PTGR3

Summary

PTGR3 (prostaglandin reductase 3, HGNC:28697) is a protein-coding gene on chromosome 18q22.3, encoding Prostaglandin reductase 3 (Q8N4Q0). Functions as 15-oxo-prostaglandin 13-reductase and acts on 15-keto-PGE1, 15-keto-PGE2, 15-keto-PGE1-alpha and 15-keto-PGE2-alpha with highest efficiency towards 15-keto-PGE2-alpha.

Predicted to enable 15-oxoprostaglandin 13-oxidase [NAD(P)+] activity. Predicted to be involved in negative regulation of fat cell differentiation. Located in mitochondrion.

Source: NCBI Gene 284273 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 89 total
• MANE Select transcript: NM_175907

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28697
Approved symbol	PTGR3
Name	prostaglandin reductase 3
Location	18q22.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC45594, PTGR-3
Ensembl gene	ENSG00000180011
Ensembl biotype	protein_coding
OMIM	620604
Entrez	284273

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000322342, ENST00000537114, ENST00000581620, ENST00000582437

RefSeq mRNA: 2 — MANE Select: NM_175907 NM_001306093, NM_175907

CCDS: CCDS12008, CCDS77198

Canonical transcript exons

ENST00000322342 — 2 exons

Exon	Start	End
ENSE00003992895	75195113	75202340
ENSE00003992904	75208850	75209139

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 93.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.9450 / max 66.8620, expressed in 1726 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172446	4.4062	1628
172445	1.8911	1136
172447	0.4284	225
172444	0.2192	103

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	93.40	gold quality
deltoid	UBERON:0001476	93.02	gold quality
vastus lateralis	UBERON:0001379	92.97	gold quality
quadriceps femoris	UBERON:0001377	92.51	gold quality
biceps brachii	UBERON:0001507	91.89	gold quality
skeletal muscle tissue	UBERON:0001134	91.75	gold quality
heart right ventricle	UBERON:0002080	91.43	gold quality
kidney epithelium	UBERON:0004819	91.41	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.23	gold quality
muscle tissue	UBERON:0002385	90.88	gold quality
ventricular zone	UBERON:0003053	90.85	gold quality
muscle of leg	UBERON:0001383	90.84	gold quality
gastrocnemius	UBERON:0001388	90.73	gold quality
rectum	UBERON:0001052	90.52	gold quality
islet of Langerhans	UBERON:0000006	90.44	gold quality
tibialis anterior	UBERON:0001385	90.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.08	gold quality
stromal cell of endometrium	CL:0002255	89.87	gold quality
cardiac muscle of right atrium	UBERON:0003379	89.51	gold quality
adrenal tissue	UBERON:0018303	89.48	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.78	gold quality
pigmented layer of retina	UBERON:0001782	88.36	gold quality
myocardium	UBERON:0002349	88.36	gold quality
cardiac ventricle	UBERON:0002082	88.33	gold quality
heart left ventricle	UBERON:0002084	88.32	gold quality
monocyte	CL:0000576	87.78	gold quality
endothelial cell	CL:0000115	87.73	gold quality
leukocyte	CL:0000738	87.70	gold quality
primary visual cortex	UBERON:0002436	87.39	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.33	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	5111.50
E-ANND-3	yes	4.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

205 targeting PTGR3, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-144-3P	99.94	73.98	2698

Literature-anchored findings (GeneRIF, showing 3)

• In patients with late-onset Alzheimer disease, a number of differentially methylated postitions were hypomethylated in ZADH2 compared with controls. (PMID:30372681)
• Thermal proteome profiling identifies PIP4K2A and ZADH2 as off-targets of Polo-like kinase 1 inhibitor volasertib. (PMID:34143546)
• [Mechanism of miRNA-3679 Inhibiting Downstream ZADH2-Target Genes to Promote Hepatocellular Carcinoma Cell Proliferation]. (PMID:36224673)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ptgr3	ENSMUSG00000049090
rattus_norvegicus	Ptgr3	ENSRNOG00000016239
drosophila_melanogaster	CG4836	FBGN0270925
caenorhabditis_elegans		WBGENE00010790
caenorhabditis_elegans		WBGENE00010791
caenorhabditis_elegans		WBGENE00017060

Paralogs (17): PTGR1 (ENSG00000106853), VAT1 (ENSG00000108828), TP53I3 (ENSG00000115129), MECR (ENSG00000116353), CRYZ (ENSG00000116791), RTN4IP1 (ENSG00000130347), PTGR2 (ENSG00000140043), SORD (ENSG00000140263), VAT1L (ENSG00000171724), ADH6 (ENSG00000172955), ADH1A (ENSG00000187758), ADH7 (ENSG00000196344), ADH1B (ENSG00000196616), ADH5 (ENSG00000197894), ADH4 (ENSG00000198099), CRYZL1 (ENSG00000205758), ADH1C (ENSG00000248144)

Protein

Protein identifiers

Prostaglandin reductase 3 — Q8N4Q0 (reviewed: Q8N4Q0)

Alternative names: Zinc-binding alcohol dehydrogenase domain-containing protein 2

All UniProt accessions (3): Q8N4Q0, J3KTQ8, J3QQQ7

UniProt curated annotations — full annotation on UniProt →

Function. Functions as 15-oxo-prostaglandin 13-reductase and acts on 15-keto-PGE1, 15-keto-PGE2, 15-keto-PGE1-alpha and 15-keto-PGE2-alpha with highest efficiency towards 15-keto-PGE2-alpha. Overexpression represses transcriptional activity of PPARG and inhibits adipocyte differentiation.

Subcellular location. Peroxisome.

Similarity. Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N4Q0-1	1	yes
Q8N4Q0-2	2

RefSeq proteins (2): NP_001293022, NP_787103* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002364	Quin_OxRdtase/zeta-crystal_CS	Conserved_site
IPR011032	GroES-like_sf	Homologous_superfamily
IPR013149	ADH-like_C	Domain
IPR013154	ADH-like_N	Domain
IPR020843	ER	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR051397	Zn-ADH-like_protein	Family

Pfam: PF00107, PF08240

Catalyzed reactions (Rhea), 4 shown:

• 13,14-dihydro-15-oxo-prostaglandin E2 + NADP(+) = 15-oxoprostaglandin E2 + NADPH + H(+) (RHEA:11912)
• 13,14-dihydro-15-oxo-prostaglandin E1 + NADP(+) = 15-oxoprostaglandin E1 + NADPH + H(+) (RHEA:50584)
• 13,14-dihydro-15-oxo-PGF2alpha + NADP(+) = 15-oxoprostaglandin F2alpha + NADPH + H(+) (RHEA:50588)
• 13,14-dihydro-15-oxo-prostaglandin F1alpha + NADP(+) = 15-oxoprostaglandin F1alpha + NADPH + H(+) (RHEA:50592)

UniProt features (50 total): strand 16, helix 16, binding site 9, turn 4, modified residue 2, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2C0C	X-RAY DIFFRACTION	1.45
2X7H	X-RAY DIFFRACTION	1.6
2X1H	X-RAY DIFFRACTION	1.75
7ZEJ	X-RAY DIFFRACTION	1.79
2WEK	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4Q0-F1	92.98	0.90

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 (9): 185; 205; 209; 224; 247; 269; 275; 303–305; 361

Post-translational modifications (2): 35, 299

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 244 (showing top): RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, FREAC2_01, BENPORATH_ES_WITH_H3K27ME3, HNF3ALPHA_Q6, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, TAL1ALPHAE47_01, FOXO4_01, FOXO1_01, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, FOXD3_01, NFKB_Q6

GO Biological Process (3): prostaglandin metabolic process (GO:0006693), negative regulation of fat cell differentiation (GO:0045599), lipid metabolic process (GO:0006629)

GO Molecular Function (3): zinc ion binding (GO:0008270), 15-oxoprostaglandin 13-reductase [NAD(P)+] activity (GO:0047522), oxidoreductase activity (GO:0016491)

GO Cellular Component (2): mitochondrion (GO:0005739), peroxisome (GO:0005777)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
prostanoid metabolic process	1
fat cell differentiation	1
negative regulation of cell differentiation	1
regulation of fat cell differentiation	1
primary metabolic process	1
transition metal ion binding	1
oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
microbody	1

Protein interactions and networks

STRING

1552 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTGR3	SMIM21	Q3B7S5	621
PTGR3	ZNF407	Q9C0G0	577
PTGR3	TSHZ1	Q6ZSZ6	572
PTGR3	TYSND1	Q2T9J0	547
PTGR3	LINC03040	Q8N319	543
PTGR3	ARMC6	Q6NXE6	524
PTGR3	NUDT19	A8MXV4	513
PTGR3	GALK2	Q01415	503
PTGR3	WDR6	Q9NNW5	470
PTGR3	INO80E	Q8NBZ0	469
PTGR3	QPCTL	Q9NXS2	446
PTGR3	FKBP9	O95302	445
PTGR3	EXOC6B	Q9Y2D4	436
PTGR3	ZNF516	Q92618	422
PTGR3	DTYMK	P23919	420

IntAct

18 interactions, top by confidence:

A	B	Type	Score
ATG101	ATG13	psi-mi:“MI:0914”(association)	0.950
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
PTGR3	DBT	psi-mi:“MI:0914”(association)	0.640
FGL1	LCMT2	psi-mi:“MI:0914”(association)	0.640
FGL1	DNM1L	psi-mi:“MI:0914”(association)	0.350
PEX5	AGPS	psi-mi:“MI:0914”(association)	0.350
RBKS	RPS4Y1	psi-mi:“MI:0914”(association)	0.350
MRPL21	GTPBP6	psi-mi:“MI:0914”(association)	0.350
DARS2	DBT	psi-mi:“MI:0914”(association)	0.350
	HNRNPR	psi-mi:“MI:0914”(association)	0.350
RPL18A	ZFC3H1	psi-mi:“MI:0914”(association)	0.350
CAT	VWA8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (46): ZADH2 (Affinity Capture-MS), ZADH2 (Affinity Capture-MS), ZADH2 (Affinity Capture-MS), MAD1L1 (Affinity Capture-MS), CCNB1 (Affinity Capture-MS), ZADH2 (Affinity Capture-MS), C7orf43 (Affinity Capture-MS), DBT (Affinity Capture-MS), TRAPPC10 (Affinity Capture-MS), CKS2 (Affinity Capture-MS), ZADH2 (Proximity Label-MS), ZADH2 (Affinity Capture-MS), ZADH2 (Affinity Capture-MS), ZADH2 (Affinity Capture-MS), ZADH2 (Proximity Label-MS)

ESM2 similar proteins: A0A2U1Q018, A1L4Y2, A7RK30, O46649, O46650, O57380, O97959, P00326, P00327, P00328, P00329, P06757, P07327, P08319, P14139, P19333, P19631, P22797, P25405, P25406, P26325, P28332, P28469, P40394, P41680, P41681, P41682, P42865, P80222, P80338, P80468, P80512, P86883, P86885, Q03505, Q24K16, Q4W4Z2, Q5R1W2, Q5R7Z8, Q5RBP7

Diamond homologs: A0A0D2YG03, G0LET7, N4WR35, O00097, O23939, O34812, P08843, P42865, P76113, P97584, Q03102, Q14914, Q28719, Q29073, Q32L99, Q39172, Q39173, Q3SZJ4, Q5AY39, Q5BK81, Q5R806, Q6WAU0, Q84V25, Q8N4Q0, Q8N8N7, Q8VDQ1, Q91YR9, Q941I0, Q9C0Y6, Q9EQZ5, Q9SLN8, W7NCN7, A0A1W5SKT4, A0A2Z5TIQ0, A0A4P8W733, A0A8K1AWG4, A2QTF1, G3XMC6, G4MWB1, K4BW79

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

601 predictions. Top by Δscore:

Variant	Effect	Δscore
18:75202341:C:CC	acceptor_gain	0.9900
18:75205312:C:CT	acceptor_gain	0.9900
18:75205314:C:CT	acceptor_gain	0.9900
18:75205315:A:T	acceptor_gain	0.9900
18:75202336:CAAAT:C	acceptor_gain	0.9800
18:75205312:C:T	acceptor_gain	0.9800
18:75208844:GCTCA:G	donor_loss	0.9800
18:75208845:CT:C	donor_loss	0.9800
18:75208846:TCA:T	donor_loss	0.9800
18:75208847:C:CG	donor_loss	0.9800
18:75208848:A:AC	donor_gain	0.9800
18:75208849:C:CC	donor_gain	0.9800
18:75203139:A:C	donor_gain	0.9700
18:75205304:C:CT	acceptor_gain	0.9700
18:75202281:A:C	donor_gain	0.9600
18:75202338:AATC:A	acceptor_loss	0.9600
18:75202339:ATC:A	acceptor_loss	0.9600
18:75202340:TCT:T	acceptor_loss	0.9600
18:75202341:C:CA	acceptor_loss	0.9600
18:75202342:T:A	acceptor_loss	0.9600
18:75204291:T:TA	donor_gain	0.9600
18:75204676:C:CA	donor_gain	0.9600
18:75201425:A:AC	donor_gain	0.9500
18:75201426:C:CC	donor_gain	0.9500
18:75202352:C:CT	acceptor_loss	0.9500
18:75202353:A:T	acceptor_loss	0.9500
18:75208843:GGCT:G	donor_loss	0.9500
18:75202356:C:CT	acceptor_loss	0.9400
18:75202357:A:T	acceptor_loss	0.9400
18:75204731:AGG:A	donor_gain	0.9300

AlphaMissense

2414 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:75202061:G:C	S163R	0.994
18:75202061:G:T	S163R	0.994
18:75202063:T:G	S163R	0.994
18:75208859:A:T	V67D	0.992
18:75208865:A:G	L65P	0.983
18:75202082:A:C	S156R	0.982
18:75202082:A:T	S156R	0.982
18:75202084:T:G	S156R	0.982
18:75201641:G:C	F303L	0.980
18:75201641:G:T	F303L	0.980
18:75201643:A:G	F303L	0.980
18:75202252:C:G	G100R	0.977
18:75202325:G:C	N75K	0.975
18:75202325:G:T	N75K	0.975
18:75202246:C:A	G102W	0.974
18:75201984:G:T	A189D	0.973
18:75208862:A:G	L66P	0.973
18:75201760:C:A	G264W	0.972
18:75201450:A:T	V367D	0.971
18:75202245:C:T	G102E	0.970
18:75202071:G:T	A160E	0.969
18:75202234:C:G	A106P	0.968
18:75202080:C:T	G157D	0.967
18:75202162:C:G	A130P	0.967
18:75201819:A:T	V244D	0.964
18:75202023:A:T	V176D	0.964
18:75202329:A:T	V74D	0.964
18:75202260:C:T	G97D	0.963
18:75201459:T:A	K364I	0.962
18:75202251:C:T	G100D	0.962

dbSNP variants (sampled 300 via entrez): RS1000386489 (18:75196721 G>A), RS1000517151 (18:75195683 C>A,G), RS1000585425 (18:75196969 A>G), RS1000646725 (18:75195755 TA>T,TAA), RS1000793284 (18:75201190 C>T), RS1000855862 (18:75202633 T>C), RS1001024424 (18:75200920 A>G), RS1001095136 (18:75207087 A>G), RS1001163283 (18:75200852 A>G), RS1001641110 (18:75196496 G>A), RS1001690107 (18:75196864 C>T), RS1001722700 (18:75197203 T>G), RS1001874606 (18:75200555 C>A,G,T), RS1001976292 (18:75195434 G>A,C), RS1002279658 (18:75200823 C>T)

Disease associations

OMIM: gene MIM:620604 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003403_10	Vascular endothelial growth factor levels	6.000000e-10
GCST90002402_630	Platelet count	1.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, affects expression, increases expression	4
Valproic Acid	affects cotreatment, decreases expression	3
entinostat	decreases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
Nickel	decreases expression	2
Asbestos, Serpentine	increases expression, increases methylation	2
methylmercuric chloride	decreases expression	1
bisphenol A	decreases methylation, affects cotreatment	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
butyraldehyde	decreases expression	1
resorcinol	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenic	affects methylation	1
Carbamazepine	affects expression	1
Demecolcine	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TY48	HAP1 ZADH2 (-) 1	Cancer cell line	Male
CVCL_XV22	HAP1 ZADH2 (-) 2	Cancer cell line	Male
CVCL_XV23	HAP1 ZADH2 (-) 3	Cancer cell line	Male
CVCL_XV24	HAP1 ZADH2 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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