	G399D	1.000
2:10441555:C:G	G399R	1.000
2:10441556:A:C	N398K	1.000
2:10441556:A:T	N398K	1.000
2:10441558:T:C	N398D	1.000
2:10441559:G:C	F397L	1.000
2:10441559:G:T	F397L	1.000
2:10441560:A:C	F397C	1.000
2:10441560:A:G	F397S	1.000
2:10441561:A:C	F397V	1.000
2:10441561:A:G	F397L	1.000
2:10441561:A:T	F397I	1.000
2:10441572:G:T	A393D	1.000
2:10441581:G:A	T390I	1.000
2:10441585:A:G	Y389H	1.000
2:10441590:C:A	G387V	1.000
2:10441590:C:T	G387D	1.000
2:10441591:C:A	G387C	1.000
2:10441591:C:G	G387R	1.000
2:10441612:A:G	W380R	1.000
2:10441612:A:T	W380R	1.000
2:10441653:A:T	I366N	1.000
2:10441658:A:C	D364E	1.000
2:10441658:A:T	D364E	1.000
2:10441659:T:A	D364V	1.000
2:10441659:T:C	D364G	1.000
2:10441659:T:G	D364A	1.000
2:10441660:C:A	D364Y	1.000
2:10441660:C:G	D364H	1.000

dbSNP variants (sampled 300 via entrez): RS1000101367 (2:10447155 T>C), RS1000614261 (2:10446692 C>G), RS1000665289 (2:10446949 C>A,T), RS1000979644 (2:10442798 C>A,T), RS1000993585 (2:10449014 C>G,T), RS1001108181 (2:10448171 C>G,T), RS1001175881 (2:10448964 C>T), RS1001216573 (2:10447082 G>A), RS1001231746 (2:10449293 A>G), RS1001264897 (2:10442925 C>G,T), RS1001393081 (2:10444075 C>T), RS1002093349 (2:10442246 G>A,C), RS1002145873 (2:10442450 T>C), RS1002326096 (2:10447861 G>A), RS1002342359 (2:10445387 C>T)

Disease associations

OMIM: gene MIM:165640 | disease phenotypes: MIM:619075

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with alopecia and brain abnormalities	Strong	Autosomal dominant

Mondo (2): neurodevelopmental disorder with alopecia and brain abnormalities (MONDO:0033642), intellectual disability (MONDO:0001071)

Orphanet (2): Global developmental delay-alopecia-macrocephaly-facial dysmorphism-structural brain anomalies syndrome (Orphanet:544488), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1869 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 108,804 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL165	RESVERATROL	3	60,144
CHEMBL222838	EFLORNITHINE, (S)-	2	4,448
CHEMBL44	GENISTEIN	2	44,212

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Decarboxylases

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
APA	Inhibition	7.46	pIC50
eflornithine	Inhibition	4.89	pKd

ChEMBL bioactivities

25 potent at pChembl≥5 of 29 total, top 25 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.52	IC50	30	nM	CHEMBL6171251
7.40	IC50	40	nM	CHEMBL281021
7.30	IC50	50	nM	CHEMBL6164810
7.05	IC50	90	nM	CHEMBL6150184
7.00	IC50	100	nM	CHEMBL6134618
6.82	IC50	150	nM	CHEMBL6166335
6.80	IC50	160	nM	CHEMBL6171916
6.75	IC50	180	nM	CHEMBL6133966
6.68	IC50	210	nM	CHEMBL6164636
6.44	IC50	360	nM	CHEMBL6160761
6.30	Kd	500	nM	ALPHA-HYDRAZINE ORNITHINE
6.16	IC50	700	nM	CHEMBL6171554
6.11	IC50	770	nM	CHEMBL6120831
6.11	IC50	780	nM	CHEMBL6163104
5.96	IC50	1100	nM	CHEMBL464609
5.68	IC50	2100	nM	CHEMBL451703
5.66	IC50	2200	nM	CHEMBL455606
5.64	IC50	2300	nM	CHEMBL516860
5.58	IC50	2600	nM	LONCHOCARPUSONE
5.47	IC50	3400	nM	ZAPOTIN
5.44	IC50	3600	nM	CHEMBL463206
5.41	IC50	3900	nM	CHEMBL463011
5.33	IC50	4700	nM	CHEMBL362378
5.28	IC50	5200	nM	CHEMBL463404
5.13	IC50	7400	nM	CHEMBL463598

PubChem BioAssay actives

11 with measured affinity, of 65 total; 11 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-5-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-8,8-dimethyl-6-(3-methylbut-2-enyl)-2,3-dihydropyrano[2,3-h]chromen-4-one	378353: Inhibition of phorbol ester-induced ornithine decarboxylase in human MCF7 cells after 6 hrs	ic50	1.1000	uM
(2S)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-8,8-dimethyl-6-(3-methylbut-2-enyl)-2,3-dihydropyrano[2,3-h]chromen-4-one	378353: Inhibition of phorbol ester-induced ornithine decarboxylase in human MCF7 cells after 6 hrs	ic50	2.1000	uM
(2S)-2-(3,4-dimethoxyphenyl)-5-hydroxy-8,8-dimethyl-6-(3-methylbut-2-enyl)-2,3-dihydropyrano[2,3-h]chromen-4-one	378353: Inhibition of phorbol ester-induced ornithine decarboxylase in human MCF7 cells after 6 hrs	ic50	2.2000	uM
(2S)-2-(3,4-dimethoxyphenyl)-8,8-dimethyl-6-(3-methylbut-2-enyl)-2,3-dihydropyrano[2,3-h]chromen-4-one	378353: Inhibition of phorbol ester-induced ornithine decarboxylase in human MCF7 cells after 6 hrs	ic50	2.3000	uM
8,8-dimethyl-3-(2,4,5-trimethoxyphenyl)-2,3-dihydropyrano[2,3-f]chromen-4-one	378353: Inhibition of phorbol ester-induced ornithine decarboxylase in human MCF7 cells after 6 hrs	ic50	2.6000	uM
2-(2,6-dimethoxyphenyl)-5,6-dimethoxychromen-4-one	275747: Inhibition of TPA-induced ODC activity in T24 cells	ic50	3.4000	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-(4-hydroxy-3-methoxyphenyl)prop-2-en-1-one	378353: Inhibition of phorbol ester-induced ornithine decarboxylase in human MCF7 cells after 6 hrs	ic50	3.6000	uM
2,2-dimethyl-7-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]chromene	378353: Inhibition of phorbol ester-induced ornithine decarboxylase in human MCF7 cells after 6 hrs	ic50	3.9000	uM
(E)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)-3-(4-hydroxyphenyl)prop-2-en-1-one	378353: Inhibition of phorbol ester-induced ornithine decarboxylase in human MCF7 cells after 6 hrs	ic50	4.7000	uM
4-[(E)-2-(5-methoxy-2,2-dimethylchromen-7-yl)ethenyl]phenol	378353: Inhibition of phorbol ester-induced ornithine decarboxylase in human MCF7 cells after 6 hrs	ic50	5.2000	uM
2-methoxy-4-[(E)-2-(5-methoxy-2,2-dimethylchromen-7-yl)ethenyl]phenol	378353: Inhibition of phorbol ester-induced ornithine decarboxylase in human MCF7 cells after 6 hrs	ic50	7.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	decreases expression, increases expression	5
Estradiol	increases activity, affects expression, decreases expression, increases expression, decreases reaction	4
bisphenol A	affects expression, decreases expression, decreases methylation	3
Resveratrol	decreases reaction, decreases activity, decreases expression	3
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	3
Plant Extracts	decreases expression, increases expression, affects expression	3
Valproic Acid	affects expression, increases expression	3
Aspirin	increases expression, increases response to substance	2
Dimethyl Sulfoxide	decreases reaction, increases activity, increases expression	2
Hydrogen Peroxide	affects expression, decreases activity	2
Nickel	increases expression	2
Tetradecanoylphorbol Acetate	decreases reaction, increases expression, increases activity	2
Tobacco Smoke Pollution	increases expression	2
Tretinoin	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
fluxapyroxad	increases expression	1
GSK-J4	increases expression	1
afuresertib	decreases expression	1
Glupearl 19S	increases expression	1
tempol	increases activity, decreases reaction	1
thermozymocidin	decreases activity, decreases reaction	1
4-oxoretinoic acid	decreases expression	1
cinobufagin	decreases expression	1
bismuth tripotassium dicitrate	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
chlortoluron	increases expression	1
geraniol	decreases activity	1

ChEMBL screening assays

21 unique, capped per target: 21 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1008926	Binding	Inhibition of ornithine decarboxylase in human HT-29 cells assessed as release of radioactive CO2 from [14C-carboxyl] ornithine	Antitumor activity of new substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and 3-(5-imidazo[2,1-b]thiadiazolylmethylene)-2-indolinones: selectivity against colon tumor cells and effect on cell cycle-related events. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1XX	Abcam A-549 ODC1 KO	Cancer cell line	Male
CVCL_D2C6	Abcam HCT 116 ODC1 KO	Cancer cell line	Male
CVCL_D2NR	Abcam THP-1 ODC1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders