TBXAS1

Summary

TBXAS1 (thromboxane A synthase 1, HGNC:11609) is a protein-coding gene on chromosome 7q34, encoding Thromboxane-A synthase (P24557). Catalyzes the conversion of prostaglandin H2 (PGH2) to thromboxane A2 (TXA2), a potent inducer of blood vessel constriction and platelet aggregation.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostglandin H2 to thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation. The enzyme plays a role in several pathophysiological processes including hemostasis, cardiovascular disease, and stroke. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6916 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ghosal hematodiaphyseal dysplasia (Definitive, ClinGen)
• GWAS associations: 15
• Clinical variants (ClinVar): 378 total — 17 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 22
• Druggable target: yes — 46 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001061

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11609
Approved symbol	TBXAS1
Name	thromboxane A synthase 1
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	CYP5, CYP5A1, THAS, TXS, TXAS, TS
Ensembl gene	ENSG00000059377
Ensembl biotype	protein_coding
OMIM	274180
Entrez	6916

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 10 protein_coding, 6 protein_coding_CDS_not_defined, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000336425, ENST00000411653, ENST00000414041, ENST00000422328, ENST00000425687, ENST00000438104, ENST00000448866, ENST00000455353, ENST00000458722, ENST00000462053, ENST00000462275, ENST00000469630, ENST00000473948, ENST00000474763, ENST00000476637, ENST00000481440, ENST00000492560, ENST00000493340, ENST00000494876, ENST00000887871, ENST00000950315, ENST00000950316

RefSeq mRNA: 8 — MANE Select: NM_001061 NM_001061, NM_001130966, NM_001166253, NM_001166254, NM_001314028, NM_001366537, NM_001366538, NM_030984

CCDS: CCDS55174, CCDS55175, CCDS5855, CCDS5856, CCDS94215

Canonical transcript exons

ENST00000448866 — 13 exons

Exon	Start	End
ENSE00003480397	139875585	139875637
ENSE00003510802	139955459	139955607
ENSE00003522183	140007091	140007182
ENSE00003543755	139957634	139957764
ENSE00003593660	140015723	140015860
ENSE00003605278	139961919	139962233
ENSE00003608433	139872235	139872328
ENSE00003627039	139953368	139953456
ENSE00003638661	139911225	139911321
ENSE00003669379	140017671	140017833
ENSE00003786559	139936191	139936307
ENSE00003901772	140020025	140020293
ENSE00003902870	139829264	139829479

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.6595 / max 926.0372, expressed in 991 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81476	10.6341	557
81478	6.8039	434
81475	1.9011	425
81474	0.9675	490
81477	0.3530	141

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.65	gold quality
mononuclear cell	CL:0000842	98.05	gold quality
leukocyte	CL:0000738	98.02	gold quality
granulocyte	CL:0000094	97.30	gold quality
blood	UBERON:0000178	94.68	gold quality
spleen	UBERON:0002106	93.85	gold quality
right lung	UBERON:0002167	93.80	gold quality
gall bladder	UBERON:0002110	92.38	gold quality
upper lobe of left lung	UBERON:0008952	90.97	gold quality
upper lobe of lung	UBERON:0008948	89.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.57	gold quality
rectum	UBERON:0001052	85.21	gold quality
minor salivary gland	UBERON:0001830	85.15	gold quality
vermiform appendix	UBERON:0001154	84.18	gold quality
colonic epithelium	UBERON:0000397	84.12	gold quality
bone marrow cell	CL:0002092	83.93	gold quality
right coronary artery	UBERON:0001625	83.81	gold quality
esophagus mucosa	UBERON:0002469	83.71	gold quality
omental fat pad	UBERON:0010414	83.59	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.53	gold quality
peritoneum	UBERON:0002358	83.47	gold quality
metanephros cortex	UBERON:0010533	83.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.38	gold quality
lower esophagus mucosa	UBERON:0035834	83.28	gold quality
descending thoracic aorta	UBERON:0002345	82.78	gold quality
left adrenal gland	UBERON:0001234	82.39	gold quality
left adrenal gland cortex	UBERON:0035825	82.30	gold quality
adipose tissue of abdominal region	UBERON:0007808	82.19	gold quality
bone marrow	UBERON:0002371	82.18	gold quality
left coronary artery	UBERON:0001626	81.71	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	1435.56
E-GEOD-180759	yes	1338.25
E-GEOD-131882	yes	1099.81
E-HCAD-35	yes	43.41
E-CURD-112	yes	32.25
E-MTAB-6678	yes	22.63
E-HCAD-25	yes	18.56
E-HCAD-10	yes	15.68
E-CURD-119	yes	6.48
E-MTAB-9543	yes	4.65
E-HCAD-30	no	1075.75
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BACH1, EP300, ETS1, NFE2, NFE2L2, NFE2L3, NRF1, PPARG, SPI1, TP53

miRNA regulators (miRDB)

10 targeting TBXAS1, 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-4503	99.85	71.45	1869
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-362-5P	95.87	66.02	554
HSA-MIR-500B-5P	95.87	66.04	557

Literature-anchored findings (GeneRIF, showing 36)

• Gene transfer of thromboxane A(2) synthase and prostaglandin I(2) synthase antithetically altered tumor angiogenesis and tumor growth. (PMID:11782360)
• Transcriptional control of the human thromboxane synthase gene in vivo and in vitro. (PMID:11956185)
• structure and function of the gene and protein - review (PMID:12432933)
• Cox-2 and TBXAS may play an important role in pituitary tumor development and progression (PMID:15067173)
• Significantly higher expression of thromboxane synthase is associated with metastasis in non-small cell lung cancer (PMID:15870920)
• Overexpression of thromboxane synthase is associated with invasive bladder cancer (PMID:16357168)
• Thromboxane synthase mutations in an increased bone density disorder (Ghosal syndrome). (PMID:18264100)
• TBXAS1 genetic variation is associated with incident myocardial infarction. (PMID:19046748)
• The results suggest specific TBXAS1 gene polymorphisms may be a useful marker for development of cerebral infarction, especially SAO type in Korean population. (PMID:19403042)
• In humans, TXAS was expressed in the atherosclerotic lesion, associated with increased inflammatory cells, in particular M2 polarized macrophages, and increased in atherosclerotic lesions of patients with recent symptoms of thrombotic events. (PMID:20383787)
• Apoptosis induced in lung cancer cells by the thromboxane synthase inhibitor 1-benzylimidazole is associated with the over-production of ROS and the reduction of NF-kappaB. (PMID:20647010)
• The TC genotype and T allele of thromboxane synthase are risk factors of myocardial infarction. (PMID:20931532)
• Rs10487667 polymorphism in the CYP5A1 gene might be a risk factor of myocardial infarction in the Uigur population in Xinjiang. (PMID:21215134)
• Data suggest that targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC. (PMID:21388528)
• The rare allele of rs6962291 may play a protective role against aspirin hypersensitivity via a lower catalytic activity of the TBXAS1 gene, attributed to the increase of a nonfunctioning isoform of TBXAS1. (PMID:21449675)
• these results showed that visfatin promoted IL-8 production by upregulation of TXAS, leading to angiogenic activation in endothelial cells. (PMID:22293189)
• Data show that that DNA methylation of the TBXAS1 promoter was decreased and thromboxane synthase expression was increased in omental arteries of preeclamptic women as compared with normal pregnant women. (PMID:22493072)
• The increased Km and decreased Vmax values observed with L357V suggest that this variant may generate less TXA2 at the low levels of PGH2 expected in vivo, raising the possibility of attenuated signaling through the thromboxane pathway. (PMID:22735388)
• In this study we have showed, for the first time, a significant role of the minor allele rs6962291 of TBXAS1 in patients with NSAID acute cutaneous hypersensitivity. (PMID:23763970)
• 12-HHT is produced by both TxAS-dependent and TxAS-independent pathways in vitro and in vi (PMID:24009185)
• study suggests that the anti-tumor effect of glycyrrhizin in lung adenocarcinoma is, at least in part, TxAS-dependent. (PMID:24556579)
• The carriage of Thromboxane A synthase 1 gene polymorphism AA was shown to affect the risk of clopidogrel resistance. (PMID:26027242)
• The cardiovascular events significantly morefrequently occurred during 12 and 18 months in resistant diabetics and in the patients with an allele lacking the *2/*3 CYP2C9 gene function and AT/TT polymorphism of the thromboxane synthase gene TBS1. (PMID:26117917)
• Single nucleotide polymorphisms of TBXAS1 are associated with susceptibility to gout in ethnic Han males population. (PMID:26252103)
• the administration of salted drinking water (2.7% NaCl) to wild-type mice resulted in elevated placental TXA2 synthase (TXAS) and plasma thromboxane A2, but not prostacyclin, levels, which was also found in clinical preeclampsia placenta samples. (PMID:26974824)
• RS41708TT is not only independent risk factor for symptomatic carotid artery or intracranial arterial stenosis, but is also independent risk predictor for neurologic deterioration in ischemic stroke patients. (PMID:28108096)
• TXAS1 rs2267679TT and rs41708TT genotypes are associated with carotid plaque vulnerability, platelet activation and TXA2 levels in ischemic stroke patients. (PMID:28704403)
• Sequencing revealed two novel biallelic variants of unknown significance within the thromboxane A synthase gene, TBXAS1 (c.266T > C; c.989T > C), bioinformatically predicted to disrupt the protein. TBXAS1 mutations result in Ghosal hematodiaphyseal dysplasia (OMIM 231095), the autosomal recessive syndrome associated with abnormal bone structure and BMF. (PMID:28868793)
• The available theoretical and experimental data have elucidated the very important role of the thromboxane A2 - thromboxane A synthase - thromboxane A2 receptor axis in the pathogenesis of thrombotic diseases. Systematic studies are required to verify genetic markers in patients at high cardiovascular risk, in order to achieve more effective diagnostics and treatment. [review] (PMID:30039765)
• Thromboxane A synthase 1 gene expression and promotor haplotypes are associated with risk of large artery-atherosclerosis stroke in Iranian population. (PMID:31026093)
• Ghosal hematodiaphyseal dysplasia and response to corticosteroid therapy. (PMID:33185009)
• A new insight into subinteractomes of functional antagonists: Thromboxane (CYP5A1) and prostacyclin (CYP8A1) synthases. (PMID:33527589)
• Novel compound heterozygous variants of TBXAS1 presenting with Ghosal hematodiaphyseal dysplasia treated with steroids. (PMID:33595912)
• Novel TBXAS1 variants in two Indian children with Ghosal hematodiaphyseal dysplasia: A concise report. (PMID:35395429)
• TBXAS1 Gene Polymorphism Is Associated with the Risk of Ischemic Stroke of Metabolic Syndrome in a Chinese Han Population. (PMID:35923246)
• Genome-wide association study implicates the role of TBXAS1 in the pathogenesis of depressive symptoms among the Korean population. (PMID:38320993)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbxas1	ENSDARG00000002249
mus_musculus	Tbxas1	ENSMUSG00000029925
rattus_norvegicus	Tbxas1	ENSRNOG00000007918

Protein

Protein identifiers

Thromboxane-A synthase — P24557 (reviewed: P24557)

Alternative names: Cytochrome P450 5A1, Hydroperoxy icosatetraenoate dehydratase

All UniProt accessions (5): P24557, A0A498U6I9, C9JS68, F8WC80, F8WD37

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the conversion of prostaglandin H2 (PGH2) to thromboxane A2 (TXA2), a potent inducer of blood vessel constriction and platelet aggregation. Also cleaves PGH2 to 12-hydroxy-heptadecatrienoicacid (12-HHT) and malondialdehyde, which is known to act as a mediator of DNA damage. 12-HHT and malondialdehyde are formed stoichiometrically in the same amounts as TXA2. Additionally, displays dehydratase activity, toward (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (15(S)-HPETE) producing 15-KETE and 15-HETE.

Subunit / interactions. Monomer.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Platelets, lung, kidney, spleen, macrophages and lung fibroblasts.

Disease relevance. Ghosal hematodiaphyseal dysplasia (GHDD) [MIM:231095] Rare autosomal recessive disorder characterized by increased bone density with predominant diaphyseal involvement and aregenerative corticosteroid-sensitive anemia. Aregenerative anemia is characterized by bone marrow failure, so that functional marrow cells are regenerated slowly or not at all. The disease is caused by variants affecting the gene represented in this entry. Thromboxane synthetase deficiency has been detected in some patients with a bleeding disorder due to platelet dysfunction.

Pathway. Lipid metabolism; fatty acid metabolism.

Similarity. Belongs to the cytochrome P450 family.

Isoforms (4)

UniProt ID	Names	Canonical?
P24557-1	1	yes
P24557-2	2
P24557-3	3
P24557-4	4

RefSeq proteins (8): NP_001052, NP_001124438, NP_001159725, NP_001159726, NP_001300957, NP_001353466, NP_001353467, NP_112246 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002401	Cyt_P450_E_grp-I	Family
IPR017972	Cyt_P450_CS	Conserved_site
IPR036396	Cyt_P450_sf	Homologous_superfamily
IPR050705	Cytochrome_P450_3A	Family

Pfam: PF00067

Catalyzed reactions (Rhea), 5 shown:

• prostaglandin H2 = thromboxane A2 (RHEA:17137)
• (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo-(5Z,8Z,11Z,13E)-eicosatetraenoate + H2O (RHEA:48636)
• prostaglandin H2 = (12S)-hydroxy-(5Z,8E,10E)-heptadecatrienoate + malonaldehyde (RHEA:48644)
• (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + AH2 = (15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + A + H2O (RHEA:48856)
• a hydroperoxyeicosatetraenoate = an oxoeicosatetraenoate + H2O (RHEA:55556)

UniProt features (59 total): sequence variant 30, mutagenesis site 9, topological domain 5, sequence conflict 5, splice variant 4, transmembrane region 4, chain 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P24557-F1	91.50	0.76

Functional residue map

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

Ligand- & substrate-binding residues (1): 479 (axial binding residue)

Mutagenesis-validated functional residues (9):

Position	Phenotype
109	loss of thromboxane-a synthase activity. decreased heme-binding.
132	loss of thromboxane-a synthase activity. decreased heme-binding.
134	does not affect thromboxane-a synthase activity. does not affect heme-binding.
136	loss of thromboxane-a synthase activity. decreased heme-binding.
409	does not affect thromboxane-a synthase activity. does not affect heme-binding.
412	loss of thromboxane-a synthase activity. decreased heme-binding.
414	does not affect thromboxane-a synthase activity. does not affect heme-binding.
477	loss of thromboxane-a synthase activity. decreased heme-binding.
479	loss of thromboxane-a synthase activity. decreased heme-binding.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-211979	Eicosanoids
R-HSA-2162123	Synthesis of Prostaglandins (PG) and Thromboxanes (TX)
R-HSA-5579032	Defective TBXAS1 causes GHDD
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-211859	Biological oxidations
R-HSA-211897	Cytochrome P450 - arranged by substrate type
R-HSA-211945	Phase I - Functionalization of compounds
R-HSA-2142753	Arachidonate metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-5579029	Metabolic disorders of biological oxidation enzymes
R-HSA-5668914	Diseases of metabolism
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 341 (showing top): MODULE_93, AP1_01, GOBP_RESPONSE_TO_ETHANOL, REACTOME_BIOLOGICAL_OXIDATIONS, BENPORATH_ES_WITH_H3K27ME3, HNF3ALPHA_Q6, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, NKX25_02, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, MODULE_45, TGACCTY_ERR1_Q2, HNF1_Q6, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS

GO Biological Process (12): prostaglandin biosynthetic process (GO:0001516), icosanoid metabolic process (GO:0006690), intracellular chloride ion homeostasis (GO:0030644), long-chain fatty acid biosynthetic process (GO:0042759), response to ethanol (GO:0045471), positive regulation of vasoconstriction (GO:0045907), prostanoid biosynthetic process (GO:0046457), response to fatty acid (GO:0070542), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), fatty acid biosynthetic process (GO:0006633), prostaglandin metabolic process (GO:0006693)

GO Molecular Function (12): monooxygenase activity (GO:0004497), thromboxane-A synthase activity (GO:0004796), iron ion binding (GO:0005506), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), heme binding (GO:0020037), 12-hydroxyheptadecatrienoic acid synthase activity (GO:0036134), hydroperoxy icosatetraenoate dehydratase activity (GO:0106256), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), lyase activity (GO:0016829), isomerase activity (GO:0016853), metal ion binding (GO:0046872)

GO Cellular Component (5): endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Metabolism	2
Cytochrome P450 - arranged by substrate type	1
Arachidonate metabolism	1
Metabolic disorders of biological oxidation enzymes	1
Phase I - Functionalization of compounds	1
Biological oxidations	1
Fatty acid metabolism	1
Diseases of metabolism	1
Disease	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	3
prostanoid metabolic process	2
oxidoreductase activity	2
cytoplasm	2
cellular anatomical structure	2
prostaglandin metabolic process	1
prostanoid biosynthetic process	1
carboxylic acid metabolic process	1
intracellular monoatomic anion homeostasis	1
chloride ion homeostasis	1
long-chain fatty acid metabolic process	1
fatty acid biosynthetic process	1
response to alcohol	1
regulation of vasoconstriction	1
vasoconstriction	1
positive regulation of multicellular organismal process	1
unsaturated fatty acid biosynthetic process	1
icosanoid biosynthetic process	1
response to lipid	1
response to oxygen-containing compound	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
intramolecular oxidoreductase activity	1
transition metal ion binding	1
tetrapyrrole binding	1
oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor	1
hydro-lyase activity	1
binding	1
cation binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum	1
intracellular organelle lumen	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

2060 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBXAS1	PTGIS	Q16647	861
TBXAS1	PTGS1	P23219	858
TBXAS1	MGAM2	Q2M2H8	822
TBXAS1	TNFRSF11B	O00300	683
TBXAS1	PTGES	O14684	668
TBXAS1	PTGES2	Q9H7Z7	602
TBXAS1	TBXA2R	P21731	599
TBXAS1	AKR1C3	P42330	558
TBXAS1	CYSLTR1	Q9Y271	548
TBXAS1	LTA4H	P09960	545
TBXAS1	PTGDS	P41222	545
TBXAS1	PTGES3	Q15185	517
TBXAS1	PTGIR	P43119	507
TBXAS1	TNFSF11	O14788	507
TBXAS1	CYP2E1	P05181	506

IntAct

6 interactions, top by confidence:

A	B	Type	Score
TBXAS1	EEF1A2	psi-mi:“MI:0915”(physical association)	0.590
TBXAS1	DKC1	psi-mi:“MI:0915”(physical association)	0.400
	TBXAS1	psi-mi:“MI:0915”(physical association)	0.370
	PGRMC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): EEF1A2 (Affinity Capture-MS), TBXAS1 (Proximity Label-MS), TBXAS1 (Proximity Label-MS), EEF1A2 (Affinity Capture-MS), TBXAS1 (Affinity Capture-RNA), TBXAS1 (Reconstituted Complex)

ESM2 similar proteins: A2RRT9, O18596, O44221, O46054, P24557, P33269, P33274, P36423, P49430, P51869, P51870, P51871, P98187, Q27589, Q27606, Q27698, Q2KIG5, Q2PG45, Q3MID2, Q5RCN6, Q6NT55, Q6ZWL3, Q99N16, Q9DBW0, Q9EP75, Q9GLL1, Q9GQM9, Q9HCS2, Q9V3S0, Q9V4T3, Q9V4T5, Q9V557, Q9V674, Q9V675, Q9V676, Q9V7G5, Q9V9L1, Q9VHP4, Q9VL92, Q9VLZ7

Diamond homologs: A0A067DE75, A0A067ELB0, A0A098D1J7, A0A0B4L1W8, A0A0S2II38, A0A0U2U8U5, A0A140JWM8, A0A1I9Q5Z0, A0A2Z5U6I9, A0A343URW7, A0A3Q7HBJ5, A0A3Q7HS74, A0A4P8DJC8, A0A6J4BC30, A0AAW1JA93, A0AAW1NEA3, A2Z212, A5BFI4, A9QNE7, C0SJS3, D5JBW9, D5JBX1, E1B2Z9, F6H9N6, H2DH16, I7C6E8, I7CT85, K4CEE8, K4CI52, O18993, O42563, O70537, P05183, P0DO14, P0DOX0, P0DXH8, P17177, P17178, P24557, P30437

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
EP300	“up-regulates quantity by expression”	TBXAS1	“transcriptional regulation”
NFE2L2	“up-regulates quantity by expression”	TBXAS1	“transcriptional regulation”
TP53	“down-regulates quantity by repression”	TBXAS1	“transcriptional regulation”
ETS1	“up-regulates quantity by expression”	TBXAS1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	11
Uncertain significance	151
Likely benign	116
Benign	30

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
1031016	NM_001061.7(TBXAS1):c.193G>T (p.Glu65Ter)	Pathogenic
11886	NM_001061.7(TBXAS1):c.1460T>C (p.Leu487Pro)	Pathogenic
11888	NM_001061.7(TBXAS1):c.1441G>T (p.Gly481Trp)	Pathogenic
1450444	NC_000007.13:g.(?139611004)(139611140_?)del	Pathogenic
1930061	NM_001061.7(TBXAS1):c.614_615del (p.Pro205fs)	Pathogenic
2051451	NM_001061.7(TBXAS1):c.1109_1110del (p.Glu370fs)	Pathogenic
2058503	NM_001061.7(TBXAS1):c.1083dup (p.Asp362Ter)	Pathogenic
2415982	NC_000007.14:g.139955459del	Pathogenic
2423590	NC_000007.13:g.(?139715503)(139715680_?)del	Pathogenic
2425346	NC_000007.13:g.(?130781014)(150301047_?)del	Pathogenic
2896668	NM_001061.7(TBXAS1):c.950_951del (p.His317fs)	Pathogenic
2966137	NM_001061.7(TBXAS1):c.943del (p.Arg315fs)	Pathogenic
3010034	NM_001061.7(TBXAS1):c.396G>A (p.Trp132Ter)	Pathogenic
3358487	NM_001061.7(TBXAS1):c.373_374del (p.Leu125fs)	Pathogenic
4768487	NM_001061.7(TBXAS1):c.765dup (p.Asn256Ter)	Pathogenic
686007	GRCh37/hg19 7q34(chr7:139548076-139680096)x1	Pathogenic
992886	NM_001061.7(TBXAS1):c.122_135del (p.Lys41fs)	Pathogenic
1695387	NM_001061.7(TBXAS1):c.859C>T (p.His287Tyr)	Likely pathogenic
1967396	NM_001061.7(TBXAS1):c.1417G>A (p.Gly473Arg)	Likely pathogenic
2990227	NM_001061.7(TBXAS1):c.688+2T>G	Likely pathogenic
3341863	NM_001061.7(TBXAS1):c.819+1G>A	Likely pathogenic
3626024	NM_001061.7(TBXAS1):c.1365-2A>G	Likely pathogenic
3717255	NM_001061.7(TBXAS1):c.333+2T>C	Likely pathogenic
3769419	NM_001061.7(TBXAS1):c.90-1G>A	Likely pathogenic
3897816	NM_001061.7(TBXAS1):c.451-2A>T	Likely pathogenic
4539368	NM_001061.7(TBXAS1):c.372dup (p.Leu125fs)	Likely pathogenic
4845772	NM_001061.7(TBXAS1):c.79del (p.Leu27fs)	Likely pathogenic
626225	NM_001061.7(TBXAS1):c.580_581del (p.Ala194fs)	Likely pathogenic

SpliceAI

4480 predictions. Top by Δscore:

Variant	Effect	Δscore
7:139777601:TTA:T	donor_loss	1.0000
7:139777602:TAC:T	donor_loss	1.0000
7:139777604:C:CG	donor_loss	1.0000
7:139787332:CTTTA:C	acceptor_loss	1.0000
7:139787333:TTTA:T	acceptor_loss	1.0000
7:139787335:TA:T	acceptor_loss	1.0000
7:139787336:A:G	acceptor_loss	1.0000
7:139787337:GGA:G	acceptor_gain	1.0000
7:139870123:G:T	donor_gain	1.0000
7:139872229:CTCCA:C	acceptor_loss	1.0000
7:139872230:TCCAG:T	acceptor_loss	1.0000
7:139872231:CCA:C	acceptor_loss	1.0000
7:139872232:CAG:C	acceptor_loss	1.0000
7:139872233:A:G	acceptor_loss	1.0000
7:139872234:G:A	acceptor_loss	1.0000
7:139911219:TCCCA:T	acceptor_loss	1.0000
7:139911220:CCCAG:C	acceptor_loss	1.0000
7:139911221:CCAG:C	acceptor_loss	1.0000
7:139911222:CA:C	acceptor_loss	1.0000
7:139911223:A:G	acceptor_loss	1.0000
7:139911224:G:GA	acceptor_loss	1.0000
7:139911317:GAATG:G	donor_gain	1.0000
7:139911319:ATGG:A	donor_loss	1.0000
7:139911322:G:GA	donor_loss	1.0000
7:139911323:TA:T	donor_loss	1.0000
7:139936308:G:A	donor_loss	1.0000
7:139936309:T:A	donor_loss	1.0000
7:139940069:G:GT	donor_gain	1.0000
7:139955608:G:GG	donor_gain	1.0000
7:139957632:A:G	acceptor_gain	1.0000

AlphaMissense

3499 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:140007161:G:C	R402T	0.994
7:140017672:T:C	F456L	0.994
7:140017674:C:A	F456L	0.994
7:140017674:C:G	F456L	0.994
7:140007162:G:C	R402S	0.993
7:140007162:G:T	R402S	0.993
7:140007161:G:T	R402M	0.992
7:140007152:A:T	E399V	0.991
7:139911307:T:C	F107L	0.989
7:139911309:T:A	F107L	0.989
7:139911309:T:G	F107L	0.989
7:140015847:T:C	F451L	0.989
7:140015849:C:A	F451L	0.989
7:140015849:C:G	F451L	0.989
7:140017720:T:C	F472L	0.989
7:140017722:C:A	F472L	0.989
7:140017722:C:G	F472L	0.989
7:139936253:G:C	W132C	0.985
7:139936253:G:T	W132C	0.985
7:139872310:C:A	N55K	0.984
7:139872310:C:G	N55K	0.984
7:139936224:A:C	S123R	0.984
7:139936226:C:A	S123R	0.984
7:139936226:C:G	S123R	0.984
7:140007153:G:C	E399D	0.984
7:140007153:G:T	E399D	0.984
7:139911318:A:C	R110S	0.982
7:139911318:A:T	R110S	0.982
7:139936251:T:A	W132R	0.982
7:139936251:T:C	W132R	0.982

dbSNP variants (sampled 300 via entrez): RS1000006606 (7:139955151 C>G), RS1000015406 (7:139869004 G>A,C), RS1000018763 (7:139991431 C>T), RS1000022280 (7:139952374 T>G), RS1000022467 (7:139806165 C>T), RS1000032123 (7:139952015 A>G,T), RS1000035820 (7:140012551 C>A,G,T), RS1000039118 (7:139980505 C>T), RS1000053716 (7:139814964 A>G), RS1000060496 (7:139910412 G>A), RS1000075595 (7:139865250 C>A), RS1000085511 (7:139822792 C>T), RS1000090358 (7:139904108 C>T), RS1000103054 (7:139994947 C>G,T), RS1000113086 (7:139948618 T>C)

Disease associations

OMIM: gene MIM:274180 | disease phenotypes: MIM:231095, MIM:614158, MIM:207500, MIM:301800

GenCC curated gene-disease

Disease	Classification	Inheritance
ghosal hematodiaphyseal dysplasia	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ghosal hematodiaphyseal dysplasia	Definitive	AR

Mondo (7): ghosal hematodiaphyseal dysplasia (MONDO:0009274), intellectual disability (MONDO:0001071), thrombocytopenia (MONDO:0002049), platelet-type bleeding disorder 14 (MONDO:0013597), imperforate anus (MONDO:0001046), urethral stricture (MONDO:0002127), patent foramen ovale (MONDO:0020439)

Orphanet (4): Ghosal hematodiaphyseal dysplasia (Orphanet:1802), Non-syndromic anorectal malformation (Orphanet:557), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Patent foramen ovale (Orphanet:99108)

HPO phenotypes

22 total (24 of 22 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000944	Abnormal metaphysis morphology
HP:0001744	Splenomegaly
HP:0001873	Thrombocytopenia
HP:0001882	Decreased total leukocyte count
HP:0001903	Anemia
HP:0002167	Abnormal speech pattern
HP:0002644	Abnormal pelvic girdle bone morphology
HP:0002823	Abnormal femur morphology
HP:0002992	Abnormal tibia morphology
HP:0003103	Abnormal cortical bone morphology
HP:0003312	Abnormal form of the vertebral bodies
HP:0004493	Craniofacial hyperostosis
HP:0005019	Diaphyseal undertubulation
HP:0005505	Refractory anemia
HP:0005528	Bone marrow hypocellularity
HP:0005890	Hyperostosis cranialis interna
HP:0006487	Bowing of the long bones
HP:0010978	Abnormality of immune system physiology
HP:0011001	Increased bone mineral density
HP:0011974	Myelofibrosis
HP:0100252	Diaphyseal dysplasia
HP:0012227	Urethral stricture
HP:0001655	Patent foramen ovale

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001693_7	Acute lymphoblastic leukemia (childhood)	2.000000e-06
GCST001762_496	Obesity-related traits	9.000000e-06
GCST002203_2	Gray matter volume (schizophrenia interaction)	1.000000e-07
GCST002337_42	Amyotrophic lateral sclerosis (sporadic)	2.000000e-06
GCST003815_121	Late-onset Alzheimer’s disease	3.000000e-06
GCST004833_3	Cervical cancer	2.000000e-06
GCST005194_116	Coronary artery disease	4.000000e-06
GCST006222_1	Cerebellum growth	4.000000e-06
GCST006979_218	Heel bone mineral density	2.000000e-09
GCST007267_327	Systolic blood pressure	1.000000e-09
GCST008053_175	Height	4.000000e-09
GCST008053_184	Height	2.000000e-07
GCST010866_127	Coronary artery disease	1.000000e-08
GCST011365_71	Myocardial infarction	2.000000e-10
GCST90002407_496	White blood cell count	7.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005109	energy expenditure
EFO:0005420	grey matter volume measurement
EFO:1001870	late-onset Alzheimers disease
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D001006	Anus, Imperforate	C06.198.050; C16.131.314.094
D054092	Foramen Ovale, Patent	C14.240.400.560.375.258; C14.280.400.560.375.258; C16.131.240.400.560.375.258
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
D014525	Urethral Stricture	C12.050.351.968.767.700.700; C12.200.777.767.700.700; C12.950.767.700.700
C565551	Ghosal Hematodiaphyseal Dysplasia (supp.)
C562866	Thromboxane Synthetase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1835 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

46 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,326,433 (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
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL11359	CISPLATIN	4
CHEMBL114	SAQUINAVIR	4	39,899
CHEMBL116	AMPRENAVIR	4	29,221
CHEMBL11662	OZAGREL	4	3,006
CHEMBL1201469	GRAMICIDIN	4
CHEMBL121	ROSIGLITAZONE	4	58,849
CHEMBL1221	SULCONAZOLE	4	12,121
CHEMBL1262	OXICONAZOLE	4	48
CHEMBL157101	KETOCONAZOLE	4	75,361
CHEMBL159	VINBLASTINE	4	412,636
CHEMBL163	RITONAVIR	4	53,773
CHEMBL193	NIFEDIPINE	4	74,353
CHEMBL290106	BITHIONOL	4	6,439
CHEMBL291338	3,3’,4’,5-TETRACHLOROSALICYLANILIDE	4	721
CHEMBL408	TROGLITAZONE	4	38,856
CHEMBL411	DIETHYLSTILBESTROL	4	353,912
CHEMBL421	SULFASALAZINE	4	73,629
CHEMBL428	TROVAFLOXACIN	4	17,587
CHEMBL442	ERGOTAMINE	4	19,697
CHEMBL488	AMINOGLUTETHIMIDE	4
CHEMBL496	HEXACHLOROPHENE	4
CHEMBL506247	TANNIC ACID	4
CHEMBL584	NELFINAVIR	4
CHEMBL6	INDOMETHACIN	4
CHEMBL603	ZAFIRLUKAST	4
CHEMBL787	MONTELUKAST	4
CHEMBL808	ECONAZOLE	4
CHEMBL83	TAMOXIFEN	4
CHEMBL91	MICONAZOLE	4

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs6962291	Toxicity	3	aspirin	Asthma

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6962291	TBXAS1	3	1.75	1	aspirin

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CYP5, CYP7 and CYP8 families

Most potent curated ligand interactions (6 total), top 6:

Ligand	Action	Affinity	Parameter
compound 10a [PMID: 1447738]	Inhibition	8.7	pIC50
dazoxiben	Inhibition	8.5	pIC50
ozagrel	Inhibition	8.22	pIC50
furegrelate sodium	Inhibition	7.8	pIC50
compound 7p [PMID: 7861416]	Inhibition	5.0	pIC50
picotamide	Inhibition	3.8	pIC50

Binding affinities (BindingDB)

32 measured of 36 human assays (37 total across all organisms); most potent 32 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
7-(3-Pyridin-3-yl-bicyclo[2.2.1]hept-2-yl)-heptanoic acid	IC50	7 nM
6-(3-Pyridin-3-yl-bicyclo[2.2.1]hept-2-yl)-hex-4-enoic acid	IC50	29 nM
7-(3-Pyridin-3-yl-bicyclo[2.2.1]hept-2-yl)-hept-5-enoic acid	IC50	50 nM
7-(3-Pyridin-3-yl-bicyclo[2.2.1]hept-2-yl)-heptanoic acid	IC50	54 nM
7-(3-Pyridin-3-yl-bicyclo[2.2.1]hept-2-yl)-hept-5-enoic acid	IC50	54 nM
6-(3-Pyridin-3-yl-bicyclo[2.2.1]hept-2-yl)-hex-4-enoic acid	IC50	78 nM
7-[3-(Biphenyl-4-yloxymethyl)-2-pyridin-3-yl-bicyclo[2.2.1]hept-2-yl]-hept-5-enoic acid	IC50	120 nM
7-(3-Pyridin-3-yl-bicyclo[2.2.1]hept-2-yl)-heptanoic acid	IC50	125 nM
5-(1H-imidazol-1-ylmethyl)-5,6,7,8-tetrahydroquinoline	IC50	160 nM
8-(3-Pyridin-3-yl-bicyclo[2.2.1]hept-2-yl)-oct-6-enoic acid	IC50	165 nM
5-(1H-imidazol-1-ylmethyl)-7,8-dihydroquinoline	IC50	170 nM
5-[3-(Imidazol-1-yl)propyl]-7,8-dihydroquinoline	IC50	220 nM
6-{3-[(4-Chloro-benzenesulfonylamino)-methyl]-2-pyridin-3-yl-bicyclo[2.2.1]hept-2-yl}-hex-4-enoic acid	IC50	340 nM
5-[2-(Imidazol-1-yl)ethyl]quinoline	IC50	350 nM
5-[3-(1H-imidazol-1-yl)propyl]-5,6,7,8-tetrahydroquinoline	IC50	350 nM
5-[2-(Imidazol-1-yl)ethyl]-5,6,7,8-tetrahydroquinoline	IC50	380 nM
1-[2-(4,5,6,7-tetrahydro-1-benzothiophen-4-yl)ethyl]-1H-imidazole	IC50	440 nM
5-[2-(Imidazol-1-yl)ethyl]-7,8-dihydroquinoline	IC50	500 nM
1-[(2E)-2-(6,7-dihydro-1-benzothien-4(5H)-ylidene)ethyl]-1H-imidazole	IC50	680 nM
1-[2-(1,2,3,4-tetrahydronaphthalen-1-yl)ethyl]-1H-imidazole	IC50	700 nM
7-[3-(5-Phenyl-pentyl)-3-pyridin-3-yl-bicyclo[2.2.1]hept-2-yl]-hept-5-enoic acid	IC50	790 nM
1-[2-(4,5,6,7-Tetrahydrobenzo[b]furan-4-yl)ethyl]-1H-imidazole	IC50	920 nM
CHEMBL3251056	IC50	1000 nM
7-[(Imidazol-1-yl)methyl]isoquinoline	IC50	1380 nM
4-[2-(1H-imidazol-1-yl)ethoxy]benzoic acid	KI	2300 nM
1-{2-[(4E)-4,5,6,7-tetrahydro-1-benzofuran-4-ylidene]ethyl}-1H-imidazole	IC50	2400 nM
6-(1H-imidazol-1-yl)isoquinoline	IC50	3060 nM
1-[2-(1-benzothiophen-4-yl)ethyl]-1H-imidazole	IC50	3560 nM
1-[(2Z)-2-(6,7-dihydro-1-benzothien-4(5H)-ylidene)ethyl]-1H-imidazole	IC50	3900 nM
1-{2-[(4Z)-4,5,6,7-tetrahydro-1-benzofuran-4-ylidene]ethyl}-1H-imidazole	IC50	6000 nM
5-(Imidazol-1-yl)-5,6,7,8-tetrahydroquinoline	IC50	6400 nM
8-(1H-imidazol-1-yl)-5,6,7,8-tetrahydroquinoline	IC50	111000 nM

ChEMBL bioactivities

926 potent at pChembl≥5 of 964 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.05	IC50	0.9	nM	ISBOGREL
9.05	IC50	0.89	nM	(E)-ISBOGREL
9.00	IC50	1	nM	CHEMBL117233
9.00	IC50	1	nM	CHEMBL137402
9.00	IC50	1	nM	CHEMBL435590
9.00	IC50	1	nM	CHEMBL338420
9.00	IC50	1	nM	CHEMBL136762
9.00	IC50	1	nM	CHEMBL165575
8.92	IC50	1.2	nM	CHEMBL116975
8.82	IC50	1.5	nM	CHEMBL136738
8.74	IC50	1.8	nM	CHEMBL117816
8.70	IC50	2	nM	CHEMBL65414
8.70	IC50	2	nM	CHEMBL339269
8.70	IC50	2	nM	CHEMBL139372
8.70	IC50	2	nM	CHEMBL341686
8.70	IC50	2	nM	CHEMBL301550
8.64	IC50	2.3	nM	CHEMBL53346
8.59	IC50	2.6	nM	CHEMBL63904
8.59	IC50	2.6	nM	CHEMBL151083
8.57	IC50	2.7	nM	CHEMBL151091
8.54	IC50	2.9	nM	(E)-ISBOGREL
8.52	IC50	3	nM	CHEMBL21954
8.52	IC50	3	nM	CHEMBL282884
8.52	IC50	3	nM	RIDOGREL
8.52	IC50	3	nM	CHEMBL21639
8.52	IC50	3	nM	CHEMBL21852
8.52	IC50	3	nM	CHEMBL416374
8.52	IC50	3	nM	DAZOXIBEN
8.52	IC50	3	nM	PIRMAGREL
8.52	IC50	3	nM	CHEMBL344457
8.52	IC50	3	nM	CHEMBL63904
8.52	IC50	3	nM	CHEMBL136371
8.52	IC50	3	nM	CHEMBL134580
8.52	IC50	3	nM	CHEMBL136934
8.52	IC50	3	nM	CHEMBL543256
8.49	IC50	3.2	nM	PIRMAGREL
8.46	IC50	3.5	nM	CHEMBL68058
8.44	IC50	3.6	nM	CHEMBL263227
8.40	IC50	4	nM	CHEMBL136904
8.40	IC50	4	nM	SAMIXOGREL
8.40	IC50	4	nM	CHEMBL21303
8.40	IC50	4	nM	RIDOGREL
8.40	IC50	4	nM	TERBOGREL
8.40	IC50	4	nM	CHEMBL21647
8.40	IC50	4	nM	CHEMBL40736
8.40	IC50	4	nM	CHEMBL130470
8.40	IC50	4	nM	CHEMBL137505
8.40	IC50	4	nM	CHEMBL138328
8.40	IC50	4	nM	CHEMBL127380
8.40	IC50	4	nM	CHEMBL338419

PubChem BioAssay actives

823 with measured affinity, of 1456 total; 50 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
(E)-7-phenyl-7-pyridin-3-ylhept-6-enoic acid	212615: In vitro inhibition of TXB2 production by incubating prostaglandin H2 with human platelet microsomes.	ic50	0.0009	uM
(Z)-7-phenyl-7-pyridin-3-ylhept-6-enoic acid	212629: Thromboxane A2 synthase inhibitory activity was measured from inhibition of thromboxane B2 production in human platelet microsomes	ic50	0.0009	uM
8-[(4-chlorophenyl)sulfonylamino]-4-[3-(4-methyl-3-pyridinyl)propyl]octanoic acid	212606: In vitro inhibition of Thromboxane A2 synthase	ic50	0.0010	uM
8-[(4-methylphenyl)sulfonylamino]-4-(3-pyridin-3-ylpropyl)octanoic acid	212606: In vitro inhibition of Thromboxane A2 synthase	ic50	0.0010	uM
ethyl 5-[(Z)-[phenyl(pyridin-3-yl)methylidene]amino]oxypentanoate	212615: In vitro inhibition of TXB2 production by incubating prostaglandin H2 with human platelet microsomes.	ic50	0.0010	uM
ethyl 5-[(E)-[phenyl(pyridin-3-yl)methylidene]amino]oxypentanoate	212971: In vitro inhibition of thromboxane synthase (TXA2) in human platelet microsomes [reduced formation of TXB2 from prostaglandin H2(PGH2)]	ic50	0.0010	uM
(E)-6-[2-[(4-fluorophenyl)sulfonylamino]-2,3-dihydro-1H-inden-5-yl]-6-pyridin-3-ylhex-5-enoic acid	212099: Inhibition test of thromboxane A2 synthetase in human gel-filtered platelets.	ic50	0.0010	uM
8-[(4-fluorophenyl)sulfonylamino]-4-(3-pyridin-3-ylpropyl)octanoic acid	212606: In vitro inhibition of Thromboxane A2 synthase	ic50	0.0010	uM
ethyl 5-[(Z)-[pyridin-3-yl-[3-[(3-pyridin-3-yl-1,3-dihydropyrrolo[1,2-c][1,3]thiazole-7-carbonyl)amino]phenyl]methylidene]amino]oxypentanoate	212615: In vitro inhibition of TXB2 production by incubating prostaglandin H2 with human platelet microsomes.	ic50	0.0012	uM
8-(naphthalen-2-ylsulfonylamino)-4-(3-pyridin-3-ylpropyl)octanoic acid	212606: In vitro inhibition of Thromboxane A2 synthase	ic50	0.0015	uM
5-[(E)-[[3-[[[4-[(2-methylimidazo[4,5-c]pyridin-1-yl)methyl]phenyl]sulfonylamino]methyl]phenyl]-pyridin-3-ylmethylidene]amino]oxypentanoic acid	212615: In vitro inhibition of TXB2 production by incubating prostaglandin H2 with human platelet microsomes.	ic50	0.0018	uM
4-(3-pyridin-3-ylpropyl)-8-[[4-(trifluoromethyl)phenyl]sulfonylamino]octanoic acid	212606: In vitro inhibition of Thromboxane A2 synthase	ic50	0.0020	uM
2-[8-[(4-chlorophenyl)sulfonylamino]-1-pyridin-3-yloctan-4-yl]sulfanylacetic acid	212606: In vitro inhibition of Thromboxane A2 synthase	ic50	0.0020	uM
6-(5-chloro-1-methyl-2-pyridin-3-ylindol-3-yl)hexanoic acid	212096: Tested for 50% inhibition of thromboxane synthase (TxS) in human platelets (in vitro)	ic50	0.0020	uM
8-[(4-chlorophenyl)sulfonylamino]-4-(3-pyridin-3-ylpropyl)octanoic acid	212628: The compound was tested in vitro for its inhibitory activity against thromboxane synthase A2 (TXA2)	ic50	0.0020	uM
6-[4-[2-[(4-chlorophenyl)sulfonylamino]ethyl]phenyl]-6-pyridin-3-ylhexanoic acid	212099: Inhibition test of thromboxane A2 synthetase in human gel-filtered platelets.	ic50	0.0020	uM
sodium (Z)-7-[(1R,2S,3S)-3-(benzenesulfonamido)-2-bicyclo[2.2.1]heptanyl]hept-5-enoate	212778: Inhibition of thromboxane A2 synthetase from human platelets by 1 uM of the compound	ic50	0.0023	uM
8-[(4-chlorophenyl)sulfonylamino]-4-(2-pyridin-3-yloxyethyl)octanoic acid	215775: In vitro inhibition of thromboxane synthetase in microsomal platelet preparation	ic50	0.0026	uM
(E)-7-[4-[4-(2-phenoxyethylcarbamoyl)-1,3-oxazol-2-yl]phenyl]-7-pyridin-3-ylhept-6-enoic acid	213115: In vitro for inhibitory activity against thromboxane synthase	ic50	0.0026	uM
(E)-7-[4-[4-[3-(4-methoxyphenyl)propylcarbamoyl]-1,3-oxazol-2-yl]phenyl]-7-pyridin-3-ylhept-6-enoic acid	213115: In vitro for inhibitory activity against thromboxane synthase	ic50	0.0027	uM
8-[(4-chlorophenyl)sulfonylamino]-4-(3-imidazol-1-ylpropyl)octanoic acid	212606: In vitro inhibition of Thromboxane A2 synthase	ic50	0.0030	uM
8-[(4-chlorophenyl)sulfonylamino]-2-methyl-4-(3-pyridin-3-ylpropyl)octanoic acid	212606: In vitro inhibition of Thromboxane A2 synthase	ic50	0.0030	uM
8-[(4-chlorophenyl)sulfonylamino]-4-[3-(1-oxidopyridin-1-ium-3-yl)propyl]octanoic acid	212606: In vitro inhibition of Thromboxane A2 synthase	ic50	0.0030	uM
8-[(4-methoxyphenyl)sulfonylamino]-4-(3-pyridin-3-ylpropyl)octanoic acid	212606: In vitro inhibition of Thromboxane A2 synthase	ic50	0.0030	uM
(E)-6-[3-[(N-cyano-N’-cyclohexylcarbamimidoyl)amino]phenyl]-6-pyridin-3-ylhex-5-enoic acid	212612: In vitro activity on thromboxane A2 synthase inhibition in gel filtered human platelets.	ic50	0.0030	uM
(E)-6-[3-[[N-cyano-N’-(3-methylbutyl)carbamimidoyl]amino]phenyl]-6-pyridin-3-ylhex-5-enoic acid	212612: In vitro activity on thromboxane A2 synthase inhibition in gel filtered human platelets.	ic50	0.0030	uM
(E)-6-[3-[[N’-(1-adamantyl)-N-cyanocarbamimidoyl]amino]phenyl]-6-pyridin-3-ylhex-5-enoic acid	212612: In vitro activity on thromboxane A2 synthase inhibition in gel filtered human platelets.	ic50	0.0030	uM
(E)-6-[3-[(N-cyano-N’-cyclopentylcarbamimidoyl)amino]phenyl]-6-pyridin-3-ylhex-5-enoic acid	212612: In vitro activity on thromboxane A2 synthase inhibition in gel filtered human platelets.	ic50	0.0030	uM
(E)-6-[3-[[N-(benzenesulfonyl)-N’-tert-butylcarbamimidoyl]amino]phenyl]-6-pyridin-3-ylhex-5-enoic acid	212612: In vitro activity on thromboxane A2 synthase inhibition in gel filtered human platelets.	ic50	0.0030	uM
(Z)-2-methyl-3-[4-(pyridin-3-ylmethyl)phenyl]prop-2-enoic acid;hydrochloride	213125: Inhibitory activity against Thromboxane synthetase	ic50	0.0030	uM
4-(2-imidazol-1-ylethoxy)benzoic acid	212779: Inhibitory activity against thromboxane A2 synthetase	ic50	0.0030	uM
5-[(E)-[pyridin-3-yl-[3-(trifluoromethyl)phenyl]methylidene]amino]oxypentanoic acid	212606: In vitro inhibition of Thromboxane A2 synthase	ic50	0.0030	uM
6-imidazo[1,5-a]pyridin-5-ylhexanoic acid	212782: In vitro inhibitory activity against thromboxane A2 synthetase with lysed human platelets as the enzyme source.	ic50	0.0032	uM
(4S)-8-[(4-chlorophenyl)sulfonylamino]-4-(2-pyridin-3-yloxyethyl)octanoic acid	215775: In vitro inhibition of thromboxane synthetase in microsomal platelet preparation	ic50	0.0035	uM
ethyl 5-[(E)-[pyridin-3-yl-[4-[(3-pyridin-3-yl-1,3-dihydropyrrolo[1,2-c][1,3]thiazole-7-carbonyl)amino]phenyl]methylidene]amino]oxypentanoate	212615: In vitro inhibition of TXB2 production by incubating prostaglandin H2 with human platelet microsomes.	ic50	0.0036	uM
(E)-6-[3-[2-[(4-chlorophenyl)sulfonylamino]ethyl]phenyl]-6-pyridin-3-ylhex-5-enoic acid	212099: Inhibition test of thromboxane A2 synthetase in human gel-filtered platelets.	ic50	0.0040	uM
(E)-6-[4-[2-[(4-fluorophenyl)sulfonylamino]ethyl]phenyl]-6-pyridin-3-ylhex-5-enoic acid	212099: Inhibition test of thromboxane A2 synthetase in human gel-filtered platelets.	ic50	0.0040	uM
8-[(4-azidophenyl)sulfonylamino]-4-(3-pyridin-3-ylpropyl)octanoic acid	212606: In vitro inhibition of Thromboxane A2 synthase	ic50	0.0040	uM
11-(pyridin-3-ylmethylsulfanyl)-6,11-dihydrobenzo[c][1]benzoxepine-2-carboxylic acid	210346: Activity against TXA2 synthase in bovine platelet microsome	ic50	0.0040	uM
(E)-6-[4-[2-[(4-chlorophenyl)sulfonyl-(2-morpholin-4-ylethyl)amino]ethyl]phenyl]-6-pyridin-3-ylhex-5-enoic acid	212099: Inhibition test of thromboxane A2 synthetase in human gel-filtered platelets.	ic50	0.0040	uM
8-[(4-methylsulfonylphenyl)sulfonylamino]-4-(3-pyridin-3-ylpropyl)octanoic acid	212606: In vitro inhibition of Thromboxane A2 synthase	ic50	0.0040	uM
(E)-6-[4-[2-[(4-chlorophenyl)sulfonyl-ethylamino]ethyl]phenyl]-6-pyridin-3-ylhex-5-enoic acid	212099: Inhibition test of thromboxane A2 synthetase in human gel-filtered platelets.	ic50	0.0040	uM
(Z)-6-[5-[2-[(4-fluorophenyl)sulfonylamino]ethyl]-1-methylpyrrol-2-yl]-6-pyridin-3-ylhex-5-enoic acid	212099: Inhibition test of thromboxane A2 synthetase in human gel-filtered platelets.	ic50	0.0040	uM
(E)-6-[3-[(N-benzoyl-N’-cyclopentylcarbamimidoyl)amino]phenyl]-6-pyridin-3-ylhex-5-enoic acid	212612: In vitro activity on thromboxane A2 synthase inhibition in gel filtered human platelets.	ic50	0.0040	uM
(Z)-6-[3-[(N’-tert-butyl-N-cyanocarbamimidoyl)amino]phenyl]-6-pyridin-3-ylhex-5-enoic acid	210474: In vitro inhibitory concentration of compound against thromboxane A2 synthase	ic50	0.0040	uM
(E)-6-[3-(tert-butylcarbamoylamino)phenyl]-6-pyridin-3-ylhex-5-enoic acid	212612: In vitro activity on thromboxane A2 synthase inhibition in gel filtered human platelets.	ic50	0.0040	uM
(E)-3-[4-(imidazol-1-ylmethyl)phenyl]-2-methylprop-2-enoic acid;hydrochloride	213125: Inhibitory activity against Thromboxane synthetase	ic50	0.0040	uM
dipotassium;(2S)-2-[[(3R)-1-(carboxylatomethyl)-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]amino]-6-[6-(5-chloro-1-methyl-2-pyridin-3-ylindol-3-yl)hexanoylamino]hexanoate	212096: Tested for 50% inhibition of thromboxane synthase (TxS) in human platelets (in vitro)	ic50	0.0040	uM
3-[(E)-2-[4-[2-[(4-chlorophenyl)sulfonylamino]ethyl]phenyl]-2-pyridin-3-ylethenyl]benzoic acid	212099: Inhibition test of thromboxane A2 synthetase in human gel-filtered platelets.	ic50	0.0040	uM
(E)-3-[3-(imidazol-1-ylmethyl)phenyl]-2-methylprop-2-enoic acid;hydrochloride	213124: Inhibitory activity against human thromboxane synthetase	ic50	0.0040	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	decreases expression, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Oxygen	decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
Cadmium Chloride	increases expression	2
aminomethylphosphonic acid (AMPA)	increases expression	1
chloroacetaldehyde	increases expression	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	increases expression	1
12-hydroxy-5,8,10-heptadecatrienoic acid	decreases activity, decreases chemical synthesis	1
beta-lapachone	decreases expression	1
sodium bichromate	decreases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
bisphenol S	increases methylation	1
jinfukang	increases expression	1
gardiquimod	decreases expression, decreases reaction	1
(+)-JQ1 compound	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Cidofovir	increases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Asbestos	increases expression	1

ChEMBL screening assays

210 unique, capped per target: 138 binding, 72 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1050562	Binding	Inhibition of TX synthase	Discovery of disubstituted phenanthrene imidazoles as potent, selective and orally active mPGES-1 inhibitors. — Bioorg Med Chem Lett
CHEMBL669887	Functional	Ex vivo thromboxane receptor (TXA2 synthase) inhibitory activity after 1 hr of oral dosing (1 mg/kg) in the dog	Dual-acting thromboxane receptor antagonist/synthase inhibitors: synthesis and biological properties of [2-substituted-4-(3-pyridyl)-1,3-dioxan-5-yl] alkenoic acids. — J Med Chem

Clinical trials (associated diseases)

300 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
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
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
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura
NCT00420914	PHASE3	TERMINATED	Strategies for Transfusion of Platelets (SToP)
NCT00501345	PHASE3	TERMINATED	Aspirin in Patients With Myocardial Infarction and Thrombocytopenia
NCT00508820	PHASE3	COMPLETED	An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP
NCT00678587	PHASE3	TERMINATED	Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
NCT01438840	PHASE3	COMPLETED	Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
NCT01444417	PHASE3	COMPLETED	Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
NCT01805648	PHASE3	UNKNOWN	Efficacy and Safety Study of Maintenance Treatment With rhTPO in Thrombocytopenic Subjects With ITP
NCT02244658	PHASE3	UNKNOWN	Recombinant Human Thrombopoietin (rhTPO) in Management of Chemotherapy-induced Thrombocytopenia in Acute Myelocytic Leukemia
NCT02389621	PHASE3	COMPLETED	Safety and Efficacy Study of Lusutrombopag for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Elective Invasive Procedures
NCT02444728	PHASE3	TERMINATED	Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE
NCT02487563	PHASE3	COMPLETED	Prospective Study of Patients With Thrombocytopenia Following HSCT