ITGB3

Summary

ITGB3 (integrin subunit beta 3, HGNC:6156) is a protein-coding gene on chromosome 17q21.32, encoding Integrin beta-3 (P05106). Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor.

The ITGB3 protein product is the integrin beta chain beta 3. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain. A given chain may combine with multiple partners resulting in different integrins. Integrin beta 3 is found along with the alpha IIb chain in platelets. Integrins are known to participate in cell adhesion as well as cell-surface mediated signalling.

Source: NCBI Gene 3690 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Glanzmann thrombasthenia (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 14
• Clinical variants (ClinVar): 847 total — 116 pathogenic, 60 likely-pathogenic
• Phenotypes (HPO): 46
• Druggable target: yes — 18 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000212

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6156
Approved symbol	ITGB3
Name	integrin subunit beta 3
Location	17q21.32
Locus type	gene with protein product
Status	Approved
Aliases	CD61, GPIIIa
Ensembl gene	ENSG00000259207
Ensembl biotype	protein_coding
OMIM	173470
Entrez	3690

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000559488, ENST00000571680, ENST00000573377, ENST00000696963

RefSeq mRNA: 1 — MANE Select: NM_000212 NM_000212

CCDS: CCDS11511

Canonical transcript exons

ENST00000559488 — 15 exons

Exon	Start	End
ENSE00002546868	47310139	47313743
ENSE00002552451	47253827	47253940
ENSE00003464756	47300478	47300578
ENSE00003484617	47290185	47290274
ENSE00003485071	47299308	47299530
ENSE00003492438	47287070	47287231
ENSE00003500572	47290954	47291088
ENSE00003528760	47284443	47284695
ENSE00003541409	47274419	47274504
ENSE00003588679	47289681	47289776
ENSE00003637493	47283354	47283549
ENSE00003648908	47292139	47292568
ENSE00003662168	47302721	47302840
ENSE00003670494	47286260	47286422
ENSE00003969064	47307471	47307637

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 97.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.6327 / max 344.3460, expressed in 931 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161345	4.2549	908
161344	0.3778	124

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.19	gold quality
mononuclear cell	CL:0000842	96.57	gold quality
leukocyte	CL:0000738	95.87	gold quality
thoracic aorta	UBERON:0001515	91.20	gold quality
ascending aorta	UBERON:0001496	91.19	gold quality
descending thoracic aorta	UBERON:0002345	91.00	gold quality
right lobe of thyroid gland	UBERON:0001119	90.59	gold quality
left lobe of thyroid gland	UBERON:0001120	90.34	gold quality
tendon of biceps brachii	UBERON:0008188	90.07	gold quality
thyroid gland	UBERON:0002046	89.94	gold quality
aorta	UBERON:0000947	89.90	gold quality
popliteal artery	UBERON:0002250	89.10	gold quality
tibial artery	UBERON:0007610	89.07	gold quality
right coronary artery	UBERON:0001625	89.00	gold quality
colonic epithelium	UBERON:0000397	88.76	gold quality
islet of Langerhans	UBERON:0000006	88.70	gold quality
stromal cell of endometrium	CL:0002255	88.45	gold quality
left coronary artery	UBERON:0001626	87.08	gold quality
coronary artery	UBERON:0001621	86.43	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.24	gold quality
buccal mucosa cell	CL:0002336	83.70	silver quality
lower esophagus muscularis layer	UBERON:0035833	83.53	gold quality
lower esophagus	UBERON:0013473	83.45	gold quality
smooth muscle tissue	UBERON:0001135	82.26	gold quality
left uterine tube	UBERON:0001303	82.18	gold quality
sigmoid colon	UBERON:0001159	82.11	gold quality
metanephros cortex	UBERON:0010533	81.45	gold quality
blood	UBERON:0000178	81.02	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	80.94	gold quality
tendon	UBERON:0000043	80.74	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-GEOD-150728	yes	8321.64
E-GEOD-75367	yes	1471.69
E-ENAD-20	yes	160.95
E-CURD-112	yes	38.12
E-HCAD-4	yes	33.27
E-CURD-122	yes	24.23
E-MTAB-9221	yes	21.20
E-CURD-119	yes	20.19
E-HCAD-10	yes	17.74
E-MTAB-9067	yes	14.73
E-HCAD-1	yes	6.90
E-ENAD-17	no	526.75
E-CURD-7	no	189.24
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ODAM	Activation

Upstream regulators (CollecTRI, top): ELF5, ETS1, FOSL1, FOXC2, FOXF1, HIF1A, HOXA10, HOXB4, HOXD3, JUND, NFATC1, SP1, SP3, THRB

miRNA regulators (miRDB)

115 targeting ITGB3, 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-8485	100.00	77.57	4731
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	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-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-3605-5P	99.96	67.12	932

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Distinct domains of alphaIIbbeta3 support different aspects of outside-in signal transduction and platelet activation induced by LSARLAF. (PMID:11583324)
• Both the high affinity thrombin receptor (GPIb-IX-V) and GPIIb/IIIa are implicated in expression of thrombin-induced platelet procoagulant activity. (PMID:11686325)
• A naturally occurring point mutation in the beta3 integrin MIDAS-like domain affects differently alphavbeta3 and alphaIIIbbeta3 receptor function. (PMID:11776310)
• Lateral clustering of platelet GP Ib-IX complexes leads to up-regulation of the adhesive function of integrin alpha IIbbeta 3 (PMID:11812775)
• Review. Alpha(v)beta3 integrins are involved in vascular repair processes. The challenge is to develop a therapeutic agent that will prove effective in reducing restenosis in humans following percutaneous coronary intervention (PCI). (PMID:11858476)
• GPIIb-IIIa complexes are not in an activated conformational state after dissociation of abciximab unless there is an additional source of activation. (PMID:11858493)
• beta3-Integrin expression was directly up-regulated by HOXA10 in the endometrium (PMID:11875117)
• location was observed on or near the cell surface suggesting it might participate in surface membrane transport of iron (PMID:11891802)
• A novel 196Leu to Pro substitution in the beta3 subunit of the alphaIIbbeta3 integrin in a patient with a variant form of Glanzmann thrombasthenia prevents GPIIbIIIa from binding fibrinogen when platelets are activated. (PMID:11897046)
• Unique ability of integrin alpha(v)beta 3 to support tumor cell arrest under dynamic flow conditions (Integrin alpha-v beta-3) (PMID:11934894)
• Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton (PMID:11940607)
• Del1 mediates vascular smooth muscle cell adhesion, migration, and proliferation through interaction with integrin alpha(v)beta(3). (PMID:11959660)
• Immunohistochemical analysis of human tumor sections from several organs showed a heterogeneus distribution of CD61 in metastatic cases from colon and breast carcinoma. However, no staining was found in metastasis from melanoma. (PMID:11962738)
• Relationships between Rap1b, affinity modulation of integrin alpha IIbbeta 3, and the actin cytoskeleton (integrin alpha(IIb)beta(3)) (PMID:11994301)
• Site-directed mutagenesis of residues on the top surface of the integrin beta3 I-domain that contains a putative ligand binding site identified D158 and N215 as novel residues critical for ligand binding. (PMID:12008962)
• Factor XIII mediates adhesion of platelets to endothelial cells through alpha(v)beta(3) and glycoprotein IIb/IIIa integrins. (PMID:12031826)
• A new platelet polymorphism Duv(a+), localized within the RGD binding domain of glycoprotein IIIa, is associated with neonatal thrombocytopenia (PMID:12036875)
• collagen receptor glycoprotein VI and alphaIIbbeta3 trigger distinct patterns of receptor signalling in platelets, leading to tyrosine phosphorylation of PLCgamma2 (integrin alphaiibbeta3) (PMID:12049640)
• Integrin alpha IIbbeta 3 has agonist-specific activation states and causes intrasubunit and intersubunit allosteric effects (PMID:12140290)
• Two different beta3 cysteine substitutions alter alphaIIb beta3 maturation and result in Glanzmann thrombasthenia. (PMID:12152649)
• Integrin-linked kinase transiently associates with and phosphorylates beta3, regulating platelet integrin alphaIIb beta3 in a PI3-kinase dependent manner (PMID:12152651)
• Alpha(v)beta(3) integrin engagement enhances cell invasiveness in human multiple myeloma. (PMID:12161360)
• integrin alphaVbeta3 expression is reduced when ROR alpha is activated in prostate cancer cells (PMID:12168086)
• Integrin alphavbeta3. Expression of integrin alpha v beta 3 promotes the metastatic phenotype in human melanoma by supporting specific adhesive, invasive and migratory properties of the tumor cells (PMID:12198771)
• Disruption of the long-range GPIIIa Cys(5)-Cys(435) disulfide bond results in the production of constitutively active GPIIb-IIIa (alpha(IIb)beta(3)) integrin complexes. (PMID:12200372)
• Role for beta3 integrins in human melanoma growth and survival. (PMID:12209993)
• alpha v beta 3 integrin signaling through Shc recruitment in response to mechanical stimulation in human osteoblasts (PMID:12210725)
• regulation of integrin function by CD47 ligands: differential effects on integrin-mediated adhesion (PMID:12218055)
• phosphoinositide 3-kinase C2alpha was found to be differentially regulated by alpha(v)beta(3) engagement (PMID:12237112)
• promotion of integrin alpha Vbeta 3-dependent endothelial cell adhesion by PGE2 (PMID:12237321)
• co-stimulation of G(12/13) and G(i) pathways is sufficient to activate GPIIb/IIIa in human platelets in a mechanism that involves intracellular calcium (PMID:12297512)
• Data show clearly that integrin alpha(v)beta(3) interacts with the latency-associated peptide (LAPbeta1 and 3) RGD motif. (PMID:12358597)
• role in mediating pro-angiogenic activity of CYR61 (PMID:12364323)
• An autocrine loop of the integrin alpha(V)beta(3)/CD47 receptor complex and thrombospondin-1 is identified as the molecular coupling device between mechanical loading and apoptosis. (PMID:12370491)
• in patients with endometriosis a significant negative correlation was observed between luminal expression of eNOS and alpha(v)beta(3) integrin and between glandular expression of eNOS and luminal expression of alpha(v)beta(3) integrin (PMID:12372469)
• thrombin interacts with alphavbeta3 as demonstrated by direct binding of alphavbeta3 protein to immobilized thrombin. (PMID:12372811)
• a 17-amino acid sequence is identified as a common epitope for antibodies associated with quinine-induced immune thrombocytopenia (PMID:12393510)
• activation state of alphaVbeta3 integrin is an important regulator of the duration of insulin-like growth factor I receptor phosphorylation and this regulation is mediated through changes in the subcellular localization of SHP-2 (PMID:12399420)
• Ligand binding promotes the entropy-driven oligomerization of this protein (PMID:12426312)
• Data show a novel mechanism by which ECM regulates membrane-type 1 matrix metalloproteinase (MT1-MMP) association with beta1 or alphavbeta3 integrins, thus modulating its internalization, activity, and function on human endothelial cells. (PMID:12427871)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	itgb3b	ENSDARG00000045070
danio_rerio	itgb3a	ENSDARG00000056767
mus_musculus	Itgb3	ENSMUSG00000020689
rattus_norvegicus	Itgb3	ENSRNOG00000048449

Paralogs (8): ITGB5 (ENSG00000082781), ITGB8 (ENSG00000105855), ITGB6 (ENSG00000115221), ITGB4 (ENSG00000132470), ITGB7 (ENSG00000139626), ITGB1 (ENSG00000150093), ITGB2 (ENSG00000160255), ITGBL1 (ENSG00000198542)

Protein

Protein identifiers

Integrin beta-3 — P05106 (reviewed: P05106)

Alternative names: Platelet membrane glycoprotein IIIa

All UniProt accessions (3): P05106, I3L4X8, Q16157

UniProt curated annotations — full annotation on UniProt →

Function. Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 (ITGA2B:ITGB3) is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. Fibrinogen binding enhances SELP expression in activated platelets. ITGAV:ITGB3 binds to fractalkine (CX3CL1) and acts as its coreceptor in CX3CR1-dependent fractalkine signaling. ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling. ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling. ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling. ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling. ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling. ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling. ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1. ITGAV:ITGB3 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1. In brain, plays a role in synaptic transmission and plasticity. Involved in the regulation of the serotonin neurotransmission, is required to localize to specific compartments within the synapse the serotonin receptor SLC6A4 and for an appropriate reuptake of serotonin. Controls excitatory synaptic strength by regulating GRIA2-containing AMPAR endocytosis, which affects AMPAR abundance and composition. ITGAV:ITGB3 act as a receptor for CD40LG. ITGAV:ITGB3 acts as a receptor for IBSP and promotes cell adhesion and migration to IBSP. Integrin ITGA2B:ITGB3 is also the receptor of the erythrocyte-specific ICAM4 ligand involved in heterotypic cell-cell adhesion between erythrocytes and activated platelets. (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Herpes virus 8/HHV-8. (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Coxsackievirus A9. (Microbial infection) Acts as a receptor for Hantaan virus. (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Cytomegalovirus/HHV-5. (Microbial infection) Integrin ITGA5:ITGB3 acts as a receptor for Human metapneumovirus. (Microbial infection) Integrin ITGAV:ITGB3 acts aP05556s a receptor for Human parechovirus 1. (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for West nile virus. (Microbial infection) In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi’s sarcoma lesions.

Subunit / interactions. Heterodimer of an alpha and a beta subunit. Beta-3 (ITGB3) associates with either alpha-IIb (ITGA2B) or alpha-V (ITGAV). Isoform Beta-3C interacts with FLNB. Interacts with COMP. Interacts with PDIA6 following platelet stimulation. Interacts with SYK; upon activation by ITGB3 promotes platelet adhesion. Interacts with MYO10. Interacts with DAB2. Interacts with FERMT2. Interacts with EMP2; regulates the levels of the heterodimer ITGA5:ITGB3 integrin expression on the plasma membrane. Integrin ITGAV:ITGB3 interacts with FBLN5 (via N-terminus). ITGAV:ITGB3 interacts with CCN3. ITGAV:ITGB3 and ITGA2B:ITGB3 interact with SELP (via C-type lectin domain); the interaction mediates cell-cell interaction and adhesion. ITGAV:ITGB3 is found in a ternary complex with CX3CR1 and CX3CL1. ITGAV:ITGB3 is found in a ternary complex with NRG1 and ERBB3. ITGAV:ITGB3 is found in a ternary complex with FGF1 and FGFR1. ITGAV:ITGB3 interacts with FGF2; it is likely that FGF2 can simultaneously bind ITGAV:ITGB3 and FGF receptors. ITGAV:ITGB3 binds to IL1B. ITGAV:ITGB3 is found in a ternary complex with IGF1 and IGF1R. ITGAV:ITGB3 interacts with IGF2. ITGAV:ITGB3 interacts with FBN1. ITGAV:ITGB3 interacts with CD9, CD81 and CD151 (via second extracellular domain). Interacts (via the allosteric site (site 2)) with CXCL12 in a CXCR4-independent manner. Interacts with MXRA8/DICAM; the interaction inhibits ITGAV:ITGB3 heterodimer formation. ITGAV:ITGB3 interacts with PTN. Forms a complex with PTPRZ1 and PTN that stimulates endothelial cell migration through ITGB3 Tyr-773 phosphorylation. ITGAV:ITGB3 interacts with SLC6A4. Interacts with SLC6A4 (via C-terminus); this interaction regulates SLC6A4 trafficking. ITGA2B:ITGB3 interacts with PPIA/CYPA; the interaction is ROS and PPIase activity-dependent and is increased in the presence of thrombin. Interacts with tensin TNS3; TNS3 also interacts with PEAK1, thus acting as an adapter molecule to bridge the association of PEAK1 with ITGB3. Interacts with TM4SF19. ITGAV:ITGB3 interacts with Bothrops moojeni disintegrin Moojecin; the interaction may inhibit ADP-induced platelet aggregation in human plasma. (Microbial infection) Integrin ITGAV:ITGB3 interacts with herpes virus 8/HHV-8 glycoprotein B. (Microbial infection) Integrin ITGAV:ITGB3 interacts with coxsackievirus A9 capsid proteins. (Microbial infection) Interacts with Hantaan virus glycoprotein G. (Microbial infection) Integrin ITGAV:ITGB3 interacts with cytomegalovirus/HHV-5 gH:gL proteins. (Microbial infection) Integrin ITGA5:ITGB3 interacts with human metapneumovirus fusion protein. (Microbial infection) Integrin ITGAV:ITGB3 interacts with human parechovirus 1 capsid proteins. (Microbial infection) Integrin ITGAV:ITGB3 interacts with west nile virus envelope protein E. (Microbial infection) Interacts with HIV-1 Tat. ITGAV:ITGB3 interacts with AGRA2.

Subcellular location. Cell membrane. Cell projection. Lamellipodium membrane. Cell junction. Focal adhesion. Postsynaptic cell membrane. Synapse.

Tissue specificity. Isoform beta-3A and isoform beta-3C are widely expressed. Isoform beta-3A is specifically expressed in osteoblast cells; isoform beta-3C is specifically expressed in prostate and testis.

Post-translational modifications. Phosphorylated on tyrosine residues in response to thrombin-induced platelet aggregation. Probably involved in outside-in signaling. A peptide (AA 740-762) is capable of binding GRB2 only when both Tyr-773 and Tyr-785 are phosphorylated. Phosphorylation of Thr-779 inhibits SHC binding.

Disease relevance. Fetomaternal alloimmune thrombocytopenia 1 (FMAIT1) [MIM:621264] A form of fetomaternal alloimmune thrombocytopenia, a bleeding disorder caused by maternal/fetal incompatibility for platelet alloantigens and arising when a fetus inherits a paternal platelet alloantigen that the mother does not possess. During pregnancy, as well as parturition, maternal alloantibodies against paternally-inherited platelet antigens cause destruction of fetal platelets and fetal/neonatal thrombocytopenia. Disease severity and clinical features in the fetus or neonate are heterogeneous. While most fetuses remain asymptomatic, others develop skin bleedings (petechiae) or internal organ bleedings. The most severe symptom is intracranial hemorrhage that is mostly discovered postnatally and can result in neurological complications or even death. Mothers with circulating platelet alloantibodies may experience miscarriage. FMAIT1 transmission pattern is consistent with autosomal dominant paternal inheritance. Disease susceptibility is associated with variants affecting the gene represented in this entry. Glanzmann thrombasthenia 2 (GT2) [MIM:619267] A form of Glanzmann thrombasthenia, a disorder characterized by failure of platelet aggregation, absent or diminished clot retraction, and mucocutaneous bleeding of mild-to-moderate severity. Glanzmann thrombasthenia has been classified into clinical types I and II. In type I, platelets show absence of glycoprotein IIb-IIIa complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express glycoprotein IIb-IIIa complexes at reduced levels, have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. The disease is caused by variants affecting the gene represented in this entry. Bleeding disorder, platelet-type, 24 (BDPLT24) [MIM:619271] An autosomal dominant disorder of platelet production characterized by congenital macrothrombocytopenia and platelet anisocytosis. Affected individuals may have no or only mildly increased bleeding tendency. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The VWFA domain (or beta I domain) contains three cation-binding sites: the ligand-associated metal ion-binding site (LIMBS or SyMBS), the metal ion-dependent adhesion site (MIDAS), and the adjacent MIDAS site (ADMIDAS). This domain is also part of the ligand-binding site.

Polymorphism. Genetic variants in ITGB3 define different platelet-specific alloantigen systems that are involved in fetomaternal alloimmune thromobocytopenia. Alloantigen system Pl(A), also known as Zw or HPA-1, is characterized by variant p.Pro59Leu (alloantigen Pl(A1) or HPA-1A) and by variant p.Leu59Pro (alloantigen Pl(A2) or HPA-1B). Alloantigen system Pen, also known as Yuk or HPA-4, is characterized by variant p.Gln169Arg (alloantigen Pen(A)) and variant p.Arg169Gln (alloantigen Pen(B)). Alloantigen system Mo is characterized by variant p.Pro433Ala (alloantigen Mo(+)) and variant p.Ala433Pro (alloantigen Mo(-)). Alloantigen system CA/TU is characterized by variant p.Gln515Arg (alloantigen CA(-)/TU(-)) and variant p.Arg515Gln (alloantigen CA(+)/TU(+)). Alloantigen system Sra is characterized by variant p.Cys662Arg (alloantigen Sra(-)) and variant p.Arg662Cys (alloantigen Sra(+)). Alloantigen system Sec(a) is characterized by variant p.Lys606Asn (alloantigen Sec(a+)) and variant p.Asn606Lys (alloantigen Sec(a-)). Additional platelet-specific alloantigens involved in fetomaternal alloimmune thromobocytopenia are known.

Miscellaneous. The constitutive activation of ITGAV:ITGB3 on neoplastic cells may contribute to tumor growth and metastatic potential.

Similarity. Belongs to the integrin beta chain family.

Isoforms (3)

UniProt ID	Names	Canonical?
P05106-1	Beta-3A	yes
P05106-2	Beta-3B
P05106-3	Beta-3C

RefSeq proteins (1): NP_000203* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002369	Integrin_bsu_VWA	Domain
IPR012896	Integrin_bsu_tail	Domain
IPR013111	EGF_extracell	Domain
IPR014836	Integrin_bsu_cyt_dom	Domain
IPR015812	Integrin_bsu	Family
IPR016201	PSI	Domain
IPR032695	Integrin_dom_sf	Homologous_superfamily
IPR033760	Integrin_beta_N	Domain
IPR036349	Integrin_bsu_tail_dom_sf	Homologous_superfamily
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR040622	EGF_integrin_1	Domain
IPR057073	EGF_integrin_2	Domain
IPR057243	Integrin_I-EGF_CS	Conserved_site

Pfam: PF00362, PF07965, PF07974, PF08725, PF17205, PF18372, PF23105

UniProt features (222 total): strand 52, sequence variant 46, helix 30, disulfide bond 28, turn 15, binding site 14, domain 6, sequence conflict 6, glycosylation site 6, mutagenesis site 5, modified residue 4, region of interest 2, topological domain 2, splice variant 2, signal peptide 1, chain 1, short sequence motif 1, transmembrane region 1

Structure

Experimental structures (PDB)

123 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
1MIZ	X-RAY DIFFRACTION	1.9
7UDH	X-RAY DIFFRACTION	2
4HXJ	X-RAY DIFFRACTION	2
7UBR	X-RAY DIFFRACTION	2.05
6BXJ	X-RAY DIFFRACTION	2.09
1MK7	X-RAY DIFFRACTION	2.2
3T3P	X-RAY DIFFRACTION	2.2
7TMZ	X-RAY DIFFRACTION	2.2
2Q6W	X-RAY DIFFRACTION	2.25
3NIG	X-RAY DIFFRACTION	2.25
7U9V	X-RAY DIFFRACTION	2.25
3NID	X-RAY DIFFRACTION	2.3
7L8P	X-RAY DIFFRACTION	2.35
7UCY	X-RAY DIFFRACTION	2.35
3ZE2	X-RAY DIFFRACTION	2.35
7UKT	X-RAY DIFFRACTION	2.37
6BXB	X-RAY DIFFRACTION	2.39
2VDR	X-RAY DIFFRACTION	2.4
3NIF	X-RAY DIFFRACTION	2.4
7UJK	X-RAY DIFFRACTION	2.43
3ZDX	X-RAY DIFFRACTION	2.45
3ZDY	X-RAY DIFFRACTION	2.45
7UJE	X-RAY DIFFRACTION	2.5
7TCT	X-RAY DIFFRACTION	2.5
2VDO	X-RAY DIFFRACTION	2.51
3FCS	X-RAY DIFFRACTION	2.55
7U60	X-RAY DIFFRACTION	2.55
2VDQ	X-RAY DIFFRACTION	2.59
4Z7N	X-RAY DIFFRACTION	2.6
3T3M	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05106-F1	87.19	0.60

Antibody-complex structures (SAbDab): 54 — 2VC2, 2VDK, 2VDL, 2VDM, 2VDN, 2VDO, 2VDP, 2VDQ, 2VDR, 3NID, 3NIF, 3NIG, 3T3M, 3T3P, 3ZDX, 3ZDY, 3ZDZ, 3ZE0, 3ZE1, 3ZE2, 4O02, 4Z7N, 4Z7O, 4Z7Q, 5HDB (+29 more)

Functional residue map

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

Ligand- & substrate-binding residues (14): 147 (in midas binding site); 149 (in admidas binding site); 149 (in midas binding site); 152 (in admidas binding site); 153 (in admidas binding site); 184 (in limbs binding site); 241 (in limbs binding site); 243 (in limbs binding site); 245 (in limbs binding site); 246 (in limbs binding site); 246 (in midas binding site); 277 (in admidas binding site and liganded-open conformation) …

Post-translational modifications (4): 767, 773, 779, 785

Disulfide bonds (28): 31–49, 39–461, 42–64, 52–75, 203–210, 258–299, 400–412, 432–459, 463–483, 474–486, 488–497, 499–529, 512–527, 521–532, 534–547, 549–570, 554–568, 562–573, 575–584, 586–609 …

Glycosylation sites (6): 125, 346, 397, 478, 585, 680

Mutagenesis-validated functional residues (5):

Position	Phenotype
502–508	increases ligand-binding activity.
659	slight increase in ligand-binding activity; when associated with 698-d–k-702 del.
698–702	slight increase in ligand-binding activity; when associated with a-659.
773	no effect on cell surface location but impairs interaction with tns3 and peak1.
785	no effect on cell surface location but impairs interaction with tns3 and peak1.

Function

Pathways and Gene Ontology

Reactome pathways

49 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-1566948	Elastic fibre formation
R-HSA-210990	PECAM1 interactions
R-HSA-2129379	Molecules associated with elastic fibres
R-HSA-216083	Integrin cell surface interactions
R-HSA-2173789	TGF-beta receptor signaling activates SMADs
R-HSA-3000170	Syndecan interactions
R-HSA-3000178	ECM proteoglycans
R-HSA-354192	Integrin signaling
R-HSA-354194	GRB2:SOS provides linkage to MAPK signaling for Integrins
R-HSA-372708	p130Cas linkage to MAPK signaling for integrins
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-445144	Signal transduction by L1
R-HSA-5674135	MAP2K and MAPK activation
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948	Signaling by high-kinase activity BRAF mutants
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-9649948	Signaling downstream of RAS mutants
R-HSA-9656223	Signaling by RAF1 mutants
R-HSA-9769733	Fibrin formation
R-HSA-9856532	Mechanical load activates signaling by PIEZO1 and integrins in osteocytes
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells
R-HSA-109582	Hemostasis
R-HSA-1266738	Developmental Biology
R-HSA-1474244	Extracellular matrix organization
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-170834	Signaling by TGF-beta Receptor Complex
R-HSA-194138	Signaling by VEGF

MSigDB gene sets: 748 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LIPID_STORAGE, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, PID_S1P_S1P1_PATHWAY, BROWNE_HCMV_INFECTION_6HR_DN, GOBP_PROTEIN_ACTIVATION_CASCADE, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, BIOCARTA_EDG1_PATHWAY, GOBP_NEUROTRANSMITTER_UPTAKE

GO Biological Process (74): positive regulation of endothelial cell proliferation (GO:0001938), positive regulation of cell-matrix adhesion (GO:0001954), cell-substrate junction assembly (GO:0007044), cell adhesion (GO:0007155), cell-matrix adhesion (GO:0007160), integrin-mediated signaling pathway (GO:0007229), embryo implantation (GO:0007566), blood coagulation (GO:0007596), positive regulation of endothelial cell migration (GO:0010595), positive regulation of gene expression (GO:0010628), negative regulation of macrophage derived foam cell differentiation (GO:0010745), positive regulation of fibroblast migration (GO:0010763), negative regulation of lipid storage (GO:0010888), negative regulation of low-density lipoprotein particle clearance (GO:0010989), response to activity (GO:0014823), smooth muscle cell migration (GO:0014909), positive regulation of smooth muscle cell migration (GO:0014911), cell migration (GO:0016477), platelet activation (GO:0030168), positive regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030949), cell-substrate adhesion (GO:0031589), negative regulation of lipid transport (GO:0032369), regulation of protein localization (GO:0032880), regulation of actin cytoskeleton organization (GO:0032956), cell adhesion mediated by integrin (GO:0033627), positive regulation of cell adhesion mediated by integrin (GO:0033630), positive regulation of osteoblast proliferation (GO:0033690), heterotypic cell-cell adhesion (GO:0034113), substrate adhesion-dependent cell spreading (GO:0034446), tube development (GO:0035295), wound healing, spreading of epidermal cells (GO:0035313), cellular response to platelet-derived growth factor stimulus (GO:0036120), apolipoprotein A-I-mediated signaling pathway (GO:0038027), wound healing (GO:0042060), apoptotic cell clearance (GO:0043277), regulation of bone resorption (GO:0045124), positive regulation of angiogenesis (GO:0045766), positive regulation of bone resorption (GO:0045780), symbiont entry into host cell (GO:0046718), platelet-derived growth factor receptor signaling pathway (GO:0048008)

GO Molecular Function (20): virus receptor activity (GO:0001618), fibronectin binding (GO:0001968), protease binding (GO:0002020), protein disulfide isomerase activity (GO:0003756), protein kinase C binding (GO:0005080), platelet-derived growth factor receptor binding (GO:0005161), integrin binding (GO:0005178), coreceptor activity (GO:0015026), enzyme binding (GO:0019899), identical protein binding (GO:0042802), vascular endothelial growth factor receptor 2 binding (GO:0043184), metal ion binding (GO:0046872), cell adhesion molecule binding (GO:0050839), extracellular matrix binding (GO:0050840), fibrinogen binding (GO:0070051), protein binding (GO:0005515), fibroblast growth factor binding (GO:0017134), C-X3-C chemokine binding (GO:0019960), insulin-like growth factor I binding (GO:0031994), neuregulin binding (GO:0038132)

GO Cellular Component (35): nucleus (GO:0005634), nucleoplasm (GO:0005654), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), focal adhesion (GO:0005925), integrin complex (GO:0008305), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), apical plasma membrane (GO:0016324), platelet alpha granule membrane (GO:0031092), lamellipodium membrane (GO:0031258), filopodium membrane (GO:0031527), microvillus membrane (GO:0031528), ruffle membrane (GO:0032587), protein-containing complex (GO:0032991), integrin alphav-beta3 complex (GO:0034683), alphav-beta3 integrin-PKCalpha complex (GO:0035866), alphav-beta3 integrin-IGF-1-IGF1R complex (GO:0035867), alphav-beta3 integrin-HMGB1 complex (GO:0035868), melanosome (GO:0042470), signaling receptor complex (GO:0043235), synapse (GO:0045202), postsynaptic membrane (GO:0045211), extracellular exosome (GO:0070062), integrin alphaIIb-beta3 complex (GO:0070442), alphav-beta3 integrin-vitronectin complex (GO:0071062), alpha9-beta1 integrin-ADAM8 complex (GO:0071133), glycinergic synapse (GO:0098690), glutamatergic synapse (GO:0098978), ruffle (GO:0001726), membrane (GO:0016020), filopodium (GO:0030175), cell projection (GO:0042995), anchoring junction (GO:0070161), synaptic membrane (GO:0097060)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Oncogenic MAPK signaling	5
Extracellular matrix organization	3
Integrin signaling	2
Response to elevated platelet cytosolic Ca2+	1
Cell surface interactions at the vascular wall	1
Elastic fibre formation	1
Signaling by TGF-beta Receptor Complex	1
Non-integrin membrane-ECM interactions	1
Signal Transduction	1
Platelet Aggregation (Plug Formation)	1
Signaling by VEGF	1
L1CAM interactions	1
RAF/MAP kinase cascade	1
Signaling by RAS mutants	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	4
cell projection membrane	4
positive regulation of cell migration	3
plasma membrane protein complex	3
protein-containing complex binding	2
binding	2
growth factor binding	2
cellular anatomical structure	2
leading edge membrane	2
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
regulation of cell-matrix adhesion	1
cell-matrix adhesion	1
positive regulation of cell-substrate adhesion	1
cell junction assembly	1
cell-substrate junction organization	1
cellular process	1
cell-substrate adhesion	1
cell surface receptor signaling pathway	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
hemostasis	1
wound healing	1
coagulation	1
regulation of endothelial cell migration	1
endothelial cell migration	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
negative regulation of cell differentiation	1
fibroblast migration	1
regulation of fibroblast migration	1
regulation of lipid storage	1
lipid storage	1
negative regulation of cellular process	1
negative regulation of lipid localization	1

Protein interactions and networks

STRING

3040 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITGB3	ITGAV	P06756	999
ITGB3	ITGA2B	P08514	999
ITGB3	VTN	P01141	997
ITGB3	FN1	P02751	995
ITGB3	TLN1	Q9Y490	991
ITGB3	VWF	P04275	984
ITGB3	ITGA5	P08648	981
ITGB3	SRC	P12931	972
ITGB3	TLN2	Q9Y4G6	966
ITGB3	IL32	P24001	962
ITGB3	SPP1	P10451	949
ITGB3	GNA13	Q14344	948
ITGB3	KDR	P35968	944
ITGB3	FERMT3	Q86UX7	890
ITGB3	ILK	P57043	868

IntAct

135 interactions, top by confidence:

A	B	Type	Score
ITGAV	ITGB3	psi-mi:“MI:0407”(direct interaction)	0.930
ITGB3	ITGAV	psi-mi:“MI:0407”(direct interaction)	0.930
ITGB3	ITGAV	psi-mi:“MI:0915”(physical association)	0.930
ITGAV	ITGB3	psi-mi:“MI:0915”(physical association)	0.930
ITGB3	Tln1	psi-mi:“MI:0407”(direct interaction)	0.840
Tln1	ITGB3	psi-mi:“MI:0407”(direct interaction)	0.840
ITGA2B	ITGB3	psi-mi:“MI:0407”(direct interaction)	0.810
ITGB3	ITGA2B	psi-mi:“MI:0915”(physical association)	0.810
ITGA2B	ITGB3	psi-mi:“MI:0915”(physical association)	0.810
ITGA2B	ITGB3	psi-mi:“MI:0407”(direct interaction)	0.760
ITGB3	ITGA2B	psi-mi:“MI:0915”(physical association)	0.760
ITGB3	ITGA2B	psi-mi:“MI:0407”(direct interaction)	0.760

BioGRID (99): ITGA5 (Affinity Capture-Western), P4HB (Reconstituted Complex), ITGB3 (Co-fractionation), PLA2G4A (Affinity Capture-Western), ITGB3 (Affinity Capture-Western), VIM (Affinity Capture-Western), PLA2G4A (Reconstituted Complex), PRKCB (Affinity Capture-Western), ITGB3 (Biochemical Activity), SHC1 (Affinity Capture-Western), PTK2 (Affinity Capture-Western), ITGB3 (Reconstituted Complex), ITGB3 (Reconstituted Complex), KDR (Co-localization), KDR (Affinity Capture-Western)

ESM2 similar proteins: A0A0D3QS98, A0A0D3QS99, C5H5C4, O70309, O97583, P05106, P17405, P18084, P18424, P50747, P52849, P52850, P58242, P61642, P70207, P80747, Q04519, Q0V8G3, Q0VBD0, Q0VD19, Q13219, Q5NDF2, Q5QQ51, Q5STE3, Q64687, Q6DFZ6, Q6KFX9, Q6MZW2, Q6P988, Q6PCX7, Q6UWX4, Q6YGZ1, Q6ZXD2, Q71RP1, Q7TQ33, Q812F8, Q8BJQ9, Q8C1F4, Q8N6G5, Q8R116

Diamond homologs: A2A863, A5Z1X6, B0FYY4, O08680, O54890, O70309, P05106, P05107, P05556, P07228, P09055, P11584, P11835, P12606, P12607, P16144, P18084, P18563, P18564, P26010, P26011, P26012, P29319, P29320, P32592, P49134, P53712, P53713, P53714, P80747, Q07409, Q07441, Q09062, Q0VBD0, Q1RPR6, Q27591, Q27874, Q2VJ42, Q3UH53, Q3UV74

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
RGS6	down-regulates	ITGB3	binding
SRC	“down-regulates activity”	ITGB3	phosphorylation
AKT1	“down-regulates activity”	ITGB3	phosphorylation
PLAUR	“up-regulates activity”	ITGB3	binding
ITGB1BP1	“down-regulates activity”	ITGB3	binding
DOK1	“down-regulates activity”	ITGB3	binding
ITGB3	“up-regulates activity”	PTK2
Kindlin	“up-regulates activity”	ITGB3	binding
TLN1	“up-regulates activity”	ITGB3	binding
FERMT3	“up-regulates activity”	ITGB3	binding
PDK1	“down-regulates activity”	ITGB3	phosphorylation
PDPK1	“down-regulates activity”	ITGB3	phosphorylation
AKT	“down-regulates activity”	ITGB3	phosphorylation
ITGB3	“form complex”	“AIIB/b3 integrin”	binding
ITGB3	“form complex”	“Av/b3 integrin”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 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
p130Cas linkage to MAPK signaling for integrins	5	131.3×	3e-08
GRB2:SOS provides linkage to MAPK signaling for Integrins	5	123.1×	3e-08
Integrin signaling	6	87.5×	1e-08
Signaling by high-kinase activity BRAF mutants	5	54.7×	1e-06
MAP2K and MAPK activation	5	49.2×	2e-06
Signaling by RAF1 mutants	5	48.0×	2e-06
Signaling by moderate kinase activity BRAF mutants	5	43.8×	2e-06
Paradoxical activation of RAF signaling by kinase inactive BRAF	5	43.8×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
integrin-mediated signaling pathway	8	36.7×	2e-08
cell-matrix adhesion	6	28.1×	1e-05
cell-cell adhesion	6	17.4×	1e-04
actin cytoskeleton organization	5	11.3×	4e-03
cell adhesion	6	6.4×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	116
Likely pathogenic	60
Uncertain significance	291
Likely benign	311
Benign	54

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1210170	NM_000212.3(ITGB3):c.774T>A (p.Cys258Ter)	Pathogenic
1210177	NM_000212.3(ITGB3):c.728A>T (p.Asp243Val)	Pathogenic
1210183	NM_000212.3(ITGB3):c.1522del (p.Gln508fs)	Pathogenic
1210187	NM_000212.3(ITGB3):c.1456del (p.Cys486fs)	Pathogenic
1210194	NM_000212.3(ITGB3):c.1801T>C (p.Cys601Arg)	Pathogenic
1210208	NM_000212.3(ITGB3):c.2080C>T (p.Gln694Ter)	Pathogenic
1330313	NM_000212.3(ITGB3):c.225_226del (p.Ala76fs)	Pathogenic
1330314	NM_000212.3(ITGB3):c.1288C>T (p.Arg430Ter)	Pathogenic
1330315	NM_000212.3(ITGB3):c.1129dup (p.Ile377fs)	Pathogenic
1330316	NM_000212.3(ITGB3):c.2068_2069del (p.Val690fs)	Pathogenic
1330322	NM_000212.3(ITGB3):c.1300del (p.Gln434fs)	Pathogenic
1330323	NM_000212.3(ITGB3):c.1784_1802delinsGTCACA (p.Ser595fs)	Pathogenic
1330324	NM_000212.3(ITGB3):c.1736G>A (p.Trp579Ter)	Pathogenic
1330331	NM_000212.3(ITGB3):c.1728del (p.Ser577fs)	Pathogenic
1330332	NM_000212.3(ITGB3):c.892C>T (p.Gln298Ter)	Pathogenic
1330334	NM_000212.3(ITGB3):c.1980C>A (p.Tyr660Ter)	Pathogenic
1330336	NM_000212.3(ITGB3):c.1525del (p.Gln509fs)	Pathogenic
1330337	NM_000212.3(ITGB3):c.861del (p.Arg287fs)	Pathogenic
1330338	NM_000212.3(ITGB3):c.1402G>T (p.Glu468Ter)	Pathogenic
1330340	NM_000212.3(ITGB3):c.361+1G>A	Pathogenic
1330341	NM_000212.3(ITGB3):c.613_614+2del	Pathogenic
1330349	NM_000212.3(ITGB3):c.921C>A (p.Tyr307Ter)	Pathogenic
1330352	NM_000212.3(ITGB3):c.153del (p.Trp51fs)	Pathogenic
13553	NM_000212.3(ITGB3):c.719G>A (p.Arg240Gln)	Pathogenic
13554	NM_000212.3(ITGB3):c.433G>T (p.Asp145Tyr)	Pathogenic
13560	NM_000212.3(ITGB3):c.165+1G>T	Pathogenic
13562	NM_000212.3(ITGB3):c.1199G>A (p.Cys400Tyr)	Pathogenic
13563	NG_008332.2:g.48605_58661del	Pathogenic
13565	NM_000212.3(ITGB3):c.1924G>T (p.Glu642Ter)	Pathogenic
13567	NM_000212.3(ITGB3):c.428T>G (p.Leu143Trp)	Pathogenic

SpliceAI

2731 predictions. Top by Δscore:

Variant	Effect	Δscore
17:47274413:TTGCA:T	acceptor_loss	1.0000
17:47274414:TGCA:T	acceptor_loss	1.0000
17:47274415:GCA:G	acceptor_loss	1.0000
17:47274416:CA:C	acceptor_loss	1.0000
17:47274416:CAG:C	acceptor_loss	1.0000
17:47274417:A:AG	acceptor_gain	1.0000
17:47274417:A:C	acceptor_loss	1.0000
17:47274417:AG:A	acceptor_gain	1.0000
17:47274417:AGG:A	acceptor_gain	1.0000
17:47274418:G:A	acceptor_loss	1.0000
17:47274418:G:GG	acceptor_gain	1.0000
17:47274418:G:GT	acceptor_gain	1.0000
17:47274418:GG:G	acceptor_gain	1.0000
17:47274418:GGG:G	acceptor_gain	1.0000
17:47274418:GGGC:G	acceptor_gain	1.0000
17:47274418:GGGCC:G	acceptor_gain	1.0000
17:47274505:GTAAG:G	donor_loss	1.0000
17:47274506:T:A	donor_loss	1.0000
17:47274506:T:G	donor_loss	1.0000
17:47283349:TACA:T	acceptor_loss	1.0000
17:47283351:CA:C	acceptor_loss	1.0000
17:47283351:CAG:C	acceptor_loss	1.0000
17:47283352:A:AC	acceptor_loss	1.0000
17:47284438:TCCA:T	acceptor_loss	1.0000
17:47284439:CCA:C	acceptor_loss	1.0000
17:47284440:CA:C	acceptor_loss	1.0000
17:47284441:A:AG	acceptor_gain	1.0000
17:47284441:A:AT	acceptor_loss	1.0000
17:47284441:AGAT:A	acceptor_gain	1.0000
17:47284442:G:GT	acceptor_gain	1.0000

AlphaMissense

5202 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:47287084:G:C	W264C	1.000
17:47287084:G:T	W264C	1.000
17:47274492:G:C	W51C	0.999
17:47274492:G:T	W51C	0.999
17:47284514:G:C	D145H	0.999
17:47284515:A:C	D145A	0.999
17:47284515:A:G	D145G	0.999
17:47284515:A:T	D145V	0.999
17:47284516:C:A	D145E	0.999
17:47284516:C:G	D145E	0.999
17:47284521:C:T	S147F	0.999
17:47284531:G:A	M150I	0.999
17:47284531:G:C	M150I	0.999
17:47284531:G:T	M150I	0.999
17:47284614:G:A	G178D	0.999
17:47284616:T:C	F179L	0.999
17:47284618:C:A	F179L	0.999
17:47284618:C:G	F179L	0.999
17:47284619:G:T	G180W	0.999
17:47284620:G:A	G180E	0.999
17:47284625:T:C	F182L	0.999
17:47284627:T:A	F182L	0.999
17:47284627:T:G	F182L	0.999
17:47284688:T:A	C203S	0.999
17:47284689:G:A	C203Y	0.999
17:47284689:G:C	C203S	0.999
17:47286273:T:C	C210R	0.999
17:47286275:C:G	C210W	0.999
17:47286330:T:C	F229L	0.999
17:47286331:T:C	F229S	0.999

dbSNP variants (sampled 300 via entrez): RS1000002591 (17:47266515 A>T), RS1000002694 (17:47269816 C>G), RS1000034353 (17:47262308 G>A,T), RS1000124545 (17:47305635 T>C), RS1000139859 (17:47272716 T>C,G), RS1000231933 (17:47276946 C>G,T), RS1000232 (17:47279195 T>A,C), RS1000261710 (17:47266731 C>T), RS1000308608 (17:47312796 T>G), RS1000386283 (17:47306008 T>A), RS1000464121 (17:47259371 C>G), RS1000465424 (17:47276610 A>G), RS1000495159 (17:47261039 C>T), RS1000510671 (17:47273073 C>G), RS1000552799 (17:47262877 C>A,T)

Disease associations

OMIM: gene MIM:173470 | disease phenotypes: MIM:619271, MIM:273800, MIM:619267, MIM:608446, MIM:187800, MIM:621264

GenCC curated gene-disease

Disease	Classification	Inheritance
Glanzmann thrombasthenia 2	Definitive	Autosomal recessive
bleeding disorder, platelet-type, 24	Strong	Autosomal dominant
platelet-type bleeding disorder 16	Strong	Autosomal dominant
autosomal dominant macrothrombocytopenia	Supportive	Autosomal dominant
Glanzmann’s thrombasthenia	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
Glanzmann thrombasthenia	Definitive	AR
platelet-type bleeding disorder 16	Definitive	AD

Mondo (11): bleeding disorder, platelet-type, 24 (MONDO:0030996), Glanzmann thrombasthenia (MONDO:0100326), Glanzmann thrombasthenia 1 (MONDO:0031332), Glanzmann thrombasthenia 2 (MONDO:0031009), myocardial infarction, susceptibility to (MONDO:0012039), platelet-type bleeding disorder 16 (MONDO:0008552), fetomaternal alloimmune thrombocytopenia 1 (MONDO:0980723), fetal and neonatal alloimmune thrombocytopenia (MONDO:0019415), thrombocytopenia (MONDO:0002049), autosomal dominant macrothrombocytopenia (MONDO:0015372), (MONDO:0010119)

Orphanet (3): Glanzmann thrombasthenia (Orphanet:849), Autosomal dominant macrothrombocytopenia (Orphanet:140957), Fetal and neonatal alloimmune thrombocytopenia (Orphanet:853)

HPO phenotypes

46 total (30 of 46 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000225	Gingival bleeding
HP:0000421	Epistaxis
HP:0000618	Blindness
HP:0000707	Abnormality of the nervous system
HP:0000790	Hematuria
HP:0000967	Petechiae
HP:0000978	Bruising susceptibility
HP:0000979	Purpura
HP:0001263	Global developmental delay
HP:0001873	Thrombocytopenia
HP:0001892	Abnormal bleeding
HP:0001975	Decreased platelet glycoprotein IIb-IIIa
HP:0002138	Subarachnoid hemorrhage
HP:0002170	Intracranial hemorrhage
HP:0002239	Gastrointestinal hemorrhage
HP:0002249	Melena
HP:0003010	Prolonged bleeding time
HP:0003623	Neonatal onset
HP:0004406	Spontaneous, recurrent epistaxis
HP:0004809	Neonatal alloimmune thrombocytopenia
HP:0004846	Prolonged bleeding after surgery
HP:0004866	Impaired ADP-induced platelet aggregation
HP:0006298	Prolonged bleeding after dental extraction
HP:0007420	Spontaneous hematomas
HP:0008148	Impaired epinephrine-induced platelet aggregation
HP:0008320	Impaired collagen-induced platelet aggregation
HP:0008619	Bilateral sensorineural hearing impairment

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST002690_12	Very long-chain saturated fatty acid levels (fatty acid 20:0)	4.000000e-07
GCST002783_127	Body mass index	5.000000e-06
GCST002783_358	Body mass index	5.000000e-06
GCST004599_125	Mean platelet volume	2.000000e-10
GCST007932_39	Medication use (thyroid preparations)	3.000000e-14
GCST008939_2	Chromosomal aberration frequency (chromosome type) in genotoxic compound exposure	8.000000e-06
GCST008954_4	High chromosomal aberration frequency (chromosome type)	3.000000e-06
GCST010703_72	Brain morphology (MOSTest)	3.000000e-08
GCST90002381_121	Eosinophil count	1.000000e-10
GCST90002382_422	Eosinophil percentage of white cells	4.000000e-10
GCST90013466_19	Height	1.000000e-12
GCST90020028_1385	Hip circumference adjusted for BMI	1.000000e-08
GCST90020028_1386	Hip circumference adjusted for BMI	3.000000e-13
GCST90020028_1388	Hip circumference adjusted for BMI	2.000000e-11

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0004340	body mass index
EFO:0009933	Thyroid preparation use measurement
EFO:0009861	chromosome-type aberration frequency
EFO:0004346	neuroimaging measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D013915	Thrombasthenia	C15.378.100.100.820; C15.378.140.810; C15.378.463.810; C16.320.099.820
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C566061	Glanzmann Thrombasthenia, Autosomal Dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL1907598 (PROTEIN COMPLEX), CHEMBL207 (SINGLE PROTEIN), CHEMBL2093869 (PROTEIN COMPLEX), CHEMBL2111425 (PROTEIN COMPLEX GROUP), CHEMBL2111443 (SELECTIVITY GROUP), CHEMBL2111461 (PROTEIN COMPLEX), CHEMBL4106150 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

18 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,086,512 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1174	EPTIFIBATIDE	4	17,269
CHEMBL428647	PACLITAXEL	4	332,542
CHEMBL916	TIROFIBAN	4	16,908
CHEMBL25	ASPIRIN	4	694,602
CHEMBL429876	CILENGITIDE	3	10,123
CHEMBL273264	NAFAMOSTAT	3	7,063
CHEMBL108111	LAMIFIBAN	2	2,653
CHEMBL18301	ROXIFIBAN	2	822
CHEMBL3085474	FRADAFIBAN	2	925
CHEMBL356301	LOTRAFIBAN	2	964
CHEMBL435176	SIBRAFIBAN	2	1,159
CHEMBL64706	ORBOFIBAN	2	16
CHEMBL76098	XEMILOFIBAN	2	1,312
CHEMBL78871	GANTOFIBAN	2	11
CHEMBL87728	ELAROFIBAN	2	30
CHEMBL3319236	GLPG-0187	1	96
CHEMBL4241824	GSK-3008348 FREE BASE	1	8
CHEMBL4246089	GSK-3008348	1	9

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs5918	Efficacy	3	clopidogrel	Coronary Artery Disease;Myocardial Infarction
rs5918	Efficacy	4	aspirin	Acute coronary syndrome;Coronary Artery Disease

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs5918	ITGB3	3	3.75	2	clopidogrel;aspirin
rs8069732	ITGB3		0.00	0
rs2317676	ITGB3		0.00	0
rs11871251	ITGB3		0.00	0
rs3785873	ITGB3		0.00	0
rs58847127	ITGB3		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Integrins

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

Ligand	Action	Affinity	Parameter
compound 7 [PMID: 31381331]	Inhibition	6.8	pKi

Binding affinities (BindingDB)

53 measured of 53 human assays (53 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(S)-3-[3’-(2-cyclopropylamino-3,4-dioxo-cyclobut-1-enylamino)-biphenyl-4-yl]-2-((R)-7,7-dimethyl-2-oxo-bicyclo[2.2.1]heptane-1-sulfonylamino)-propionic acid	KI	0.1 nM
(3S)-3-[3-bromo-5-(trifluoromethyl)phenyl]-3-[[2-[[5-[(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino]pyridine-3-carbonyl]amino]acetyl]amino]propanoic acid	IC50	0.3 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(S)-3-(3-Adamantan-1-yl-propionylamino)-6-[2-(4-carbamimidoyl-phenyl)-acetylamino]-hexanoic acid	IC50	0.37 nM
(3S)-3-[3-chloro-5-(difluoromethyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido]propanoic acid	IC50	0.5 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3-bromo-5-methyl-phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid	IC50	0.5 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3-bromo-5-chloro-phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido]propanoic acid	IC50	0.6 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-(3-bromo-5-chloro-phenyl)-3-[[2-[[5-[(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino]pyridine-3-carbonyl]amino]acetyl]amino]propanoic acid	IC50	0.6 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3-bromo-5-fluoro-phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid	IC50	0.6 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-(3,5-dibromophenyl)-3-[[2-[[5-[(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino]pyridine-3-carbonyl]amino]acetyl]amino]propanoic acid	IC50	0.6 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3-bromo-5-(difluoromethyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido]propanoic acid	IC50	0.7 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3-chloro-5-(trifluoromethyl)phenyl]3-[[2-[[5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino]pyridine-3-carbonyl]amino]acetyl]amino]propanoic acid	IC50	0.7 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-(3-bromo-5-(trifluoromethyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid	IC50	0.8 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3-chloro-5-(trifluoromethyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido]propanoic acid	IC50	0.8 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-(3,5-dibromophenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid	IC50	1 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3,5-bis(trifluoromethyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido]propanoic acid	IC50	1 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3,5-dichloro-phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid	IC50	1 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3-chloro-5-(trifluoromethoxy)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid	IC50	1 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-(3-bromo-5-(trifluoromethoxy)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid	IC50	1 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(S)-2-((S)-7,7-Dimethyl-2-oxo-bicyclo[2.2.1]hept-1-ylmethanesulfonylamino)-3-[3’-(3-propyl-ureido)-biphenyl-4-yl]-propionic acid	KI	1 nM
(3S)-3-[3-chloro-5-methyl-phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid	IC50	2 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(S)-N-((S)-Adamantan-1-yl-carboxy-methyl)-3-{(S)-3-[2-(4-carbamimidoyl-phenyl)-acetylamino]-2-oxo-pyrrolidin-1-yl}-succinamic acid; TFA	IC50	2 nM
(S)-3-(2-Adamantan-1-yl-acetylamino)-6-[2-(4-carbamimidoyl-phenyl)-acetylamino]-hexanoic acid	IC50	2.2 nM
(3S)-3-[5-[2-[4-(2-fluoroethoxy)phenyl]ethyl]-3-pyridinyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	3 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(3S)-3-[5-[2-[3-(2-fluoroethoxy)phenyl]ethyl]-3-pyridinyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	3 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(3S)-3-[5-[2-[4-(2-fluoroethoxy)phenyl]ethynyl]-3-pyridinyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	5 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(S)-N-((S)-2-Adamantan-1-yl-1-carboxy-ethyl)-3-{(S)-3-[2-(4-carbamimidoyl-phenyl)-acetylamino]-2-oxo-pyrrolidin-1-yl}-succinamic acid; TFA	IC50	5 nM
(3S)-3-[5-[2-[3-(2-fluoroethoxy)phenyl]ethynyl]-3-pyridinyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	6 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(3S)-3-[5-[(4-cyano-3-fluorophenyl)methoxy]-3-pyridinyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	7 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(3S)-3-[5-[(E)-2-[3-(2-fluoroethoxy)phenyl]ethenyl]-3-pyridinyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	7 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(3S)-3-[5-[(3-cyano-4-fluorophenyl)methoxy]-3-pyridinyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	8 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(3S)-3-[5-[4-(2-fluoroethoxy)phenyl]-3-pyridinyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	11 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
RP-444	IC50	13 nM
(3S)-3-[5-[2-(2-fluoroethoxy)phenyl]-3-pyridinyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	14 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(3S)-3-[5-(4-fluoro-3-nitrophenyl)-3-pyridinyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	14 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(3S)-3-[5-(4-cyano-3-fluorophenyl)-3-pyridinyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	15 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(3S)-3-(4-cyano-3-fluorophenyl)-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	15 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(3S)-3-[5-[2-[2-(2-fluoroethoxy)ethoxy]ethoxy]-3-pyridinyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	16 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(3S)-3-[5-[3-(2-fluoroethoxy)phenyl]-3-pyridinyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	16 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(3S)-3-[5-(2-fluoroethoxy)-3-pyridinyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	20 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(S)-N-((S)-2-Adamantan-1-yl-1-methoxycarbonyl-ethyl)-3-{(S)-3-[2-(4-carbamimidoyl-phenyl)-acetylamino]-2-oxo-pyrrolidin-1-yl}-succinamic acid; TFA	IC50	20 nM
(3S)-3-[5-(3-cyano-4-fluorophenyl)-3-pyridinyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	21 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(3S)-3-[4-(2-fluoroethoxy)phenyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	29 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(3S)-3-[3-fluoro-5-[4-(2-fluoroethoxy)phenyl]phenyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	35 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(S)-2-(Adamantan-1-ylmethoxycarbonylamino)-3-{[5-(2-guanidinocarbonyl-cyclopropyl)-thiophene-2-carbonyl]-amino}-propionic acid	IC50	69 nM
(3S)-3-[3-[2-[2-(2-fluoroethoxy)ethoxy]ethoxy]phenyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	84 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(S)-N-Adamantan-1-ylmethyl-3-{2-[3-(4-carbamimidoyl-phenyl)-4,5-dihydro-isoxazol-5-yl]-acetylamino}-succinamic acid; TFA	IC50	95 nM
(3S)-3-[3-(2-fluoroethoxy)phenyl]-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	IC50	101 nM	US-9744252: Compounds for binding to the platelet specific glycoprotein IIb/IIIa and their use for imaging of thrombi
(S)-N-Adamantan-2-yl-3-{2-[3-(4-carbamimidoyl-phenyl)-4,5-dihydro-isoxazol-5-yl]-acetylamino}-succinamic acid; TFA	IC50	140 nM
2-((S)-(1R,7S)-7,7-Dimethyl-2-oxo-bicyclo[2.2.1]hept-1-ylmethanesulfonylamino)-3-{4-[2-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-ethyl]-benzoylamino}-propionic acid	IC50	157 nM
(S)-2-(Adamantan-1-ylmethoxycarbonylamino)-3-{[5-(3-guanidino-3-oxo-propyl)-thiophene-2-carbonyl]-amino}-propionic acid	IC50	480 nM

ChEMBL bioactivities

4393 potent at pChembl≥5 of 4819 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.80	IC50	0.016	nM	CHEMBL315008
10.64	IC50	0.023	nM	CHEMBL1782661
10.64	Kd	0.023	nM	CHEMBL293601
10.59	Kd	0.026	nM	CHEMBL80432
10.57	IC50	0.027	nM	CHEMBL421547
10.52	IC50	0.03	nM	CHEMBL378530
10.52	IC50	0.03	nM	CHEMBL410050
10.52	ED50	0.03	nM	CHEMBL293601
10.48	IC50	0.033	nM	CHEMBL1180969
10.40	IC50	0.04	nM	CHEMBL151142
10.40	IC50	0.04	nM	CHEMBL5268482
10.40	ED50	0.04	nM	CHEMBL94393
10.40	IC50	0.04	nM	CHEMBL357486
10.40	ED50	0.04	nM	CHEMBL78503
10.40	ED50	0.04	nM	CHEMBL78517
10.40	IC50	0.04	nM	CHEMBL116123
10.39	IC50	0.041	nM	CHEMBL329015
10.37	Ki	0.043	nM	CHEMBL2071603
10.37	IC50	0.043	nM	CHEMBL329871
10.33	ED50	0.047	nM	CHEMBL78760
10.33	Ki	0.0465	nM	CHEMBL8572
10.26	IC50	0.055	nM	CHEMBL87372
10.25	ED50	0.056	nM	CHEMBL57040
10.25	Kd	0.056	nM	CHEMBL57040
10.25	IC50	0.056	nM	CHEMBL314636
10.24	IC50	0.057	nM	CHEMBL88944
10.24	IC50	0.058	nM	CHEMBL312929
10.22	Kd	0.06	nM	CHEMBL332914
10.22	ED50	0.06	nM	CHEMBL327216
10.22	IC50	0.06	nM	ELAROFIBAN
10.21	IC50	0.061	nM	CHEMBL328528
10.20	IC50	0.063	nM	CHEMBL84578
10.17	IC50	0.068	nM	CHEMBL88826
10.15	IC50	0.07	nM	CHEMBL123262
10.15	IC50	0.07	nM	CHEMBL186552
10.15	ED50	0.07	nM	CHEMBL92091
10.15	ED50	0.07	nM	CHEMBL96788
10.15	ED50	0.07	nM	CHEMBL310964
10.15	Kd	0.07	nM	CHEMBL78760
10.14	IC50	0.073	nM	CHEMBL128906
10.10	IC50	0.08	nM	CHEMBL332914
10.10	ED50	0.08	nM	CHEMBL298655
10.10	IC50	0.08	nM	CHEMBL123374
10.10	IC50	0.08	nM	CHEMBL187289
10.10	IC50	0.08	nM	CHEMBL437072
10.10	IC50	0.08	nM	CHEMBL145085
10.10	Kd	0.08	nM	CHEMBL298655
10.10	ED50	0.08	nM	CHEMBL78570
10.10	Kd	0.08	nM	CHEMBL311048
10.09	IC50	0.082	nM	CHEMBL2153647

PubChem BioAssay actives

4000 with measured affinity, of 5933 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
(2S)-2-(phenylmethoxycarbonylamino)-3-[[3-[(E)-2-piperidin-4-ylethenyl]-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-8-carbonyl]amino]propanoic acid	92831: Inhibition of thrombin-induced human gel-filtered platelet aggregation	ic50	<0.0001	uM
(2S)-2-[(4-chlorophenyl)sulfonylamino]-3-[[2-(2-piperidin-4-ylethyl)thieno[2,3-b]thiophene-5-carbonyl]amino]propanoic acid	73144: Equilibrium dissociation constant was measured from displacement of L-762,745 from Fibrinogen receptor of human platelets by flow cytometry	kd	<0.0001	uM
3-[[(5Z)-5-[(2-chloro-4,5-dimethoxyphenyl)methylidene]-3-methyl-4-oxo-1,3-thiazolidin-2-ylidene]amino]benzoic acid	266645: Inhibition of [125I]echistatin binding to integrin alphaVbeta3 receptor	ic50	<0.0001	uM
2-[(1S,4S,10S,13S)-10-[3-(diaminomethylideneamino)propyl]-3,6,9,12-tetraoxo-14-propanoyl-2,5,8,11,14-pentazabicyclo[11.2.1]hexadecan-4-yl]acetic acid	317269: Displacement of [125I]echistatin from human integrin alpha-V-beta-3 receptor high affinity state by solid phase assay	ic50	<0.0001	uM
(2S)-2-(phenylmethoxycarbonylamino)-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	92831: Inhibition of thrombin-induced human gel-filtered platelet aggregation	ic50	<0.0001	uM
(2S)-2-(benzylsulfonylamino)-3-[[3-[(E)-2-piperidin-4-ylethenyl]-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-8-carbonyl]amino]propanoic acid	92831: Inhibition of thrombin-induced human gel-filtered platelet aggregation	ic50	<0.0001	uM
(2S)-2-(benzenesulfonamido)-3-[[5-[4-(diaminomethylideneamino)phenyl]thiophene-2-carbonyl]amino]propanoic acid;2,2,2-trifluoroacetic acid	218638: Inhibition of fibrinogen binding to integrin alphaIIb-beta3	ic50	<0.0001	uM
(2S)-2-(benzenesulfonamido)-3-[[5-[2-[(diaminomethylideneamino)methyl]phenyl]thiophene-2-carbonyl]amino]propanoic acid;2,2,2-trifluoroacetic acid	218638: Inhibition of fibrinogen binding to integrin alphaIIb-beta3	ic50	<0.0001	uM
(3S)-3-[[2-[2-oxo-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]acetyl]amino]-3-quinolin-3-ylpropanoic acid	217313: Inhibition of Vitronectin receptor, integrin alphaV-beta3 expressed in HEK 293 cells	ic50	<0.0001	uM
2-[1-[2-[[4-(1H-benzimidazol-2-ylamino)cyclohexyl]methylamino]-2-oxoethyl]-2-oxo-4,5-dihydro-3H-1-benzazepin-5-yl]acetic acid	1924406: Antagonist activity against human integrin alphaVbeta3 expressed in CHO-K1 cells measured after 4 hrs by Cell adhesion assay	ic50	<0.0001	uM
(2S)-2-(benzenesulfonamido)-3-[[3-chloro-4-[4-(1,4,5,6-tetrahydropyrimidin-2-ylamino)piperidin-1-yl]benzoyl]amino]propanoic acid	600450: Antagonist activity at alpha2bbeta3 integrin receptor	ic50	<0.0001	uM
2-[(2S,5R,8S,11S)-5-benzyl-8-[4-[3-[(2E)-2-[(2E,4E,6E)-7-[3-[3-[4-[(2S,5S,11S,14R)-14-benzyl-5-(3-carbamimidamidopropyl)-11-(carboxymethyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]butylamino]-3-oxopropyl]-1,1-dimethylbenzo[e]indol-3-ium-2-yl]hepta-2,4,6-trienylidene]-1,1-dimethylbenzo[e]indol-3-yl]propanoylamino]butyl]-11-(3-carbamimidamidopropyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid bromide	678142: Displacement of [125I]-c(RGDyK) from human integrin alphavbeta3 after 16 hrs by scintillation counting	ki	<0.0001	uM
(3S)-3-[[2-[(3S)-2-oxo-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]acetyl]amino]-3-quinolin-3-ylpropanoic acid	35526: Inhibition of high affinity radioligand binding to human alphaV-beta3 integrin	ic50	<0.0001	uM
(2S)-3-[[5-[3-(diaminomethylideneamino)phenyl]thiophene-2-carbonyl]amino]-2-[(2,4,6-trimethylphenyl)sulfonylamino]propanoic acid;2,2,2-trifluoroacetic acid	220605: Inhibition of fibrinogen binding to K562 cells expressing integrin alphaV-beta3	ic50	<0.0001	uM
3-[2-(4-carbamimidoylbenzoyl)imino-3,4-dimethyl-1,3-thiazol-5-yl]propanoic acid	219096: Affinity for purified activated GPIIb/IIIa fibrinogen receptor by ELISA	ki	<0.0001	uM
(2S)-2-(benzenesulfonamido)-3-[[5-[3-[(diaminomethylideneamino)methyl]phenyl]thiophene-2-carbonyl]amino]propanoic acid	1177813: Antagonist activity at alphavbeta3 integrin receptor (unknown origin) by cell-based ELISA	ic50	<0.0001	uM
(3S)-3-[[3-(2-piperidin-4-ylethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-8-carbonyl]amino]-3-pyridin-3-ylpropanoic acid	92831: Inhibition of thrombin-induced human gel-filtered platelet aggregation	ic50	<0.0001	uM
(2S)-2-(benzenesulfonamido)-3-[[2-(2-piperidin-4-ylethyl)thieno[2,3-b]thiophene-5-carbonyl]amino]propanoic acid	73144: Equilibrium dissociation constant was measured from displacement of L-762,745 from Fibrinogen receptor of human platelets by flow cytometry	kd	<0.0001	uM
2-[(3S)-6-[[4-(morpholine-4-carboximidoyl)benzoyl]amino]-3,4-dihydro-2H-chromen-3-yl]acetic acid	73134: Inhibition of Fibrinogen binding to Immobilized Human Fibrinogen Receptor.	ic50	0.0001	uM
(3S)-3-[[3-[(E)-2-piperidin-4-ylethenyl]-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-8-carbonyl]amino]-3-pyridin-3-ylpropanoic acid	92831: Inhibition of thrombin-induced human gel-filtered platelet aggregation	ic50	0.0001	uM
(2S)-2-(benzenesulfonamido)-3-[[2-(2-piperidin-4-ylethyl)thieno[3,2-b]thiophene-5-carbonyl]amino]propanoic acid	33000: Dissociation constant for alpha IIb beta-3 integrin rested platelets	kd	0.0001	uM
(3S)-3-(2-methoxypyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid	242026: Inhibitory activity against alpha v beta-3 receptor using scintillation proximity assay (SPAV3)	ic50	0.0001	uM
(3S)-3-(2,3-dihydro-1-benzofuran-6-yl)-3-[2-oxo-3-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl]imidazolidin-1-yl]propanoic acid	220465: Inhibition of alphaV-beta3 integrin binding	ic50	0.0001	uM
(2S)-2-(benzenesulfonamido)-3-[[4-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]benzoyl]amino]propanoic acid	217313: Inhibition of Vitronectin receptor, integrin alphaV-beta3 expressed in HEK 293 cells	ic50	0.0001	uM
(2S)-3-[[3-fluoro-4-[4-(1,4,5,6-tetrahydropyrimidin-2-ylamino)piperidin-1-yl]benzoyl]amino]-2-[(4-hydroxyphenyl)sulfonylamino]propanoic acid	600449: Antagonist activity at alphavbeta3 integrin receptor	ic50	0.0001	uM
2-[(5S,11S,14S)-11-[3-(diaminomethylideneamino)propyl]-14-ethyl-12-methyl-4,7,10,13,16-pentaoxo-3,6,9,12,15-pentazabicyclo[15.3.1]henicosa-1(21),17,19-trien-5-yl]acetic acid	33003: Dissociation constant for [3H]-DMP728 binding to alphaIIb beta III integrin	ki	0.0001	uM
(2S)-3-[[4-[2-(6-amino-2-pyridinyl)ethyl]benzoyl]amino]-2-[(4-iodophenyl)sulfonylamino]propanoic acid	217313: Inhibition of Vitronectin receptor, integrin alphaV-beta3 expressed in HEK 293 cells	ic50	0.0001	uM
2-[7-[(4-carbamimidoylbenzoyl)amino]-1,2,3,4-tetrahydronaphthalen-2-yl]acetic acid	73134: Inhibition of Fibrinogen binding to Immobilized Human Fibrinogen Receptor.	ic50	0.0001	uM
2-[6-[[4-(N’-prop-2-ynylcarbamimidoyl)benzoyl]amino]-3,4-dihydro-2H-chromen-3-yl]acetic acid	73134: Inhibition of Fibrinogen binding to Immobilized Human Fibrinogen Receptor.	ic50	0.0001	uM
(3S)-3-(6-chloro-3-pyridinyl)-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	73015: In vitro inhibition of biotinylated fibrinogen binding to immobilized fibrinogen receptor.	ic50	0.0001	uM
(2S)-3-[[2-(2-piperidin-4-ylethyl)thieno[2,3-b]thiophene-5-carbonyl]amino]-2-(thiophen-2-ylsulfonylamino)propanoic acid	73144: Equilibrium dissociation constant was measured from displacement of L-762,745 from Fibrinogen receptor of human platelets by flow cytometry	kd	0.0001	uM
(3S)-3-(6-methyl-3-pyridinyl)-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]propanoic acid	73015: In vitro inhibition of biotinylated fibrinogen binding to immobilized fibrinogen receptor.	ic50	0.0001	uM
2-[7-[[4-(morpholine-4-carboximidoyl)benzoyl]amino]-1,2,3,4-tetrahydronaphthalen-2-yl]acetic acid	73134: Inhibition of Fibrinogen binding to Immobilized Human Fibrinogen Receptor.	ic50	0.0001	uM
(2S)-3-[[2-(2-piperidin-4-ylethyl)thieno[3,2-b]thiophene-5-carbonyl]amino]-2-(pyridin-3-ylsulfonylamino)propanoic acid	73148: Displacement of L-762,745 from Fibrinogen Receptor of human platelets by flow cytometry	kd	0.0001	uM
(2S)-3-[[1-[3-(1H-imidazol-2-ylamino)propyl]indazole-4-carbonyl]amino]-2-[(2,4,6-trimethylphenyl)sulfonylamino]propanoic acid	217308: Inhibition of Vitronectin receptor (alpha V beta 3) binding	ic50	0.0001	uM
2-[6-[(4-carbamimidoylbenzoyl)amino]-3,4-dihydro-2H-chromen-3-yl]acetic acid	73134: Inhibition of Fibrinogen binding to Immobilized Human Fibrinogen Receptor.	ic50	0.0001	uM
2-[7-[[4-(N’-propylcarbamimidoyl)benzoyl]amino]-1,2,3,4-tetrahydronaphthalen-2-yl]acetic acid	73134: Inhibition of Fibrinogen binding to Immobilized Human Fibrinogen Receptor.	ic50	0.0001	uM
(2S)-3-[[2-(2-piperidin-4-ylethyl)thieno[3,2-b]thiophene-5-carbonyl]amino]-2-(thiophen-2-ylsulfonylamino)propanoic acid	73144: Equilibrium dissociation constant was measured from displacement of L-762,745 from Fibrinogen receptor of human platelets by flow cytometry	kd	0.0001	uM
(2S)-3-[[4-[2-(6-amino-2-pyridinyl)ethyl]benzoyl]amino]-2-(benzenesulfonamido)propanoic acid	217306: Inhibition of binding to human Vitronectin receptor (integrin alphaV-beta3)	ic50	0.0001	uM
(3S)-3-[(3R)-2-oxo-3-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl]pyrrolidin-1-yl]-3-quinolin-3-ylpropanoic acid	220466: Displacement of [125I]-labeled nonpeptide from purified recombinant human alphaV-beta3 integrin	ic50	0.0001	uM
(2S)-5-oxo-2-(phenylmethoxycarbonylamino)-5-[4-[3-(1,4,5,6-tetrahydropyrimidin-2-ylamino)phenyl]piperazin-1-yl]pentanoic acid	217305: Inhibitory activity was determined against human vitronectin receptor (alpha V beta 3)	ic50	0.0001	uM
3-[[3-benzyl-2-(4-carbamimidoylbenzoyl)imino-4-methyl-1,3-thiazole-5-carbonyl]amino]propanoic acid	219092: Affinity for purified activated GPIIb/IIIa fibrinogen receptor in ELISA	ic50	0.0001	uM
3-[[3-butyl-2-(4-carbamimidoylbenzoyl)imino-4-methyl-1,3-thiazole-5-carbonyl]amino]propanoic acid	219092: Affinity for purified activated GPIIb/IIIa fibrinogen receptor in ELISA	ic50	0.0001	uM
(2S)-2-[(4-methylphenyl)sulfonylamino]-3-[[4-oxo-5-(2-piperidin-4-ylethyl)-7,8-dihydro-6H-pyrazolo[1,5-a][1,4]diazepine-2-carbonyl]amino]propanoic acid	220879: Competition with [1251]L-692,884 for binding to purified alpha IIb/beta3 integrin, activated by coating onto yttrium silicate scintillation proximity assay fluomicrospheres.	kd	0.0001	uM
(2S)-2-(benzenesulfonamido)-3-[[5-(2-piperidin-4-ylethoxy)-1H-indole-2-carbonyl]amino]propanoic acid	220879: Competition with [1251]L-692,884 for binding to purified alpha IIb/beta3 integrin, activated by coating onto yttrium silicate scintillation proximity assay fluomicrospheres.	kd	0.0001	uM
2-[6-[[4-(morpholine-4-carboximidoyl)benzoyl]amino]-3,4-dihydro-2H-chromen-3-yl]acetic acid	73134: Inhibition of Fibrinogen binding to Immobilized Human Fibrinogen Receptor.	ic50	0.0001	uM
(3S)-3-[[3-[(E)-2-piperidin-4-ylethenyl]-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-8-carbonyl]amino]-3-quinolin-3-ylpropanoic acid	92831: Inhibition of thrombin-induced human gel-filtered platelet aggregation	ic50	0.0001	uM
2-(benzenesulfonamido)-3-[4-[[3-(1,4,5,6-tetrahydropyrimidin-2-ylamino)benzoyl]amino]phenyl]propanoic acid	35524: Binding affinity towards alpha V-beta3 receptor expressed in HEK293 cells	ic50	0.0001	uM
(3S)-3-[[(3R)-1-(3-piperidin-4-ylpropanoyl)piperidine-3-carbonyl]amino]-3-pyridin-3-ylpropanoic acid	241901: Inhibition of human Biotinylated Fg binding to immobilized Alpha II beta-3	ic50	0.0001	uM
2-[(1S,4S,10S,13S)-10-[3-(diaminomethylideneamino)propyl]-14-heptyl-3,6,9,12-tetraoxo-2,5,8,11,14-pentazabicyclo[11.2.1]hexadecan-4-yl]acetic acid	317269: Displacement of [125I]echistatin from human integrin alpha-V-beta-3 receptor high affinity state by solid phase assay	ic50	0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aspirin	decreases expression, decreases response to substance, affects cleavage, decreases reaction, increases expression (+3 more)	7
Estradiol	affects cotreatment, decreases expression, increases expression	4
Progesterone	decreases expression, increases expression, affects cotreatment	4
Tetradecanoylphorbol Acetate	increases reaction, decreases reaction, increases expression	4
bisphenol A	decreases expression, increases expression, affects binding, decreases activity, decreases reaction	3
Resveratrol	decreases reaction, increases phosphorylation, increases reaction, affects localization, affects binding	3
sodium arsenite	decreases expression, increases expression	2
arginyl-glycyl-aspartic acid	affects binding, affects localization, decreases reaction, affects activity	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects binding, affects localization, decreases reaction, increases expression, affects activity	2
monomethylarsonous acid	decreases expression, increases expression	2
dimethylarsinous acid	decreases expression, increases expression	2
Clopidogrel	affects response to substance, decreases response to substance	2
Benzo(a)pyrene	decreases reaction, increases expression, increases methylation, affects binding	2
Cisplatin	decreases expression, decreases response to substance, increases expression	2
Glucose	decreases reaction, increases expression, decreases expression	2
Nickel	increases expression	2
Quercetin	increases expression, decreases reaction	2
Serotonin	affects abundance	2
Tetrachlorodibenzodioxin	decreases reaction, increases expression	2
Arachidonic Acid	increases expression, decreases reaction	2
Genistein	affects expression, decreases expression	2
p-carboxymethylphenyl 1,1-bis(3’-indolyl)-1-(p-carboxymethylphenyl)methane	decreases expression	1
sotorasib	affects cotreatment, decreases expression	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
diphenyleneiodonium	decreases reaction, increases expression	1
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid	decreases reaction, increases expression	1
trichostatin A	increases expression	1
hydroxyhydroquinone	increases expression	1
mancozeb	decreases expression	1

ChEMBL screening assays

771 unique, capped per target: 575 binding, 183 functional, 13 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1013695	Binding	Binding affinity to integrin alphaVbeta3 expressed in human K562 cells at 1 uM for 30 mins by flow cytometry	Discovery of targeting ligands for breast cancer cells using the one-bead one-compound combinatorial method. — J Med Chem
CHEMBL1786464	Functional	Antagonist activity at alphavbeta3 integrin receptor	Improvement in aqueous solubility in small molecule drug discovery programs by disruption of molecular planarity and symmetry. — J Med Chem
CHEMBL4001095	ADMET	Drug internalization in human EPC assessed as alphavbeta3-mediated drug uptake by measuring intracellular content per mg protein at 1 uM measured after 1 hr by HPLC-ESI-MS/MS analysis	Synthesis of Novel c(AmpRGD)-Sunitinib Dual Conjugates as Molecular Tools Targeting the αvβ3 Integrin/VEGFR2 Couple and Impairing Tumor-Associated Angiogenesis. — J Med Chem

Cellosaurus cell lines

14 cell lines: 13 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0RK	CAL-27 2B1	Cancer cell line	Male
CVCL_C0RL	CAL-27 2B3	Cancer cell line	Male
CVCL_D1X3	Abcam A-549 ITGB3 KO	Cancer cell line	Male
CVCL_E0FK	Ubigene HeLa ITGB3 KO	Cancer cell line	Female
CVCL_E2T9	HP-alphaIIbbeta3	Cancer cell line	Female
CVCL_E2TE	HP-1b	Cancer cell line	Female
CVCL_E2TF	HP-3b	Cancer cell line	Female
CVCL_E2TG	HP-4b	Cancer cell line	Female
CVCL_E2TI	HP-6b	Cancer cell line	Female
CVCL_E2TJ	HP-7 variant	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura
NCT00420914	PHASE3	TERMINATED	Strategies for Transfusion of Platelets (SToP)
NCT00501345	PHASE3	TERMINATED	Aspirin in Patients With Myocardial Infarction and Thrombocytopenia
NCT00508820	PHASE3	COMPLETED	An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP
NCT00678587	PHASE3	TERMINATED	Eltrombopag To Reduce The Need For Platelet Transfusion In Subjects With Chronic Liver Disease And Thrombocytopenia Undergoing Elective Invasive Procedures
NCT01438840	PHASE3	COMPLETED	Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)
NCT01444417	PHASE3	COMPLETED	Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients
NCT01805648	PHASE3	UNKNOWN	Efficacy and Safety Study of Maintenance Treatment With rhTPO in Thrombocytopenic Subjects With ITP
NCT02244658	PHASE3	UNKNOWN	Recombinant Human Thrombopoietin (rhTPO) in Management of Chemotherapy-induced Thrombocytopenia in Acute Myelocytic Leukemia
NCT02389621	PHASE3	COMPLETED	Safety and Efficacy Study of Lusutrombopag for Thrombocytopenia in Patients With Chronic Liver Disease Undergoing Elective Invasive Procedures
NCT02444728	PHASE3	TERMINATED	Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE
NCT02487563	PHASE3	COMPLETED	Prospective Study of Patients With Thrombocytopenia Following HSCT
NCT02578901	PHASE3	COMPLETED	American Trial Using Tranexamic Acid in Thrombocytopenia
NCT03326843	PHASE3	TERMINATED	Avatrombopag for the Treatment of Thrombocytopenia in Adults Scheduled for a Surgical Procedure
NCT03515096	PHASE3	COMPLETED	Eltrombopag vs. rhTPO to Increase Platelet Level After HSCT
NCT05563064	PHASE3	UNKNOWN	Effect of Herbal Formulation on Thrombocytes Count
NCT07442513	PHASE3	RECRUITING	Comparison of Etamsylate Versus Placebo to Prevent Bleeding in HSCT