THBS1

Summary

THBS1 (thrombospondin 1, HGNC:11785) is a protein-coding gene on chromosome 15q14, encoding Thrombospondin-1 (P07996). Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions.

The protein encoded by this gene is a subunit of a disulfide-linked homotrimeric protein. This protein is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein can bind to fibrinogen, fibronectin, laminin, type V collagen and integrins alpha-V/beta-1. This protein has been shown to play roles in platelet aggregation, angiogenesis, and tumorigenesis.

Source: NCBI Gene 7057 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital glaucoma (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 147 total
• Druggable target: yes
• MANE Select transcript: NM_003246

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11785
Approved symbol	THBS1
Name	thrombospondin 1
Location	15q14
Locus type	gene with protein product
Status	Approved
Aliases	TSP1, THBS, TSP, THBS-1, TSP-1
Ensembl gene	ENSG00000137801
Ensembl biotype	protein_coding
OMIM	188060
Entrez	7057

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 retained_intron, 5 protein_coding

ENST00000260356, ENST00000397591, ENST00000466755, ENST00000484734, ENST00000490247, ENST00000497720, ENST00000559746, ENST00000560894, ENST00000880750, ENST00000880751, ENST00000880752

RefSeq mRNA: 1 — MANE Select: NM_003246 NM_003246

CCDS: CCDS32194

Canonical transcript exons

ENST00000260356 — 22 exons

Exon	Start	End
ENSE00000883769	39589805	39590023
ENSE00000883770	39590516	39590623
ENSE00000883771	39591191	39591350
ENSE00000883772	39591505	39591623
ENSE00000883773	39592568	39592802
ENSE00000883774	39593000	39593227
ENSE00000883775	39593397	39593668
ENSE00000883776	39594099	39594196
ENSE00000930951	39595362	39599466
ENSE00000995828	39581079	39581228
ENSE00001674053	39585470	39585563
ENSE00001706898	39584300	39584422
ENSE00001710663	39588959	39589086
ENSE00001725099	39583988	39584187
ENSE00001738791	39587347	39587520
ENSE00001758707	39583617	39583692
ENSE00001783863	39588526	39588699
ENSE00001792284	39582193	39582752
ENSE00002289128	39581829	39581924
ENSE00003471372	39589202	39589354
ENSE00003484406	39594301	39594440
ENSE00003558157	39588042	39588218

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 99.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 854.5905 / max 33702.3050, expressed in 1623 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
145912	835.3182	1620
145947	6.4356	838
145941	4.3342	809
145942	4.2029	770
145978	2.1007	609
145948	0.8321	388
145911	0.4825	248
145981	0.3841	231
145949	0.3656	207
145950	0.1347	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.80	gold quality
mucosa of stomach	UBERON:0001199	99.64	gold quality
pericardium	UBERON:0002407	99.50	gold quality
gall bladder	UBERON:0002110	99.46	gold quality
left uterine tube	UBERON:0001303	99.33	gold quality
calcaneal tendon	UBERON:0003701	99.27	gold quality
right lung	UBERON:0002167	99.11	gold quality
smooth muscle tissue	UBERON:0001135	99.07	gold quality
vena cava	UBERON:0004087	99.03	gold quality
upper lobe of left lung	UBERON:0008952	99.03	gold quality
upper lobe of lung	UBERON:0008948	98.94	gold quality
nerve	UBERON:0001021	98.90	gold quality
tibial nerve	UBERON:0001323	98.90	gold quality
colonic epithelium	UBERON:0000397	98.86	gold quality
lower lobe of lung	UBERON:0008949	98.85	gold quality
saphenous vein	UBERON:0007318	98.84	gold quality
omental fat pad	UBERON:0010414	98.54	gold quality
peritoneum	UBERON:0002358	98.53	gold quality
sural nerve	UBERON:0015488	98.33	gold quality
rectum	UBERON:0001052	98.27	gold quality
vermiform appendix	UBERON:0001154	98.19	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.09	gold quality
tibia	UBERON:0000979	97.88	gold quality
body of uterus	UBERON:0009853	97.55	gold quality
minor salivary gland	UBERON:0001830	97.38	gold quality
right coronary artery	UBERON:0001625	97.31	gold quality
left coronary artery	UBERON:0001626	97.23	gold quality
cartilage tissue	UBERON:0002418	97.21	gold quality
caecum	UBERON:0001153	97.16	gold quality
myometrium	UBERON:0001296	97.04	gold quality

Single-cell (SCXA)

Detected in 26 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	11896.93
E-HCAD-15	yes	4968.66
E-GEOD-83139	yes	3286.09
E-GEOD-81383	yes	3255.64
E-MTAB-8221	yes	2819.11
E-MTAB-9067	yes	2448.42
E-GEOD-81608	yes	2318.91
E-GEOD-149689	yes	2049.82
E-CURD-6	yes	1107.53
E-MTAB-10137	yes	727.00
E-HCAD-1	yes	67.44
E-MTAB-10287	yes	59.30
E-MTAB-9543	yes	17.18
E-HCAD-10	yes	15.73
E-CURD-88	yes	13.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, ATF1, BMP4, CEBPZ, CREB1, CUX1, DMTF1, E2F1, EAF2, EGR1, ETS1, ETS2, F2R, F2RL1, FLCN, FOSL1, FOXC1, HIF1A, ID1, ID3, IL18, JUN, KLF2, MAX, MYC, NFKB, NR1I2, NR4A2, PAX5, PGR, RUNX2, RUNX3, SMAD2, SMAD4, SNAI1, SP1, TBP, TP53, USF1

miRNA regulators (miRDB)

188 targeting THBS1, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7B-5P	99.98	72.31	1790
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-LET-7D-5P	99.96	71.76	1632

Literature-anchored findings (GeneRIF, showing 40)

• Increased expression is associated with breast tumor metastasis (PMID:11801541)
• Immobilized TSP-1, as well as its 70-kDa proteolytic fragment containing the type 1 repeats, enhances IL-6 release from monocytic U937 cells stimulated with phorbol myristate acetate and LPS, whereas it inhibits IL-10 release. (PMID:11820799)
• Stromally derived TSP-1 upregulates the production of MMP-9 and regulates matrix remodeling of tumor invasion in pancreatic adenocarcinoma (PMID:11882904)
• T lymphocytes express thrombospondin-1 (TSP-1). Endogenous TSP-1 is part of an adhesion-dependent mechanism controlling cytoplasmic spreading and migration in T lymphocytes. (PMID:11920574)
• Thrombin activation leads to the rapid and specific association of a large amount of secreted alpha-granular TSP-1 with the actin cytoskeleton. (PMID:11964147)
• Interactions of thrombospondins with alpha4beta1 integrin and CD47 differentially modulate T cell behavior (PMID:11980922)
• level spontaneously secreted by patient CLL B-cells quantified; consistently secreted in all patient samples. (PMID:11986954)
• mediates adhesion of osteosarcoma to the core region of thrombospondin 1 (alpha 4 beta 1 integrin) (PMID:12054567)
• structural characterization (PMID:12147243)
• Anti-adhesive activity mediated by the N-terminal domain of cell surface calreticulin (PMID:12147682)
• Interaction of the TSP1 module of complement component C8 beta subunit with the membrane attack/perforin domain determines the binding specificity of C8 beta toward C8 alpha. (PMID:12220191)
• All adrenal tissues (control adrenals, nonfunctional adenomas and ACTH-dependent aldosterone-producing adenomas) expressed both TSP1 and TSP2 mRNAs. Correlated closely with the expression of ACTH receptor. (PMID:12358136)
• a novel, antiparallel, three-stranded fold that consists of alternating stacked layers of tryptophan and arginine, capped by disulfide bonds; the front face contains a right-handed spiral, positively charged groove that might be the “recognition” face. (PMID:12391027)
• thrombospondin-1 plays a role in the up-regulation of MMP-9 expression in gastric cancer. (PMID:12443715)
• The anti-angiogenic type 1 repeat domains of TSP1 have been biophysically characterized and the disulfide bond connectivity of the peptides determined. (PMID:12450399)
• Thrombospondin-1 is differently expressed in subcutaneous and visceral fat of obese subjects. The difference in expression between the depots was greater in women than in men. (PMID:12530526)
• TSP1 is expressed in tumor stroma in colorectal cancer, inhibits tumor angiogenesis and suppresses tumor growth by activating TGF beta-1. (PMID:12553016)
• Macrophage recognition and phagocytosis of apoptotic fibroblasts is critically dependent on this protein. (PMID:12598312)
• Mutation of p53 gene endows gliomas with an angiogenic phenotype by reducing thrombospondin-1 production as well as enhancing the angiogenesis inducers in the early phase of malignant progression. (PMID:12609716)
• the migration of retinal pigment cells in epiretinal membranes is modulated by TSP1 and SPARC and thus that these two proteins ultimately may represent therapeutic targets in the management of the membranes. (PMID:12658547)
• TSP1 is the critical regulator of angiogenesis driven by ras proteins in a genetically defined tumor model. (PMID:12676576)
• TSP-1-induced inhibition of megakaryocytopoiesis is probably mediated in part by the binding of TSP-1 to CD36 expressed on the megakaryocytic progenitors (PMID:12679131)
• interactions among the three structural motifs of the C-terminal region of this protein (PMID:12718556)
• Our results suggest that transcriptional inactivation of TSP1 by aberrant DNA methylation of the promoter region may participate partly in stomach carcinogenesis through TSP1 down-regulation. (PMID:12759541)
• thrombospondin-1 (4N1-1) stimulates platelet aggregation by a novel mechanism involving both an activation-independent agglutination and an activation-dependent, glycoprotein (GP) IIb/IIIa-mediated aggregation which involves GPVI signaling (PMID:12782324)
• Thrombospondin-1 mediates platelet adhesion at high shear via glycoprotein Ib. (PMID:12824298)
• Interaction of thrombospondin-1 with its ligand CD47 contributes to the perpetuation of inflammation in rheumatoid synovitis. (PMID:12902472)
• thrombospondin-1 and thrombospondin-2 have N-terminal regions for binding to alpha6beta1 integrin (PMID:12909644)
• TSP1 expression is significantly higher in malignant epithelial sources over normal and benign epithelial sources, but no difference in expression levels is evident between primary tumors with or without metastases. (PMID:12927044)
• TSP-1 acts as a scavenger for matrix-associated angiogenic factors, affecting their location, bioavailability, and function. (PMID:12947001)
• thrombospondin-1 has a role in motility and proteolytic activity of oral squamous cell carcinoma cells (PMID:12964017)
• Hepatocyte growth factor mediates angiogenesis in cultured cancer cells by regulating the expression of VEGF and this protein. (PMID:14555767)
• Expression of TSP-1 along with other genes suppresses neuronblastoma tumor growth. (PMID:14559817)
• DC-derived TSP serves as a previously unappreciated negative regulator contributing to arrest of cytokine production, further supporting its fundamental role in vivo in the active resolution of inflammation and maintenance of steady state. (PMID:14568985)
• ANG II-induced activation of latent TGF-beta1 in human mesangial cells operates via TSP-1. (PMID:14583433)
• TSP-1 might mediate AGE-induced distal renal tubule hypertrophy. There are several putative transcription factor binding sites in the TSP-1 promoter, including those for AP-1, CREB, NF-kappaB, SRF, and HSF. (PMID:14683523)
• results indicate that TSP-1 binding to low density lipoprotein-related protein does not require prior or concomitant interaction with cell surface heparan sulfate proteoglycans but suggest subsequent endocytosis requires high-affinity heparin-binding (PMID:14991768)
• functional and structural differences between the Ser-700 and Asn-700 thrombospondin-1 variants (PMID:15007078)
• crystal structure of a cell-binding TSP-1 fragment, spanning three T3 repeats and the C-terminal globular domain, reveals a compact assembly (PMID:15014436)
• Review: thrombospondin-1 described as a modulator of angiogenesis through its role in regulating endothelial cell apoptosis, protease expression, and vascular endothelial growth factor expression (PMID:15034804)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	thbs1b	ENSDARG00000010785
		ENSDARG00000103775
mus_musculus	Thbs1	ENSMUSG00000040152
rattus_norvegicus	Thbs1	ENSRNOG00000045829
drosophila_melanogaster	Tsp	FBGN0031850

Paralogs (5): ISM1 (ENSG00000101230), COMP (ENSG00000105664), THBS4 (ENSG00000113296), THBS3 (ENSG00000169231), THBS2 (ENSG00000186340)

Protein

Protein identifiers

Thrombospondin-1 — P07996 (reviewed: P07996)

Alternative names: Glycoprotein G

All UniProt accessions (2): A8MZG1, P07996

UniProt curated annotations — full annotation on UniProt →

Function. Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Multifunctional, involved in inflammation, angiogenesis, wound healing, reactive oxygen species (ROS) signaling, nitrous oxide (NO) signaling, apoptosis, senescence, aging, cellular self-renewal, stemness, and cardiovascular and metabolic homeostasis. Negatively modulates dendritic cell activation and cytokine release, as part of an autocrine feedback loop, contributing to the resolution of inflammation and immune homeostasis. Ligand for receptor CD47. Modulates nitrous oxide (NO) signaling via CD47, hence playing a role as a pressor agent, supporting blood pressure. Plays a role in endothelial cell senescence, acting via CD47, by increasing the abundance and activation of NADPH oxidase NOX1, and so generating excess ROS. Inhibits stem cell self-renewal, acting via CD47 signaling, probably by regulation of the stem cell transcription factors POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4. Negatively modulates wound healing, acting via CD47. Ligand for receptor CD36. Involved in inducing apoptosis in podocytes in response to elevated free fatty acids, acting via CD36. Plays a role in suppressing angiogenesis, acting, depending on context, via CD36 or CD47. Promotes cellular senescence in a TP53-CDKN1A-RB1 signaling-dependent manner. Ligand for immunoglobulin-like cell surface receptor SIRPA. Involved in ROS signaling in non-phagocytic cells, stimulating NADPH oxidase-derived ROS production, acting via interaction with SIRPA. Plays a role in metabolic dysfunction in diet-induced obesity, perhaps acting by exacerbating adipose inflammatory activity; its effects may be mediated, at least in part, through enhanced adipocyte proliferation. Plays a role in ER stress response, via its interaction with the activating transcription factor 6 alpha (ATF6) which produces adaptive ER stress response factors. May be involved in age-related conditions, including metabolic dysregulation, during normal aging.

Subunit / interactions. Homotrimer; disulfide-linked. Can bind to fibrinogen, fibronectin, laminin, type V collagen and integrins alpha-V/beta-1, alpha-V/beta-3 and alpha-IIb/beta-3. Binds heparin. Interacts (via the C-terminal domain) with CD47. Interacts (via the TSP type I repeats) with CD36; the interaction conveys an antiangiogenic effect. Interacts (via the TSP type I repeats) with HRG; the interaction blocks the antiangiogenic effect of THBS1 with CD36. Interacts with ATF6 (via lumenal domain). Interacts with FN1; this interaction is enhanced by TNFAIP6, which may act as a bridging molecule between FN1 and THBS1. Interacts with SIRPA; the interaction stimulates phosphorylation of SIRPA.

Subcellular location. Secreted. Cell surface. Extracellular space. Extracellular matrix. Endoplasmic reticulum. Sarcoplasmic reticulum.

Tissue specificity. Expressed by platelets (at protein level). Expressed by monocyte-derived immature and mature dendritic cells (at protein level).

Induction. Expression is induced by PGE2, S.aureus and lipopolysaccharide. Induced in arteries and lung parenchyma following injury or stress. Expression in vasculature, including arteries, increases in normal aging.

Similarity. Belongs to the thrombospondin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P07996-1	1	yes
P07996-2	2

RefSeq proteins (1): NP_003237* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR000884	TSP1_rpt	Repeat
IPR001007	VWF_dom	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR003367	Thrombospondin_3-like_rpt	Repeat
IPR008859	Thrombospondin_C	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR017897	Thrombospondin_3_rpt	Repeat
IPR028974	TSP_type-3_rpt	Homologous_superfamily
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR048287	TSPN-like_N	Domain

Pfam: PF00090, PF00093, PF02412, PF05735

UniProt features (145 total): strand 41, disulfide bond 30, turn 12, glycosylation site 12, helix 11, repeat 8, domain 8, sequence conflict 7, region of interest 3, compositionally biased region 3, sequence variant 3, mutagenesis site 3, signal peptide 1, chain 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
2ERF	X-RAY DIFFRACTION	1.45
1Z78	X-RAY DIFFRACTION	1.8
2ES3	X-RAY DIFFRACTION	1.85
1LSL	X-RAY DIFFRACTION	1.9
1UX6	X-RAY DIFFRACTION	1.9
1ZA4	X-RAY DIFFRACTION	1.9
2OUJ	X-RAY DIFFRACTION	1.9
5FOE	X-RAY DIFFRACTION	1.98
2OUH	X-RAY DIFFRACTION	2.4
3R6B	X-RAY DIFFRACTION	2.4
7YYK	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07996-F1	84.73	0.55

Functional residue map

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

Disulfide bonds (30): 171–232, 270, 274, 391–423, 395–428, 406–413, 447–484, 451–489, 462–474, 504–541, 508–546, 519–531, 551–562, 556–572, 575–586, 592–608, 599–617, 620–644, 650–663, 657–676 …

Glycosylation sites (12): 248, 360, 385, 394, 438, 441, 450, 498, 507, 553, 708, 1067

Mutagenesis-validated functional residues (3):

Position	Phenotype
926	reduces attachment to cells and retention in extracellular matrix (ecm); retention in ecm partially dependent on beta-1
1019–1021	reduces attachment to cells and retention in extracellular matrix.
1067	loss of n-glycosylation site.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-186797	Signaling by PDGF
R-HSA-216083	Integrin cell surface interactions
R-HSA-3000170	Syndecan interactions
R-HSA-5083635	Defective B3GALTL causes PpS
R-HSA-5173214	O-glycosylation of TSR domain-containing proteins
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function

MSigDB gene sets: 798 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_REGULATION_OF_CELL_ACTIVATION, BROWNE_HCMV_INFECTION_4HR_UP, MODULE_52, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_OR_POLYSACCHARIDE_ANTIGEN_VIA_MHC_CLASS_II, GOBP_PROTEIN_ACTIVATION_CASCADE, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_BEHAVIOR, GOBP_POSITIVE_REGULATION_OF_MACROPHAGE_ACTIVATION, GU_PDEF_TARGETS_DN, GOBP_REGULATION_OF_WOUND_HEALING

GO Biological Process (74): response to hypoxia (GO:0001666), negative regulation of endothelial cell proliferation (GO:0001937), negative regulation of cell-matrix adhesion (GO:0001953), sprouting angiogenesis (GO:0002040), chronic inflammatory response (GO:0002544), negative regulation of antigen processing and presentation of peptide or polysaccharide antigen via MHC class II (GO:0002581), negative regulation of dendritic cell antigen processing and presentation (GO:0002605), apoptotic process (GO:0006915), inflammatory response (GO:0006954), immune response (GO:0006955), response to unfolded protein (GO:0006986), cell adhesion (GO:0007155), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), response to xenobiotic stimulus (GO:0009410), response to mechanical stimulus (GO:0009612), response to glucose (GO:0009749), positive regulation of endothelial cell migration (GO:0010595), negative regulation of endothelial cell migration (GO:0010596), negative regulation of long-chain fatty acid import across plasma membrane (GO:0010748), obsolete negative regulation of nitric oxide mediated signal transduction (GO:0010751), negative regulation of receptor guanylyl cyclase signaling pathway (GO:0010754), negative regulation of plasminogen activation (GO:0010757), positive regulation of macrophage chemotaxis (GO:0010759), positive regulation of fibroblast migration (GO:0010763), cell migration (GO:0016477), negative regulation of angiogenesis (GO:0016525), positive regulation of cell migration (GO:0030335), positive regulation of transforming growth factor beta receptor signaling pathway (GO:0030511), response to magnesium ion (GO:0032026), response to progesterone (GO:0032570), negative regulation of interleukin-10 production (GO:0032693), negative regulation of interleukin-12 production (GO:0032695), negative regulation of tumor necrosis factor production (GO:0032720), positive regulation of tumor necrosis factor production (GO:0032760), positive regulation of transforming growth factor beta1 production (GO:0032914), response to testosterone (GO:0033574), cellular response to heat (GO:0034605), response to endoplasmic reticulum stress (GO:0034976), nitric oxide-cGMP-mediated signaling (GO:0038060)

GO Molecular Function (18): phosphatidylserine binding (GO:0001786), fibronectin binding (GO:0001968), protease binding (GO:0002020), endopeptidase inhibitor activity (GO:0004866), integrin binding (GO:0005178), extracellular matrix structural constituent (GO:0005201), calcium ion binding (GO:0005509), heparin binding (GO:0008201), fibroblast growth factor binding (GO:0017134), low-density lipoprotein particle binding (GO:0030169), protein homodimerization activity (GO:0042803), laminin binding (GO:0043236), proteoglycan binding (GO:0043394), transforming growth factor beta binding (GO:0050431), fibrinogen binding (GO:0070051), collagen V binding (GO:0070052), protein binding (GO:0005515), extracellular matrix binding (GO:0050840)

GO Cellular Component (13): extracellular region (GO:0005576), fibrinogen complex (GO:0005577), obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), sarcoplasmic reticulum (GO:0016529), secretory granule (GO:0030141), extracellular matrix (GO:0031012), platelet alpha granule (GO:0031091), platelet alpha granule lumen (GO:0031093), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Signaling by Receptor Tyrosine Kinases	1
Extracellular matrix organization	1
Non-integrin membrane-ECM interactions	1
Diseases associated with O-glycosylation of proteins	1
O-linked glycosylation	1
Transcriptional regulation by RUNX1	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
negative regulation of antigen processing and presentation	2
cell population proliferation	2
regulation of cell population proliferation	2
regulation of endothelial cell migration	2
endothelial cell migration	2
protein-containing complex binding	2
growth factor binding	2
binding	2
cellular anatomical structure	2
endomembrane system	2
endoplasmic reticulum	2
response to stress	1
response to decreased oxygen levels	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
regulation of cell-matrix adhesion	1
cell-matrix adhesion	1
negative regulation of cell-substrate adhesion	1
angiogenesis	1
inflammatory response	1
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II	1
regulation of antigen processing and presentation of peptide or polysaccharide antigen via MHC class II	1
dendritic cell antigen processing and presentation	1
regulation of dendritic cell antigen processing and presentation	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
defense response	1
immune system process	1
response to stimulus	1
response to topologically incorrect protein	1
cellular process	1
positive regulation of cellular process	1
negative regulation of cellular process	1
response to chemical	1
response to external stimulus	1
response to abiotic stimulus	1
response to hexose	1

Protein interactions and networks

STRING

5504 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THBS1	CD47	Q08722	997
THBS1	FN1	P02751	996
THBS1	CD36	P16671	996
THBS1	SCARB2	Q14108	996
THBS1	SCARB1	Q8WTV0	994
THBS1	CALR	P27797	988
THBS1	TGFB1	P01137	973
THBS1	MMP9	P14780	964
THBS1	VLDLR	P98155	907
THBS1	SDC1	P18827	891
THBS1	LRP1	Q07954	889
THBS1	TGFB3	P10600	886
THBS1	TGFB2	P08112	886
THBS1	EFNB2	P52799	884
THBS1	KDR	P35968	869

IntAct

90 interactions, top by confidence:

A	B	Type	Score
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
	THBS1	psi-mi:“MI:0407”(direct interaction)	0.700
THBS1	FN1	psi-mi:“MI:0915”(physical association)	0.610
	THBS1	psi-mi:“MI:0407”(direct interaction)	0.610
THBS1	FN1	psi-mi:“MI:0407”(direct interaction)	0.610
PLEK	CAVIN2	psi-mi:“MI:0914”(association)	0.560
PCOLCE	THBS1	psi-mi:“MI:0407”(direct interaction)	0.560
THBS1	PCOLCE	psi-mi:“MI:0407”(direct interaction)	0.560
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
FCGRT	GOLIM4	psi-mi:“MI:0914”(association)	0.530
THBS2	AP1G2	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
TGFB1	THBS1	psi-mi:“MI:0407”(direct interaction)	0.520
	THBS1	psi-mi:“MI:0407”(direct interaction)	0.440
COL18A1	THBS1	psi-mi:“MI:0407”(direct interaction)	0.440
THBS1	TGM2	psi-mi:“MI:0407”(direct interaction)	0.440
THBS1	BGN	psi-mi:“MI:0407”(direct interaction)	0.440
APP	THBS1	psi-mi:“MI:0407”(direct interaction)	0.440
THBS1	Col11a1	psi-mi:“MI:0407”(direct interaction)	0.440
TGFB1	CILP	psi-mi:“MI:0914”(association)	0.430
TUBA1A	TUBAL3	psi-mi:“MI:2364”(proximity)	0.420
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
VEGFA	THBS1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (137): THBS1 (Affinity Capture-MS), THBS1 (Affinity Capture-MS), THBS1 (Affinity Capture-MS), THBS1 (Affinity Capture-MS), THBS1 (Affinity Capture-MS), THBS1 (Affinity Capture-MS), THBS1 (Affinity Capture-MS), THBS1 (Affinity Capture-MS), THBS1 (Proximity Label-MS), THBS1 (Proximity Label-MS), THBS1 (Affinity Capture-RNA), THBS1 (Affinity Capture-MS), THBS1 (Protein-RNA), THBS1 (Synthetic Lethality), THBS1 (Affinity Capture-MS)

ESM2 similar proteins: A0A096LNW5, A2RUV0, A8XMW6, B8JI71, G3I6Z6, O35516, O57409, O77469, P07207, P07996, P0DPK3, P10039, P10040, P10079, P21783, P24821, P34576, P35440, P35441, P35442, P35448, P46530, P46531, P49013, P78504, Q00174, Q01705, Q03350, Q04721, Q07008, Q21281, Q21313, Q28178, Q29116, Q5ZQU0, Q61982, Q63722, Q6DI48, Q70E20, Q7Z3S9

Diamond homologs: A1A5Y0, A2VCU8, A4IGL7, A5A8Y8, A6QR11, B5DFC9, O75095, O88322, P07996, P10493, P14585, P35441, P35448, P82279, P98118, Q14112, Q20911, Q24025, Q28178, Q2PC93, Q2VWQ2, Q3MHH9, Q5FW85, Q5R3Z7, Q61220, Q62918, Q62919, Q6AZ60, Q6GUQ1, Q6MG84, Q75N90, Q7T3Q2, Q7ZXL5, Q80T14, Q8AVH7, Q8AWW5, Q8VHS2, Q90827, Q90ZD5, Q91X17

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
F2RL1	“up-regulates quantity by expression”	THBS1	“transcriptional regulation”
F2R	“up-regulates quantity by expression”	THBS1	“transcriptional regulation”
TP53	“up-regulates quantity by expression”	THBS1	“transcriptional regulation”
THBS1	up-regulates	NGF	binding
DMTF1	“up-regulates quantity by expression”	THBS1	“transcriptional regulation”
THBS1	down-regulates	Angiogenesis

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 107 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Degradation of the extracellular matrix	6	9.9×	4e-03
Post-translational protein phosphorylation	7	9.9×	2e-03
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	8	9.8×	9e-04
Platelet degranulation	7	8.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	101
Likely benign	16
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

1866 predictions. Top by Δscore:

Variant	Effect	Δscore
15:39581227:AGGTA:A	donor_loss	1.0000
15:39581229:G:GG	donor_gain	1.0000
15:39581821:T:TA	acceptor_gain	1.0000
15:39581827:A:AG	acceptor_gain	1.0000
15:39581827:A:G	acceptor_loss	1.0000
15:39581828:G:GC	acceptor_loss	1.0000
15:39581828:G:GG	acceptor_gain	1.0000
15:39581923:AGGTG:A	donor_loss	1.0000
15:39581926:T:A	donor_loss	1.0000
15:39582183:T:TA	acceptor_gain	1.0000
15:39582188:A:AG	acceptor_gain	1.0000
15:39582191:A:AC	acceptor_loss	1.0000
15:39582191:A:AG	acceptor_gain	1.0000
15:39582192:G:A	acceptor_loss	1.0000
15:39582192:G:GA	acceptor_gain	1.0000
15:39582192:GA:G	acceptor_gain	1.0000
15:39582192:GAGT:G	acceptor_gain	1.0000
15:39582192:GAGTC:G	acceptor_gain	1.0000
15:39582749:CCAGG:C	donor_loss	1.0000
15:39582750:CAGGT:C	donor_loss	1.0000
15:39582752:GG:G	donor_loss	1.0000
15:39582754:T:A	donor_loss	1.0000
15:39583614:CAGG:C	acceptor_loss	1.0000
15:39583615:A:AG	acceptor_gain	1.0000
15:39583615:AG:A	acceptor_gain	1.0000
15:39583615:AGG:A	acceptor_gain	1.0000
15:39583615:AGGG:A	acceptor_gain	1.0000
15:39583615:AGGGG:A	acceptor_gain	1.0000
15:39583616:G:A	acceptor_loss	1.0000
15:39583616:G:GA	acceptor_gain	1.0000

AlphaMissense

7865 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:39584389:G:C	W331C	1.000
15:39584389:G:T	W331C	1.000
15:39587381:G:C	W385C	1.000
15:39587381:G:T	W385C	1.000
15:39587388:T:A	W388R	1.000
15:39587388:T:C	W388R	1.000
15:39587390:G:C	W388C	1.000
15:39587390:G:T	W388C	1.000
15:39587431:G:C	R402P	1.000
15:39589865:T:A	C663S	1.000
15:39589866:G:C	C663S	1.000
15:39589910:T:A	C678S	1.000
15:39589910:T:C	C678R	1.000
15:39589911:G:C	C678S	1.000
15:39589943:T:A	C689S	1.000
15:39589943:T:C	C689R	1.000
15:39589944:G:C	C689S	1.000
15:39590517:A:C	D716A	1.000
15:39590522:T:C	C718R	1.000
15:39590524:C:G	C718W	1.000
15:39591192:A:C	D752A	1.000
15:39591197:T:A	C754S	1.000
15:39591197:T:C	C754R	1.000
15:39591198:G:C	C754S	1.000
15:39591199:T:G	C754W	1.000
15:39591260:G:C	D775H	1.000
15:39591261:A:C	D775A	1.000
15:39591261:A:T	D775V	1.000
15:39591266:T:A	C777S	1.000
15:39591266:T:C	C777R	1.000

dbSNP variants (sampled 300 via entrez): RS1000003426 (15:39597935 G>A), RS1000333344 (15:39598366 G>A), RS1000576099 (15:39599600 A>G), RS1000729914 (15:39592580 T>G), RS1000801085 (15:39579452 G>T), RS1000842741 (15:39599254 C>A), RS1000864442 (15:39589287 G>A), RS1000941252 (15:39579768 G>C), RS1001044276 (15:39597285 T>G), RS1001335913 (15:39591095 G>A,T), RS1001437541 (15:39597561 A>G), RS1001599132 (15:39590469 C>A), RS1001703539 (15:39591435 T>C), RS1001725156 (15:39590901 C>G), RS1001794804 (15:39596817 T>C)

Disease associations

OMIM: gene MIM:188060 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital glaucoma	Strong	Autosomal dominant
nonsyndromic genetic hearing loss	Limited	Autosomal recessive

Mondo (5): hearing loss disorder (MONDO:0005365), primary ovarian failure (MONDO:0005387), autism spectrum disorder (MONDO:0005258), nonsyndromic genetic hearing loss (MONDO:0019497), congenital glaucoma (MONDO:0020366)

Orphanet (2): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST007005_7	Logical memory (immediate recall) in normal cognition	5.000000e-07
GCST008971_69	Urate levels	4.000000e-10
GCST011616_34	Cortical volume	1.000000e-27
GCST011616_37	Cortical volume	4.000000e-133
GCST90013405_95	Liver enzyme levels (alanine transaminase)	2.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0004531	urate measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D006871	Hydrophthalmos	C11.250.480; C11.525.381.407.480; C16.131.384.480; C16.614.438
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C580334	Nonsyndromic Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630810 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

14 measured of 15 human assays (15 total across all organisms); most potent 14 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(3R,6S,9S,12S,15S,18S,21S,24S,30S,33S,36S)-24-(4-aminobutyl)-21-(2-amino-2-oxoethyl)-36-benzyl-33-[(2S)-butan-2-yl]-12-[3-(diaminomethylideneamino)propyl]-30-(hydroxymethyl)-9,18-bis(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-6,15-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	KD	0.091 nM	US-11149066: Thrombospondin 1-binding peptide
2-[(5S,8S,11S,17S,20S,23S,26S,29S,32S,35S,38R)-17-(4-aminobutyl)-8-[(2S)-butan-2-yl]-26-butyl-29-(3-carbamimidamidopropyl)-38-carbamoyl-11-(hydroxymethyl)-23,32-bis(1H-indol-3-ylmethyl)-5-(naphthalen-2-ylmethyl)-3,6,9,12,15,18,21,24,27,30,33,36-dodecaoxo-35-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacont-20-yl]acetic acid	KD	0.091 nM	US-11149066: Thrombospondin 1-binding peptide
(3R,6S,9S,12S,15S,18S,21S,24S,30S,33S,36S)-12-(4-aminobutyl)-36-benzyl-33-[(2S)-butan-2-yl]-24-[3-(diaminomethylideneamino)propyl]-21-[(1R)-1-hydroxyethyl]-30-(hydroxymethyl)-9,18-bis(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-6,15-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	KD	0.096 nM	US-11149066: Thrombospondin 1-binding peptide
(3R,6S,9S,12S,15S,18S,21S,24S,30S,33S,36S)-12,24-bis(4-aminobutyl)-21-(2-amino-2-oxoethyl)-36-benzyl-33-[(2S)-butan-2-yl]-30-(hydroxymethyl)-9,18-bis(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-6,15-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	KD	0.12 nM	US-11149066: Thrombospondin 1-binding peptide
(3R,6S,9S,12S,15S,18S,21S,24S,30S,33S,36S)-12-(4-aminobutyl)-21-(2-amino-2-oxoethyl)-33-[(2S)-butan-2-yl]-24-(3-carbamimidamidopropyl)-30-(hydroxymethyl)-9,18-bis(1H-indol-3-ylmethyl)-36-(naphthalen-2-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-6,15-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	KD	0.12 nM	US-11149066: Thrombospondin 1-binding peptide
(3R,6S,9S,12S,15S,18S,21S,24S,30S,33S,36S)-21-(2-amino-2-oxoethyl)-33-[(2S)-butan-2-yl]-12,24-bis(3-carbamimidamidopropyl)-30-(hydroxymethyl)-9,18,36-tris(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-6,15-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	KD	0.14 nM	US-11149066: Thrombospondin 1-binding peptide
(3R,6S,9S,12S,15S,18S,21S,24S,30S,33S,36S)-21-(2-amino-2-oxoethyl)-36-benzyl-24,33-bis(3-carbamimidamidopropyl)-30-(hydroxymethyl)-9,18-bis(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-6,12,15-tri(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	KD	0.15 nM	US-11149066: Thrombospondin 1-binding peptide
2-[(3R,6S,9S,12S,15S,18S,21R,24S,30S,33S,36S)-12-(4-aminobutyl)-33-[(2S)-butan-2-yl]-15-butyl-24-(3-carbamimidamidopropyl)-3-carbamoyl-30-(hydroxymethyl)-9,18-bis(1H-indol-3-ylmethyl)-36-(naphthalen-2-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38,41-tridecaoxo-6-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40-tridecazacyclodotetracont-21-yl]acetic acid	KD	0.22 nM	US-11149066: Thrombospondin 1-binding peptide
(3R,6S,9S,12S,15S,18S,21S,24S,30S,33S,36S)-12-(4-aminobutyl)-21-(2-amino-2-oxoethyl)-33-[(2S)-butan-2-yl]-24-(3-carbamimidamidopropyl)-30-(hydroxymethyl)-9,18,36-tris(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-6,15-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	KD	0.23 nM	US-11149066: Thrombospondin 1-binding peptide
(3R,6S,9S,12S,15S,18S,21S,24S,30S,33S,36S)-12-(4-aminobutyl)-21-(2-amino-2-oxoethyl)-36-benzyl-33-[(2S)-butan-2-yl]-24-[3-(diaminomethylideneamino)propyl]-30-(hydroxymethyl)-9,18-bis(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-6,15-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	KD	0.25 nM	US-11149066: Thrombospondin 1-binding peptide
(3R,6S,9S,12S,15S,18S,21S,24S,30R,33S,36S)-21-(2-amino-2-oxoethyl)-36-benzyl-33-[(2S)-butan-2-yl]-12,24-bis(3-carbamimidamidopropyl)-30-(hydroxymethyl)-9,18-bis(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-6,15-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	KD	0.26 nM	US-11149066: Thrombospondin 1-binding peptide
(3R,6S,9S,12S,15S,18S,21S,24S,30S,33S,36S)-12-(4-aminobutyl)-21-(2-amino-2-oxoethyl)-36-benzyl-33-[(2S)-butan-2-yl]-24-[3-(diaminomethylideneamino)propyl]-30-[(1R)-1-hydroxyethyl]-9,18-bis(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-6,15-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	KD	0.38 nM	US-11149066: Thrombospondin 1-binding peptide
(3R,6S,9S,12S,15S,18S,21S,24S,30S,33S,36S)-12-(4-aminobutyl)-21-(2-amino-2-oxoethyl)-36-benzyl-24,33-bis(3-carbamimidamidopropyl)-30-(hydroxymethyl)-9,18-bis(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-6,15-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	KD	0.44 nM	US-11149066: Thrombospondin 1-binding peptide
(3R,6S,9S,12S,15S,18S,21S,24S,30S,33S,36S)-21-(2-amino-2-oxoethyl)-36-benzyl-33-[(2S)-butan-2-yl]-24-[3-(diaminomethylideneamino)propyl]-30-(hydroxymethyl)-9,18-bis(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-6,12,15-tri(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	KD	0.51 nM	US-11149066: Thrombospondin 1-binding peptide

ChEMBL bioactivities

14 potent at pChembl≥5 of 14 total, top 14 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.42	IC50	0.3802	nM	CHEMBL4649483
8.82	IC50	1.514	nM	CHEMBL4644535
8.77	IC50	1.698	nM	CHEMBL4642848
8.70	IC50	1.995	nM	CHEMBL4642780
8.65	IC50	2.239	nM	CHEMBL4633877
8.54	IC50	2.884	nM	CHEMBL4636492
8.48	IC50	3.311	nM	CHEMBL4648099
8.36	IC50	4.365	nM	CHEMBL4647669
8.28	IC50	5.248	nM	CHEMBL4644244
8.12	IC50	7.586	nM	CHEMBL4649293
8.02	IC50	9.55	nM	CHEMBL4644046
7.87	IC50	13.49	nM	CHEMBL4644197
7.85	IC50	14.13	nM	CHEMBL4645518
7.82	IC50	15.14	nM	CHEMBL4638959

PubChem BioAssay actives

14 with measured affinity, of 111 total; 14 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
(2S)-2-[[(2R)-2-acetamido-3-hydroxypropanoyl]amino]-6-amino-N-[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]hexanamide	1658301: Inhibition of TSP1 in human myeloma cells assessed reduction in TGFbeta activity incubated for 1 hr by ELISA	ic50	0.0004	uM
(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-N-[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]-6-(dimethylamino)hexanamide	1658301: Inhibition of TSP1 in human myeloma cells assessed reduction in TGFbeta activity incubated for 1 hr by ELISA	ic50	0.0015	uM
(2R)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-6-amino-N-[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]hexanamide	1658301: Inhibition of TSP1 in human myeloma cells assessed reduction in TGFbeta activity incubated for 1 hr by ELISA	ic50	0.0017	uM
(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-6-amino-N-[(2R)-1-amino-4-methyl-1-oxopentan-2-yl]hexanamide	1658301: Inhibition of TSP1 in human myeloma cells assessed reduction in TGFbeta activity incubated for 1 hr by ELISA	ic50	0.0020	uM
(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-6-amino-N-[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]-N-methylhexanamide	1658301: Inhibition of TSP1 in human myeloma cells assessed reduction in TGFbeta activity incubated for 1 hr by ELISA	ic50	0.0022	uM
(2R)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-6-amino-N-[(2S)-4-methyl-1-(methylamino)-1-oxopentan-2-yl]hexanamide	1658301: Inhibition of TSP1 in human myeloma cells assessed reduction in TGFbeta activity incubated for 1 hr by ELISA	ic50	0.0029	uM
(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-6-amino-N-[(2S)-1-(dimethylamino)-4-methyl-1-oxopentan-2-yl]hexanamide	1658301: Inhibition of TSP1 in human myeloma cells assessed reduction in TGFbeta activity incubated for 1 hr by ELISA	ic50	0.0033	uM
(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-N-[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]-6-(methylamino)hexanamide	1658301: Inhibition of TSP1 in human myeloma cells assessed reduction in TGFbeta activity incubated for 1 hr by ELISA	ic50	0.0044	uM
(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-6-amino-N-[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]hexanamide	1658301: Inhibition of TSP1 in human myeloma cells assessed reduction in TGFbeta activity incubated for 1 hr by ELISA	ic50	0.0052	uM
(2S)-2-acetamido-5-amino-N-(1-amino-2-methyl-1-oxopropan-2-yl)pentanamide	1658301: Inhibition of TSP1 in human myeloma cells assessed reduction in TGFbeta activity incubated for 1 hr by ELISA	ic50	0.0076	uM
(2S)-2-acetamido-N-[(2S)-6-amino-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]butanediamide	1658301: Inhibition of TSP1 in human myeloma cells assessed reduction in TGFbeta activity incubated for 1 hr by ELISA	ic50	0.0095	uM
(2S)-6-amino-N-[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]-2-[[(2S)-3-hydroxy-2-(propanoylamino)propanoyl]amino]hexanamide	1658301: Inhibition of TSP1 in human myeloma cells assessed reduction in TGFbeta activity incubated for 1 hr by ELISA	ic50	0.0135	uM
(2S)-2-[(2-acetamidoacetyl)amino]-6-amino-N-[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]hexanamide	1658301: Inhibition of TSP1 in human myeloma cells assessed reduction in TGFbeta activity incubated for 1 hr by ELISA	ic50	0.0141	uM
(2S)-6-acetamido-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-N-[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]hexanamide	1658301: Inhibition of TSP1 in human myeloma cells assessed reduction in TGFbeta activity incubated for 1 hr by ELISA	ic50	0.0151	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, increases reaction, affects cotreatment, decreases expression	8
Valproic Acid	increases expression, affects expression, decreases expression, affects cotreatment	8
bisphenol A	increases methylation, decreases reaction, affects expression, decreases expression, increases expression	7
methylmercuric chloride	increases expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression, decreases expression	4
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	4
(+)-JQ1 compound	decreases reaction, increases expression, decreases expression	4
Doxorubicin	decreases secretion, increases expression, decreases reaction, increases activity, increases cleavage (+2 more)	4
Progesterone	affects cotreatment, decreases expression, increases expression	4
Tobacco Smoke Pollution	affects expression, increases expression	4
Benzo(a)pyrene	decreases methylation, increases expression	3
Cisplatin	decreases expression, increases reaction, increases expression	3
Fluorouracil	affects reaction, increases expression, affects expression, affects binding, increases reaction (+2 more)	3
Indomethacin	increases expression, decreases expression	3
Methotrexate	increases expression, decreases expression	3
Nickel	increases expression	3
Quercetin	increases expression, decreases expression	3
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
Cadmium Chloride	increases expression	3
bisphenol F	decreases reaction, increases expression	2
sulindac sulfide	affects reaction, increases expression, increases reaction, increases activity, increases phosphorylation (+1 more)	2
mercuric bromide	increases expression, affects cotreatment	2
chloropicrin	affects expression, decreases expression	2
bisphenol S	increases expression, decreases reaction	2
Clopidogrel	increases expression	2
Fulvestrant	increases expression, decreases reaction	2
Acetaminophen	decreases expression, increases expression	2
Aspirin	decreases reaction, increases secretion, increases expression	2
Cadmium	affects expression, increases expression	2

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4618814	Binding	Inhibition of human TSP1 assessed residual TGFbeta activity at 1 pM preincubated for 10 mins followed by TGFbeta1 addition and measured after 20 mins by ELISA relative to control	Identification of Inhibitors of Thrombospondin 1 Activation of TGF-β. — ACS Med Chem Lett

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C0AQ	Abcam THP-1 THBS1 KO	Cancer cell line	Male
CVCL_C6TQ	FD-1-TSP-1-/-	Induced pluripotent stem cell	Male
CVCL_C7CD	Abcam PC-3 THBS1 KO	Cancer cell line	Male
CVCL_D8CF	Ubigene A-549 THBS1 KO	Cancer cell line	Male
CVCL_D8X3	Ubigene HCT 116 THBS1 KO	Cancer cell line	Male
CVCL_E0QY	Ubigene HeLa THBS1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT04947124	PHASE2	COMPLETED	A Study to Determine the Safety and Tolerability of 2 Concentrations of QLS-101
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT01460017	PHASE1	UNKNOWN	Comparison Between Deep Sclerectomy and Traditional Trabeculotomy & Trabeculectomy in Congenital Glaucoma
NCT02121171	PHASE1	UNKNOWN	Combined Trab+Trab Versus Combined Trab+Trab With Subconjunctival Implantation of Ologen for Primary Congenital Glaucoma
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations
NCT01020721	Not specified	UNKNOWN	The Genetic Characteristics in South Korean Patients With Primary Congenital Glaucoma
NCT01136460	Not specified	UNKNOWN	Genetic Testing in Primary Congenital Glaucoma Patients
NCT02945176	Not specified	COMPLETED	Safety and Performance Study of the ARGOS-IO System in Patients Undergoing Boston Keratoprosthesis Implantation
NCT03077789	Not specified	COMPLETED	Prospective Study of the Diagnostic and Therapeutic Management of Congenital Glaucoma in France
NCT03541551	Not specified	COMPLETED	Ologen® Collagen Matrix in Patients With Primary Congenital Glaucoma Undergoing Trabeculectomy
NCT04079725	Not specified	UNKNOWN	Iris Tissue in Primary Congenital Glaucoma