OAT

Summary

OAT (ornithine aminotransferase, HGNC:8091) is a protein-coding gene on chromosome 10q26.13, encoding Ornithine aminotransferase, mitochondrial (P04181). Catalyzes the reversible interconversion of L-ornithine and 2-oxoglutarate to L-glutamate semialdehyde and L-glutamate.

This gene encodes the mitochondrial enzyme ornithine aminotransferase, which is a key enzyme in the pathway that converts arginine and ornithine into the major excitatory and inhibitory neurotransmitters glutamate and GABA. Mutations that result in a deficiency of this enzyme cause the autosomal recessive eye disease Gyrate Atrophy. Alternatively spliced transcript variants encoding different isoforms have been described. Related pseudogenes have been defined on the X chromosome.

Source: NCBI Gene 4942 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ornithine aminotransferase deficiency (Definitive, ClinGen)
• Clinical variants (ClinVar): 679 total — 52 pathogenic, 59 likely-pathogenic
• Phenotypes (HPO): 24
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000274

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8091
Approved symbol	OAT
Name	ornithine aminotransferase
Location	10q26.13
Locus type	gene with protein product
Status	Approved
Aliases	HOGA
Ensembl gene	ENSG00000065154
Ensembl biotype	protein_coding
OMIM	613349
Entrez	4942

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 26 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000368845, ENST00000467675, ENST00000471127, ENST00000476917, ENST00000483711, ENST00000490096, ENST00000492376, ENST00000539214, ENST00000858831, ENST00000858832, ENST00000858833, ENST00000858834, ENST00000858835, ENST00000858836, ENST00000858837, ENST00000858838, ENST00000858839, ENST00000858840, ENST00000921311, ENST00000921312, ENST00000921313, ENST00000921314, ENST00000921315, ENST00000921316, ENST00000921317, ENST00000921318, ENST00000921319, ENST00000921320, ENST00000971960, ENST00000971961, ENST00000971962, ENST00000971963

RefSeq mRNA: 10 — MANE Select: NM_000274 NM_000274, NM_001171814, NM_001322965, NM_001322966, NM_001322967, NM_001322968, NM_001322969, NM_001322970, NM_001322971, NM_001322974

CCDS: CCDS53586, CCDS7639

Canonical transcript exons

ENST00000368845 — 10 exons

Exon	Start	End
ENSE00001747008	124418873	124418923
ENSE00002210739	124397303	124398102
ENSE00003466621	124408542	124408637
ENSE00003492307	124403798	124403920
ENSE00003549728	124405436	124405563
ENSE00003596991	124401726	124401839
ENSE00003605837	124408741	124408965
ENSE00003659414	124411973	124412200
ENSE00003666584	124402927	124403055
ENSE00003676682	124400840	124400984

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 151.1875 / max 2451.8052, expressed in 1817 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111830	150.8438	1817
111827	0.1788	63
111829	0.0635	30
111831	0.0522	18
111828	0.0492	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.97	gold quality
parotid gland	UBERON:0001831	99.78	gold quality
duodenum	UBERON:0002114	99.68	gold quality
secondary oocyte	CL:0000655	99.54	gold quality
epithelium of nasopharynx	UBERON:0001951	99.51	gold quality
pons	UBERON:0000988	99.49	gold quality
germinal epithelium of ovary	UBERON:0001304	99.47	gold quality
oocyte	CL:0000023	99.43	gold quality
esophagus squamous epithelium	UBERON:0006920	99.41	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.40	gold quality
ileal mucosa	UBERON:0000331	99.37	gold quality
seminal vesicle	UBERON:0000998	99.36	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.36	gold quality
postcentral gyrus	UBERON:0002581	99.34	gold quality
nasal cavity epithelium	UBERON:0005384	99.33	gold quality
nephron tubule	UBERON:0001231	99.29	gold quality
parietal pleura	UBERON:0002400	99.26	gold quality
tibia	UBERON:0000979	99.25	gold quality
substantia nigra pars compacta	UBERON:0001965	99.24	gold quality
oral cavity	UBERON:0000167	99.23	gold quality
middle temporal gyrus	UBERON:0002771	99.21	gold quality
trabecular bone tissue	UBERON:0002483	99.14	gold quality
epithelium of esophagus	UBERON:0001976	99.13	gold quality
superior frontal gyrus	UBERON:0002661	99.13	gold quality
mammalian vulva	UBERON:0000997	99.12	gold quality
trachea	UBERON:0003126	99.12	gold quality
nasal cavity mucosa	UBERON:0001826	99.10	gold quality
tongue squamous epithelium	UBERON:0006919	99.09	gold quality
mammary duct	UBERON:0001765	99.08	gold quality
epithelium of mammary gland	UBERON:0003244	99.08	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	906.38
E-MTAB-9388	yes	803.74
E-HCAD-4	yes	145.26
E-CURD-112	yes	58.43
E-CURD-114	yes	55.55
E-MTAB-8142	yes	36.99
E-MTAB-10042	yes	36.84
E-MTAB-3929	no	621.12
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, HNF1A, NFIA, NFKB, SP1, TFAP2A

miRNA regulators (miRDB)

37 targeting OAT, 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-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3667-3P	99.99	67.17	1636
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-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-548S	98.50	67.17	1213

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 23)

• analysis of ornithine aminotransferase substrate specificity (PMID:16096275)
• Fundus autofluorescence imaging can reveal the extent of neurosensory dysfunction in gyrate atrophy patients. (PMID:22182799)
• Molecular analysis revealed a new deletion c.532_536delTGGGG (p.Trp178X) and a known mutation c.897C>G (p.Tyr299X) in the OAT gene. (PMID:22674428)
• OAT was a highly homologous and stable protein located in the mitochondria. (PMID:22989455)
• Data suggest that other factors besides the specific ornithine aminotransferase (OAT) genotype modulate atrophy of choroid and retina (GA) phenotype in patients. (PMID:23076989)
• Our report describes the first case of gyrate atrophy in the Korean population diagnosed by OAT gene analysis and treated with vitamin B6 dietary supplementation. (PMID:24082780)
• We identified a novel frameshift mutation (p.K169DfsX10) in the OAT gene. While an early arginine-restricted dietary treatment suppressed the fundus changes (PMID:24429551)
• Neurogenesis is inhibited by X-OAT during Xenopus embryonic development, but it is essential for Xenopus embryonic development. The Arg 180 and Leu 402 are crucial for these effects of the OAT molecule in development. (PMID:25783604)
• Sequencing of the gene for ornithine aminotransferase reveals a homozygous mutation in our patient (base exchange c.498C>A in Exon 4). (PMID:26259030)
• identified Arg217 as an important hot-spot at the dimer-dimer interface of hOAT and demonstrated that the artificial dimeric variant R217A exhibits spectroscopic properties, Tm values and catalytic features similar to those of the tetrameric species. This finding indicates that the catalytic unit of hOAT is the dimer. (PMID:28345116)
• Study identifies differentially variable CpG sites in OAT gene displaying increased expression in patients with chronic obstructive pulmonary disease. (PMID:29527240)
• One novel homozygous missense mutation in OAT was identified and considered to be pathogenic in a patient with gyrate atrophy. The response for the vitamin B6 supplementation was positive. (PMID:29757052)
• OAT Val332-to-Met substitution identified in pyridoxine-responsive gyrate atrophy patients does not significantly affect the spectroscopic and kinetic properties of OAT, but during catalysis it makes the protein prone to convert into the apo-form, which undergoes unfolding and aggregation under physiological conditions. (PMID:30251682)
• Recruitment of a third-degree first cousin consanguineous marriage family with gyrate atrophy of the choroid and retina (GACR) allowed us to identify a novel pathogenic OAT variant in the Chinese population, broadening the mutation spectrum. (PMID:30366948)
• Deficit of human ornithine aminotransferase in gyrate atrophy: Molecular, cellular, and clinical aspects. (PMID:33068755)
• A novel c.980C>G variant in OAT results in identifiable gyrate atrophy phenotype associated with retinal detachment in a young female. (PMID:33243052)
• Variable phenotypes of gyrate atrophy in siblings with a nonsense mutation in OAT gene. (PMID:33463379)
• Turnover and Inactivation Mechanisms for (S)-3-Amino-4,4-difluorocyclopent-1-enecarboxylic Acid, a Selective Mechanism-Based Inactivator of Human Ornithine Aminotransferase. (PMID:34097381)
• Determination of the pH dependence, substrate specificity, and turnovers of alternative substrates for human ornithine aminotransferase. (PMID:35460691)
• Ornithine aminotransferase and carbamoyl phosphate synthetase 1 involved in ammonia metabolism serve as novel targets for early stages of gastric cancer. (PMID:36098904)
• Biochemical and Bioinformatic Studies of Mutations of Residues at the Monomer-Monomer Interface of Human Ornithine Aminotransferase Leading to Gyrate Atrophy of Choroid and Retina. (PMID:36834788)
• Ornithine aminotransferase supports polyamine synthesis in pancreatic cancer. (PMID:36991126)
• Role of lung ornithine aminotransferase in idiopathic pulmonary fibrosis: regulation of mitochondrial ROS generation and TGF-beta1 activity. (PMID:38413821)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	oat	ENSDARG00000078425
mus_musculus	Oat	ENSMUSG00000030934
rattus_norvegicus	Oat	ENSRNOG00000016807
drosophila_melanogaster	Oat	FBGN0022774
caenorhabditis_elegans		WBGENE00015814

Paralogs (4): AGXT2 (ENSG00000113492), ETNPPL (ENSG00000164089), PHYKPL (ENSG00000175309), ABAT (ENSG00000183044)

Protein

Protein identifiers

Ornithine aminotransferase, mitochondrial — P04181 (reviewed: P04181)

Alternative names: Ornithine delta-aminotransferase, Ornithine–oxo-acid aminotransferase

All UniProt accessions (2): P04181, A0A140VJQ4

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reversible interconversion of L-ornithine and 2-oxoglutarate to L-glutamate semialdehyde and L-glutamate.

Subunit / interactions. Homohexamer.

Subcellular location. Mitochondrion matrix.

Disease relevance. Hyperornithinemia with gyrate atrophy of choroid and retina (HOGA) [MIM:258870] A disorder clinically characterized by a triad of progressive chorioretinal degeneration, early cataract formation, and type II muscle fiber atrophy. Characteristic chorioretinal atrophy with progressive constriction of the visual fields leads to blindness at the latest during the sixth decade of life. Patients generally have normal intelligence. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Amino-acid biosynthesis; L-proline biosynthesis; L-glutamate 5-semialdehyde from L-ornithine: step 1/1.

Similarity. Belongs to the class-III pyridoxal-phosphate-dependent aminotransferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P04181-1	1	yes
P04181-2	2

RefSeq proteins (10): NP_000265, NP_001165285, NP_001309894, NP_001309895, NP_001309896, NP_001309897, NP_001309898, NP_001309899, NP_001309900, NP_001309903 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005814	Aminotrans_3	Family
IPR010164	Orn_aminotrans	Family
IPR015421	PyrdxlP-dep_Trfase_major	Homologous_superfamily
IPR015422	PyrdxlP-dep_Trfase_small	Homologous_superfamily
IPR015424	PyrdxlP-dep_Trfase	Homologous_superfamily
IPR049704	Aminotrans_3_PPA_site	Conserved_site
IPR050103	Class-III_PLP-dep_AT	Family

Pfam: PF00202

Enzyme classification (BRENDA):

• EC 2.6.1.13 — ornithine aminotransferase (BRENDA: 42 organisms, 62 substrates, 110 inhibitors, 128 Km, 21 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-ORNITHINE	0.59–91	56
2-OXOGLUTARATE	0.056–43.4	51
ORNITHINE	1.7–2.9	3
ACETYLORNITHINE	7.4–496	2
D-ORNITHINE	4.2	1
DL-PYRROLINE-5-CARBOXYLATE	1.4	1
GLYOXYLATE	6.7	1
L-GLUTAMATE	25	1
N-ACETYLORNITHINE	1.53	1
PYRUVATE	22	1

Catalyzed reactions (Rhea), 1 shown:

• L-ornithine + 2-oxoglutarate = L-glutamate 5-semialdehyde + L-glutamate (RHEA:25160)

UniProt features (86 total): sequence variant 29, strand 17, helix 16, modified residue 13, turn 6, transit peptide 2, chain 2, splice variant 1

Structure

Experimental structures (PDB)

27 structures.

PDB	Method	Resolution (Å)
8V9M	X-RAY DIFFRACTION	1.61
5VWO	X-RAY DIFFRACTION	1.77
6OIA	X-RAY DIFFRACTION	1.78
7LK1	X-RAY DIFFRACTION	1.79
6HX7	X-RAY DIFFRACTION	1.8
10LX	X-RAY DIFFRACTION	1.83
6V8C	X-RAY DIFFRACTION	1.9
7TEV	X-RAY DIFFRACTION	1.91
8EZ1	X-RAY DIFFRACTION	1.91
10LW	X-RAY DIFFRACTION	1.93
2OAT	X-RAY DIFFRACTION	1.95
7LON	X-RAY DIFFRACTION	1.95
7JX9	X-RAY DIFFRACTION	1.96
7LK0	X-RAY DIFFRACTION	1.96
7LNM	X-RAY DIFFRACTION	2
7LOM	X-RAY DIFFRACTION	2.1
2BYL	X-RAY DIFFRACTION	2.15
7T9Z	X-RAY DIFFRACTION	2.15
7TA1	X-RAY DIFFRACTION	2.2
6V8D	X-RAY DIFFRACTION	2.25
1GBN	X-RAY DIFFRACTION	2.3
2CAN	X-RAY DIFFRACTION	2.3
7TA0	X-RAY DIFFRACTION	2.33
1OAT	X-RAY DIFFRACTION	2.5
7TED	X-RAY DIFFRACTION	2.63
7TFP	X-RAY DIFFRACTION	2.71
2BYJ	X-RAY DIFFRACTION	3.02

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04181-F1	94.29	0.92

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 (13): 362, 362, 386, 392, 405, 405, 421, 49, 66, 102, 107, 107, 292

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8964539	Glutamate and glutamine metabolism

MSigDB gene sets: 299 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_BIOSYNTHETIC_PROCESS, XU_GH1_AUTOCRINE_TARGETS_UP, MODULE_151, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_GLUTAMATE_METABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_AMINO_ACID_BIOSYNTHETIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_METABOLIC_PROCESS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, LEE_LIVER_CANCER_CIPROFIBRATE_DN, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS

GO Biological Process (4): visual perception (GO:0007601), obsolete L-arginine catabolic process to proline via ornithine (GO:0010121), obsolete L-arginine catabolic process to L-glutamate (GO:0019544), L-proline biosynthetic process (GO:0055129)

GO Molecular Function (6): L-ornithine transaminase activity (GO:0004587), pyridoxal phosphate binding (GO:0030170), identical protein binding (GO:0042802), protein binding (GO:0005515), transaminase activity (GO:0008483), transferase activity (GO:0016740)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
sensory perception of light stimulus	1
L-proline metabolic process	1
glutamate family amino acid biosynthetic process	1
transaminase activity	1
anion binding	1
vitamin B6 binding	1
protein binding	1
binding	1
transferase activity, transferring nitrogenous groups	1
catalytic activity	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

3386 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OAT	ARG2	P78540	876
OAT	ARG1	P05089	852
OAT	PRODH	O43272	846
OAT	PRODH	O43272	844
OAT	ALDH18A1	P54886	811
OAT	ODC1	P11926	783
OAT	ALDH4A1	P30038	777
OAT	ASL	P04424	745
OAT	TBC1D25	Q3MII6	735
OAT	ASS1	P00966	725
OAT	AGXT	P21549	723
OAT	PYCR1	P32322	712
OAT	AZIN2	Q96A70	700
OAT	OGA	O60502	686
OAT	PYCR3	Q53H96	679

IntAct

106 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
OAT	APP	psi-mi:“MI:0915”(physical association)	0.560
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
TNFAIP3	LRRIQ3	psi-mi:“MI:0914”(association)	0.420
CNOT3	OAT	psi-mi:“MI:0915”(physical association)	0.400
HTR2B	OAT	psi-mi:“MI:0915”(physical association)	0.400
OAT	NUDT3	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
MYC	ILVBL	psi-mi:“MI:0914”(association)	0.350
SPHK1	TAF4	psi-mi:“MI:0914”(association)	0.350
PHOSPHO1	DDX39A	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
COX15	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
DLD	NFKBIE	psi-mi:“MI:0914”(association)	0.350
DLST		psi-mi:“MI:0914”(association)	0.350
PARK7	SAP18	psi-mi:“MI:0914”(association)	0.350
SOAT1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC15A3		psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350

BioGRID (265): OAT (Affinity Capture-MS), OAT (Affinity Capture-MS), OAT (Affinity Capture-MS), OAT (Affinity Capture-MS), ADSS (Co-fractionation), AKR1B1 (Co-fractionation), ALDH1B1 (Co-fractionation), CBS (Co-fractionation), ESD (Co-fractionation), GOT1 (Co-fractionation), NME1-NME2 (Co-fractionation), NME2 (Co-fractionation), OAT (Co-fractionation), OAT (Co-fractionation), PDXK (Co-fractionation)

ESM2 similar proteins: A0A223HDI5, A3QK15, O00097, P00333, P00504, P04181, P04182, P07754, P08843, P0C0Y4, P0C0Y5, P12863, P14219, P14673, P14674, P14675, P25141, P28032, P29401, P29758, P33097, P34937, P37769, P40142, P41177, P41747, P46226, P48491, P48493, P48494, P48495, P49724, P50137, Q05528, Q07264, Q0II68, Q29RZ0, Q2R8Z5, Q2U919, Q3ZCF5

Diamond homologs: A0QYS9, B9DIU0, B9EAM9, B9ITF9, C0ZBR4, C1EL61, C3LBX0, C3P3K3, C4L2E7, C5D6R2, O27392, O30156, O30508, O66442, P04181, P04182, P07991, P18335, P29758, P30900, P31893, P38021, P49724, P54752, P59316, P59317, P59318, P59320, P59321, P59323, P59324, P60295, P60296, P60297, P60298, P60299, P63566, P63567, P63569, P9WPZ6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
OAT	“down-regulates quantity”	L-ornithine	“chemical modification”
OAT	“up-regulates quantity”	proline	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 127 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
JNK cascade	6	14.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	52
Likely pathogenic	59
Uncertain significance	204
Likely benign	256
Benign	54

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072790	NM_000274.4(OAT):c.1A>G (p.Met1Val)	Pathogenic
1074082	NM_000274.4(OAT):c.1253_1260dup (p.Lys421delinsTrpTer)	Pathogenic
1074423	NC_000010.10:g.(?126093995)(126100239_?)del	Pathogenic
1075483	NM_000274.4(OAT):c.1150G>T (p.Glu384Ter)	Pathogenic
1076328	NM_000274.4(OAT):c.576del (p.Ser193fs)	Pathogenic
1213865	NM_000274.4(OAT):c.546_649-726del	Pathogenic
1367020	NC_000010.10:g.(?126086501)(126086681_?)del	Pathogenic
1376471	NM_000274.4(OAT):c.1159+1G>A	Pathogenic
1398334	NM_000274.4(OAT):c.881T>A (p.Leu294His)	Pathogenic
1445996	NM_000274.4(OAT):c.1179_1182dup (p.Leu395fs)	Pathogenic
1451560	NM_000274.4(OAT):c.304_305del (p.Lys102fs)	Pathogenic
1455231	NM_000274.4(OAT):c.1001dup (p.Ala335fs)	Pathogenic
1458957	NC_000010.10:g.(?126097101)(126100750_?)del	Pathogenic
146	NM_000274.4(OAT):c.3G>A (p.Met1Ile)	Pathogenic
147	NM_000274.4(OAT):c.159del (p.His53fs)	Pathogenic
148	NM_000274.4(OAT):c.550_552del (p.Ala184del)	Pathogenic
150	NM_000274.4(OAT):c.163T>C (p.Tyr55His)	Pathogenic
154	NM_000274.4(OAT):c.808G>C (p.Ala270Pro)	Pathogenic
156	NM_000274.4(OAT):c.1205T>C (p.Leu402Pro)	Pathogenic
164	NM_000274.4(OAT):c.955C>T (p.His319Tyr)	Pathogenic
165	NM_000274.4(OAT):c.425-4_429del	Pathogenic
167	NM_000274.4(OAT):c.550G>A (p.Ala184Thr)	Pathogenic
173	NM_000274.4(OAT):c.1201G>T (p.Gly401Ter)	Pathogenic
174	NC_000010.11:g.(124404664_124404669)_(124404736_124405741)del	Pathogenic
175	NM_000274.4(OAT):c.627T>A (p.Tyr209Ter)	Pathogenic
177	NM_000274.4(OAT):c.1276C>T (p.Arg426Ter)	Pathogenic
179	NM_000274.4(OAT):c.533G>A (p.Trp178Ter)	Pathogenic
1951540	NM_000274.4(OAT):c.498C>G (p.Tyr166Ter)	Pathogenic
2077266	NM_000274.4(OAT):c.1164G>A (p.Trp388Ter)	Pathogenic
2097289	NM_000274.4(OAT):c.468G>A (p.Trp156Ter)	Pathogenic

SpliceAI

1720 predictions. Top by Δscore:

Variant	Effect	Δscore
10:124398098:CCAAT:C	acceptor_gain	1.0000
10:124398099:CAAT:C	acceptor_gain	1.0000
10:124398099:CAATC:C	acceptor_gain	1.0000
10:124398102:TCTAA:T	acceptor_loss	1.0000
10:124398103:C:CA	acceptor_loss	1.0000
10:124398103:C:CC	acceptor_gain	1.0000
10:124398104:T:C	acceptor_loss	1.0000
10:124400834:CCATA:C	donor_loss	1.0000
10:124400835:CATA:C	donor_loss	1.0000
10:124400836:ATAC:A	donor_loss	1.0000
10:124400837:TA:T	donor_loss	1.0000
10:124400838:A:AC	donor_gain	1.0000
10:124400838:A:AT	donor_loss	1.0000
10:124400839:C:CC	donor_gain	1.0000
10:124400888:CGG:C	donor_gain	1.0000
10:124400980:AAAAC:A	acceptor_gain	1.0000
10:124400981:AAAC:A	acceptor_gain	1.0000
10:124400982:AAC:A	acceptor_gain	1.0000
10:124400983:AC:A	acceptor_gain	1.0000
10:124400984:CC:C	acceptor_gain	1.0000
10:124400985:C:CC	acceptor_gain	1.0000
10:124400985:C:CG	acceptor_loss	1.0000
10:124400988:CGTT:C	acceptor_gain	1.0000
10:124400990:T:TC	acceptor_gain	1.0000
10:124400991:T:C	acceptor_gain	1.0000
10:124400991:T:TC	acceptor_gain	1.0000
10:124401720:CTTTA:C	donor_loss	1.0000
10:124401721:TTTAC:T	donor_loss	1.0000
10:124401722:TTA:T	donor_loss	1.0000
10:124401723:TAC:T	donor_loss	1.0000

AlphaMissense

2855 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:124398024:C:A	R413M	0.998
10:124405553:G:C	F177L	0.998
10:124405553:G:T	F177L	0.998
10:124405555:A:G	F177L	0.998
10:124398051:G:T	A404D	0.997
10:124398080:A:C	C394W	0.996
10:124401769:C:T	G324D	0.996
10:124403015:C:G	R271T	0.996
10:124403892:G:T	A226E	0.996
10:124408609:T:A	K151N	0.996
10:124408609:T:G	K151N	0.996
10:124408907:A:C	S86R	0.996
10:124408907:A:T	S86R	0.996
10:124408909:T:G	S86R	0.996
10:124408916:A:C	S83R	0.996
10:124408916:A:T	S83R	0.996
10:124408918:T:G	S83R	0.996
10:124398024:C:G	R413T	0.995
10:124398027:A:T	I412N	0.995
10:124398057:A:G	L402P	0.995
10:124398072:A:G	L397P	0.995
10:124400864:C:G	A379P	0.995
10:124402955:C:A	G291V	0.995
10:124403014:T:A	R271S	0.995
10:124403014:T:G	R271S	0.995
10:124403810:G:C	C253W	0.995
10:124405545:C:A	R180M	0.995
10:124405545:C:G	R180T	0.995
10:124408601:C:G	R154P	0.995
10:124401779:A:G	S321P	0.994

dbSNP variants (sampled 300 via entrez): RS1000205517 (10:124418407 G>C), RS1000393689 (10:124416648 A>G), RS1000493568 (10:124409454 G>A), RS1000662188 (10:124418163 C>T), RS1000711554 (10:124411444 G>C), RS1000745655 (10:124418800 T>A,C,G), RS1000782452 (10:124409762 T>C), RS1000833172 (10:124411105 A>G), RS1000849277 (10:124417037 A>G), RS1001046920 (10:124405614 T>A,C,G), RS1001103317 (10:124399636 C>T), RS1001185267 (10:124410502 C>T), RS1001231897 (10:124410942 C>G), RS1001346611 (10:124414943 C>T), RS1001496070 (10:124408465 C>A,T)

Disease associations

OMIM: gene MIM:613349 | disease phenotypes: MIM:258870

GenCC curated gene-disease

Disease	Classification	Inheritance
ornithine aminotransferase deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
ornithine aminotransferase deficiency	Definitive	AR

Mondo (4): ornithine aminotransferase deficiency (MONDO:0009796), inherited retinal dystrophy (MONDO:0019118), optic choroid disorder (MONDO:0001898), optic atrophy (MONDO:0003608)

Orphanet (2): Gyrate atrophy of choroid and retina (Orphanet:414), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

24 total (25 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000523	Subcapsular cataract
HP:0000529	Progressive visual loss
HP:0000533	Chorioretinal atrophy
HP:0000545	Myopia
HP:0000618	Blindness
HP:0000662	Nyctalopia
HP:0001103	Abnormal macular morphology
HP:0001133	Constriction of peripheral visual field
HP:0001250	Seizure
HP:0001595	Abnormal hair morphology
HP:0003355	Aminoaciduria
HP:0003457	EMG abnormality
HP:0003701	Proximal muscle weakness
HP:0007675	Progressive night blindness
HP:0007787	Posterior subcapsular cataract
HP:0011463	Childhood onset
HP:0012026	Hyperornithinemia
HP:0012152	Foveoschisis
HP:0030498	Macular thickening
HP:0040031	Chorioretinal hyperpigmentation
HP:0000556	Retinal dystrophy

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D015862	Choroid Diseases	C11.941.160
D015799	Gyrate Atrophy	C11.270.468; C11.941.160.578; C16.320.290.468
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5954 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.68	Ki	2.1	nM	GABACULINE
8.38	Ki	4.2	nM	CHEMBL220453

PubChem BioAssay actives

2 with measured affinity, of 13 total; 2 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
(3R)-3-aminocyclohexene-1-carboxylic acid	1249759: Inhibition of human recombinant OAT using 1 mM alpha-ketoglutarate as substrate	ki	0.0021	uM
cis-(1S,3S)-3-amino-4-(1,1,1,3,3,3-hexafluoropropan-2-ylidene)cyclopentane-1-carboxylic acid	1249759: Inhibition of human recombinant OAT using 1 mM alpha-ketoglutarate as substrate	ki	0.0042	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	9
sodium arsenite	affects expression, decreases expression, increases expression	3
Acetaminophen	increases expression	3
Benzo(a)pyrene	decreases methylation, increases expression, decreases expression	3
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression, increases expression	3
2-amino-3-methylimidazo(4,5-f)quinoline	increases response to substance, affects cotreatment	2
2-amino-3,4-dimethylimidazo(4,5-f)quinoline	increases response to substance, affects cotreatment	2
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	affects cotreatment, increases response to substance	2
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	affects cotreatment, increases response to substance	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cadmium	increases expression, decreases reaction, increases abundance, increases palmitoylation	2
Plant Extracts	affects cotreatment, increases expression, decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
bisphenol A	decreases expression	1
deoxynivalenol	decreases expression	1
methylselenic acid	increases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression, increases expression	1
cobaltous chloride	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
perfluorooctanoic acid	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3626483	Binding	Inhibition of human recombinant OAT using 1 mM alpha-ketoglutarate as substrate	Suppression of Hepatocellular Carcinoma by Inhibition of Overexpressed Ornithine Aminotransferase. — ACS Med Chem Lett

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 2 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_CY54	GM06330	Finite cell line	Female
CVCL_CY59	GM09113	Finite cell line	Female
CVCL_D1PF	Abcam K-562 OAT KO	Cancer cell line	Female
CVCL_D2L1	Abcam Raji OAT KO	Cancer cell line	Male
CVCL_WQ18	Abcam Jurkat OAT KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT00001735	PHASE1	COMPLETED	Gene Therapy for Gyrate Atrophy
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT00001166	Not specified	COMPLETED	Gyrate Atrophy of the Choroid and Retina
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT05312736	Not specified	ACTIVE_NOT_RECRUITING	Gyrate Atrophy Ocular and Systemic Study
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study