PTGDS

Summary

PTGDS (prostaglandin D2 synthase, HGNC:9592) is a protein-coding gene on chromosome 9q34.3, encoding Prostaglandin-H2 D-isomerase (P41222). Catalyzes the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation.

The protein encoded by this gene is a glutathione-independent prostaglandin D synthase that catalyzes the conversion of prostaglandin H2 (PGH2) to postaglandin D2 (PGD2). PGD2 functions as a neuromodulator as well as a trophic factor in the central nervous system. PGD2 is also involved in smooth muscle contraction/relaxation and is a potent inhibitor of platelet aggregation. This gene is preferentially expressed in brain. Studies with transgenic mice overexpressing this gene suggest that this gene may be also involved in the regulation of non-rapid eye movement sleep.

Source: NCBI Gene 5730 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 35 total
• Druggable target: yes
• MANE Select transcript: NM_000954

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9592
Approved symbol	PTGDS
Name	prostaglandin D2 synthase
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	PGDS, L-PGDS
Ensembl gene	ENSG00000107317
Ensembl biotype	protein_coding
OMIM	176803
Entrez	5730

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 22 protein_coding, 5 retained_intron

ENST00000371623, ENST00000371625, ENST00000413913, ENST00000444903, ENST00000446677, ENST00000457950, ENST00000460340, ENST00000462514, ENST00000492068, ENST00000640716, ENST00000851751, ENST00000851752, ENST00000851753, ENST00000851754, ENST00000851755, ENST00000851756, ENST00000851757, ENST00000851758, ENST00000851759, ENST00000851760, ENST00000851761, ENST00000851762, ENST00000954960, ENST00000954961, ENST00000954962, ENST00000954963, ENST00000954964

RefSeq mRNA: 1 — MANE Select: NM_000954 NM_000954

CCDS: CCDS7019

Canonical transcript exons

ENST00000371625 — 7 exons

Exon	Start	End
ENSE00001043045	136981579	136981742
ENSE00003804500	136980183	136980284
ENSE00003804819	136979946	136980062
ENSE00003807359	136979223	136979299
ENSE00003810526	136978993	136979132
ENSE00003810909	136980833	136980855
ENSE00003847067	136977504	136977692

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 374.8698 / max 18221.9126, expressed in 1244 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99607	365.7821	1113
99618	1.5335	300
99612	1.4678	325
99615	1.2453	280
99613	1.2188	279
99622	0.7802	205
99619	0.5109	162
99614	0.4484	156
99610	0.3665	143
99621	0.3614	124

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.97	gold quality
right testis	UBERON:0004534	99.96	gold quality
substantia nigra	UBERON:0002038	99.93	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.93	gold quality
putamen	UBERON:0001874	99.92	gold quality
apex of heart	UBERON:0002098	99.92	gold quality
temporal lobe	UBERON:0001871	99.91	gold quality
caudate nucleus	UBERON:0001873	99.91	gold quality
amygdala	UBERON:0001876	99.91	gold quality
Ammon’s horn	UBERON:0001954	99.91	gold quality
right frontal lobe	UBERON:0002810	99.91	gold quality
right atrium auricular region	UBERON:0006631	99.91	gold quality
nucleus accumbens	UBERON:0001882	99.90	gold quality
primary visual cortex	UBERON:0002436	99.90	gold quality
heart left ventricle	UBERON:0002084	99.89	gold quality
superior frontal gyrus	UBERON:0002661	99.89	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.89	gold quality
hypothalamus	UBERON:0001898	99.88	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.86	gold quality
tibial nerve	UBERON:0001323	99.85	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.82	gold quality
frontal cortex	UBERON:0001870	99.80	gold quality
anterior cingulate cortex	UBERON:0009835	99.77	gold quality
prefrontal cortex	UBERON:0000451	99.72	gold quality
cerebellum	UBERON:0002037	99.70	gold quality
cerebellar cortex	UBERON:0002129	99.69	gold quality
cerebellar hemisphere	UBERON:0002245	99.69	gold quality
right uterine tube	UBERON:0001302	99.66	gold quality
endocervix	UBERON:0000458	99.59	gold quality
ectocervix	UBERON:0012249	99.57	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 26.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	77239.58
E-GEOD-134144	yes	60040.81
E-GEOD-135922	yes	21437.26
E-MTAB-11121	yes	18187.01
E-GEOD-137537	yes	9443.27
E-HCAD-38	yes	9409.30
E-HCAD-24	yes	7213.99
E-HCAD-25	yes	6841.91
E-MTAB-8322	yes	6648.24
E-HCAD-15	yes	6433.77
E-CURD-126	yes	5442.22
E-MTAB-9435	yes	5364.92
E-MTAB-6701	yes	3945.73
E-HCAD-11	yes	3708.10
E-MTAB-10287	yes	136.37

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, ESR2, HES1, JUN, MITF, NFKB1, NFKB, NR5A2, SPI1, SREBF1, TFAP2A, TFAP2B, THRB, TP53, USF1

miRNA regulators (miRDB)

10 targeting PTGDS, 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-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-6765-3P	97.83	64.59	1165

Literature-anchored findings (GeneRIF, showing 40)

• Pronounced eosinophilia and Th2 cytokine release in human lipocalin-type prostaglandin D synthase transgenic mice (PMID:11751991)
• Study performed in patients with kidney function ranging from normal to advanced renal failure suggests that serum beta-trace protein is an indicator of impaired glomerular filtration rate. (PMID:12900000)
• The circadian lipocalin-type PGDS pattern and its suppression by total sleep deprivation indicate an interaction of the prostaglandin D system and human sleep regulation. (PMID:15453544)
• Shear stress induces l-PGDS expression by transcriptional activation through the AP-1 binding site. (PMID:15718494)
• Results show that the lipocalin-type prostaglandin D2 synthase (PGDS)/PGD2/prostaglandin D receptor (DP1R) system plays pivotal roles in the regulation of physiological sleep. (PMID:17093043)
• Our data do not support the involvement of the PTGDS gene in the etiology of schizophrenia. (PMID:17230501)
• PGD2 synthetases, as well as receptors for PGD2, are described in testicular interstitial cells of men with spermatogenic damage and infertility. (PMID:17307169)
• Lipocalin-type prostaglandin D synthase/beta-trace is a major amyloid beta-chaperone in human cerebrospinal fluid and the disturbance of this function may be involved in the onset and progression of Alzheimer’s disease. (PMID:17404210)
• expression of L-PGDS in degenerating neurons implies that L-PGDS functions as an early stress protein to protect against neuronal death in the hypoxic-ischemic encephalopathy brain (PMID:17499437)
• The embryonic male prostaglandin D synthase (Pgds)/SOX9 pathway is expressed at both the RNA and protein levels in different types of human ovarian tumors. (PMID:17532558)
• L-PGDS gene expression in TE671 cells was activated by USF1 through the aE-box within intron 4 and cooperatively by AP-2beta in the promoter in a cell-type-specific manner. (PMID:17574780)
• Data confirm the potential of Beta-trace protein as an endogenous Glomerular Filtration Rate marker in children. (PMID:17588556)
• The cystatin C, beta2-microglobulin and beta-trace protein levels displayed changes with increased levels in the third trimester but unaltered levels during the first and second trimesters. (PMID:17852800)
• Thirteen different proteins with 3-NT modification were identified in the CSF of HIV Dementia patients. L-PGDS was the most abundant. (PMID:18077799)
• A single nucleotide polymorphism, rs3814500 (MspI site) ws found in the promoter region of the PTGDS gene among Chinese schizophrenic families. No association with schizophrenia was seen. (PMID:18349703)
• Lipocalin-type prostaglandin D synthase may have a role in coronary artery disease (PMID:18436228)
• Quantifying the prostaglandin-D-synthase/transthyretin complex in ventricular cerebrospinal fluid may be useful in the diagnosis of Alzheimer disease, possibly in its early stages. (PMID:18448869)
• Among gene transcripts elevated in depressed episodes were prostaglandin D synthetase (PTGDS) and prostaglandin D2 11-ketoreductase (AKR1C3), both involved in hibernation. We hypothesized them to account for some of the rapid cycling symptoms. (PMID:18552976)
• These results suggest that expression of DP and CRTH2 is associated with the pathophysiology of chronic rhinosinusitis, and the expression of these receptors may be regulated by h-PGDS and PGD. (PMID:18802357)
• Enhancement of PGD2 production through COX-2 and LPGDS by USF1 in human brain-derived TE671 cells under serum starvation are reported. (PMID:18817855)
• Prostaglandin D synthase-mediated SOX-9 upregulation could provide a reasonable explanation for the presence of testicular differentiation in ovarian ovarian sex cord-stromal tumours. (PMID:18830622)
• an increase in serum L-PGDS concentration is associated with the progression of atherosclerosis (PMID:19015601)
• Lipocalin-type prostaglandin D synthase might have an important role in the pathophysiology of osteoarthritis. (PMID:19094210)
• Biochemical, functional, and pharmacological characterization of AT-56, an orally active and selective inhibitor of lipocalin-type prostaglandin D synthase. (PMID:19131342)
• CC16 did not inhibit eosinophil migration towards PGD(2). (PMID:19132521)
• As the CSF is in contact with axons and mitochondria of the optic nerve, we postulate that a change in the concentration of CSF protein such as L-PGDS could exercise a harmful effect on these structures. (PMID:19598000)
• This beta-trace protein based formula was found to estimate GFR with reasonable precision (PMID:19949816)
• protein levels in nasal fluids can serve for diagnosis of cerebrospinal fluid leak (PMID:19958607)
• The expression of H-PGDS in human dendritic cells (DCs) and the regulatory mechanisms by which DCs produce prostaglandin D2, is demonstrated. (PMID:20008150)
• Using RT-PCR we demonstrated that L-PGDS gene expression decreased proportionately with tumor progression in lung cancer. (PMID:20144489)
• L-PGDS may fine-tune the retinoic acid signalling in melanocytes. (PMID:20403807)
• This study included 62 persons aged 18-30 years and cell phone exposure. EMF emissions may down-regulate the synthesis of beta-trace protein. (PMID:20596612)
• Met64 seems to function as a kinetic clamp, pushing the thiol group of Cys65 close to the site of nucleophilic attack during catalysis. (PMID:20667974)
• RBP-4, lipocalin-2 and L-PGDS do not regulate insulin sensitivity in healthy men. Rather their expression seemed to reflect inflammatory activity and were inversely correlated with alcohol intake and serum HDL levels. (PMID:21104585)
• Report the presence of L-PGDS in the COX-2-expressing cells in the mucosa of active ulcerative colitis patients in parallel with disease activity. (PMID:21163901)
• It may be feasible to test for perilymphatic fluid fistula using PTGDS in samples from the tympanic cavity. (PMID:21192373)
• Proteomic profiling of cerebrospinal fluid identifies prostaglandin D2 synthase as a putative biomarker for pediatric medulloblastoma. (PMID:21271676)
• Lipocalin-type prostaglandin D synthase is associated with coronary vasospasm and vasomotor reactivity in response to acetylcholine (PMID:21325722)
• Ascites and pleural effusion contain high concentrations of beta-TP that exceed the levels in corresponding plasma (PMID:21501068)
• two genes involved in cardiovascular diseases, ADORA1 and PTGDS, were differentially up-regulated in epicardial adipose tissue compared to mediastinal and subcutaneous adipose tissue (PMID:21603615)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptgdsb.1	ENSDARG00000027088
danio_rerio	zgc:153704	ENSDARG00000045979
danio_rerio	ptgdsb.2	ENSDARG00000071626
mus_musculus	Ptgds	ENSMUSG00000015090
rattus_norvegicus	Ptgds	ENSRNOG00000015550

Paralogs (12): PAEP (ENSG00000122133), OBP2A (ENSG00000122136), LCN2 (ENSG00000148346), LCN9 (ENSG00000148386), LCN1 (ENSG00000160349), OBP2B (ENSG00000171102), LCN15 (ENSG00000177984), LCN12 (ENSG00000184925), LCN10 (ENSG00000187922), LCN8 (ENSG00000204001), LCNL1 (ENSG00000214402), LCN6 (ENSG00000267206)

Protein

Protein identifiers

Prostaglandin-H2 D-isomerase — P41222 (reviewed: P41222)

Alternative names: Beta-trace protein, Cerebrin-28, Glutathione-independent PGD synthase, Lipocalin-type prostaglandin-D synthase, Prostaglandin-D2 synthase

All UniProt accessions (6): P41222, A0A024R8G3, A0A1W2PPU3, H0Y4L4, H0Y5A1, Q5SQ11

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation. Involved in a variety of CNS functions, such as sedation, NREM sleep and PGE2-induced allodynia, and may have an anti-apoptotic role in oligodendrocytes. Binds small non-substrate lipophilic molecules, including biliverdin, bilirubin, retinal, retinoic acid and thyroid hormone, and may act as a scavenger for harmful hydrophobic molecules and as a secretory retinoid and thyroid hormone transporter. Possibly involved in development and maintenance of the blood-brain, blood-retina, blood-aqueous humor and blood-testis barrier. It is likely to play important roles in both maturation and maintenance of the central nervous system and male reproductive system. Involved in PLA2G3-dependent maturation of mast cells. PLA2G3 is secreted by immature mast cells and acts on nearby fibroblasts upstream to PTDGS to synthesize PGD2, which in turn promotes mast cell maturation and degranulation via PTGDR.

Subunit / interactions. Monomer.

Subcellular location. Rough endoplasmic reticulum. Nucleus membrane. Golgi apparatus. Cytoplasm. Perinuclear region. Secreted.

Tissue specificity. Abundant in the brain and CNS, where it is expressed in tissues of the blood-brain barrier and secreted into the cerebro-spinal fluid. Abundantly expressed in the heart. In the male reproductive system, it is expressed in the testis, epididymis and prostate, and is secreted into the seminal fluid. Expressed in the eye and secreted into the aqueous humor. Lower levels detected in various tissue fluids such as serum, normal urine, ascitic fluid and tear fluid. Also found in a number of other organs including ovary, fimbriae of the fallopian tubes, kidney, leukocytes.

Post-translational modifications. N- and O-glycosylated. Both N-glycosylation recognition sites are almost quantitatively occupied by N-glycans of the biantennary complex type, with a considerable proportion of structures bearing a bisecting GlcNAc. N-glycan at Asn-78: dHex1Hex5HexNAc4. Agalacto structure as well as sialylated and nonsialylated oligosaccharides bearing alpha2-3- and/or alpha2-6-linked NeuNAc are present.

Domain organisation. Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.

Induction. By IL1B/interleukin-1 beta and thyroid hormone. Probably induced by dexamethasone, dihydrotestosterone (DHT), progesterone, retinoic acid and retinal. Repressed by the Notch-Hes signaling pathway.

Miscellaneous. It has been proposed that the urinary and serum levels may provide a sensitive indicator of renal damage in diabetes mellitus and hypertension. Elevated levels in the coronary circulation may also be associated with angina. Changes in charge and molecular weight microheterogeneity, due to modification of the N-linked oligosaccharides, may be associated with neurodegenerative disease and multiple sclerosis. Detected in meningioma but not in other brain tumors and may be considered a specific cell marker for meningioma. Expression levels in amniotic fluid are altered in abnormal pregnancies. Levels are lower in pregnancies with trisomic fetuses and fetuses with renal abnormalities.

Similarity. Belongs to the calycin superfamily. Lipocalin family.

RefSeq proteins (1): NP_000945* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000566	Lipocln_cytosolic_FA-bd_dom	Domain
IPR002345	Lipocalin	Family
IPR012674	Calycin	Homologous_superfamily
IPR022272	Lipocalin_CS	Conserved_site

Pfam: PF00061

Enzyme classification (BRENDA):

• EC 5.3.99.2 — Prostaglandin-D synthase (BRENDA: 13 organisms, 69 substrates, 257 inhibitors, 43 Km, 19 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PROSTAGLANDIN H2	0.0005–0.0328	28
(5Z,13E)-(15S)-9ALPHA,11ALPHA-EPIDIOXY-15-HYDROX	0.0023–0.5	6
GLUTATHIONE	0.1–8	5
1-CHLORO-2,4-DINITROBENZENE	3–5	3
GSH	0.32	1

Catalyzed reactions (Rhea), 1 shown:

• prostaglandin H2 = prostaglandin D2 (RHEA:10600)

UniProt features (33 total): strand 10, mutagenesis site 7, helix 5, glycosylation site 3, sequence conflict 2, signal peptide 1, chain 1, active site 1, turn 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
3O22	X-RAY DIFFRACTION	1.4
4ORR	X-RAY DIFFRACTION	1.4
4ORS	X-RAY DIFFRACTION	1.4
4OS3	X-RAY DIFFRACTION	1.4
5WY9	X-RAY DIFFRACTION	1.45
4ORU	X-RAY DIFFRACTION	1.55
4ORX	X-RAY DIFFRACTION	1.6
3O19	X-RAY DIFFRACTION	1.66
4ORW	X-RAY DIFFRACTION	1.66
4OS8	X-RAY DIFFRACTION	1.69
3O2Y	X-RAY DIFFRACTION	1.7
4OS0	X-RAY DIFFRACTION	1.75
4ORY	X-RAY DIFFRACTION	1.8
4IMO	X-RAY DIFFRACTION	1.88
2WWP	X-RAY DIFFRACTION	2
4IMN	X-RAY DIFFRACTION	2.09
8HTA	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41222-F1	88.13	0.74

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 (1): 65 (nucleophile)

Disulfide bonds (1): 89–186

Glycosylation sites (3): 29, 51, 78

Mutagenesis-validated functional residues (7):

Position	Phenotype
65	loss of enzyme activity.
79	reduces enzyme activity over ten-fold.
83	reduces enzyme activity about five-fold.
131	reduces enzyme activity almost ten-fold.
149	increases enzyme activity about two-fold.
59	increases enzyme activity about two-fold.
64	reduces enzyme activity almost ten-fold.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2162123	Synthesis of Prostaglandins (PG) and Thromboxanes (TX)
R-HSA-9690406	Transcriptional regulation of testis differentiation

MSigDB gene sets: 277 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, MODULE_66, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM

GO Biological Process (12): prostaglandin biosynthetic process (GO:0001516), gene expression (GO:0010467), cyclooxygenase pathway (GO:0019371), mast cell degranulation (GO:0043303), regulation of circadian sleep/wake cycle, sleep (GO:0045187), prostanoid biosynthetic process (GO:0046457), response to glucocorticoid (GO:0051384), negative regulation of male germ cell proliferation (GO:2000255), 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 (6): prostaglandin-D synthase activity (GO:0004667), retinoid binding (GO:0005501), fatty acid binding (GO:0005504), protein binding (GO:0005515), isomerase activity (GO:0016853), small molecule binding (GO:0036094)

GO Cellular Component (12): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum membrane (GO:0005789), rough endoplasmic reticulum (GO:0005791), Golgi apparatus (GO:0005794), nuclear membrane (GO:0031965), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Arachidonate metabolism	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
intracellular membrane-bounded organelle	3
prostanoid metabolic process	2
binding	2
organelle membrane	2
endomembrane system	2
prostaglandin metabolic process	1
prostanoid biosynthetic process	1
macromolecule biosynthetic process	1
prostaglandin biosynthetic process	1
arachidonate metabolic process	1
mast cell activation involved in immune response	1
mast cell mediated immunity	1
lysosome localization	1
leukocyte degranulation	1
establishment of organelle localization	1
regulation of circadian sleep/wake cycle	1
circadian sleep/wake cycle, sleep	1
unsaturated fatty acid biosynthetic process	1
icosanoid biosynthetic process	1
response to corticosteroid	1
male germ cell proliferation	1
negative regulation of germ cell proliferation	1
negative regulation of reproductive process	1
regulation of male germ cell proliferation	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
isoprenoid binding	1
lipid binding	1
monocarboxylic acid binding	1
catalytic activity	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endoplasmic reticulum	1

Protein interactions and networks

STRING

1952 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTGDS	HPGDS	O60760	911
PTGDS	PTGDR	Q13258	841
PTGDS	LCN1	P31025	764
PTGDS	CST3	P01034	722
PTGDS	C8G	P07360	719
PTGDS	PAEP	P09466	712
PTGDS	TTR	P02766	692
PTGDS	ORM1	P02763	616
PTGDS	PTGDR2	Q9Y5Y4	610
PTGDS	PTGES	O14684	608
PTGDS	OLFM3	Q96PB7	584
PTGDS	PLA2G3	Q9NZ20	581
PTGDS	PTGIS	Q16647	578
PTGDS	DPM1	O60762	572
PTGDS	DUSP4	Q13115	569

IntAct

62 interactions, top by confidence:

A	B	Type	Score
PTGDS	ATXN1	psi-mi:“MI:0915”(physical association)	0.670
ORM1	ORM2	psi-mi:“MI:0914”(association)	0.620
PTGDS	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
PTGDS		psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	PTGDS	psi-mi:“MI:0915”(physical association)	0.560
PTGDS	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
PTGDS	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.560
PTGDS	CARD10	psi-mi:“MI:0915”(physical association)	0.560
CASP6	PTGDS	psi-mi:“MI:0915”(physical association)	0.560
LAMP2	PTGDS	psi-mi:“MI:0915”(physical association)	0.560
SH3GLB1	PTGDS	psi-mi:“MI:0915”(physical association)	0.560
PTGDS	HTT	psi-mi:“MI:0915”(physical association)	0.560
EGFR	PTGDS	psi-mi:“MI:0915”(physical association)	0.550
PTGDS	EGFR	psi-mi:“MI:0915”(physical association)	0.550

BioGRID (52): PTGDS (Affinity Capture-Western), HSP90AA1 (Affinity Capture-Western), PTGDS (Affinity Capture-Western), PTGDS (Reconstituted Complex), KRTAP10-7 (Two-hybrid), KRTAP10-3 (Two-hybrid), ARRB2 (Reconstituted Complex), ARRB2 (Affinity Capture-Western), PTGDS (Reconstituted Complex), PTGDS (Two-hybrid), PTGDS (Synthetic Lethality), PTGDS (Affinity Capture-MS), CHN2 (Affinity Capture-MS), PTGDS (Two-hybrid), UBQLN2 (Two-hybrid)

ESM2 similar proteins: B3EY83, B5X0G2, H2B3G5, O02853, O09114, O18873, O97921, P02758, P02761, P04119, P07380, P09466, P11588, P11672, P13613, P19647, P20289, P22057, P30152, P31025, P33685, P33686, P33687, P33688, P41222, P41244, P53715, P62502, P62503, P80188, Q28388, Q29095, Q29487, Q29562, Q5VSP4, Q6JVE6, Q6JVL5, Q6UWW0, Q810Z1, Q8K1H9

Diamond homologs: O02853, O09114, O97921, P11672, P22057, P30152, P41222, P80188, Q01584, Q29095, Q29487, Q29562, Q6UWW0, Q8WNM0, Q8WNM1, Q9TUI1, Q9XS65, Q9XSM0, Q6JVE5, B3EY83, Q6JVL5, P00978, Q07456, Q60559, Q64240, Q9I9P7, P07360, Q28679, Q6ZST4, Q8VCG4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
HES1	“down-regulates quantity by repression”	PTGDS	“transcriptional regulation”
TFAP2B	“up-regulates quantity by expression”	PTGDS	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1190 predictions. Top by Δscore:

Variant	Effect	Δscore
9:136980063:G:GG	donor_gain	1.0000
9:136977690:AAGGT:A	donor_loss	0.9900
9:136977692:GGTG:G	donor_loss	0.9900
9:136977693:GTGAG:G	donor_loss	0.9900
9:136977694:T:A	donor_loss	0.9900
9:136979218:TACAG:T	acceptor_loss	0.9900
9:136979219:ACAGG:A	acceptor_loss	0.9900
9:136979220:CAGGA:C	acceptor_loss	0.9900
9:136979221:AGGAA:A	acceptor_loss	0.9900
9:136979300:G:GG	donor_gain	0.9900
9:136979717:G:GT	donor_gain	0.9900
9:136979944:A:AG	acceptor_gain	0.9900
9:136979944:AGACT:A	acceptor_gain	0.9900
9:136979945:G:GG	acceptor_gain	0.9900
9:136979945:GA:G	acceptor_gain	0.9900
9:136979945:GACT:G	acceptor_gain	0.9900
9:136979945:GACTG:G	acceptor_gain	0.9900
9:136979217:CTACA:C	acceptor_loss	0.9800
9:136979221:A:AG	acceptor_gain	0.9800
9:136979222:G:GG	acceptor_gain	0.9800
9:136979222:GGA:G	acceptor_gain	0.9800
9:136979718:A:T	donor_gain	0.9800
9:136979131:AG:A	donor_loss	0.9700
9:136979132:GGTG:G	donor_loss	0.9700
9:136979134:T:G	donor_loss	0.9700
9:136979286:C:G	donor_gain	0.9700
9:136979945:GAC:G	acceptor_gain	0.9700
9:136980528:G:GT	donor_gain	0.9700
9:136977693:G:GG	donor_gain	0.9600
9:136978254:G:GT	donor_gain	0.9600

AlphaMissense

1232 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:136979007:G:C	W43C	0.988
9:136979007:G:T	W43C	0.988
9:136979005:T:A	W43R	0.987
9:136979005:T:C	W43R	0.987
9:136980221:T:C	F163L	0.987
9:136980223:C:A	F163L	0.987
9:136980223:C:G	F163L	0.987
9:136979008:T:C	F44L	0.985
9:136979010:C:A	F44L	0.985
9:136979010:C:G	F44L	0.985
9:136980222:T:C	F163S	0.982
9:136979999:G:C	A129P	0.981
9:136977679:T:G	F34C	0.980
9:136979024:C:A	A49D	0.979
9:136980222:T:G	F163C	0.979
9:136979119:T:C	S81P	0.977
9:136980000:C:A	A129E	0.976
9:136980249:T:C	F172S	0.976
9:136978994:T:G	F39C	0.975
9:136978994:T:C	F39S	0.974
9:136979018:G:A	G47D	0.973
9:136978999:G:T	G41W	0.972
9:136979026:T:C	S50P	0.972
9:136979114:T:C	L79P	0.972
9:136979233:T:A	C89S	0.971
9:136979234:G:C	C89S	0.971
9:136980062:A:C	S150R	0.969
9:136980184:C:A	S150R	0.969
9:136980184:C:G	S150R	0.969
9:136980235:C:G	C167W	0.969

dbSNP variants (sampled 300 via entrez): RS1000092726 (9:136980997 C>T), RS1000652730 (9:136979309 G>A,C), RS1000941853 (9:136979672 C>A,T), RS1001446297 (9:136982051 C>T), RS1002876644 (9:136979357 C>A,G,T), RS1002956312 (9:136975726 G>A), RS1003116723 (9:136980929 G>T), RS1003258009 (9:136978083 G>T), RS1004207762 (9:136978347 T>C), RS1004550935 (9:136977331 C>G,T), RS1004613719 (9:136976912 G>A,T), RS1004644677 (9:136976747 C>G,T), RS1006100489 (9:136976481 A>G), RS1006287491 (9:136975987 C>G,T), RS1006315392 (9:136975748 C>T)

Disease associations

OMIM: gene MIM:176803 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001806_14	Corneal structure	6.000000e-12
GCST001825_1	Beta-trace protein levels	1.000000e-23
GCST90013442_14	Keratoconus	1.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004345	corneal topography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3430865 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Prostaglandin synthases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
AT-56	Inhibition	4.12	pKi

Binding affinities (BindingDB)

2 measured of 2 human assays (3 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
S 145	KI	0.34 nM
S-5751	KI	1.6 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	3
Tretinoin	affects binding	2
bufotalin	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
amentoflavone	affects binding	1
butyraldehyde	increases expression	1
ochratoxin A	increases acetylation, increases expression	1
1-anilino-8-naphthalenesulfonate	affects binding	1
potassium chromate(VI)	affects cotreatment, increases expression	1
ricinoleic acid	affects binding	1
epigallocatechin gallate	affects cotreatment, increases expression	1
pentanal	increases expression	1
11-(dansylamino)undecanoic acid	affects binding	1
acteoside	affects binding	1
hinokiflavone	affects binding	1
di-n-butylphosphoric acid	affects expression	1
enniatins	decreases expression	1
quercetin-3-O-rutinoside	affects binding	1
(+)-JQ1 compound	decreases expression	1
2,6-dichloro-(1,4)benzoquinone	increases expression	1
Celecoxib	increases expression	1
Decitabine	decreases expression, decreases reaction	1
Sunitinib	increases expression	1
Aldehydes	increases expression	1
Calcitriol	decreases expression	1
Doxorubicin	decreases expression	1
Glucose	decreases secretion	1
Hydrogen Peroxide	decreases expression	1
Latex	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3873621	Binding	Inhibition of human recombinant PGDS expressed in CHO cells assessed as reduction in conversion of PGH2 to PGE2 at 10 uM incubated for 10 mins followed by substrate addition measured after 1 min	Discovery of 2-((2-chloro-6-fluorophenyl)amino)-N-(3-fluoro-5-(trifluoromethyl)phenyl)-1-methyl-7,8-dihydro-1H-[1,4]dioxino[2’,3’:3,4]benzo[1,2-d]imidazole-5-carboxamide as potent, selective and efficacious microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitor. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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