PLAT

Summary

PLAT (plasminogen activator, tissue type, HGNC:9051) is a protein-coding gene on chromosome 8p11.21, encoding Tissue-type plasminogen activator (P00750). Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen.

This gene encodes tissue-type plasminogen activator, a secreted serine protease that converts the proenzyme plasminogen to plasmin, a fibrinolytic enzyme. The encoded preproprotein is proteolytically processed by plasmin or trypsin to generate heavy and light chains. These chains associate via disulfide linkages to form the heterodimeric enzyme. This enzyme plays a role in cell migration and tissue remodeling. Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding, while decreased activity leads to hypofibrinolysis, which can result in thrombosis or embolism. Alternative splicing of this gene results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed.

Source: NCBI Gene 5327 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thrombophilia, familial, due to decreased release of tissue plasminogen activator (Moderate, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 109 total — 1 likely-pathogenic
• GTEx eGene: eQTL in 16 tissues, sQTL in 0 (q < 0.05)
• Drug target: yes — 8 curated mechanism-of-action drugs; 8 molecules with ChEMBL bioactivity
• Approved drugs (ChEMBL mechanism of action): 4 — Alteplase, Aminocaproic Acid, Reteplase, +1 more
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.80 (unconstrained)
• MANE Select transcript: NM_000930
• Interaction hub: 2,316 STRING partners (top 5% of genes corpus-wide)
• Notable: 109 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9051
Approved symbol	PLAT
Name	plasminogen activator, tissue type
Location	8p11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000104368
Ensembl biotype	protein_coding
OMIM	173370
Entrez	5327

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 18 protein_coding, 4 nonsense_mediated_decay, 4 retained_intron

MANE Select: ENST00000220809

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 3, TSL 3: 2, TSL 4: 1, TSL 5: 3

ENST00000220809, ENST00000352041, ENST00000429089, ENST00000429710, ENST00000519510, ENST00000520523, ENST00000521042, ENST00000521647, ENST00000521694, ENST00000522812, ENST00000524009, ENST00000524261, ENST00000677722, ENST00000678083, ENST00000678676, ENST00000679151, ENST00000679300, ENST00000884022, ENST00000884023, ENST00000884024, ENST00000884025, ENST00000915840, ENST00000944404, ENST00000944405, ENST00001048420, ENST00001136428

RefSeq mRNA: 3 — MANE Select: NM_000930 NM_000930, NM_001319189, NM_033011

CCDS: CCDS6126, CCDS6127, CCDS83291

Canonical transcript exons

ENST00000220809 — 14 exons

Exon	Start	End
ENSE00000692400	42182719	42182890
ENSE00000692402	42185081	42185172
ENSE00000692406	42187906	42188016
ENSE00001128022	42187398	42187572
ENSE00001605389	42180242	42180378
ENSE00001617965	42191372	42191414
ENSE00001727998	42188934	42189071
ENSE00001793485	42179926	42180066
ENSE00002137331	42207494	42207565
ENSE00002181240	42193114	42193211
ENSE00003497155	42180490	42180685
ENSE00003633367	42181937	42182022
ENSE00003651450	42178897	42179063
ENSE00003894645	42174718	42176151

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 99.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.8258 / max 3422.5622, expressed in 1317 samples.

Highest expression (Bgee): stromal cell of endometrium, pancreatic ductal cell, urethra, vena cava, mucosa of urinary bladder.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PLAT is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

16 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	2.5e-44	+1.10	8:42256743:C:T
Skin Sun Exposed Lower leg	eqtl	7.7e-31	+0.63	8:42207691:A:G
Skin Not Sun Exposed Suprapubic	eqtl	4.2e-29	+0.63	8:42207691:A:G
Esophagus Mucosa	eqtl	3.8e-18	+0.43	8:42221283:A:C
Adipose Subcutaneous	eqtl	7.3e-12	+0.41	8:42207691:A:G
Nerve Tibial	eqtl	7.1e-09	+0.31	8:42207691:A:G
Testis	eqtl	8.0e-06	+0.31	8:42218809:G:GAC
Colon Transverse	eqtl	6.0e-03	-0.62	8:42089809:T:C
Muscle Skeletal	eqtl	2.5e-02	+0.49	8:42209976:C:T
Brain Nucleus accumbens basal ganglia	eqtl	3.5e-02	-0.59	8:42743401:T:C
Adipose Visceral Omentum	eqtl	3.9e-02	+0.14	8:41916879:G:C
Thyroid	eqtl	4.4e-02	+0.30	8:41808482:T:C
Colon Sigmoid	eqtl	4.5e-02	-0.31	8:42379786:A:G
Esophagus Muscularis	eqtl	4.6e-02	+0.42	8:41786018:C:T
Heart Atrial Appendage	eqtl	4.7e-02	+0.54	8:42207067:G:A
Brain Cerebellar Hemisphere	eqtl	5.0e-02	+0.92	8:41942126:A:G

FANTOM5 promoters

10 alternative TSS:

Promoter ID	TPM avg	Samples expressed
92896	41.3643	1236
92897	17.6812	951
92889	0.1639	68
92888	0.1332	53
92891	0.1088	44
92893	0.0912	35
92894	0.0864	29
92895	0.0858	34
92892	0.0626	30
92890	0.0484	20

Top tissues by expression

showing 100 of 291 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.23	gold quality
pancreatic ductal cell	CL:0002079	98.90	gold quality
urethra	UBERON:0000057	98.34	gold quality
vena cava	UBERON:0004087	98.17	gold quality
mucosa of urinary bladder	UBERON:0001259	98.05	gold quality
metanephros cortex	UBERON:0010533	97.46	gold quality
mammary duct	UBERON:0001765	97.36	gold quality
epithelium of mammary gland	UBERON:0003244	96.49	gold quality
pylorus	UBERON:0001166	96.42	gold quality
gall bladder	UBERON:0002110	96.36	gold quality
metanephros	UBERON:0000081	96.05	gold quality
urinary bladder	UBERON:0001255	96.04	gold quality
left uterine tube	UBERON:0001303	96.01	gold quality
cardia of stomach	UBERON:0001162	95.97	gold quality
renal medulla	UBERON:0000362	95.79	gold quality
pericardium	UBERON:0002407	95.56	gold quality
colonic epithelium	UBERON:0000397	95.50	gold quality
metanephric glomerulus	UBERON:0004736	94.78	gold quality
seminal vesicle	UBERON:0000998	94.72	gold quality
epithelial cell of pancreas	CL:0000083	94.71	gold quality
caecum	UBERON:0001153	94.59	gold quality
trigeminal ganglion	UBERON:0001675	94.19	gold quality
renal glomerulus	UBERON:0000074	94.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.87	gold quality
thoracic mammary gland	UBERON:0005200	93.70	gold quality
olfactory bulb	UBERON:0002264	93.68	gold quality
rectum	UBERON:0001052	93.67	gold quality
adult mammalian kidney	UBERON:0000082	93.65	gold quality
mammary gland	UBERON:0001911	93.63	gold quality
vermiform appendix	UBERON:0001154	93.56	gold quality
cauda epididymis	UBERON:0004360	93.47	gold quality
dorsal root ganglion	UBERON:0000044	93.30	gold quality
penis	UBERON:0000989	93.26	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.00	gold quality
smooth muscle tissue	UBERON:0001135	92.96	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.87	gold quality
sigmoid colon	UBERON:0001159	92.85	gold quality
fundus of stomach	UBERON:0001160	92.83	gold quality
omental fat pad	UBERON:0010414	92.75	gold quality
peritoneum	UBERON:0002358	92.73	gold quality
decidua	UBERON:0002450	92.70	gold quality
superficial temporal artery	UBERON:0001614	92.66	gold quality
palpebral conjunctiva	UBERON:0001812	92.62	gold quality
tibial nerve	UBERON:0001323	92.58	gold quality
large intestine	UBERON:0000059	92.16	gold quality
sural nerve	UBERON:0015488	92.15	gold quality
colon	UBERON:0001155	92.13	gold quality
transverse colon	UBERON:0001157	92.12	gold quality
myometrium	UBERON:0001296	92.05	gold quality
nasal cavity mucosa	UBERON:0001826	92.04	gold quality
adrenal cortex	UBERON:0001235	91.92	gold quality
mucosa of stomach	UBERON:0001199	91.83	gold quality
adrenal gland	UBERON:0002369	91.72	gold quality
periodontal ligament	UBERON:0008266	91.72	gold quality
adrenal tissue	UBERON:0018303	91.68	gold quality
left adrenal gland cortex	UBERON:0035825	91.67	gold quality
adult organism	UBERON:0007023	91.62	gold quality
kidney	UBERON:0002113	91.61	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.57	gold quality
intestine	UBERON:0000160	91.54	gold quality
left coronary artery	UBERON:0001626	91.54	gold quality
coronary artery	UBERON:0001621	91.37	gold quality
left adrenal gland	UBERON:0001234	91.26	gold quality
cortex of kidney	UBERON:0001225	91.21	gold quality
right adrenal gland cortex	UBERON:0035827	91.21	gold quality
descending thoracic aorta	UBERON:0002345	91.02	gold quality
colonic mucosa	UBERON:0000317	90.90	gold quality
upper lobe of lung	UBERON:0008948	90.88	gold quality
upper lobe of left lung	UBERON:0008952	90.82	gold quality
right adrenal gland	UBERON:0001233	90.72	gold quality
body of uterus	UBERON:0009853	90.67	gold quality
stomach	UBERON:0000945	90.61	gold quality
ascending aorta	UBERON:0001496	90.60	gold quality
thoracic aorta	UBERON:0001515	90.54	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.25	gold quality
body of stomach	UBERON:0001161	89.99	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.86	gold quality
lower esophagus	UBERON:0013473	89.78	gold quality
synovial joint	UBERON:0002217	89.77	gold quality
duodenum	UBERON:0002114	89.63	gold quality
small intestine	UBERON:0002108	89.52	gold quality
jejunal mucosa	UBERON:0000399	89.48	gold quality
mucosa of transverse colon	UBERON:0004991	88.99	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.80	gold quality
left lobe of thyroid gland	UBERON:0001120	88.62	gold quality
right coronary artery	UBERON:0001625	88.60	gold quality
prostate gland	UBERON:0002367	88.54	gold quality
lung	UBERON:0002048	88.47	gold quality
germinal epithelium of ovary	UBERON:0001304	88.17	gold quality
cartilage tissue	UBERON:0002418	87.87	gold quality
uterus	UBERON:0000995	87.78	gold quality
endocervix	UBERON:0000458	87.75	gold quality
thyroid gland	UBERON:0002046	87.75	gold quality
esophagus	UBERON:0001043	87.71	gold quality
ectocervix	UBERON:0012249	87.65	gold quality
visceral pleura	UBERON:0002401	87.55	gold quality
diaphragm	UBERON:0001103	87.51	silver quality
jejunum	UBERON:0002115	87.49	gold quality
islet of Langerhans	UBERON:0000006	87.16	gold quality
calcaneal tendon	UBERON:0003701	86.82	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	2624.80
E-GEOD-124858	yes	1474.20
E-CURD-114	yes	518.38
E-MTAB-10287	yes	110.05
E-GEOD-135922	yes	36.13
E-CURD-119	yes	24.92
E-CURD-112	yes	11.75
E-MTAB-5061	yes	11.25
E-MTAB-9067	yes	7.15
E-GEOD-83139	yes	6.69
E-ENAD-20	no	1002.02
E-MTAB-10137	no	740.03
E-MTAB-10290	no	138.81
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Parathyroid gland	tissue	231.2	not detected
Urinary bladder	tissue	169.0	not detected
Ovary	tissue	64.4	not detected
Spinal cord	tissue	60.8
Endometrium 1	tissue	46.4	not detected
Fallopian tube	tissue	46.0	not detected
Placenta	tissue	41.7	high
Adipose tissue	tissue	40.6	medium
Colon	tissue	38.7	not detected
Gallbladder	tissue	37.9	not detected
Medulla oblongata	tissue	36.5
Superior colliculi	tissue	36.4
Appendix	tissue	33.5	not detected
Midbrain	tissue	32.9
Smooth muscle	tissue	30.6	not detected
Adrenal gland	tissue	30.3	not detected
Substantia nigra	tissue	30.0
Stomach 1	tissue	29.3	not detected
Thalamus	tissue	28.2
Duodenum	tissue	28.2	not detected
Caudate putamen	tissue	27.9
Seminal vesicle	tissue	27.4	not detected
Kidney	tissue	27.3	low
Small intestine	tissue	26.7	not detected
Frontal cortex	tissue	26.3
Corpus callosum	tissue	26.1
Pons	tissue	24.7
Rectum	tissue	23.4	not detected
Vagina	tissue	21.6	not detected
Breast	tissue	20.4	not detected
Olfactory bulb	tissue	19.9
Putamen	tissue	16.0
Epididymis	tissue	15.8	not detected
Pancreas	tissue	15.1	medium
Hypothalamus	tissue	14.9
Ventral forebrain	tissue	14.2
Periaqueductal gray	tissue	14.0
Cerebral cortex	tissue	13.8	low
Motor cortex	tissue	13.8
Septum	tissue	13.8
Lung	tissue	13.7	not detected
Cervix	tissue	13.6	not detected
Hippocampal formation	tissue	13.6
Heart muscle	tissue	13.4	not detected
Somatosensory cortex	tissue	13.4
Entorhinal cortex	tissue	13.1
Insular cortex	tissue	12.8
Prefrontal cortex	tissue	12.6
Retrosplenial and cingulate cortex	tissue	12.4
Occipital cortex	tissue	12.4
Amygdala	tissue	12.3
Retrosplenial cortex	tissue	12.0
Temporal cortex	tissue	11.7
Esophagus	tissue	11.4	not detected
Prostate	tissue	11.4	not detected
Basal ganglia	tissue	10.8	not detected
Locus coeruleus	tissue	10.1
Thyroid gland	tissue	9.3	not detected
Hippocampus	tissue	9.3	not detected
Pituitary gland	tissue	9.1

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Ventral spinal cord (60.8), Dorsal spinal cord (58.7), Blood vessel (30.2), White matter (26.1), Posterior thalamic nucleus (23.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF2, ATF4, CREB1, CREM, DBP, DNMT1, EGR1, FOS, HIF1A, HOXB2, JUN, JUND, KLF5, MSC, NF1, RARA, RARB, RXRA, SP1, SP3, TCF3, TP53

miRNA regulators (miRDB)

Targeting PLAT by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 90 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502

Functional genomics

gnomAD constraint: pLI 6.08e-07, LOEUF 0.804, missense Z 0.977 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000220809 — one region, missense o/e 0.91.

Literature-anchored findings (GeneRIF, showing 40)

• Steps and dynamics of disintegration and reorganization of fibrin networks during tissue-type plasminogen activator-induced clot lysis. (PMID:11734662)
• mean transit time, the net quantitative turnover rate, and the sites of synthesis and catabolism (PMID:11734664)
• PAI-1/ tPA imbalance is associated with myocardial infarction at young age in Japanese men. (PMID:11816707)
• Tissue-type plasminogen activator -7,351C/T enhancer polymorphism is associated with a first myocardial infarction. Genetic markers of local tPA release and circulating steady-state tPA levels carry independent prognostic information. (PMID:11848437)
• TPA & urokinase progressed to maximum levels in late pregnancy, but decreased in labor, favoring a coagulation state despite elevated D-dimer levels suggesting enhanced fibrinolysis. (PMID:11858184)
• vWF and tPAag but not thrombomodulin in the present population are independent markers of atherosclerosis. (PMID:11864703)
• Arsenite caused a decrease of t-PA mRNA level and a rise of both PAI-1 mRNA level and activity in microvascular endothelial cells, but not umbilical vein endothelial cells, suggesting a role in Blackfoot disease, a peripheral vascular occlusive disease. (PMID:11864708)
• In a study of the differential role of UPA and TPA as inducers of fibronectin mRNA, TPA led to an increase of FN mRNA expression in early G1, led to FN assembly in the ECM, induced dimeric FN (PMID:11928812)
• Tissue-type plasminogen activator is stored in Weibel-Palade bodies in endothelial cells (PMID:11986218)
• role of the plasminogen activator and matrix metalloproteinase systems in matrix remodeling in the ovary (PMID:11988309)
• Tissue plasminogen activator as a key effector in neurobiology and neuropathology. Review. (PMID:12023848)
• tPA is induced by oncostatin M in lung tumor cells (PMID:12090757)
• interactions between the fibrinolytic and renin-angiotensin systems play an important role in the genetic architecture of plasma t-PA (PMID:12123488)
• upregulation of PAI-1, uPA, and tPA after long-term LDL exposure seems to be mediated by a delayed PKC activation associated with an increased PA inhibitory activity (PMID:12167592)
• The interactions between NSP and t-PA were distinct from those between plasmin and NSP, suggesting that the physiologic effect of t-PA-NSP interactions may be more complex than previously thought. (PMID:12228252)
• Cloning and identification of human tissue-type plasminogen activator gene. (PMID:12390834)
• Calcium-regulated secretion of tissue-type plasminogen activator in vascular endothelial cells. (PMID:12445472)
• amino acids critical for tPA-annexin A2 interaction (PMID:12468550)
• hypoxia decreased tissue plasminogen activator in both normal peritoneal fibroblasts and adhesion fibroblasts (PMID:12524082)
• reactive hyperemia stimulates t-PA release; that relationship is altered when endothelium is dysfunctional. Release of t-PA is independent of adenosine or products of muscarinic stimulation and may be related to the activity of the kininogen/kinin system. (PMID:12544724)
• Recombinant tissue plasminogen activator (alteplase)is effective for restoration of function to occluded central venous catheters in a pediatric population with thrombosis (PMID:12544772)
• The possible influence of the Alu-repeat polymorphism on t-PA release was evaluated after a venous occlusion test in venous occlusion. (PMID:12643326)
• Tetranectin binds to this protein and hepatocyte growth factor. (PMID:12694198)
• results show that the NH(2)-terminal part of PrP(c) spanning amino acids 23-110 (PrP23-110) together with low molecular weight heparin stimulates t-PA mediated plasminogen activation in vitro (PMID:12719777)
• tPA and plasma kallikrein-mediated uPA activation and tPA release contribute to endogenous fibrinolytic or thrombolytic mechanisms. (PMID:12719778)
• In normal conditions and in the presence of IL-1beta, cathepsin B is involved in the activation of plasminogen activator in osteoblasts. (PMID:12726991)
• These results suggest that the recombinant kringle domain of tissue-type plasminogen activator (t-PA) is a selective inhibitor of endothelial cell growth and identifies this molecule as a novel anti-angiogenic agent. (PMID:12727218)
• Dengue virus infection significanlty increased production of tissue plasminogen activator (tPA) in primary isolated endothelial cells, human umbilical cord veins cells, and a human microvascular endothelial cell line (PMID:12794725)
• evidence to support the hypothesis that p63 is the functional tPA binding site on VSMC (PMID:12913003)
• TAFIa inhibited lysis of model thrombi and plasma clots by uPA, scuPA and tPA, which could be partially overcome by plasminogen, consistent with TAFIa exerting its effect through modifying the binding of plasminogen and tPA to fibrin. (PMID:12941043)
• the catalytic domain of tissue-type plasminogen activator is distorted by plasminogen activator inhibitor-1, leading to the formation of stable serpin-proteinase complexes (PMID:14500731)
• High concentration of plasma tPA was an independent marker for poor prognosis in patients with ovarian cancer. (PMID:14529669)
• in response to T beta 4 stimulation, AP-1 activity increases to enhance PAI-1 transcription through its unique AP-1-like element at -59 to -52 in the PAI-1 promoter. (PMID:14592829)
• A coconut oil-based diet lowers postprandial t-PA antigen concentration. (PMID:14608053)
• anti-tPA antibodies specifically interacting with the catalytic domain of tPA can be found in patients with antiphospholipid syndrome, representing a possible cause of hypofibrinolysis. (PMID:14630788)
• t-PA antigen concentration (P =.001), fibrinogen and time on dialysis prior to transplantation (P <.05) were positive independent predictors of carotid intima media thickness in kidney transplantation. (PMID:14697941)
• t-PA mediated plasminogen activation involves prion-protein fragment PrP23-110 lysine clusters (PMID:14983221)
• Adenosine deaminase and Plasminogen bind simultaneously to CD26 in a ternary complex that stimulates the Pg activation by its physiologic activators. (PMID:15016824)
• Neuronal depolarization induces a release of t-PA. This release of t-PA is sensitive to exocytosis inhibition and calcium chelation. Released t-PA modulates NMDA receptor signaling. (PMID:15080889)
• There is a basal net release of t-PA across the human cerebral vascular bed and sympathoadrenal activation induces a local regulated release of t-PA. (PMID:15116264)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	plat	ENSDARG00000062707
mus_musculus	Plat	ENSMUSG00000031538
rattus_norvegicus	Plat	ENSRNOG00000019018

Paralogs (14): PRSS33 (ENSG00000103355), PLG (ENSG00000122194), PLGLB2 (ENSG00000125551), PRSS37 (ENSG00000165076), PRSS27 (ENSG00000172382), KLK15 (ENSG00000174562), PLGLB1 (ENSG00000183281), PRSS57 (ENSG00000185198), TMPRSS12 (ENSG00000186452), OVCH1 (ENSG00000187950), PRSS48 (ENSG00000189099), GZMM (ENSG00000197540), KLK9 (ENSG00000213022), PRSS50 (ENSG00000283706)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97610) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 39 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal acute phase protein level	3
decreased anxiety-related response	2
increased circulating corticosterone level	2
impaired synaptic plasticity	2
reduced thrombolysis	2
abnormal testis morphology	1
small testis	1
decreased exploration in new environment	1
abnormal cued conditioning behavior	1
abnormal contextual conditioning behavior	1
reduced long-term potentiation	1
absent long-term depression	1
intracerebral hemorrhage	1
heart left ventricle hypertrophy	1
decreased vertical activity	1
abnormal active avoidance behavior	1
abnormal motor learning	1
chronic joint inflammation	1
joint swelling	1
autoimmune arthritis	1
abnormal response to CNS ischemic injury	1
pulmonary interstitial fibrosis	1
decreased susceptibility to induced choroidal neovascularization	1
decreased susceptibility to induced retina damage	1
abnormal microglial cell physiology	1

+14 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pan troglodytes	Q5G271	99.2%	Diamond
Nomascus leucogenys	Q5G268	98.5%	Diamond
Gorilla gorilla gorilla	Q5G270	98.5%	Diamond
Trachypithecus phayrei	Q5G266	98.3%	Diamond
Macaca mulatta	Q5G267	98.3%	Diamond
Pongo abelii	Q5R8J0	97.9%	Diamond
Pongo pygmaeus	Q5G269	96.7%	Diamond
Saguinus labiatus	Q5G265	95.5%	Diamond
Bunodosoma caissarum	P86468	93.1%	Diamond
Bos taurus	P06868	92.9%	Diamond
Capra hircus	Q7M323	92.9%	Diamond
Papio cynocephalus	P16227	92.6%	Diamond
Desmodus rotundus	P15638	89.9%	Diamond
Canis lupus familiaris	P80009	89.7%	Diamond
Ovis aries	P81286	86.3%	Diamond
Sus scrofa	P06867	85.0%	Diamond
Oryctolagus cuniculus	Q8MHY7	83.1%	Diamond
Equus caballus	P80010	81.3%	Diamond
Erinaceus europaeus	Q29485	79.5%	Diamond
Notamacropus eugenii	O18783	75.4%	Diamond
Cavia porcellus	Q04962	73.2%	Diamond
Xenopus laevis	Q90Y90	70.1%	Diamond
Drosophila melanogaster	Q9VWU1	66.9%	Diamond
Petromyzon marinus	P33574	55.6%	Diamond
Gallus gallus	P15120	48.7%	Diamond
Holotrichia diomphalia	Q9GRW0	47.7%	Diamond
Aedes aegypti	A0A6I8TBG6	45.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
IKBKB	protein-coding	3551
POLB	protein-coding	5423
KAT6A-AS1	ncRNA	105379393
AP3M2	protein-coding	10947
IKBKB-DT	ncRNA	101929897

Protein

Protein identifiers

Tissue-type plasminogen activator — P00750 (reviewed: P00750)

All UniProt accessions (10): A0A7I2V268, A0A7I2V6D6, A0A7I2YQ93, B4DN26, B4DNJ1, E5RGA1, E5RHG4, E7ESF4, P00750, H0YBH9

UniProt curated annotations — full annotation on UniProt →

Function. Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. During oocyte activation, plays a role in cortical granule reaction in the zona reaction, which contributes to the block to polyspermy.

Subunit / interactions. Heterodimer of chain A and chain B held by a disulfide bond. Forms a heterodimer with SERPINA5. Binds to fibrin with high affinity. This interaction leads to an increase in the catalytic efficiency of the enzyme between 100-fold and 1000-fold, due to an increase in affinity for plasminogen. Similarly, binding to heparin increases the activation of plasminogen. Binds to annexin A2, cytokeratin-8, fibronectin and laminin. Binds to mannose receptor and the low-density lipoprotein receptor-related protein (LRP1); these proteins are involved in TPA clearance. Yet unidentified interactions on endothelial cells and vascular smooth muscle cells (VSMC) lead to a 100-fold stimulation of plasminogen activation. In addition, binding to VSMC reduces TPA inhibition by PAI-1 by 30-fold. Binds LRP1B; binding is followed by internalization and degradation. Interacts with SERPINE1. In complex with SERPINE1, interacts with SORL1. Interacts with apyrase from Anopheles gambiae saliva; the interaction results in PLAT activation probably via an allosteric activation mechanism.

Subcellular location. Secreted. Extracellular space.

Tissue specificity. Synthesized in numerous tissues (including tumors) and secreted into most extracellular body fluids, such as plasma, uterine fluid, saliva, gingival crevicular fluid, tears, seminal fluid, and milk.

Post-translational modifications. The single chain, almost fully active enzyme, can be further processed into a two-chain fully active form by a cleavage after Arg-310 catalyzed by plasmin, tissue kallikrein or factor Xa. Differential cell-specific N-linked glycosylation gives rise to two glycoforms, type I (glycosylated at Asn-219) and type II (not glycosylated at Asn-219). The single chain type I glycoform is less readily converted into the two-chain form by plasmin, and the two-chain type I glycoform has a lower activity than the two-chain type II glycoform in the presence of fibrin. N-glycosylation of Asn-152; the bound oligomannosidic glycan is involved in the interaction with the mannose receptor. Characterization of O-linked glycan was studied in Bowes melanoma cell line.

Disease relevance. Increased activity of TPA results in increased fibrinolysis of fibrin blood clots that is associated with excessive bleeding. Defective release of TPA results in hypofibrinolysis that can lead to thrombosis or embolism.

Activity regulation. Inhibited by SERPINA5. Inhibited by SERPINE1.

Domain organisation. Both FN1 and one of the kringle domains are required for binding to fibrin. Both FN1 and EGF-like domains are important for binding to LRP1. The FN1 domain mediates binding to annexin A2. The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the peptidase S1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
P00750-1	1, Long	yes
P00750-2	2, Short
P00750-3	3
P00750-4	4, Neonatal

RefSeq proteins (3): NP_000921, NP_001306118, NP_127509 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000001	Kringle	Domain
IPR000083	Fibronectin_type1	Domain
IPR000742	EGF	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR013806	Kringle-like	Homologous_superfamily
IPR018056	Kringle_CS	Conserved_site
IPR018114	TRYPSIN_HIS	Active_site
IPR026280	Tissue_plasm_act	Family
IPR033116	TRYPSIN_SER	Active_site
IPR038178	Kringle_sf	Homologous_superfamily
IPR043504
IPR050127	Serine_Proteases_S1	Family

Pfam: PF00008, PF00039, PF00051, PF00089

Enzyme classification (BRENDA)

• EC 3.4.21.68 — t-Plasminogen activator (BRENDA: 13 organisms, 167 substrates, 120 inhibitors, 209 Km, 185 kcat entries)

Substrate kinetics (BRENDA)

99 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
LYS-PLASMINOGEN	—	30
SPECTROZYME TPA	0.4–4.6	11
D-ILE-PRO-ARG-P-NITROANILIDE	0.0001–0.694	8
PLASMINOGEN	—	8
BOC-(P-F)-FPRANSNH-C2H5	0.0004–0.071	5
BOC-D-VGRANSNH-C4H9	0.0007–0.14	5
(P-F)-FPRANSNH-C2H5	0.0004–0.39	4
BOC-D-FVRANSNH-C2H5	0.0027–0.091	4
BOC-D-LGRANSNH-C6H11	0.0004–0.023	4
BOC-D-LPRANSNH-C3H7	0.0006–0.066	4
BOC-D-LSRANSNH-C3H7	0.0006–0.36	4
D-FVRANSNH-C2H5	0.0011–0.016	4
D-LPRANSNH-C3H7	0.0003–0.098	4
D-LSRANSNH-C3H7	0.0012–0.069	4
D-VPRANSNH-C4H9	0.0003–0.11	4

UniProt features (106 total): strand 39, disulfide bond 17, helix 10, sequence conflict 6, domain 5, splice variant 5, site 4, glycosylation site 4, sequence variant 4, active site 3, chain 3, propeptide 2, turn 2, signal peptide 1, region of interest 1

Structure

Experimental structures (PDB)

11 structures by resolution:

PDB	Title	Method	Resolution (Å)
1RTF	COMPLEX OF BENZAMIDINE WITH THE CATALYTIC DOMAIN OF HUMAN TWO CHAIN TISSUE PLASMINOGEN …	X-RAY DIFFRACTION	2.3
1PML	KRINGLE-KRINGLE INTERACTIONS IN MULTIMER KRINGLE STRUCTURES	X-RAY DIFFRACTION	2.38
1TPK	CRYSTAL STRUCTURE OF THE KRINGLE-2 DOMAIN OF TISSUE PLASMINOGEN ACTIVATOR AT …	X-RAY DIFFRACTION	2.4
1A5H	CATALYTIC DOMAIN OF HUMAN TWO-CHAIN TISSUE PLASMINOGEN ACTIVATOR COMPLEX OF A …	X-RAY DIFFRACTION	2.9
5BRR	Michaelis complex of tPA-S195A:PAI-1	X-RAY DIFFRACTION	3.16
1BDA	CATALYTIC DOMAIN OF HUMAN SINGLE CHAIN TISSUE PLASMINOGEN ACTIVATOR IN COMPLEX WITH …	X-RAY DIFFRACTION	3.35
5ZLZ	Structure of tPA and PAI-1	X-RAY DIFFRACTION	3.58
1PK2	SOLUTION STRUCTURE OF THE TISSUE-TYPE PLASMINOGEN ACTIVATOR KRINGLE 2 DOMAIN COMPLEXED TO …	SOLUTION NMR
1TPG	F1-G MODULE PAIR RESIDUES 1-91 (C83S) OF TISSUE-TYPE PLASMINOGEN ACTIVATOR (T-PA) (NMR …	SOLUTION NMR
1TPM	SOLUTION STRUCTURE OF THE FIBRIN BINDING FINGER DOMAIN OF TISSUE-TYPE PLASMINOGEN …	SOLUTION NMR
1TPN	SOLUTION STRUCTURE OF THE FIBRIN BINDING FINGER DOMAIN OF TISSUE-TYPE PLASMINOGEN …	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00750-F1	81.28	0.36

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Serine-type peptidases, Predicted secreted proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Candidate cardiovascular disease genes, Disease related genes, FDA approved drug targets, Biotech drugs, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): actin filaments

Antibody reliability (HPA): IH supported · IF approved

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 (7)

Position	Role
357	charge relay system
406	charge relay system
513	charge relay system
102	important for binding to lrp1
253	not glycosylated
464	important for single-chain activity
512	important for single-chain activity

Disulfide bonds (17)

Type	Positions
Disulfide bond	41–71, 69–78, 86–97, 91–108, 110–119, 127–208, 148–190, 179–203, 215–296, 236–278, 267–291, 342–358, 350–419, 444–519, 476–492, 509–537
Interchain (between a and b chains)	299–430

Glycosylation sites (4)

Type	Positions
O-linked (fuc) threonine	96
N-linked (glcnac…) asparagine	152, 219, 483

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-75205	Dissolution of Fibrin Clot	curated
R-HSA-186797	Signaling by PDGF	curated
R-HSA-109582	Hemostasis	—
R-HSA-162582	Signal Transduction	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—

MSigDB gene sets: 399 (showing top): MODULE_172, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_SINGLE_FERTILIZATION, MODULE_52, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_REGULATION_OF_COAGULATION, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_COAGULATION, GOCC_CELL_SURFACE, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GGGTGGRR_PAX4_03, GOBP_CELL_CELL_SIGNALING

GO Biological Process (14): proteolysis (GO:0006508), blood coagulation (GO:0007596), negative regulation of plasminogen activation (GO:0010757), smooth muscle cell migration (GO:0014909), plasminogen activation (GO:0031639), protein modification process (GO:0036211), fibrinolysis (GO:0042730), negative regulation of proteolysis (GO:0045861), platelet-derived growth factor receptor signaling pathway (GO:0048008), negative regulation of fibrinolysis (GO:0051918), prevention of polyspermy (GO:0060468), trans-synaptic signaling by BDNF, modulating synaptic transmission (GO:0099183), SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition (GO:0006617), zymogen activation (GO:0031638)

GO Molecular Function (7): serine-type endopeptidase activity (GO:0004252), signaling receptor binding (GO:0005102), phosphoprotein binding (GO:0051219), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (9): extracellular region (GO:0005576), cytoplasm (GO:0005737), cell surface (GO:0009986), secretory granule (GO:0030141), apical part of cell (GO:0045177), extracellular exosome (GO:0070062), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978), signal recognition particle, endoplasmic reticulum targeting (GO:0005786)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	1
Hemostasis	1
Signal Transduction	1

GO top-level categories

43 GO namespaces:

Category	Terms
cellular anatomical structure	4
protein metabolic process	2
protein binding	2
synapse	2
hemostasis	1
wound healing	1
coagulation	1
regulation of plasminogen activation	1
negative regulation of protein processing	1
plasminogen activation	1
muscle cell migration	1
zymogen activation	1
macromolecule modification	1
negative regulation of blood coagulation	1
proteolysis	1
regulation of proteolysis	1
negative regulation of protein metabolic process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
positive regulation of blood coagulation	1
positive regulation of response to external stimulus	1
fibrinolysis	1
negative regulation of biological process	1
regulation of fibrinolysis	1
egg activation	1
negative regulation of fertilization	1
trans-synaptic signaling by BDNF	1
trans-synaptic signaling, modulating synaptic transmission	1
SRP-dependent cotranslational protein targeting to membrane	1
protein-containing complex assembly	1
protein processing	1
endopeptidase activity	1
serine-type peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
intracellular anatomical structure	1
endomembrane system	1
secretory vesicle	1
extracellular vesicle	1
signal recognition particle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 31 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of proteolysis	BP	direct assay
plasminogen activation	BP	direct assay
cell surface	CC	direct assay
cytoplasm	CC	direct assay
extracellular exosome	CC	high-throughput assay
phosphoprotein binding	MF	physical interaction
serine-type endopeptidase activity	MF	direct assay
signaling receptor binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 2,316 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLAT	SERPINE1	P05121	968
PLAT	CPB2	Q96IY4	904
PLAT	PLG	P00747	890
PLAT	SERPINF2	P08697	887
PLAT	F3	P13726	880
PLAT	VWF	P04275	855
PLAT	SERPINC1	P01008	844
PLAT	THBD	P07204	841
PLAT	MMP9	P14780	810
PLAT	SERPINB2	P05120	808
PLAT	LOXHD1	Q8IVV2	791
PLAT	SERPINF1	P36955	777
PLAT	SERPINI1	Q99574	740
PLAT	TFPI	P10646	721
PLAT	CRP	P02741	716

IntAct

Human interaction partners of PLAT in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
SERPING1	association	0.500	2
SERPINE1	direct interaction	0.440	1
SERPINA10	association	0.350	1
SERPINB6	association	0.350	1

BioGRID (77 interactions; top human partners by supporting records): FGL1 (Affinity Capture-MS; 3 records), TMEM25 (Affinity Capture-MS; 3 records), DEFA1 (Affinity Capture-MS; 2 records), FGA (Reconstituted Complex; 2 records), IFNA14 (Affinity Capture-MS; 2 records), IGFBP1 (Affinity Capture-MS; 2 records), LRP1 (Reconstituted Complex; 2 records), PLA2G10 (Affinity Capture-MS; 2 records), SERPINA10 (Affinity Capture-MS; 2 records), SERPINB2 (Affinity Capture-MS; 2 records), SERPINB6 (Affinity Capture-MS; 2 records), SERPING1 (Affinity Capture-MS; 2 records), SERPINI1 (Biochemical Activity; 2 records), ANXA2 (Reconstituted Complex), APP (Reconstituted Complex)

SIGNOR signaling

5 signaling interactions:

A	Effect	B	Mechanism
ATF2	“up-regulates quantity by expression”	PLAT	“transcriptional regulation”
CREB1	“down-regulates quantity by repression”	PLAT	“transcriptional regulation”
PLAT	“up-regulates activity”	PLG	binding
PLG	“up-regulates activity”	PLAT	cleavage
Fibrin	up-regulates	PLAT

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
★ PLAT-PLG-THBS1 complex	3	PLAT, PLG, THBS1
★ HRG-PLAT-PLG complex	3	HRG, PLAT, PLG
★ PLAT-PLG complex	2	PLAT, PLG

Disease & clinical

Genetic variants

Variant evidence for PLAT: 109 ClinVar records (1 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	64
Likely benign	20
Benign	9

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
4890898	NM_000930.5(PLAT):c.1209del (p.Thr402_Tyr403insTer)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore PLAT’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 970):

Position(s)	Effect	Δscore	Sites
8:42179939	donor_gain	1.0000
8:42180067–42180068	acceptor_loss	1.0000	6
8:42180240–42180241	donor_loss	1.0000	5
8:42180379–42180380	acceptor_loss	1.0000	6
8:42180488–42180489	donor_loss	1.0000	3
8:42187396–42187397	donor_loss	1.0000	4
8:42187573–42187574	acceptor_loss	1.0000	6
8:42187905	donor_loss	1.0000
8:42188024	acceptor_gain	1.0000
8:42193112–42193113	donor_loss	1.0000	4

AlphaMissense

1,014 missense substitutions predicted likely pathogenic (of 3,688 scored), across 245 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M490	9	0.790	0.919
D512	8	0.984	0.995
D406	8	0.980	0.992
D507	8	0.968	0.985
S532	8	0.937	0.995
H357	8	0.935	0.979
D495	8	0.901	0.960
N181	8	0.875	0.970
N269	8	0.872	0.970
C509	7	0.993	0.998
C492	7	0.990	0.997
C358	7	0.989	0.995
C537	7	0.987	0.996
C342	7	0.985	0.993
C476	7	0.983	0.996
C278	7	0.981	0.993
C179	7	0.980	0.992
C236	7	0.980	0.991
C444	7	0.980	0.994
W151	7	0.975	0.997

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (validation)	unfavorable	0.000183
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000477
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000771

Disease associations

OMIM: gene MIM:173370 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
thrombophilia, familial, due to decreased release of tissue plasminogen activator	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
thrombophilia, familial, due to decreased release of tissue plasminogen activator	Disputed	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (6 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

6 panels:

Panel	Rating
Inherited bleeding disorders	green
Hypotonic infant	amber
Intellectual disability	amber
Leukodystrophy, childhood onset	amber
Paediatric disorders	amber
Thrombophilia with a likely monogenic cause	amber

Mondo (1): thrombophilia, familial, due to decreased release of tissue plasminogen activator (MONDO:0012872)

GWAS associations

3 associations:

Study	Trait	p-value
GCST006585_1171	Blood protein levels	1e-12
GCST002374_1	Plasma plasminogen activator levels	2e-8
GCST005752_47	Systemic lupus erythematosus	3e-8

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C567341	Thrombophilia, Familial, Due To Decreased Release Of Tissue Plasminogen Activator *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1873 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the PLAT protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

8 curated-mechanism drugs:

Drug	Modality	Max phase
ALTEPLASE	Enzyme	4
AMINOCAPROIC ACID	Small molecule	4
RETEPLASE	Enzyme	4
TENECTEPLASE	Enzyme	4
MONTEPLASE	Enzyme	3
DUTEPLASE	Enzyme	2
LANOTEPLASE	Enzyme	2
PAMITEPLASE	Enzyme	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 50,986 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

8 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1166	ARGATROBAN	4	233
CHEMBL266349	MELAGATRAN	4	5,456
CHEMBL877	TRANEXAMIC ACID	4	28,038
CHEMBL48361	DABIGATRAN	3	13,643
CHEMBL87563	GABEXATE	3	2,044
CHEMBL4112929	MILVEXIAN	3	142
CHEMBL273196	EFEGATRAN	2	1,040
CHEMBL1095032	LETAXABAN	2	390

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S1: Chymotrypsin

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

Ligand	Action	Affinity	Parameter
Dup-714	Inhibition	8.24	pKi

Binding affinities (BindingDB)

1007 measured of 1155 human assays (1220 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(S)-20-Benzyl-8,25-dichloro-18-methyl-12-oxa-1,4,18,21,23-pentaaza-tricyclo[20.3.1.0*6,11*]hexacosa-6(11),7,9,22,24-pentaene-3,26-dione	KI	0.02 nM
(S)-20-Benzyl-8,25-dichloro-12-oxa-1,4,18,21,23-pentaaza-tricyclo[20.3.1.0*6,11*]hexacosa-6(11),7,9,22,24-pentaene-3,26-dione	KI	0.05 nM
(S)-20-Benzyl-8,25-dichloro-12,15-dioxa-1,4,18,21,23-pentaaza-tricyclo[20.3.1.0*6,11*]hexacosa-6(11),7,9,22,24-pentaene-3,26-dione	KI	0.05 nM
(14Z,21S)-21-benzyl-8,26-dichloro-12,17-dioxa-1,4,19,22,24-pentaazatricyclo[21.3.1.0^{6,11}]heptacosa-6(11),7,9,14,23,25-hexaene-3,18,27-trione	KI	0.06 nM
N-(4-chloro-2-(5-chloropyridin-2-ylcarbamoyl)phenyl)-4-(N,N-dimethylcarbamimidoyl)-2-fluorobenzamide	KI	0.06 nM
(S)-20-Benzyl-25-chloro-1,4,14,18,21,23-hexaaza-tricyclo[20.3.1.0*6,11*]hexacosa-6(11),7,9,22,24-pentaene-3,26-dione	KI	0.09 nM
1-[3-(Aminomethyl)phenyl]-N-[3-fluoro-2-(methylsulfonyl)-[1,1-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide	KI	0.15 nM
(14E,21S)-21-benzyl-8,26-dichloro-12,17-dioxa-1,4,19,22,24-pentaazatricyclo[21.3.1.0^{6,11}]heptacosa-6(11),7,9,14,23,25-hexaene-3,18,27-trione	KI	0.17 nM
(S)-19-Benzyl-8,24-dichloro-12-oxa-1,4,17,20,22-pentaaza-tricyclo[19.3.1.0*6,11*]pentacosa-6(11),7,9,21,23-pentaene-3,25-dione	KI	0.2 nM
5-chloro-N-(5-chloropyridin-2-yl)-2-(4-((2-iminooxazolidin-3-yl)methyl)benzamido)benzamide	IC50	0.2 nM
5-Chloro-N-(5-chloro-pyridin-2-yl)-2-(4-{[methyl-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)-amino]-methyl}-benzoylamino)-benzamide	IC50	0.3 nM
(2R)-N-[(3-aminobenzene)sulfonyl]-2-[(4-carbamimidoyl-3-hydroxyphenyl)amino]-2-(3,5-diethoxy-2-fluorophenyl)acetamide	KI	0.35 nM
(6S,12R)-25-Chloro-11-cyclohexyl-21-oxa-3,9,12,18-tetraaza-tricyclo[20.4.0.0*5,9*]hexacosa-1(22),23,25-triene-4,10,13,19-tetraone	KI	0.4 nM
(S)-24-Chloro-11-(R)-cyclohexyl-20-oxa-3,9,12,17-tetraaza-tricyclo[19.4.0.0*5,9*]pentacosa-1(21),22,24-triene-4,10,13,18-tetraone	KI	0.4 nM
5-chloro-N-[(2S)-2-[[2-methyl-3-(2-oxopyrrolidin-1-yl)phenyl]sulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]thiophene-2-carboxamide	IC50	0.43 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
2-(1-Methyl-1H-imidazol-2-yl)ethyl 3-{[(5-chloro-2-thienyl)carbonyl]amino}-N-{[2-methyl-3-(2-oxopyrrolidin-1-yl)phenyl]sulfonyl}-S-alaninate	IC50	0.45 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
3-(1-Methyl-1H-imidazol-2-yl)propyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-[2-ethyl-3-(2-oxopyrrolidin-1-yl)benzene-1-sulfonyl]-S-alaninate hydrochloride	IC50	0.48 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
CHEMBL6192325	IC50	0.49 nM
Methyl 3-{[(5-chloro-2-thienyl)carbonyl]amino}-N-{[2-methyl-3-(2-oxopyrrolidin-1-yl)phenyl]-sulfonyl}-S-alaninate	IC50	0.49 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
2-(1-Methyl-1H-imidazol-2-yl)ethyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-{2-ethyl-3-[(3S)-3-hydroxy-2-oxopyrrolidin-1-yl]benzene-1-sulfonyl}-S-alaninate hydrochloride	IC50	0.49 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
(2R,3R)-2-(3-Carbamimidoyl-benzyl)-3-[(3’-carbamoyl-biphenyl-4-carbonyl)-amino]-butyric acid methyl ester	KI	0.5 nM
(R)-5-Guanidino-2-phenylmethanesulfonylamino-pentanoic acid {[(R)-4-guanidino-1-(thiazole-2-carbonyl)-butylcarbamoyl]-methyl}-amide	IC50	0.5 nM
5-chloro-N-(5-chloro-pyridin-2-yl)-2-[4-(N,N-dimethyl-carbamimidoyl)-benzoylamino]-benzamide	IC50	0.5 nM
2-[4-(5-Chloro-3-methyl-benzo[b]thiophene-2-sulfonyl)-2-oxo-piperazin-1-yl]-N-[4-guanidino-1-(thiazole-2-carbonyl)-butyl]-acetamide	IC50	0.51 nM
(S)-20-Benzyl-25-chloro-1,4,13,18,21,23-hexaaza-tricyclo[20.3.1.0*6,11*]hexacosa-6(11),7,9,22,24-pentaene-3,26-dione	KI	0.51 nM
Methyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-[2-ethyl-3-(2-oxopyrrolidin-1-yl)benzene-1-sulfonyl]-S-alaninate	IC50	0.54 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
2-(1-Methyl-1H-imidazol-2-yl)ethyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-{3-[(3S)-3-hydroxy-2-oxopyrrolidin-1-yl]-2-methylbenzene-1-sulfonyl}-S-alaninate hydrochloride	IC50	0.61 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
2-(1-Methyl-1H-imidazol-2-yl)ethyl 3-{[(5-chloro-2-thienyl)carbonyl]amino}-N-{[2-ethyl-3-(2-oxopyrrolidin-1-yl)phenyl]sulfonyl}-S-alaninate hydrochloride	IC50	0.63 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
Methyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-{2-ethyl-3-[(3S)-3-hydroxy-2-oxopyrrolidin-1-yl]benzene-1-sulfonyl}-S-alaninate	IC50	0.68 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
2-(1-Methyl-1H-imidazol-2-yl)ethyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-{2-ethyl-3-[(3R)-3-hydroxy-2-oxopyrrolidin-1-yl]benzene-1-sulfonyl}-S-alaninate hydrochloride	IC50	0.68 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
4-hydroxy-3-{[(3S)-2-oxo-3-{thieno[3,2-b]pyridine-2-sulfonamido}pyrrolidin-1-yl]methyl}benzene-1-carboximidamide	KI	0.7 nM
5-Chloro-N-(5-chloro-pyridin-2-yl)-2-[4-(N,N’-dimethyl-guanidinomethyl)-benzoylamino]-benzamide	IC50	0.7 nM
N-(2-(5-chloropyridin-2-ylcarbamoyl)-4-methoxyphenyl)-4-(N,N-dimethylcarbamimidoyl)-2-fluorobenzamide	IC50	0.7 nM
4-{4-[3-(5-Carbamimidoyl-2-hydroxy-phenyl)-allylcarbamoyl]-phenyl}-pyridine-2-carboxylic acid amide	KI	0.75 nM
Methyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-{2-ethyl-3-[(3R)-3-hydroxy-2-oxopyrrolidin-1-yl]benzene-1-sulfonyl}-S-alaninate	IC50	0.76 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
2-[4-(5-Chloro-naphthalene-2-sulfonyl)-2-oxo-piperazin-1-yl]-N-[4-guanidino-1-(thiazole-2-carbonyl)-butyl]-acetamide	IC50	0.79 nM
3-(1-Methyl-1H-imidazol-2-yl)propyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-{2-ethyl-3-[(3R)-3-hydroxy-2-oxopyrrolidin-1-yl]benzene-1-sulfonyl}-S-alaninate	IC50	0.79 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
{4-[4-Chloro-2-(5-chloro-pyridin-2-ylcarbamoyl)-phenylcarbamoyl]-benzyl}-trimethyl-ammonium	IC50	0.8 nM
5-Chloro-N-(5-chloro-pyridin-2-yl)-2-[4-(N,N’,N’’-trimethyl-guanidinomethyl)-benzoylamino]-benzamide	IC50	0.8 nM
2-(1-Methyl-1H-imidazol-5-yl)ethyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-[2-ethyl-3-(2-oxopyrrolidin-1-yl)benzene-1-sulfonyl]-S-alaninate hydrochloride	IC50	0.89 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
5-Chloro-N-(5-chloro-pyridin-2-yl)-2-[4-(N’,N’-dimethyl-hydrazinomethyl)-benzoylamino]-benzamide	IC50	0.9 nM
2-{4-[(Acetimidoyl-methyl-amino)-methyl]-benzoylamino}-5-chloro-N-(5-chloro-pyridin-2-yl)-benzamide	IC50	0.9 nM
CHEMBL6192725	IC50	0.91 nM
3-(1-Methyl-1H-imidazol-2-yl)propyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-{2-ethyl-3-[(3S)-3-hydroxy-2-oxopyrrolidin-1-yl]benzene-1-sulfonyl}-S-alaninate hydrochloride	IC50	0.93 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
5-Chloro-N-(5-chloro-pyridin-2-yl)-2-{4-[(N-methyl-guanidino)-methyl]-benzoylamino}-benzamide	IC50	1 nM
CHEMBL6189853	IC50	1 nM
2-[4-({[2-(Acetimidoyl-methyl-amino)-ethyl]-methyl-amino}-methyl)-benzoylamino]-5-chloro-N-(5-chloro-pyridin-2-yl)-benzamide	IC50	1.1 nM
2-(Dimethylamino)ethyl 3-{[(5-chloro-2-thienyl)carbonyl]amino}-N-{[2-methyl-3-(2-oxopyrrolidin-1-yl)phenyl]sulfonyl-S-alaninate hydrochloride	IC50	1.1 nM
2-(1-Methyl-1H-imidazol-2-yl)ethyl 3-[(5-chlorothiophene-2-carbonyl)amino]-N-{3-[(3R)-3-hydroxy-2-oxopyrrolidin-1-yl]-2-methylbenzene-1-sulfonyl}-S-alaninate hydrochloride	IC50	1.1 nM	US-20230391761: SUBSTITUTED S-ALANINATE DERIVATIVES
[2-(5-Chloro-2-[1,2,4]triazol-1-yl-benzyl)-oxazolo[4,5-c]pyridin-4-yl]-(2,2-difluoro-2-piperidin-2-yl-ethyl)-amine	KI	1.2 nM

ChEMBL bioactivities

729 potent at pChembl≥5 of 864 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.54	Ki	0.29	nM	CHEMBL439678
9.15	IC50	0.7	nM	CHEMBL105819
8.52	Ki	3	nM	CHEMBL92615
8.24	Ki	5.7	nM	CHEMBL290376
8.22	IC50	6	nM	CHEMBL5901486
8.22	Ki	6	nM	CHEMBL418965
8.22	Ki	6	nM	CHEMBL94952
8.10	IC50	8	nM	CHEMBL4457757
8.10	IC50	8	nM	CHEMBL4460436
8.09	IC50	8.2	nM	CHEMBL5964796
8.06	IC50	8.7	nM	CHEMBL5905253
8.05	IC50	9	nM	CHEMBL5901046
8.05	IC50	9	nM	CHEMBL5962457
8.01	IC50	9.7	nM	CHEMBL5787485
8.00	IC50	10	nM	CHEMBL5862509
8.00	IC50	10	nM	CHEMBL5757367
8.00	IC50	10	nM	CHEMBL5985991
8.00	IC50	10	nM	CHEMBL5831764
7.96	IC50	11	nM	CHEMBL5946146
7.96	IC50	11	nM	CHEMBL5747109
7.96	IC50	11	nM	CHEMBL5856374
7.96	IC50	11	nM	CHEMBL5903246
7.96	IC50	11	nM	CHEMBL5758338
7.96	IC50	11	nM	CHEMBL6007660
7.96	IC50	11	nM	CHEMBL5940635
7.96	IC50	11	nM	CHEMBL5984212
7.96	IC50	11	nM	CHEMBL5874921
7.92	IC50	12	nM	CHEMBL5869606
7.92	IC50	12	nM	CHEMBL5816419
7.92	IC50	12	nM	CHEMBL5821304
7.92	IC50	12	nM	CHEMBL5858525
7.92	IC50	12	nM	CHEMBL6060319
7.92	IC50	12	nM	CHEMBL5879772
7.89	IC50	13	nM	CHEMBL6039037
7.89	IC50	13	nM	CHEMBL5950561
7.89	IC50	13	nM	CHEMBL6041995
7.89	IC50	13	nM	CHEMBL5948508
7.89	IC50	13	nM	CHEMBL6014715
7.85	IC50	14	nM	CHEMBL5751381
7.85	IC50	14	nM	CHEMBL6062932
7.85	IC50	14	nM	CHEMBL5998861
7.85	IC50	14	nM	CHEMBL5967117
7.85	IC50	14	nM	CHEMBL5896322
7.85	IC50	14	nM	CHEMBL6003517
7.85	IC50	14	nM	CHEMBL6016504
7.85	IC50	14	nM	CHEMBL5880017
7.85	IC50	14	nM	CHEMBL5826722
7.85	IC50	14	nM	CHEMBL5792440
7.85	IC50	14	nM	CHEMBL5799725
7.82	IC50	15	nM	CHEMBL5896355

PubChem BioAssay actives

260 with measured affinity, of 1109 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
2-[(3-chlorophenyl)methyl]-N-(2-piperidin-2-ylethyl)-[1,3]oxazolo[4,5-c]pyridin-4-amine	254331: Inhibitory constant against tissue plasminogen activator	ki	0.0003	uM
(2S)-2-[[(2S)-2-[4-(diaminomethylideneamino)butanoylamino]-3-(4-nitrophenyl)propanoyl]-methylamino]-3-hydroxy-N-[(1R)-1-phenylethyl]butanamide	225436: Concentration required to inhibit tissue-type plasminogen activator (t-PA) was determined	ic50	0.0007	uM
(20S)-20-benzyl-8,25-dichloro-18-methyl-12-oxa-1,4,18,21,23-pentazatricyclo[20.3.1.06,11]hexacosa-6(11),7,9,22,24-pentaene-3,26-dione	210577: Inhibitory activity against Tissue plasminogen activator	ki	0.0030	uM
(20S)-20-benzyl-8,25-dichloro-12-oxa-1,4,18,21,23-pentazatricyclo[20.3.1.06,11]hexacosa-6(11),7,9,22,24-pentaene-3,26-dione	210577: Inhibitory activity against Tissue plasminogen activator	ki	0.0060	uM
(14Z,21S)-21-benzyl-8,26-dichloro-12,17-dioxa-1,4,19,22,24-pentazatricyclo[21.3.1.06,11]heptacosa-6(11),7,9,14,23,25-hexaene-3,18,27-trione	210577: Inhibitory activity against Tissue plasminogen activator	ki	0.0060	uM
[2,3-dihydroxy-5-[[3,4,5,6-tetrakis[[3,4-dihydroxy-5-(3,4,5-trihydroxybenzoyl)oxybenzoyl]oxy]oxan-2-yl]methoxycarbonyl]phenyl] 3,4,5-trihydroxybenzoate	1799783: Enzymatic Assay from Article 10.1074/jbc.M109.067967: “Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.”	ic50	0.0080	uM
[(2R,3S,4S,5R)-3,4,5,6-tetrakis[(3,4,5-trihydroxybenzoyl)oxy]oxan-2-yl]methyl 3,4,5-trihydroxybenzoate	1799783: Enzymatic Assay from Article 10.1074/jbc.M109.067967: “Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.”	ic50	0.0120	uM
2,3-bis[(3,4,5-trihydroxybenzoyl)oxy]propyl 3,4,5-trihydroxybenzoate	1799783: Enzymatic Assay from Article 10.1074/jbc.M109.067967: “Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.”	ic50	0.0180	uM
2-(2-hydroxy-5-nitro-3-phenylphenyl)-1H-indole-5-carboximidamide	228025: Inhibition of Human Serine Protease tissue type Plasminogen Activator (t-PA).	ki	0.0190	uM
(19S)-19-benzyl-8,24-dichloro-12-oxa-1,4,17,20,22-pentazatricyclo[19.3.1.06,11]pentacosa-6(11),7,9,21,23-pentaene-3,25-dione	210577: Inhibitory activity against Tissue plasminogen activator	ki	0.0200	uM
[(1R,2S)-2-(3,4,5-trihydroxybenzoyl)oxycyclohexyl] 3,4,5-trihydroxybenzoate	1799783: Enzymatic Assay from Article 10.1074/jbc.M109.067967: “Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.”	ic50	0.0280	uM
(2R)-N-[2-[[(2S)-1-(1,3-benzoxazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxoethyl]-5-(diaminomethylideneamino)-2-(2-phenylethylsulfonylamino)pentanamide	321207: Inhibition of tPA	ic50	0.0290	uM
(2S)-N-[(2S)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(2R)-2-(methylamino)-3-phenylpropanoyl]pyrrolidine-2-carboxamide	210922: Concentration required to inhibit Tissue-type plasminogen activator (t-PA) was determined	ic50	0.0340	uM
(2E,7E)-2,7-bis[[4-(diaminomethyl)phenyl]methylidene]cycloheptan-1-one	210925: Inhibitory activity against human tissue-type plasminogen activator expressed as dissociation constant	ki	0.0350	uM
2-(2-hydroxy-3-phenoxyphenyl)-1H-indole-5-carboximidamide	210928: Inhibition of tissue-type plasminogen activator	ki	0.0350	uM
2-(2-hydroxy-3-phenylphenyl)-1H-indole-5-carboximidamide	1797164: Enzyme Assay and Determination of the Inhibition Constants from Article 10.1016/S1074-5521(01)00084-9: “Engineering inhibitors highly selective for the S1 sites of Ser190 trypsin-like serine protease drug targets.”	ki	0.0350	uM
2-[(2R)-2-[3-[(3S)-3-amino-2,3-dihydro-1-benzofuran-5-yl]-5-propan-2-ylphenyl]-3,4-dihydro-2H-1,4-benzoxazin-8-yl]acetic acid	1660735: Inhibition of human tPa using fluorescent peptide as substrate by florescence assay	ic50	0.0500	uM
ethyl 2-[2-[2-[[2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-yl]amino]ethyl]piperidin-1-yl]acetate	254331: Inhibitory constant against tissue plasminogen activator	ki	0.0670	uM
2-[[(2R)-1-[(2S)-2-[(5-carbamimidoylthiophen-2-yl)methylcarbamoyl]-2,5-dihydropyrrol-1-yl]-3-cyclohexyl-1-oxopropan-2-yl]amino]acetic acid	264687: Inhibition of tPA	ic50	0.0700	uM
[2-(3,4,5-trihydroxybenzoyl)oxyphenyl] 3,4,5-trihydroxybenzoate	1799783: Enzymatic Assay from Article 10.1074/jbc.M109.067967: “Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.”	ic50	0.0860	uM
2-[2-[[3-[(3S)-3-amino-2,3-dihydro-1-benzofuran-5-yl]-5-propan-2-ylphenyl]methoxy]phenyl]acetic acid	1660735: Inhibition of human tPa using fluorescent peptide as substrate by florescence assay	ic50	0.0900	uM
2-[2-[3-[(3S)-3-amino-2,3-dihydro-1-benzofuran-5-yl]-5-propan-2-ylphenyl]ethoxy]benzoic acid	1660735: Inhibition of human tPa using fluorescent peptide as substrate by florescence assay	ic50	0.0900	uM
(3S,6R)-6-amino-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-6-benzyl-2,3,5,7,8,8a-hexahydro-1H-indolizine-3-carboxamide	210915: Inhibitory concentration against Tissue type plasminogen activator	ic50	0.0930	uM
2-(5-bromo-2-hydroxy-3-phenylphenyl)-1H-indole-5-carboximidamide	228026: Inhibition of Human Serine Protease tissue type Plasminogen Activator	ki	0.0940	uM
2-[2-[2-[[2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-yl]amino]ethyl]piperidin-1-yl]ethanol	254331: Inhibitory constant against tissue plasminogen activator	ki	0.0960	uM
N-[2-(1-benzylpiperidin-2-yl)ethyl]-2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-amine	254331: Inhibitory constant against tissue plasminogen activator	ki	0.1000	uM
2-[2-[[5-[(3S)-3-amino-2,3-dihydro-1-benzofuran-5-yl]-3,3-dimethyl-2H-1-benzofuran-7-yl]methoxy]phenyl]acetic acid	1660735: Inhibition of human tPa using fluorescent peptide as substrate by florescence assay	ic50	0.1000	uM
(2S)-1-[(2R)-2-amino-3-phenylpropanoyl]-N-[(2S)-1-chloro-5-(diaminomethylideneamino)pentan-2-yl]pyrrolidine-2-carboxamide	210920: Compound was evaluated for the inhibition of Tissue type plasminogen activator (tissue plasminogen activator)	ki	0.1060	uM
2-[2-[2-[[2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-yl]amino]ethyl]piperidin-1-yl]acetic acid	254331: Inhibitory constant against tissue plasminogen activator	ki	0.1100	uM
6-chloro-2-(2-hydroxy-3-phenylphenyl)-1H-indole-5-carboximidamide	225425: The compound was tested for inhibition of human plasmin	ki	0.1100	uM
2-(2-hydroxy-5-methyl-3-phenylphenyl)-1H-indole-5-carboximidamide	228026: Inhibition of Human Serine Protease tissue type Plasminogen Activator	ki	0.1100	uM
2-[[(2S)-1-[(2S)-2-[(5-carbamimidoylthiophen-2-yl)methylcarbamoyl]pyrrolidin-1-yl]-1-oxo-3,3-diphenylpropan-2-yl]amino]acetic acid	766526: Inhibition of human t-PA	ki	0.1130	uM
2-[[4-[(6Z)-6-(iodomethylidene)-2-oxooxan-3-yl]phenyl]methyl]guanidine	210723: Compound was tested for its binding affinity against the enzyme Tissue plasminogen activator	ki	0.1200	uM
2-[[(2R)-1-[(2S)-2-[(4-carbamimidoylfuran-2-yl)methylcarbamoyl]-2,5-dihydropyrrol-1-yl]-3-cyclohexyl-1-oxopropan-2-yl]amino]acetic acid	264687: Inhibition of tPA	ic50	0.1250	uM
6-carbamimidoyl-4-(oxolan-3-yl)-N-(3-propan-2-yloxyphenyl)naphthalene-2-carboxamide	210919: Binding affinity towards tissue type plasminogen activator	ki	0.1300	uM
2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-N-(2-piperidin-2-ylethyl)-[1,3]oxazolo[4,5-c]pyridin-4-amine	254331: Inhibitory constant against tissue plasminogen activator	ki	0.1400	uM
(20S)-20-benzyl-8,25-dichloro-12,15-dioxa-1,4,18,21,23-pentazatricyclo[20.3.1.06,11]hexacosa-6(11),7,9,22,24-pentaene-3,26-dione	210577: Inhibitory activity against Tissue plasminogen activator	ki	0.1500	uM
N-[5-(diaminomethylideneamino)-1-oxo-1-(1,3-thiazol-2-yl)pentan-2-yl]-2-(2-oxo-4-quinolin-8-ylsulfonylpiperazin-1-yl)acetamide	210758: Inhibitory activity against tissue plasminogen activator (tissue plasminogen activator)	ic50	0.1500	uM
2-(5-chloro-2-hydroxy-3-phenylphenyl)-1H-indole-5-carboximidamide	228026: Inhibition of Human Serine Protease tissue type Plasminogen Activator	ki	0.1600	uM
2-(2-hydroxy-3-phenylphenyl)-3H-benzimidazole-5-carboximidamide	1797164: Enzyme Assay and Determination of the Inhibition Constants from Article 10.1016/S1074-5521(01)00084-9: “Engineering inhibitors highly selective for the S1 sites of Ser190 trypsin-like serine protease drug targets.”	ki	0.1600	uM
2-[[(2R)-1-[(2S)-2-[(4-carbamimidoyl-1,3-thiazol-2-yl)methylcarbamoyl]-2,5-dihydropyrrol-1-yl]-3-cyclohexyl-1-oxopropan-2-yl]amino]acetic acid	264687: Inhibition of tPA	ic50	0.1730	uM
[(1R,2R)-2-(3,4,5-trihydroxybenzoyl)oxycyclohexyl] 3,4,5-trihydroxybenzoate	1799783: Enzymatic Assay from Article 10.1074/jbc.M109.067967: “Characterization of a novel class of polyphenolic inhibitors of plasminogen activator inhibitor-1.”	ic50	0.1740	uM
6-carbamimidoyl-4-(furan-3-yl)-N-phenylnaphthalene-2-carboxamide	238775: Binding affinity value against Tissue plasminogen activator	ki	0.1760	uM
2-[2-[[5-[(4R)-4-amino-3,4-dihydro-2H-chromen-6-yl]-3,3-dimethyl-2H-1-benzofuran-7-yl]methoxy]phenyl]acetic acid	1660735: Inhibition of human tPa using fluorescent peptide as substrate by florescence assay	ic50	0.1900	uM
N-(4-carbamimidoylphenyl)-2-hydroxy-3-iodo-5-methylbenzamide	1797164: Enzyme Assay and Determination of the Inhibition Constants from Article 10.1016/S1074-5521(01)00084-9: “Engineering inhibitors highly selective for the S1 sites of Ser190 trypsin-like serine protease drug targets.”	ki	0.1900	uM
2-(2-hydroxy-3-phenylphenyl)-6-methyl-1H-indole-5-carboximidamide	225425: The compound was tested for inhibition of human plasmin	ki	0.2100	uM
2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-N-(2,2-difluoro-2-piperidin-2-ylethyl)-[1,3]oxazolo[4,5-c]pyridin-4-amine	254331: Inhibitory constant against tissue plasminogen activator	ki	0.2400	uM
1-[(2S)-2-[3-[(3S)-3-amino-2,3-dihydro-1-benzofuran-5-yl]-5-propan-2-ylphenyl]-2-hydroxyethyl]indole-7-carboxylic acid	1660735: Inhibition of human tPa using fluorescent peptide as substrate by florescence assay	ic50	0.2500	uM
2-(5-chloro-2-hydroxy-3-phenylphenyl)-3H-benzimidazole-5-carboximidamide	228026: Inhibition of Human Serine Protease tissue type Plasminogen Activator	ki	0.2800	uM
(2R)-2-(benzylsulfonylamino)-N-[(2S)-1-[[2-[4-(diaminomethylideneamino)phenyl]-1-diphenoxyphosphorylethyl]amino]-1-oxopropan-2-yl]-3-hydroxypropanamide	270829: Inhibition of recombinant tPA	ic50	0.2800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases reaction, increases secretion, affects expression, affects cotreatment, increases expression (+1 more)	10
Tretinoin	decreases expression, increases expression	8
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	6
Valproic Acid	increases expression, affects cotreatment	5
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression, affects expression	4
bisphenol A	affects cotreatment, decreases methylation, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
(+)-JQ1 compound	decreases reaction, increases expression, decreases expression	3
Air Pollutants	increases abundance, increases expression, decreases expression	3
Dexamethasone	affects cotreatment, decreases activity, decreases expression	3
Ethinyl Estradiol	affects cotreatment, decreases expression, increases activity	3
Nicotine	increases expression, affects expression, affects cotreatment	3
Quercetin	decreases expression, affects binding, decreases reaction, increases reaction, increases expression (+1 more)	3
Levonorgestrel	affects cotreatment, decreases expression, increases activity	3
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid	affects expression, decreases expression, decreases reaction, affects cotreatment	2
arsenite	decreases expression, decreases reaction, decreases activity, decreases secretion, affects reaction	2
geranylgeraniol	decreases reaction, increases expression	2
nickel sulfate	increases expression	2
notoginsenoside R1	increases expression, affects binding	2
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	affects cotreatment, decreases reaction, increases expression, increases degradation, increases reaction (+1 more)	2
Arsenic Trioxide	decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	increases expression	2
Blood Glucose	affects cotreatment, decreases reaction, increases expression, increases degradation, increases reaction	2
Cadmium	decreases activity, increases expression	2
Dactinomycin	increases expression, increases secretion, decreases reaction, affects cotreatment	2
Mevalonic Acid	decreases reaction, increases expression	2
Oxygen	increases degradation, increases reaction, affects cotreatment, decreases reaction, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2

ChEMBL screening assays

249 unique, capped per target: 243 binding, 5 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1008042	Binding	Inhibition of recombinant tissue plasminogen activator	Design, structure-activity relationships, X-ray crystal structure, and energetic contributions of a critical P1 pharmacophore: 3-chloroindole-7-yl-based factor Xa inhibitors. — *J Med Chem*
CHEMBL4621405	ADMET	Inhibition of human tPa using fluorescent peptide as substrate by florescence assay	Structure-Based Design and Preclinical Characterization of Selective and Orally Bioavailable Factor XIa Inhibitors: Demonstrating the Power of an Integrated S1 Protease Family Approach. — *J Med Chem*
CHEMBL6108564	Functional	Inhibition of recombinant human tissue plasminogen activator (rt-PA)-induced fibrinolysis in human fresh whole blood assessed as thrombus dissolution within 30 mins after reaching maximum amplitude (LY30) by thromboelastography analysis	Discovery of BT-114143, a Novel and Potent Phosphoric Acid-Containing Small-Molecule Plasminogen Activation Inhibitor for Hyperfibrinolysis. — *J Med Chem*

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_6339	CHO 1-15 500	Transformed cell line	Female
CVCL_V634	JH-2/TPA	Cancer cell line	Male
CVCL_V643	CHL-2	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00187408	Phase 4	COMPLETED	The D-KAF (Dalteparin in Knee-to-Ankle Fracture) Trial
NCT00196118	Phase 4	COMPLETED	Study of IVC Filter Retrieval With the Günther Tulip Vena Cava Filter
NCT00214929	Phase 4	UNKNOWN	Home Treatment of Pulmonary Embolism
NCT00233740	Phase 4	COMPLETED	Protection From Pulmonary Embolism With the Permanent OptEase™ Filter (PROOF)
NCT00264277	Phase 4	COMPLETED	D-dimer to Establish Duration of Anticoagulation After Venous Thromboembolism
NCT00351754	Phase 4	COMPLETED	Detection of Pulmonary Embolism With CECT
NCT00365950	Phase 4	COMPLETED	3 Months’ Versus 6 Months’ Anticoagulation in Patients With DVT and/or PE
NCT00377091	Phase 4	WITHDRAWN	Is Using Fondaparinux (Blood Thinner) to Treat Lung Clot Cheaper Than Traditional Therapy
NCT00381511	Phase 4	COMPLETED	Deferment of Imaging for Pulmonary Embolism
NCT00442234	Phase 4	COMPLETED	Post-marketing Study of Monteplase (Cleactor) in Patients With Acute Pulmonary Embolism
NCT00457158	Phase 4	COMPLETED	PREPIC 2 : Prevention of Recurrent Pulmonary Embolism by Vena Cava Interruption
NCT00511173	Phase 4	COMPLETED	Comparison of Warfarin Dosing Using Decision Model Versus Pharmacogenetic Algorithm
NCT00586287	Phase 4	COMPLETED	Study to Find Out the Appropriate Initial Dose of the Anticoagulant Drug Phenprocoumon
NCT00603317	Phase 4	COMPLETED	Pharmacodynamic Drug Interaction Between Warfarin and Amoxicillin-clavulanic Acid
NCT00711308	Phase 4	COMPLETED	Tinzaparin in the Treatment of the Acute Pulmonary Embolism
NCT00781378	Phase 4	COMPLETED	Low Dosage of rt-PA in the Treatment of Pulmonary Thromboembolism in China
NCT00796692	Phase 4	COMPLETED	Nadroparin for the Initial Treatment of Pulmonary Thromboembolism
NCT00799968	Phase 4	COMPLETED	12-h and 2-h Urokinase Regimes of Pulmonary Thromboembolism in China
NCT00968929	Phase 4	COMPLETED	Recombinant Streptokinase Versus Urokinase in Pulmonary Embolism in China (RESUPEC)
NCT01014156	Phase 4	COMPLETED	Epoprostenol in Pulmonary Embolism
NCT01104337	Phase 4	COMPLETED	Drug Interaction Between Paracetamol and Warfarin
NCT01134068	Phase 4	COMPLETED	Age-adjusted D-dimer Cut-off Levels to Rule Out Pulmonary Embolism
NCT01252420	Phase 4	UNKNOWN	Two Weeks of Low Molecular Weight Heparin for Distal Vein Thrombosis
NCT01531829	Phase 4	UNKNOWN	Low Dose Rt-PA for Acute Normotensive Pulmonary Embolism With RVD
NCT01610141	Phase 4	UNKNOWN	Applying Pharmacogenetics to Warfarin Dosing in Chinese Patients
NCT01638468	Phase 4	TERMINATED	Multicenter, Nonrandomized, Prospective Study of Pulmonary Embolism Removal With the AngioJet 6F Ultra System
NCT01729559	Phase 4	COMPLETED	Venous Thromboembolic Prophylaxis After Trauma: Three Times a Day Unfractionated Heparin Versus Twice a Day Enoxaparin
NCT01828697	Phase 4	COMPLETED	Comparison of Low and Intermediate Dose Low-molecular-weight Heparin to Prevent Recurrent Venous Thromboembolism in Pregnancy
NCT02029456	Phase 4	UNKNOWN	Low Dose Prolonged Infusion of Tissue Type Plasminogen Activator Therapy in Massive Pulmonary Embolism
NCT02132689	Phase 4	COMPLETED	Comparison of Thrombgolytic and Anticoagulation Therapy in Submassive Pulmonary Embolism
NCT02161965	Phase 4	COMPLETED	Vascular CalcIfiCation and sTiffness Induced by ORal antIcoAgulation
NCT02234375	Phase 4	WITHDRAWN	Use of Gadolinium in CT Pulmonary Angiography
NCT02474212	Phase 4	COMPLETED	: Pharmacokinetics of Enoxaparin After Coronary Artery Bypass Graft Surgery
NCT02476526	Phase 4	COMPLETED	Safety of Low Dose IV Contrast CT Scanning in Chronic Kidney Disease
NCT02483143	Phase 4	COMPLETED	NAC, NaHCO3 and NS Prophylaxis for CTPA in the ED on Suspicion of PE: A Randomized Controlled Trial
NCT02506985	Phase 4	TERMINATED	XENITH: Rivaroxaban for Pulmonary Embolism Managed With Catheter Directed Thrombolysis
NCT02531581	Phase 4	COMPLETED	Diuretic Vascular Filling in the Initial Management of Acute PE With Right Ventricular Dysfunction Normotensive
NCT02584660	Phase 4	COMPLETED	A Study of Rivaroxaban for Early Discharge of Low Risk Pulmonary Embolism From the Emergency Department
NCT02596555	Phase 4	TERMINATED	Low Molecular Weight Heparin for 72 Hours Followed by Dabigatran for Acute Intermediate-Risk Pulmonary Embolism.
NCT02644473	Phase 4	WITHDRAWN	Safety of Topical Tranexamic Acid in Total Joint Arthroplasty in High Risk Patients
NCT02810704	Phase 4	COMPLETED	Comparative Effectiveness of Pulmonary Embolism Prevention After Hip and Knee Replacement
NCT03006562	Phase 4	TERMINATED	PREvention of VENous ThromboEmbolism Following Radical Prostatectomy
NCT03129555	Phase 4	ACTIVE_NOT_RECRUITING	The Danish Non-vitamin K Antagonist Oral Anticoagulation Study in Patients With Venous Thromboembolism (DANNOAC-VTE)
NCT03581877	Phase 4	ACTIVE_NOT_RECRUITING	Peripheral Systemic Thrombolysis Versus Catheter Directed Thrombolysis for Submassive PE
NCT03862755	Phase 4	COMPLETED	Chemoprophylaxis Plus Early Ambulation
NCT03937583	Phase 4	UNKNOWN	Screening for Cancer in Patients With Unprovoked VTE
NCT03988231	Phase 4	WITHDRAWN	Enoxaparin Versus Placebo for Venous Thromboembolism Prevention in Low Risk Cancer Patients After Surgical Procedures: a Randomized, Double Blind, Placebo Controlled Clinical Trial Pilot Study
NCT03988842	Phase 4	TERMINATED	Standard-dose Apixaban AFtEr Very Low-dose ThromboLYSis for Acute Intermediate-high Risk Acute Pulmonary Embolism
NCT04168203	Phase 4	COMPLETED	Extended-Duration Low-Intensity Apixaban to Prevent Recurrence in High-Risk Patients With Provoked Venous Thromboembolism
NCT04263038	Phase 4	RECRUITING	Clinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism
NCT04373707	Phase 4	COMPLETED	Weight-Adjusted vs Fixed Low Doses of Low Molecular Weight Heparin For Venous Thromboembolism Prevention in COVID-19
NCT04558125	Phase 4	TERMINATED	Low-Dose Tenecteplase in Covid-19 Diagnosed With Pulmonary Embolism
NCT04731558	Phase 4	RECRUITING	Pre- Vs Postoperative Thromboprophylaxis for Liver Resection
NCT04790370	Phase 4	ACTIVE_NOT_RECRUITING	Ultrasound-facilitated, Catheter-directed, Thrombolysis in Intermediate-high Risk Pulmonary Embolism
NCT05493163	Phase 4	COMPLETED	Catheter-directed Thrombolysis in Intermediate-high Risk Acute Pulmonary Embolism
NCT06581965	Phase 4	RECRUITING	inDividual, Targeted thrombosIS Prophylaxis Versus the Standard ‘One Size Fits All’ Approach in Patients Undergoing Total hIp or Total kNee replaCemenT
NCT07250763	Phase 4	ACTIVE_NOT_RECRUITING	Therapeutic Initial Heparin Dosing for Patients With Clots or Certain Heart Conditions Admitted to the Hospital
NCT07617376	Phase 4	RECRUITING	Pre-discharge Influenza Vaccination in Patients Hospitalized for Acute Cardiac Conditions
NCT07713875	Phase 4	NOT_YET_RECRUITING	Extended Prophylactic Anticoagulation Following Spinal Surgery for Metastatic Disease
NCT07816978	Phase 4	NOT_YET_RECRUITING	Reduced-Dose Versus Full-Dose Alteplase for High-Risk Pulmonary Embolism

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PLAT across ~30M SureChEMBL compounds — explore on Sugi Predict.