ITGA2

Summary

ITGA2 (integrin subunit alpha 2, HGNC:6137) is a protein-coding gene on chromosome 5q11.2, encoding Integrin alpha-2 (P17301). Integrin alpha-2/beta-1 is a receptor for laminin, collagen, collagen C-propeptides, fibronectin and E-cadherin.

This gene encodes the alpha subunit of a transmembrane receptor for collagens and related proteins. The encoded protein forms a heterodimer with a beta subunit and mediates the adhesion of platelets and other cell types to the extracellular matrix. Loss of the encoded protein is associated with bleeding disorder platelet-type 9. Antibodies against this protein are found in several immune disorders, including neonatal alloimmune thrombocytopenia. This gene is located adjacent to a related alpha subunit gene. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3673 — RefSeq curated summary.

At a glance

• Gene–disease (curated): platelet-type bleeding disorder 9 (Strong, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 410 total
• Phenotypes (HPO): 17
• Druggable target: yes
• MANE Select transcript: NM_002203

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6137
Approved symbol	ITGA2
Name	integrin subunit alpha 2
Location	5q11.2
Locus type	gene with protein product
Status	Approved
Aliases	GPIa, VLAA2, HPA-5
Ensembl gene	ENSG00000164171
Ensembl biotype	protein_coding
OMIM	192974
Entrez	3673

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 nonsense_mediated_decay, 2 protein_coding

ENST00000296585, ENST00000503810, ENST00000509814, ENST00000509960, ENST00000510722, ENST00000513685, ENST00000860895

RefSeq mRNA: 1 — MANE Select: NM_002203 NM_002203

CCDS: CCDS3957

Canonical transcript exons

ENST00000296585 — 30 exons

Exon	Start	End
ENSE00001082059	53026748	53026868
ENSE00001262757	53090519	53094779
ENSE00002047974	52989352	52989532
ENSE00003460991	53059874	53060012
ENSE00003464640	53055538	53055688
ENSE00003467174	53045001	53045092
ENSE00003469138	53048643	53048770
ENSE00003512243	53060901	53061046
ENSE00003516785	53048363	53048477
ENSE00003520307	53078772	53078874
ENSE00003522901	53071938	53072048
ENSE00003523489	53081592	53081696
ENSE00003527256	53072613	53072695
ENSE00003557144	53058025	53058101
ENSE00003564438	53064912	53065115
ENSE00003566730	53083340	53083453
ENSE00003571886	53055984	53056149
ENSE00003575433	53086952	53087041
ENSE00003587275	53074385	53074477
ENSE00003591414	53073118	53073259
ENSE00003609085	53042112	53042221
ENSE00003611535	53067118	53067257
ENSE00003647702	53075061	53075137
ENSE00003650933	53065841	53065977
ENSE00003651136	53051411	53051559
ENSE00003652084	53080511	53080621
ENSE00003668906	53062786	53062929
ENSE00003673148	53075221	53075304
ENSE00003673848	53070109	53070260
ENSE00003687230	53089946	53090062

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 95.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.8678 / max 1074.7090, expressed in 1322 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56413	17.9976	1158
56412	3.1274	909
56410	0.4473	260
56411	0.2057	79
56409	0.0898	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	95.91	gold quality
epithelium of nasopharynx	UBERON:0001951	94.73	gold quality
nasopharynx	UBERON:0001728	94.71	gold quality
bronchial epithelial cell	CL:0002328	94.55	gold quality
islet of Langerhans	UBERON:0000006	92.11	gold quality
visceral pleura	UBERON:0002401	91.74	gold quality
upper leg skin	UBERON:0004262	91.51	gold quality
epithelium of bronchus	UBERON:0002031	90.93	gold quality
bronchus	UBERON:0002185	90.62	gold quality
skin of hip	UBERON:0001554	90.18	gold quality
esophagus squamous epithelium	UBERON:0006920	89.49	gold quality
gingival epithelium	UBERON:0001949	89.28	gold quality
gingiva	UBERON:0001828	88.90	gold quality
mammalian vulva	UBERON:0000997	88.33	gold quality
seminal vesicle	UBERON:0000998	88.33	gold quality
urethra	UBERON:0000057	87.95	gold quality
epithelium of esophagus	UBERON:0001976	87.13	gold quality
oral cavity	UBERON:0000167	87.12	gold quality
stromal cell of endometrium	CL:0002255	86.81	gold quality
nasal cavity mucosa	UBERON:0001826	86.78	gold quality
jejunal mucosa	UBERON:0000399	86.60	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.41	gold quality
nasal cavity epithelium	UBERON:0005384	86.26	silver quality
mammary duct	UBERON:0001765	85.50	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.28	gold quality
squamous epithelium	UBERON:0006914	85.05	gold quality
penis	UBERON:0000989	84.77	gold quality
tibia	UBERON:0000979	84.73	gold quality
epithelium of mammary gland	UBERON:0003244	83.46	gold quality
palpebral conjunctiva	UBERON:0001812	83.43	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-38	yes	402.00
E-GEOD-124858	yes	255.77
E-CURD-119	yes	31.69
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, ESR1, EZH2, IL1B, JUN, NFKB, PARP1, SP1, SP3, TGFB1

miRNA regulators (miRDB)

145 targeting ITGA2, 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-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-3065-5P	99.97	71.56	3281

Literature-anchored findings (GeneRIF, showing 40)

• Bromodeoxyuridine induces integrin expression at transcriptional (alpha2 subunit) and post-transcriptional (beta1 subunit) levels, and alters the adhesive properties of two human lung tumour cell lines. (PMID:11775028)
• Reduction in integrin alpha 2 is related to changes seen during immortalization and malignant progression (PMID:11809527)
• The C807T polymorphism of integrin alpha2 gene in Suzhou Han population was different from that observed in other populations. (PMID:11877061)
• Trimucytin, a collagen-like snake venom protein, activates platelets independent of I-domain within alpha2 subunit of alpha2beta1 integrin. (PMID:11958806)
• the rGPIa/IIa-collagen interaction dominates the adhesion of rGPIa/IIa-Ib alpha-liposomes to the collagen surface at low shear rates; the rGPIa/IIa-collagen and rGPIb alpha-VWF interactions synergistically support liposome adhesion at high shear rates. (PMID:12070018)
• Data report the identification of signaling pathways required for suppression of integrin alpha2beta1 function by c-erbB2. (PMID:12181354)
• initial adhesion of endometrial cells to mesothelium is not mediated by alpha(2)beta(1)integrin (PMID:12372459)
• findings demonstrate that E-cadherin can interact with alpha2beta1 and suggest that heterotypic interactions between E-cadherin and integrins may be more common than originally thought (PMID:12392763)
• role of the GP Ia C807T/G873A polymorphism as a risk factor for thrombosis in Behcet disease (PMID:12412731)
• R-Ras promotes focal adhesion formation by signaling to FAK and p130(Cas) through a novel mechanism that differs from but synergizes with the alpha2beta1 integrin. (PMID:12529399)
• genetic variation of platelet glycoprotein Ia may play a particularly important role during the advanced stages of diabetic retinopathy (PMID:12540964)
• twins developed ischaemic strokes and were shown to be homozygous for the alpha2 807T allele (PMID:12544734)
• linkage with extracellular signal-regulated kinase is functionally linked in highly malignant autocrine transforming growth factor-alpha-driven colon cancer cells (PMID:12657625)
• Data show that NADPH oxidase activation production of reactive oxygen species are involved in the increase of alpha2beta1-integrin plasma membrane expression in Caco-2 cells stimulated with type IV collagen. (PMID:12681287)
• role of polymorphisms in cardiovascular thrombotic disease [review] (PMID:12690916)
• signaling through both constitutively expressed alpha2 integrin and Matrigel-induced alpha3 integrin expression is required to acquire a differentiated phenotype in Caco-2 cells. (PMID:12717361)
• capillary morphogenesis requires endothelial alpha2beta1 integrin engagement of a single type I collagen integrin-binding site, possibly signaling via p38 MAPK and focal adhesion disassembly/FAK inactivation. (PMID:12788934)
• adhesion to the alpha2beta1-specific peptide was disulfide-exchange dependent and protein disulfide isomerase (PDI) mediated in platelets (PMID:12791669)
• results of a case-control study involving 180 stroke patients and 172 controls do not support a role for the integrin alpha2 C807T and GPVI Q317L polymorphisms in the development of first-ever ischemic stroke (PMID:12871362)
• Monkey rotavirus binding to alpha2beta1 integrin requires the alpha2 I domain and is facilitated by the homologous beta1 subunit. (PMID:12915563)
• role in inhibiting Fas-mediated apoptosis in T-lymphocytes (PMID:13679375)
• There were significant differences in the distribution of T and C alleles between myocardial infarction and control groups. (PMID:14556196)
• human platelet deposition on collagen depends on the concerted interplay of several receptors: GPIb in synergy with alpha(2)beta(1) mediating primary adhesion, reinforced by activation through GPVI, which further regulates the thrombus formation. (PMID:14563646)
• results suggest that matrix metalloproteinase-1 can stimulate dephosphorylation of Akt protein and neuronal death through a non-proteolytic mechanism that involves changes in integrin alpha2beta1 signaling (PMID:14679206)
• Since the platelet alpha2 C807T gene polymorphism is associated with alpha2beta1 receptor density on the platelet surface, the level of alpha2beta1 on platelets may be an additional factor affecting Glanzmann’s thromboasthenia clinical expression. (PMID:14687991)
• virus attachment to alpha(2) integrin on the cell surface was found to result in integrin clustering, which can give rise to signaling and facilitate the initiation of the viral entry (PMID:14701832)
• VEGF-A induced alpha1 & alpha2 integrins, promoting lymphatic endothelial tube formation & haptotactic migration. Lineage-specific integrin receptor expression contribute to the distinct dynamics of wound-associated angiogenesis & lymphangiogenesis. (PMID:15132990)
• alpha2beta1 integrin has a role in endorepellin-induced endothelial cell disassembly of actin cytoskeleton and focal adhesions (PMID:15240572)
• alpha2beta1 integrin and GPVI regulate stress fiber formation in megakarocytes, the primary actin structures needed for cell contraction (PMID:15265786)
• alpha2beta1 integrin and CD44/CSPG receptor binding on human melanoma cell activation has been evaluated herein using triple-helical peptide ligands incorporating collagen peptides. (PMID:15292257)
• ILK regulates alpha 2 beta 1 in HEL cells, is activated in platelets and associates with beta 1-integrins (PMID:15304053)
• the interaction of platelet GP Ib with VWF mediates the activation of alpha2beta1, increasing its affinity for collagen (PMID:15514009)
• Data demonstrate that type I collagen synergistically enhances platelet-derived growth factor (PDGF)-induced smooth muscle cell proliferation through Src-dependent crosstalk between the alpha2beta1 integrin and the PDGF receptor beta. (PMID:15522237)
• alpha2807TT genotype of the platelet membrane integrin alpha2beta1 is associated with premature onset of early fetal loss. It appears that this risk factor does not induce the pathomechanism, but modulates the course of fetal loss (PMID:15630502)
• Data show that the recombinant Scl protein p176 promotes adhesion and spreading of human lung fibroblast cells through an alpha2beta1 integrin-mediated interaction. (PMID:15647274)
• Alpha2beta1 integrin is required for up-regulation of IL-1 beta-dependent airway smooth muscle secretory responses by fibronectin; while alpha2beta1 is also an important transducer for type I collagen. (PMID:15699160)
• Binds to vimentin, but this association is lost after prolonged adhesion of endothelial cells to collagen. (PMID:15777792)
• individual effect of each polymorphism located either in the coding or promoter sequence of the alpha2 gene may act in combination to modulate variations in platelets alpha2beta1 receptor density (PMID:15947241)
• analysis of platelet glycoprotein I(b)alpha and integrin alpha2beta1 polymorphisms in diverse populations (PMID:15978109)
• platelet membrane integrins alpha IIb(beta)3 (HPA-1b/Pl) and alpha2(beta)1 (alpha807TT) polymorphisms may have a role in premature myocardial infarction (PMID:15978110)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	itga2.2	ENSDARG00000062974
danio_rerio	itga2.1	ENSDARG00000069390
danio_rerio	itga2.3	ENSDARG00000086838
mus_musculus	Itga2	ENSMUSG00000015533
rattus_norvegicus	Itga2	ENSRNOG00000058111
drosophila_melanogaster	if	FBGN0001250
drosophila_melanogaster	ItgaPS4	FBGN0034005
drosophila_melanogaster	ItgaPS5	FBGN0034880
drosophila_melanogaster	scb	FBGN0286785
caenorhabditis_elegans		WBGENE00003929

Paralogs (17): ITGAL (ENSG00000005844), ITGA3 (ENSG00000005884), ITGA2B (ENSG00000005961), ITGA8 (ENSG00000077943), ITGAE (ENSG00000083457), ITGA6 (ENSG00000091409), ITGA4 (ENSG00000115232), ITGA7 (ENSG00000135424), ITGA11 (ENSG00000137809), ITGAV (ENSG00000138448), ITGAX (ENSG00000140678), ITGA10 (ENSG00000143127), ITGA9 (ENSG00000144668), ITGAD (ENSG00000156886), ITGA5 (ENSG00000161638), ITGAM (ENSG00000169896), ITGA1 (ENSG00000213949)

Protein

Protein identifiers

Integrin alpha-2 — P17301 (reviewed: P17301)

Alternative names: CD49 antigen-like family member B, Collagen receptor, Platelet membrane glycoprotein Ia, VLA-2 subunit alpha

All UniProt accessions (6): D6R9H3, D6RG08, E7EMF1, E7ESP4, E9PB77, P17301

UniProt curated annotations — full annotation on UniProt →

Function. Integrin alpha-2/beta-1 is a receptor for laminin, collagen, collagen C-propeptides, fibronectin and E-cadherin. It recognizes the proline-hydroxylated sequence G-F-P-G-E-R in collagen. It is responsible for adhesion of platelets and other cells to collagens, modulation of collagen and collagenase gene expression, force generation and organization of newly synthesized extracellular matrix. (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human rotavirus A. (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human echoviruses 1 and 8.

Subunit / interactions. Heterodimer of an alpha and a beta subunit. Alpha-2 associates with beta-1. Interacts with HPS5 and RAB21. (Microbial infection) Integrin ITGA2:ITGB1 interacts (via ITAG2 I-domain) with rotavirus A VP4 protein. (Microbial infection) Integrin ITGA2:ITGB1 interacts with human echoviruses 1 and 8 capsid proteins.

Subcellular location. Membrane.

Disease relevance. Fetomaternal alloimmune thrombocytopenia 3 (FMAIT3) [MIM:621267] 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. FMAIT3 transmission pattern is consistent with autosomal dominant paternal inheritance. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Domain organisation. The integrin I-domain (insert) is a VWFA domain. Integrins with I-domains do not undergo protease cleavage.

Polymorphism. Genetic variants in ITGA2 define different platelet-specific alloantigen systems that are involved in fetomaternal alloimmune thromobocytopenia. Alloantigen system Br, also known as HPA-5, is characterized by variant p.Glu534Lys (alloantigen Br(a) or HPA-5B) and variant p.Lys534Glu (alloantigen Br(b) or HPA-5A). Alloantigen system Sit is characterized by variant p.Thr828Met (alloantigen Sit(a+)) and variant p.Met828Thr (alloantigen Sit(a-)).

Similarity. Belongs to the integrin alpha chain family.

RefSeq proteins (1): NP_002194* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000413	Integrin_alpha	Family
IPR002035	VWF_A	Domain
IPR013517	FG-GAP	Repeat
IPR013519	Int_alpha_beta-p	Repeat
IPR018184	Integrin_alpha_C_CS	Conserved_site
IPR028994	Integrin_alpha_N	Homologous_superfamily
IPR032695	Integrin_dom_sf	Homologous_superfamily
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR048285	Integrin_alpha_Ig-like_2	Domain
IPR048286	Integrin_alpha_Ig-like_3	Domain

Pfam: PF00092, PF01839, PF20805, PF20806

UniProt features (74 total): binding site 12, helix 11, glycosylation site 10, repeat 7, mutagenesis site 7, disulfide bond 6, sequence variant 6, strand 5, topological domain 2, signal peptide 1, chain 1, region of interest 1, short sequence motif 1, transmembrane region 1, sequence conflict 1, turn 1, domain 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
9VB8	X-RAY DIFFRACTION	1.6
1V7P	X-RAY DIFFRACTION	1.9
1AOX	X-RAY DIFFRACTION	2.1
1DZI	X-RAY DIFFRACTION	2.1
5HJ2	X-RAY DIFFRACTION	2.15
6ND8	X-RAY DIFFRACTION	2.9
6ND9	X-RAY DIFFRACTION	2.9
6NDH	X-RAY DIFFRACTION	2.9
5THP	X-RAY DIFFRACTION	3.01
4BJ3	X-RAY DIFFRACTION	3.04
6NDD	X-RAY DIFFRACTION	3.05
6NDF	X-RAY DIFFRACTION	3.05
6NDA	X-RAY DIFFRACTION	3.15
6NDG	X-RAY DIFFRACTION	3.15
6NDB	X-RAY DIFFRACTION	3.2
6NDC	X-RAY DIFFRACTION	3.35
6NDE	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17301-F1	85.80	0.51

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 (12): 499; 501; 503; 507; 563; 565; 567; 571; 627; 629; 631; 635

Disulfide bonds (6): 83–92, 680–737, 789–795, 865–876, 1019–1050, 1055–1060

Glycosylation sites (10): 105, 112, 343, 432, 460, 475, 699, 1057, 1074, 1081

Mutagenesis-validated functional residues (7):

Position	Phenotype
1159	no significant reduction of rab21-binding by co-immunoprecipitation assay; when associated with a-1160 and a-1162.
1160	no effect on rab21-binding. significant reduction of rab21-binding; when associated with a-1161. shows defective cytokin
1161	significant reduction of rab21-binding; when associated with a-1160. shows defective cytokinesis on collagen, but not on
1162	no significant reduction of rab21-binding by co-immunoprecipitation assay; when associated with a-1159 and a-1160.
1162	markedly weakens rab21-binding. shows defective cytokinesis on collagen, but not on fibronectin.
1164	significant reduction of rab21-binding; when associated with a-1160; a-1161 and a-1165.
1165	significant reduction of rab21-binding; when associated with a-1160; a-1161 and a-1164.

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-216083	Integrin cell surface interactions
R-HSA-3000157	Laminin interactions
R-HSA-3000170	Syndecan interactions
R-HSA-3000178	ECM proteoglycans
R-HSA-447041	CHL1 interactions
R-HSA-75892	Platelet Adhesion to exposed collagen
R-HSA-8874081	MET activates PTK2 signaling
R-HSA-9926550	Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition
R-HSA-109582	Hemostasis
R-HSA-1266738	Developmental Biology
R-HSA-1474244	Extracellular matrix organization
R-HSA-162582	Signal Transduction
R-HSA-3000171	Non-integrin membrane-ECM interactions
R-HSA-373760	L1CAM interactions
R-HSA-422475	Axon guidance
R-HSA-6806834	Signaling by MET
R-HSA-8875878	MET promotes cell motility
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9675108	Nervous system development
R-HSA-9730414	MITF-M-regulated melanocyte development
R-HSA-9856651	MITF-M-dependent gene expression

MSigDB gene sets: 503 (showing top): MORF_ITGA2, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_RESPONSE_TO_AMINE, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_DETECTION_OF_MECHANICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION, GCANCTGNY_MYOD_Q6, GOBP_FOCAL_ADHESION_ASSEMBLY

GO Biological Process (40): response to hypoxia (GO:0001666), positive regulation of leukocyte migration (GO:0002687), substrate-dependent cell migration (GO:0006929), hypotonic response (GO:0006971), cell adhesion (GO:0007155), cell-matrix adhesion (GO:0007160), integrin-mediated signaling pathway (GO:0007229), female pregnancy (GO:0007565), blood coagulation (GO:0007596), response to xenobiotic stimulus (GO:0009410), animal organ morphogenesis (GO:0009887), positive regulation of epithelial cell migration (GO:0010634), response to amine (GO:0014075), response to muscle activity (GO:0014850), positive regulation of smooth muscle cell migration (GO:0014911), extracellular matrix organization (GO:0030198), mammary gland development (GO:0030879), positive regulation of cell projection organization (GO:0031346), cell-substrate adhesion (GO:0031589), positive regulation of collagen biosynthetic process (GO:0032967), response to L-ascorbic acid (GO:0033591), cell adhesion mediated by integrin (GO:0033627), collagen-activated signaling pathway (GO:0038065), skin morphogenesis (GO:0043589), positive regulation of translation (GO:0045727), positive regulation of cell adhesion (GO:0045785), positive regulation of smooth muscle contraction (GO:0045987), focal adhesion assembly (GO:0048041), mesodermal cell differentiation (GO:0048333), positive regulation of smooth muscle cell proliferation (GO:0048661), positive regulation of positive chemotaxis (GO:0050927), detection of mechanical stimulus involved in sensory perception of pain (GO:0050966), positive regulation of transmission of nerve impulse (GO:0051971), positive regulation of phagocytosis, engulfment (GO:0060100), hepatocyte differentiation (GO:0070365), response to parathyroid hormone (GO:0071107), cellular response to mechanical stimulus (GO:0071260), cellular response to estradiol stimulus (GO:0071392), cell-cell adhesion (GO:0098609), symbiont entry into host cell (GO:0046718)

GO Molecular Function (12): amyloid-beta binding (GO:0001540), virus receptor activity (GO:0001618), integrin binding (GO:0005178), collagen binding (GO:0005518), signaling receptor activity (GO:0038023), collagen receptor activity (GO:0038064), laminin binding (GO:0043236), heparan sulfate proteoglycan binding (GO:0043395), protein-containing complex binding (GO:0044877), metal ion binding (GO:0046872), collagen binding involved in cell-matrix adhesion (GO:0098639), protein binding (GO:0005515)

GO Cellular Component (13): plasma membrane (GO:0005886), focal adhesion (GO:0005925), integrin complex (GO:0008305), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), integrin alpha2-beta1 complex (GO:0034666), axon terminus (GO:0043679), basal part of cell (GO:0045178), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020), axon (GO:0030424), cell projection (GO:0042995), presynapse (GO:0098793)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Extracellular matrix organization	4
Developmental Biology	2
Non-integrin membrane-ECM interactions	1
L1CAM interactions	1
Hemostasis	1
MET promotes cell motility	1
MITF-M-dependent gene expression	1
Axon guidance	1
Nervous system development	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by MET	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
positive regulation of cell migration	3
protein-containing complex binding	2
collagen binding	2
binding	2
response to stress	1
response to decreased oxygen levels	1
positive regulation of immune system process	1
regulation of leukocyte migration	1
leukocyte migration	1
cell migration	1
response to osmotic stress	1
cellular process	1
cell-substrate adhesion	1
cell surface receptor signaling pathway	1
multi-organism reproductive process	1
multi-multicellular organism process	1
hemostasis	1
wound healing	1
coagulation	1
response to chemical	1
anatomical structure morphogenesis	1
animal organ development	1
epithelial cell migration	1
regulation of epithelial cell migration	1
response to nitrogen compound	1
response to activity	1
smooth muscle cell migration	1
regulation of smooth muscle cell migration	1
extracellular structure organization	1
external encapsulating structure organization	1
gland development	1
cell projection organization	1
regulation of cell projection organization	1
positive regulation of cellular component organization	1
cell adhesion	1
positive regulation of biosynthetic process	1
positive regulation of collagen metabolic process	1
collagen biosynthetic process	1
regulation of collagen biosynthetic process	1

Protein interactions and networks

STRING

2306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITGA2	ITGB1	P05556	997
ITGA2	GP6	Q9HCN6	975
ITGA2	FN1	P02751	962
ITGA2	CLDN7	O95471	857
ITGA2	FCER1G	P30273	854
ITGA2	ITGB3	P05106	824
ITGA2	CLDN1	O95832	796
ITGA2	COL1A1	P02452	779
ITGA2	ITGB5	P18084	774
ITGA2	ITGA6	P23229	726
ITGA2	ITGB2	P05107	723
ITGA2	PLCG2	P16885	721
ITGA2	COL3A1	P02461	720
ITGA2	ITGB6	P18564	715
ITGA2	CD44	P16070	715
ITGA2	DDR2	Q16832	715

IntAct

130 interactions, top by confidence:

A	B	Type	Score
TSPAN15	ADAM10	psi-mi:“MI:0914”(association)	0.840
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
TSPAN14	ADAM10	psi-mi:“MI:0914”(association)	0.740
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
ITGA2	ITGB1	psi-mi:“MI:0915”(physical association)	0.680
ITGA2	ITGB1	psi-mi:“MI:0914”(association)	0.680
ITGB1	ITGA2	psi-mi:“MI:0915”(physical association)	0.680
KCNJ2	KCNJ18	psi-mi:“MI:2364”(proximity)	0.660
SHARPIN	ITGA2	psi-mi:“MI:0915”(physical association)	0.660
ITGA2	SHARPIN	psi-mi:“MI:0407”(direct interaction)	0.660
Rab21	ITGA2	psi-mi:“MI:0915”(physical association)	0.630
ITGA2	Rab21	psi-mi:“MI:0915”(physical association)	0.630

BioGRID (142): ITGA2 (Affinity Capture-MS), ITGA2 (Affinity Capture-MS), ITGA2 (Affinity Capture-MS), ITGA2 (Affinity Capture-MS), ITGA2 (Affinity Capture-MS), ITGA2 (Affinity Capture-MS), ITGA2 (Affinity Capture-MS), ITGA2 (Affinity Capture-MS), ITGA2 (Affinity Capture-MS), ITGA2 (Two-hybrid), ITGA2 (Affinity Capture-MS), ITGA2 (Affinity Capture-MS), ITGA2 (Affinity Capture-MS), ITGA2 (Affinity Capture-MS), ITGA2 (Affinity Capture-MS)

ESM2 similar proteins: A2ARA8, B0S5N4, B8JK39, F1MMS9, O08665, P05555, P06756, P08514, P08648, P11215, P11688, P13612, P17301, P17852, P18564, P20701, P23229, P24063, P26006, P26007, P26008, P26009, P38570, P43406, P53708, P53710, P53711, P61622, P61625, P80746, Q00651, Q06274, Q13683, Q13797, Q60677, Q61738, Q61739, Q62469, Q62470, Q63258

Diamond homologs: A2AX52, A6H584, A6NMZ7, A8TX70, E1BMV3, E7FF10, O00339, O08746, O35701, O42401, O75578, P12111, P13944, P15989, P17301, P18614, P20785, P32018, P34576, P51942, P53710, P56199, P61622, P84552, Q02388, Q05707, Q13349, Q21281, Q21540, Q28902, Q3V3R4, Q5EA64, Q60847, Q62469, Q63870, Q641F3, Q642A6, Q801S8, Q80X19, Q8C6K9

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
TGFB1	“up-regulates quantity by expression”	ITGA2	“transcriptional regulation”
IL1B	“up-regulates quantity by expression”	ITGA2	“transcriptional regulation”
ITGA2	“form complex”	“A2/b1 integrin”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	199
Likely benign	31
Benign	138

Top pathogenic / likely-pathogenic (0)

SpliceAI

3657 predictions. Top by Δscore:

Variant	Effect	Δscore
5:52989531:AGGT:A	donor_loss	1.0000
5:53026869:G:GG	donor_gain	1.0000
5:53042106:TTCTA:T	acceptor_loss	1.0000
5:53042107:TCTA:T	acceptor_loss	1.0000
5:53042108:CTAG:C	acceptor_loss	1.0000
5:53042109:TA:T	acceptor_loss	1.0000
5:53042110:A:C	acceptor_loss	1.0000
5:53042111:G:GA	acceptor_loss	1.0000
5:53042217:GCAAA:G	donor_gain	1.0000
5:53042220:AA:A	donor_gain	1.0000
5:53042222:G:GG	donor_gain	1.0000
5:53044995:T:A	acceptor_gain	1.0000
5:53044999:A:AG	acceptor_gain	1.0000
5:53045000:G:GG	acceptor_gain	1.0000
5:53045093:G:GG	donor_gain	1.0000
5:53048641:A:AG	acceptor_gain	1.0000
5:53048642:G:GG	acceptor_gain	1.0000
5:53048642:GCCT:G	acceptor_gain	1.0000
5:53055686:GCA:G	donor_gain	1.0000
5:53055689:G:GG	donor_gain	1.0000
5:53058099:AATGT:A	donor_loss	1.0000
5:53058101:TG:T	donor_loss	1.0000
5:53058102:G:GC	donor_loss	1.0000
5:53058102:G:GG	donor_gain	1.0000
5:53058103:T:G	donor_loss	1.0000
5:53060895:TTTTA:T	acceptor_loss	1.0000
5:53060896:TTTAG:T	acceptor_loss	1.0000
5:53060897:TTAGG:T	acceptor_loss	1.0000
5:53060898:TA:T	acceptor_loss	1.0000
5:53060899:A:AG	acceptor_gain	1.0000

AlphaMissense

7803 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:53048679:A:T	D180V	0.999
5:53048684:T:C	S182P	0.999
5:53048704:G:C	W188C	0.999
5:53048704:G:T	W188C	0.999
5:53055606:A:T	D283V	0.999
5:53048678:G:C	D180H	0.998
5:53048679:A:C	D180A	0.998
5:53048680:T:A	D180E	0.998
5:53048680:T:G	D180E	0.998
5:53048690:A:C	S184R	0.998
5:53048692:T:A	S184R	0.998
5:53048692:T:G	S184R	0.998
5:53048702:T:A	W188R	0.998
5:53048702:T:C	W188R	0.998
5:53055607:C:A	D283E	0.998
5:53055607:C:G	D283E	0.998
5:53090009:A:C	S1138R	0.998
5:53090011:T:A	S1138R	0.998
5:53090011:T:G	S1138R	0.998
5:53048670:T:A	V177D	0.997
5:53048685:C:T	S182L	0.997
5:53048720:T:C	F194L	0.997
5:53048722:T:A	F194L	0.997
5:53048722:T:G	F194L	0.997
5:53051529:C:T	T250I	0.997
5:53051537:T:C	F253L	0.997
5:53051539:C:A	F253L	0.997
5:53051539:C:G	F253L	0.997
5:53055603:C:T	T282I	0.997
5:53055605:G:C	D283H	0.997

dbSNP variants (sampled 300 via entrez): RS1000043759 (5:53058862 A>G), RS1000098952 (5:53072246 T>C), RS1000146556 (5:53067178 G>A), RS1000183469 (5:53091907 G>C), RS1000219501 (5:53042047 A>C,G), RS1000250883 (5:53005962 A>G), RS1000280746 (5:53047651 C>T), RS1000298020 (5:53092140 G>A,C), RS1000381481 (5:53078477 C>T), RS1000417453 (5:53011427 C>T), RS1000436110 (5:52998863 G>C), RS1000442933 (5:53030225 A>G), RS1000545100 (5:53086361 G>T), RS1000554614 (5:53035139 C>A), RS1000557923 (5:52991012 G>C)

Disease associations

OMIM: gene MIM:192974 | disease phenotypes: MIM:614200, MIM:621264, MIM:621267, MIM:252160

GenCC curated gene-disease

Disease	Classification	Inheritance
platelet-type bleeding disorder 9	Strong	Autosomal dominant

Mondo (4): platelet-type bleeding disorder 9 (MONDO:0013622), fetal and neonatal alloimmune thrombocytopenia (MONDO:0019415), fetomaternal alloimmune thrombocytopenia 3 (MONDO:0980725), sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1 (MONDO:0009644)

Orphanet (5): Bleeding diathesis due to a collagen receptor defect (Orphanet:73271), Bleeding diathesis due to integrin alpha2-beta1 deficiency (Orphanet:98886), Fetal and neonatal alloimmune thrombocytopenia (Orphanet:853), Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B (Orphanet:308393), Encephalopathy due to sulfite oxidase deficiency (Orphanet:833)

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000618	Blindness
HP:0000707	Abnormality of the nervous system
HP:0000790	Hematuria
HP:0000967	Petechiae
HP:0000979	Purpura
HP:0001263	Global developmental delay
HP:0001892	Abnormal bleeding
HP:0002138	Subarachnoid hemorrhage
HP:0002170	Intracranial hemorrhage
HP:0002239	Gastrointestinal hemorrhage
HP:0002249	Melena
HP:0004809	Neonatal alloimmune thrombocytopenia
HP:0007420	Spontaneous hematomas
HP:0008619	Bilateral sensorineural hearing impairment
HP:0012541	Cephalohematoma
HP:0031364	Ecchymosis
HP:0100021	Cerebral palsy

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002481_13	Acne (severe)	5.000000e-09
GCST006484_5	Type 2 diabetes	4.000000e-06
GCST009600_3	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	1.000000e-08
GCST90002395_665	Mean platelet volume	3.000000e-11
GCST90002401_158	Platelet distribution width	1.000000e-10
GCST90013442_6	Keratoconus	3.000000e-18

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C566000	Glycoprotein IA Deficiency (supp.)
C565373	Molybdenum Cofactor Deficiency, Complementation Group B (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2111461 (PROTEIN COMPLEX), CHEMBL3137268 (PROTEIN COMPLEX), CHEMBL4998 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1062535	Efficacy	3	aspirin	Myocardial Infarction
rs1062535	Efficacy	3	aspirin;clopidogrel
rs1126643	Efficacy	3	aspirin;clopidogrel	Coronary Artery Disease;Coronary Disease;Myocardial Infarction

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1062535	ITGA2	3	2.25	2	aspirin;aspirin;clopidogrel
rs1126643	ITGA2	3	1.00	1	aspirin;clopidogrel

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Integrins

Binding affinities (BindingDB)

20 measured of 28 human assays (28 total across all organisms); most potent 20 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(2S)-3-[(benzylcarbamoyl)amino]-2-{[(2S)-1-[(3,5-difluorobenzene)sulfonyl]pyrrolidin-2-yl]formamido}propanoic acid	IC50	35 nM
(2S)-3-[(benzylcarbamoyl)amino]-2-{[(2S)-1-[(4-methylbenzene)sulfonyl]pyrrolidin-2-yl]formamido}propanoic acid	IC50	36 nM
(2S)-3-[(benzylcarbamoyl)amino]-2-{[(2S)-1-{[3,5-bis(trifluoromethyl)benzene]sulfonyl}pyrrolidin-2-yl]formamido}propanoic acid	IC50	39 nM
(2S)-3-[(benzylcarbamoyl)amino]-2-{[(2S)-1-[(4-methanesulfonylbenzene)sulfonyl]pyrrolidin-2-yl]formamido}propanoic acid	IC50	70 nM
(2S)-3-[(benzylcarbamoyl)amino]-2-{[(2S)-1-[(4-nitrobenzene)sulfonyl]pyrrolidin-2-yl]formamido}propanoic acid	IC50	105 nM
(2S)-2-{[(2R)-1-(benzenesulfonyl)pyrrolidin-2-yl]formamido}-3-({[(2-chlorophenyl)methyl]carbamoyl}amino)propanoic acid	IC50	107 nM
(2S)-2-{[(2R)-1-(benzenesulfonyl)pyrrolidin-2-yl]formamido}-3-({[(4-methoxyphenyl)methyl]carbamoyl}amino)propanoic acid	IC50	108 nM
(2S)-3-[(benzylcarbamoyl)amino]-2-{[(2S)-1-[(4-acetamidobenzene)sulfonyl]pyrrolidin-2-yl]formamido}propanoic acid	IC50	131 nM
(2S)-2-{[(2S)-1-[(4-aminobenzene)sulfonyl]pyrrolidin-2-yl]formamido}-3-[(benzylcarbamoyl)amino]propanoic acid	IC50	144 nM
(2S)-3-[(benzylcarbamoyl)amino]-2-{[(2S)-1-({4-[(phenylcarbamoyl)amino]benzene}sulfonyl)pyrrolidin-2-yl]formamido}propanoic acid	IC50	151 nM
(2S)-2-{[(2R)-1-(benzenesulfonyl)pyrrolidin-2-yl]formamido}-3-({[(3-methoxyphenyl)methyl]carbamoyl}amino)propanoic acid	IC50	160 nM
(2S)-2-{[(2R)-1-(benzenesulfonyl)pyrrolidin-2-yl]formamido}-3-{[(benzyloxy)carbonyl]amino}propanoic acid	IC50	185 nM
(2S)-2-{[(2R)-1-(benzenesulfonyl)pyrrolidin-2-yl]formamido}-3-[(tert-butylcarbamoyl)amino]propanoic acid	IC50	185 nM
(2S)-3-[(benzylcarbamoyl)amino]-2-{[(2S)-1-{[4-(2-phenylacetamido)benzene]sulfonyl}pyrrolidin-2-yl]formamido}propanoic acid	IC50	236 nM
(2S)-3-[(benzylcarbamoyl)amino]-2-{[(2S)-1-[(4-phenylbenzene)sulfonyl]pyrrolidin-2-yl]formamido}propanoic acid	IC50	287 nM
(2S)-2-{[(2R)-1-(benzenesulfonyl)pyrrolidin-2-yl]formamido}-3-[(phenylcarbamoyl)amino]propanoic acid	IC50	296 nM
(2S)-2-{[(2R)-1-(benzenesulfonyl)pyrrolidin-2-yl]formamido}-3-[(propylcarbamoyl)amino]propanoic acid	IC50	357 nM
(2S)-2-{[(2R)-1-(benzenesulfonyl)pyrrolidin-2-yl]formamido}-3-(3-phenylpropanamido)propanoic acid	IC50	367 nM
(2S)-2-{[(2R)-1-(benzenesulfonyl)pyrrolidin-2-yl]formamido}-3-({[(2-methoxyphenyl)methyl]carbamoyl}amino)propanoic acid	IC50	467 nM
(2S)-2-{[(2R)-1-(benzenesulfonyl)pyrrolidin-2-yl]formamido}-3-(phenylformamido)propanoic acid	IC50	660 nM

ChEMBL bioactivities

71 potent at pChembl≥5 of 73 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.15	IC50	0.7	nM	CHEMBL376893
9.10	IC50	0.8	nM	CHEMBL218963
9.00	IC50	1	nM	CHEMBL220128
8.43	IC50	3.7	nM	CHEMBL385939
8.40	IC50	4	nM	CHEMBL3115061
8.30	IC50	5	nM	CHEMBL219051
8.26	IC50	5.5	nM	CHEMBL1836344
8.22	IC50	6	nM	CHEMBL5277760
8.19	IC50	6.5	nM	CHEMBL1836347
8.19	IC50	6.5	nM	CHEMBL1836351
8.17	IC50	6.8	nM	CHEMBL1836345
8.10	IC50	8	nM	CHEMBL218200
8.05	IC50	9	nM	CHEMBL219603
7.92	IC50	12	nM	CHEMBL3115056
7.92	IC50	12	nM	CHEMBL4645996
7.92	IC50	12	nM	CHEMBL5266636
7.82	IC50	15	nM	CHEMBL429088
7.77	IC50	17	nM	CHEMBL393213
7.77	IC50	17	nM	CHEMBL5266675
7.66	IC50	22	nM	CHEMBL1836355
7.64	IC50	23	nM	CHEMBL401237
7.60	IC50	25	nM	CHEMBL5286317
7.60	IC50	25	nM	CHEMBL32960
7.54	IC50	29	nM	CHEMBL391118
7.50	IC50	32	nM	CHEMBL218226
7.47	IC50	34	nM	CHEMBL3115059
7.44	IC50	36	nM	CHEMBL3115067
7.43	IC50	37	nM	CHEMBL1836350
7.42	IC50	38	nM	CHEMBL3115057
7.30	IC50	50	nM	CHEMBL238779
7.17	IC50	67	nM	CHEMBL429088
7.09	IC50	82	nM	CHEMBL5276382
7.08	IC50	83	nM	CHEMBL393213
7.05	IC50	89	nM	CHEMBL391118
7.00	IC50	101	nM	CHEMBL3114869
6.99	IC50	102	nM	CHEMBL401237
6.97	IC50	106	nM	CHEMBL3114868
6.94	IC50	114	nM	CHEMBL3114861
6.89	EC50	130	nM	CHEMBL4303254
6.87	IC50	134	nM	CHEMBL3115054
6.86	IC50	138	nM	CHEMBL429088
6.85	IC50	142	nM	CHEMBL3114863
6.80	EC50	160	nM	CHEMBL4649149
6.79	IC50	163	nM	CHEMBL3114860
6.75	IC50	176	nM	CHEMBL3115073
6.75	IC50	178	nM	CHEMBL3114867
6.75	IC50	177	nM	CHEMBL238779
6.75	IC50	180	nM	CHEMBL5276876
6.67	IC50	214	nM	CHEMBL81990
6.63	IC50	233	nM	CHEMBL3114862

PubChem BioAssay actives

100 with measured affinity, of 133 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
3-(3,4-dimethoxyphenyl)-3-[[3-(1,2,3,4-tetrahydroisoquinolin-7-ylcarbamoyl)benzoyl]amino]propanoic acid	274143: Displacement of FITC-Fg from integrin alpha2beta3 receptor expressed in human activated platelets	ic50	0.0007	uM
3-(4-methoxyphenyl)-3-[[3-(1,2,3,4-tetrahydroisoquinolin-7-ylcarbamoyl)benzoyl]amino]propanoic acid	274143: Displacement of FITC-Fg from integrin alpha2beta3 receptor expressed in human activated platelets	ic50	0.0008	uM
3-phenyl-3-[[3-(1,2,3,4-tetrahydroisoquinolin-7-ylcarbamoyl)benzoyl]amino]propanoic acid	274143: Displacement of FITC-Fg from integrin alpha2beta3 receptor expressed in human activated platelets	ic50	0.0010	uM
3-(3,4-dimethoxyphenyl)-3-[[3-nitro-5-(1,2,3,4-tetrahydroisoquinolin-7-ylcarbamoyl)benzoyl]amino]propanoic acid	274143: Displacement of FITC-Fg from integrin alpha2beta3 receptor expressed in human activated platelets	ic50	0.0037	uM
(4S,11E)-18-chloro-2-oxo-14-oxa-3,7,9-triazatricyclo[13.3.1.16,9]icosa-1(18),6(20),7,11,15(19),16-hexaene-4-carboxylic acid;hydrochloride	1067602: Antagonist activity at recombinant integrin alpha2 beta1 receptor (unknown origin) assessed as inhibition of interaction with biotinylated collagen type-1 after 3 hrs by solid phase ELISA-type assay	ic50	0.0040	uM
3-(4-methoxyphenyl)-3-[[3-nitro-5-(1,2,3,4-tetrahydroisoquinolin-7-ylcarbamoyl)benzoyl]amino]propanoic acid	274143: Displacement of FITC-Fg from integrin alpha2beta3 receptor expressed in human activated platelets	ic50	0.0050	uM
3-[3-oxo-5-(4-piperidin-4-ylbutanoylamino)-1H-isoindol-2-yl]propanoic acid;2,2,2-trifluoroacetic acid	620659: Displacement of FITC-labeled fibrinogen from alpha2beta3 in human platelets	ic50	0.0055	uM
(2S)-2-[[(2R,4R)-3-(benzenesulfonyl)-2,5-dimethyl-1,3-thiazolidine-4-carbonyl]amino]-3-(benzylcarbamoylamino)propanoic acid	1926204: Inhibition of alpha2beta1 integrin-mediated cell adhesion to type 1 collagen in human platelets incubated for 30 mins in presence of ADP by microplate reader analysis	ic50	0.0060	uM
3-[3-oxo-5-(1,2,3,4-tetrahydroisoquinoline-7-carbonylamino)-1H-isoindol-2-yl]propanoic acid;hydrochloride	620659: Displacement of FITC-labeled fibrinogen from alpha2beta3 in human platelets	ic50	0.0065	uM
3-[3-oxo-5-(1,2,3,4-tetrahydroisoquinoline-7-carbonylamino)-1H-isoindol-2-yl]butanoic acid;hydrochloride	620659: Displacement of FITC-labeled fibrinogen from alpha2beta3 in human platelets	ic50	0.0065	uM
3-[3-oxo-5-[(4-piperidin-4-ylbenzoyl)amino]-1H-isoindol-2-yl]propanoic acid;2,2,2-trifluoroacetic acid	620659: Displacement of FITC-labeled fibrinogen from alpha2beta3 in human platelets	ic50	0.0068	uM
3-[[3-nitro-5-(1,2,3,4-tetrahydroisoquinolin-7-ylcarbamoyl)benzoyl]amino]-3-phenylpropanoic acid	274143: Displacement of FITC-Fg from integrin alpha2beta3 receptor expressed in human activated platelets	ic50	0.0080	uM
3-[[3-(1,2,3,4-tetrahydroisoquinolin-7-ylcarbamoyl)benzoyl]amino]propanoic acid	274143: Displacement of FITC-Fg from integrin alpha2beta3 receptor expressed in human activated platelets	ic50	0.0090	uM
2-[[(4R)-3-(benzenesulfonyl)-5,5-dimethyl-1,3-thiazolidine-4-carbonyl]amino]-3-(benzylcarbamoylamino)propanoic acid	1647700: Inhibition of human alpha2 beta1 in human platelets assessed as reduction in platelet adhesion to collagen type 1 incubated for 30 mins	ic50	0.0120	uM
(3S,13E)-7-chloro-5-oxo-11-oxa-4,16-diazatetracyclo[14.6.1.16,10.017,22]tetracosa-1(23),6,8,10(24),13,17,19,21-octaene-3-carboxylic acid	1067602: Antagonist activity at recombinant integrin alpha2 beta1 receptor (unknown origin) assessed as inhibition of interaction with biotinylated collagen type-1 after 3 hrs by solid phase ELISA-type assay	ic50	0.0120	uM
(2S)-2-[[(4R)-3-(benzenesulfonyl)-5,5-dimethyl-1,3-thiazolidine-4-carbonyl]amino]-3-(benzylcarbamoylamino)propanoic acid	1926204: Inhibition of alpha2beta1 integrin-mediated cell adhesion to type 1 collagen in human platelets incubated for 30 mins in presence of ADP by microplate reader analysis	ic50	0.0120	uM
(2S)-2-[[(2S)-1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]-3-(benzylcarbamoylamino)propanoic acid	302373: Inhibition of integrin alpha-2-beta-1-mediated human platelets adhesion to collagen 1	ic50	0.0150	uM
(2S)-2-[[1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]-3-(benzylcarbamoylamino)propanoic acid	1797815: Human Platelet Adhesion Assay from Article 10.1021/jm070252b: “Small molecule inhibitors of integrin alpha2beta1.”	ic50	0.0150	uM
(2S)-2-[[(4R)-3-(benzenesulfonyl)-1,3-thiazolidine-4-carbonyl]amino]-3-(benzylcarbamoylamino)propanoic acid	1926204: Inhibition of alpha2beta1 integrin-mediated cell adhesion to type 1 collagen in human platelets incubated for 30 mins in presence of ADP by microplate reader analysis	ic50	0.0170	uM
(2S)-3-(benzylcarbamoylamino)-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carbonyl]amino]propanoic acid	1797815: Human Platelet Adhesion Assay from Article 10.1021/jm070252b: “Small molecule inhibitors of integrin alpha2beta1.”	ic50	0.0170	uM
3-[3-(1,2,3,4-tetrahydroisoquinoline-7-carbonylamino)propanoylamino]propanoic acid;hydrochloride	620659: Displacement of FITC-labeled fibrinogen from alpha2beta3 in human platelets	ic50	0.0220	uM
(2S)-3-[(4-aminophenyl)methylcarbamoylamino]-2-[[(2S)-1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]propanoic acid	302373: Inhibition of integrin alpha-2-beta-1-mediated human platelets adhesion to collagen 1	ic50	0.0230	uM
(2S)-3-[(4-aminophenyl)methylcarbamoylamino]-2-[[1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]propanoic acid	1797815: Human Platelet Adhesion Assay from Article 10.1021/jm070252b: “Small molecule inhibitors of integrin alpha2beta1.”	ic50	0.0230	uM
(2S)-2-[[(2R,4S)-3-(benzenesulfonyl)-2,5-dimethyl-1,3-oxazolidine-4-carbonyl]amino]-3-(benzylcarbamoylamino)propanoic acid	1926204: Inhibition of alpha2beta1 integrin-mediated cell adhesion to type 1 collagen in human platelets incubated for 30 mins in presence of ADP by microplate reader analysis	ic50	0.0250	uM
3-[[3-oxo-2-(2-piperidin-4-ylethyl)-1H-isoindole-5-carbonyl]amino]propanoic acid	620658: Antagonist activity at integrin alpha2beta3-mediated aggregation in ADP-stimulated human platelets	ic50	0.0250	uM
(2S)-3-(benzylcarbamoylamino)-2-[[(2S)-1-(3,5-dimethylphenyl)sulfonylpyrrolidine-2-carbonyl]amino]propanoic acid	1797815: Human Platelet Adhesion Assay from Article 10.1021/jm070252b: “Small molecule inhibitors of integrin alpha2beta1.”	ic50	0.0290	uM
3-[[3-nitro-5-(1,2,3,4-tetrahydroisoquinolin-7-ylcarbamoyl)benzoyl]amino]propanoic acid	274143: Displacement of FITC-Fg from integrin alpha2beta3 receptor expressed in human activated platelets	ic50	0.0320	uM
(4S,11E)-18-chloro-2-oxo-14-oxa-3,7,8,9-tetrazatricyclo[13.3.1.16,9]icosa-1(18),6(20),7,11,15(19),16-hexaene-4-carboxylic acid	1067602: Antagonist activity at recombinant integrin alpha2 beta1 receptor (unknown origin) assessed as inhibition of interaction with biotinylated collagen type-1 after 3 hrs by solid phase ELISA-type assay	ic50	0.0340	uM
(2S)-3-(benzylcarbamoylamino)-2-[[(2S)-1-(3,5-difluorophenyl)sulfonylpyrrolidine-2-carbonyl]amino]propanoic acid	1797815: Human Platelet Adhesion Assay from Article 10.1021/jm070252b: “Small molecule inhibitors of integrin alpha2beta1.”	ic50	0.0350	uM
(2S)-3-(benzylcarbamoylamino)-2-[[(2S)-1-(4-methylphenyl)sulfonylpyrrolidine-2-carbonyl]amino]propanoic acid	1797815: Human Platelet Adhesion Assay from Article 10.1021/jm070252b: “Small molecule inhibitors of integrin alpha2beta1.”	ic50	0.0360	uM
(4S,11E)-18-chloro-2-oxo-14-oxa-3,7,9,19-tetrazatricyclo[13.3.1.16,9]icosa-1(18),6(20),7,11,15(19),16-hexaene-4-carboxylic acid	1067602: Antagonist activity at recombinant integrin alpha2 beta1 receptor (unknown origin) assessed as inhibition of interaction with biotinylated collagen type-1 after 3 hrs by solid phase ELISA-type assay	ic50	0.0360	uM
3-[3-oxo-5-[(4-piperazin-1-ylbenzoyl)amino]-1H-isoindol-2-yl]butanoic acid;hydrochloride	620659: Displacement of FITC-labeled fibrinogen from alpha2beta3 in human platelets	ic50	0.0370	uM
(4S,11E)-18-chloro-2-oxo-14-oxa-3,6,7,8-tetrazatricyclo[13.3.1.16,9]icosa-1(18),7,9(20),11,15(19),16-hexaene-4-carboxylic acid	1067602: Antagonist activity at recombinant integrin alpha2 beta1 receptor (unknown origin) assessed as inhibition of interaction with biotinylated collagen type-1 after 3 hrs by solid phase ELISA-type assay	ic50	0.0380	uM
(2S)-3-(benzylcarbamoylamino)-2-[[(2S)-1-[3,5-bis(trifluoromethyl)phenyl]sulfonylpyrrolidine-2-carbonyl]amino]propanoic acid	1797815: Human Platelet Adhesion Assay from Article 10.1021/jm070252b: “Small molecule inhibitors of integrin alpha2beta1.”	ic50	0.0390	uM
(2S)-3-(benzylcarbamoylamino)-2-[[(2S)-1-naphthalen-2-ylsulfonylpyrrolidine-2-carbonyl]amino]propanoic acid	1797815: Human Platelet Adhesion Assay from Article 10.1021/jm070252b: “Small molecule inhibitors of integrin alpha2beta1.”	ic50	0.0500	uM
(2S)-3-(benzylcarbamoylamino)-2-[[(2S)-1-(4-methylsulfonylphenyl)sulfonylpyrrolidine-2-carbonyl]amino]propanoic acid	1797815: Human Platelet Adhesion Assay from Article 10.1021/jm070252b: “Small molecule inhibitors of integrin alpha2beta1.”	ic50	0.0700	uM
(2S)-2-[[(4S)-3-(benzenesulfonyl)-1,3-oxazolidine-4-carbonyl]amino]-3-(benzylcarbamoylamino)propanoic acid	1926204: Inhibition of alpha2beta1 integrin-mediated cell adhesion to type 1 collagen in human platelets incubated for 30 mins in presence of ADP by microplate reader analysis	ic50	0.0820	uM
(3S,13E)-7-chloro-5-oxo-11,16-dioxa-4-azatricyclo[15.2.2.16,10]docosa-1(20),6,8,10(22),13,17(21),18-heptaene-3-carboxylic acid	1067602: Antagonist activity at recombinant integrin alpha2 beta1 receptor (unknown origin) assessed as inhibition of interaction with biotinylated collagen type-1 after 3 hrs by solid phase ELISA-type assay	ic50	0.1010	uM
(2S)-3-(benzylcarbamoylamino)-2-[[(2S)-1-(4-nitrophenyl)sulfonylpyrrolidine-2-carbonyl]amino]propanoic acid	1797815: Human Platelet Adhesion Assay from Article 10.1021/jm070252b: “Small molecule inhibitors of integrin alpha2beta1.”	ic50	0.1050	uM
(3S)-7-chloro-5-oxo-12,17-dioxa-4-azatricyclo[16.2.2.06,11]docosa-1(21),6(11),7,9,18(22),19-hexaene-3-carboxylic acid	1067602: Antagonist activity at recombinant integrin alpha2 beta1 receptor (unknown origin) assessed as inhibition of interaction with biotinylated collagen type-1 after 3 hrs by solid phase ELISA-type assay	ic50	0.1060	uM
(2S)-2-[[1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]-3-[(2-chlorophenyl)methylcarbamoylamino]propanoic acid	1797815: Human Platelet Adhesion Assay from Article 10.1021/jm070252b: “Small molecule inhibitors of integrin alpha2beta1.”	ic50	0.1070	uM
(2S)-2-[[1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]-3-[(4-methoxyphenyl)methylcarbamoylamino]propanoic acid	1797815: Human Platelet Adhesion Assay from Article 10.1021/jm070252b: “Small molecule inhibitors of integrin alpha2beta1.”	ic50	0.1080	uM
(4S)-19-chloro-2-oxo-11,16-dioxa-3-azatricyclo[15.2.2.16,10]docosa-1(19),6(22),7,9,17,20-hexaene-4-carboxylic acid	1067602: Antagonist activity at recombinant integrin alpha2 beta1 receptor (unknown origin) assessed as inhibition of interaction with biotinylated collagen type-1 after 3 hrs by solid phase ELISA-type assay	ic50	0.1140	uM
1-[4-[[1-(4-fluorophenyl)pyrazol-4-yl]sulfonyl-methylamino]phenyl]-3-phenylurea	1647699: Inhibition of human alpha2 beta1 expressed in CHO cells assessed as reduction in cell adhesion to collagen type 1 incubated for 5 mins by DiOC6 dye based fluorescence microscopy	ec50	0.1300	uM
(2S)-2-[[(2S)-1-(4-acetamidophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-(benzylcarbamoylamino)propanoic acid	1797815: Human Platelet Adhesion Assay from Article 10.1021/jm070252b: “Small molecule inhibitors of integrin alpha2beta1.”	ic50	0.1310	uM
(3S,13E)-7-chloro-5-oxo-11,16-dioxa-4,18-diazatricyclo[15.2.2.16,10]docosa-1(19),6,8,10(22),13,17,20-heptaene-3-carboxylic acid	1067602: Antagonist activity at recombinant integrin alpha2 beta1 receptor (unknown origin) assessed as inhibition of interaction with biotinylated collagen type-1 after 3 hrs by solid phase ELISA-type assay	ic50	0.1340	uM
(4S)-20-chloro-2-oxo-11,16-dioxa-3-azatricyclo[15.3.1.16,10]docosa-1(20),6(22),7,9,17(21),18-hexaene-4-carboxylic acid	1067602: Antagonist activity at recombinant integrin alpha2 beta1 receptor (unknown origin) assessed as inhibition of interaction with biotinylated collagen type-1 after 3 hrs by solid phase ELISA-type assay	ic50	0.1420	uM
(2S)-2-[[(2S)-1-(4-aminophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-(benzylcarbamoylamino)propanoic acid	1797815: Human Platelet Adhesion Assay from Article 10.1021/jm070252b: “Small molecule inhibitors of integrin alpha2beta1.”	ic50	0.1440	uM
(2S)-3-(benzylcarbamoylamino)-2-[[(2S)-1-[4-(phenylcarbamoylamino)phenyl]sulfonylpyrrolidine-2-carbonyl]amino]propanoic acid	1797815: Human Platelet Adhesion Assay from Article 10.1021/jm070252b: “Small molecule inhibitors of integrin alpha2beta1.”	ic50	0.1510	uM
(2S)-2-[[1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]-3-[(3-methoxyphenyl)methylcarbamoylamino]propanoic acid	1797815: Human Platelet Adhesion Assay from Article 10.1021/jm070252b: “Small molecule inhibitors of integrin alpha2beta1.”	ic50	0.1600	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	8
Estradiol	affects expression, affects cotreatment, decreases expression, increases expression	7
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression	6
Tetrachlorodibenzodioxin	increases expression, affects cotreatment, decreases expression	4
Tobacco Smoke Pollution	affects expression, increases expression	4
Cyclosporine	increases expression, decreases expression	4
bisphenol A	affects reaction, affects expression, decreases methylation, increases expression	3
Aspirin	affects cotreatment, affects response to substance, decreases response to substance	3
Aflatoxin B1	affects expression, decreases methylation, increases expression	3
Particulate Matter	decreases reaction, increases expression, increases abundance	3
sodium arsenite	increases expression	2
cobaltous chloride	decreases expression, increases expression	2
perfluorooctanoic acid	increases expression	2
perfluorooctane sulfonic acid	increases expression	2
perfluoro-n-nonanoic acid	increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Clopidogrel	affects cotreatment, affects response to substance	2
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Arsenic Trioxide	decreases expression, decreases response to substance	2
Calcitriol	increases expression, affects cotreatment	2
Carbamazepine	affects expression	2
Copper	increases phosphorylation, increases reaction, affects binding, increases expression	2
Doxorubicin	decreases expression, increases expression	2
Plant Extracts	decreases expression, increases abundance, increases expression	2
Tetradecanoylphorbol Acetate	affects cotreatment, decreases reaction, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
napabucasin	decreases expression	1
sotorasib	affects cotreatment, decreases expression	1
fulvic acid	affects cotreatment, decreases reaction, increases expression	1

ChEMBL screening assays

21 unique, capped per target: 20 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1117468	Binding	Inhibition of integrin alpha-2-beta-3-mediated aggregation in ADP-stimulated platelets at 30 uM	Small molecule antagonist of leukocyte function associated antigen-1 (LFA-1): structure-activity relationships leading to the identification of 6-((5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonan-7-yl)nicotinic acid (BMS-688521). — J Med Chem
CHEMBL1839794	Functional	Antagonist activity at integrin alpha2beta3-mediated aggregation in ADP-stimulated human platelets	RGD mimetics containing phthalimidine fragment as novel ligands of fibrinogen receptor. — Bioorg Med Chem Lett

Cellosaurus cell lines

15 cell lines: 15 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_2510	HRA-19a1.1 Alpha2Alpha1 B	Cancer cell line	Male
CVCL_2511	HRA-19a1.1 Alpha2Alpha1 E	Cancer cell line	Male
CVCL_2512	HRA-19a1.1 Alpha2 B	Cancer cell line	Male
CVCL_2513	HRA-19a1.1 Alpha2 F	Cancer cell line	Male
CVCL_B1UV	Abcam HeLa ITGA2 KO	Cancer cell line	Female
CVCL_B8IQ	Abcam HCT 116 ITGA2 KO	Cancer cell line	Male
CVCL_B8XK	Abcam MCF-7 ITGA2 KO	Cancer cell line	Female
CVCL_B9L0	Abcam A-549 ITGA2 KO	Cancer cell line	Male
CVCL_D8NG	Ubigene HCT 116 ITGA2 KO	Cancer cell line	Male
CVCL_E2TA	HP-13b	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06435845	PHASE2	TERMINATED	Phase 2 Study on the Pharmacokinetics and Safety of RLYB212 in Pregnant Women at Higher Risk for HPA-1a Alloimmunization
NCT03561909	Not specified	COMPLETED	Kinetics of Blood Platelets Transfused to Healthy Subjects
NCT04067375	Not specified	COMPLETED	Towards Routine HPA-screening In Pregnancy to Prevent FNAIT
NCT04529382	Not specified	UNKNOWN	Neurodevelopmental Outcome After Fetal Neonatal AlloImmune Thrombocytopenia
NCT05345561	Not specified	COMPLETED	Study to Assess the Occurrence of HPA-1a Alloimmunization in Women With Higher Risk for Fetal and Neonatal Alloimmune Thrombocytopenia