ITGB2

Summary

ITGB2 (integrin subunit beta 2, HGNC:6155) is a protein-coding gene on chromosome 21q22.3, encoding Integrin beta-2 (P05107). Integrin ITGAL:ITGB2 is a receptor for ICAM1, ICAM2 and ICAM3.

This gene encodes an integrin beta chain, which combines with multiple different alpha chains to form different integrin heterodimers. Integrins are integral cell-surface proteins that participate in cell adhesion as well as cell-surface mediated signalling. The encoded protein plays an important role in immune response and defects in this gene cause leukocyte adhesion deficiency. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3689 — RefSeq curated summary.

At a glance

• Gene–disease (curated): leukocyte adhesion deficiency 1 (Definitive, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 936 total — 57 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 19
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000211

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6155
Approved symbol	ITGB2
Name	integrin subunit beta 2
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	LFA-1, MAC-1
Ensembl gene	ENSG00000160255
Ensembl biotype	protein_coding
OMIM	600065
Entrez	3689

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 30 protein_coding, 5 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000302347, ENST00000320216, ENST00000355153, ENST00000397846, ENST00000397850, ENST00000397852, ENST00000397854, ENST00000397857, ENST00000475170, ENST00000479202, ENST00000479849, ENST00000498666, ENST00000517563, ENST00000517819, ENST00000518033, ENST00000520389, ENST00000521987, ENST00000521995, ENST00000522688, ENST00000522931, ENST00000523126, ENST00000523323, ENST00000523663, ENST00000524251, ENST00000652462, ENST00000696946, ENST00000909411, ENST00000909412, ENST00000909413, ENST00000909414, ENST00000909415, ENST00000909416, ENST00000909417, ENST00000909418, ENST00000909419, ENST00000909420, ENST00000909421, ENST00000961802, ENST00000961803, ENST00000961804

RefSeq mRNA: 3 — MANE Select: NM_000211 NM_000211, NM_001127491, NM_001303238

CCDS: CCDS13716

Canonical transcript exons

ENST00000652462 — 16 exons

Exon	Start	End
ENSE00002135256	44920821	44920899
ENSE00003470757	44889978	44890222
ENSE00003475946	44886736	44886902
ENSE00003491446	44885953	44886430
ENSE00003562837	44891809	44891996
ENSE00003569344	44901492	44901733
ENSE00003596110	44893404	44893544
ENSE00003610265	44888693	44888895
ENSE00003621554	44889276	44889495
ENSE00003634407	44910725	44910785
ENSE00003648854	44900320	44900475
ENSE00003688153	44906915	44907095
ENSE00003692776	44894971	44895060
ENSE00003784896	44903365	44903535
ENSE00003786943	44899067	44899162
ENSE00003791070	44910284	44910372

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 99.68.

FANTOM5 (CAGE): breadth broad, TPM avg 150.6145 / max 2707.2181, expressed in 799 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190805	116.9182	594
190804	30.5094	515
190806	1.5215	297
190809	0.4939	168
190808	0.4385	144
190800	0.3246	162
190792	0.2110	131
190807	0.0903	49
190802	0.0511	31
190810	0.0337	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.68	gold quality
monocyte	CL:0000576	99.63	gold quality
leukocyte	CL:0000738	99.63	gold quality
mononuclear cell	CL:0000842	99.63	gold quality
blood	UBERON:0000178	99.34	gold quality
spleen	UBERON:0002106	98.28	gold quality
bone marrow cell	CL:0002092	98.27	gold quality
vermiform appendix	UBERON:0001154	97.81	gold quality
bone marrow	UBERON:0002371	97.22	gold quality
trabecular bone tissue	UBERON:0002483	97.21	gold quality
lymph node	UBERON:0000029	97.03	gold quality
right lung	UBERON:0002167	96.47	gold quality
bone element	UBERON:0001474	95.74	gold quality
upper lobe of left lung	UBERON:0008952	95.44	gold quality
upper lobe of lung	UBERON:0008948	95.10	gold quality
thymus	UBERON:0002370	94.25	gold quality
gall bladder	UBERON:0002110	93.99	gold quality
right coronary artery	UBERON:0001625	93.83	gold quality
periodontal ligament	UBERON:0008266	93.21	gold quality
caecum	UBERON:0001153	93.11	gold quality
lower lobe of lung	UBERON:0008949	92.86	gold quality
amniotic fluid	UBERON:0000173	92.45	gold quality
lung	UBERON:0002048	92.23	gold quality
decidua	UBERON:0002450	91.60	gold quality
descending thoracic aorta	UBERON:0002345	90.44	gold quality
omental fat pad	UBERON:0010414	90.42	gold quality
peritoneum	UBERON:0002358	90.37	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.97	gold quality
epithelium of nasopharynx	UBERON:0001951	89.61	gold quality

Single-cell (SCXA)

Detected in 29 experiment(s), a significant marker in 25.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	1232.86
E-MTAB-6701	yes	947.48
E-HCAD-4	yes	145.39
E-HCAD-1	yes	129.67
E-CURD-122	yes	82.04
E-MTAB-9467	yes	66.11
E-GEOD-135922	yes	53.32
E-MTAB-8410	yes	45.67
E-GEOD-84465	yes	43.28
E-HCAD-10	yes	42.85
E-CURD-46	yes	35.05
E-GEOD-134144	yes	33.59
E-CURD-112	yes	33.46
E-MTAB-10287	yes	29.77
E-MTAB-9221	yes	27.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CUX1, ETS1, GABPA, HIF1A, KLF5, NR3C1, POU2F1, RARA, RUNX1, RUNX3, SP1, SPI1, STAT3

miRNA regulators (miRDB)

15 targeting ITGB2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-6769A-5P	97.99	64.16	851
HSA-MIR-4494	97.86	64.93	850
HSA-MIR-4732-3P	97.15	65.45	881
HSA-MIR-1226-5P	96.50	65.28	643
HSA-MIR-3675-5P	95.90	65.80	474

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• determined the spatial relationship and functional properties of the integrin beta(2) NTR and mid-region (PMID:11477072)
• Studies of CD18 activation epitopes show that stimulation of T lymphocytes appears to be accompanied by a conformational change in a subpopulation of LFA-1 that does not require ligand binding. (PMID:11714770)
• role in Leukocyte adhesion deficiency syndromes (PMID:11753075)
• Small molecule inhibitors induce conformational changes in the I domain and the I-like domain of LFA-1 (PMID:11781316)
• mutations and polymorphisms in leukocyte adhesion deficiency [review] (PMID:11831866)
• Down-regulation of cell adhesion molecules LFA-1 and ICAM-1 after in vitro treatment with the anti-TNF-alpha agent thalidomide. (PMID:11838958)
• identification of mutations in CD18 from genomic DNA from patients with leukocyte adhesion deficiency (PMID:11882363)
• NMR structure: Cysteine-rich module structure reveals a fulcrum for integrin rearrangement upon activation (PMID:11896403)
• role of the specificity-determining loop of the integrin beta subunit I-like domain in autonomous expression, association with the alpha subunit, and ligand binding (PMID:11914080)
• beta1 and beta2 integrins activate different signalling pathways in monocytes. (PMID:11931654)
• No association between the CD14 C(-260)T and CD18 codon 441 gene polymorphisms and the incidence of stroke was found in a large, prospective, matched case-control sample from the Physicians’ Health Study. (PMID:11935032)
• CD18 may play an important role in pathogenic process(in COPD) (PMID:11953106)
• novel role for beta1 integrin in regulating fibroblast viability through a PI3K/Akt/protein kinase B signaling pathway in response to a matrix-derived mechanical stimulus (PMID:11986332)
• beta2 integrin avidity in neutrophils regulated by protein kinase A (PMID:12050191)
• The active form of LFA-1 regulates its own function on primary T cells by directing the remodeling of the F-actin cytoskeleton to strengthen T cell adhesion to ICAM-1. (PMID:12055249)
• ICAM-1/beta2 integrin(CD18 antigen) interactions mediate monocyte adhesion to human saphenous vein (PMID:12097820)
• There was a trend toward increased expression of CD18 in Crohn’s disease (PMID:12139949)
• Increased expression of CD11b/CD18 adhesion molecules was obtained in PV and ET patients, which could be associated with increased leukocyte adehesiveness contributing to the hypercoagulable state. (PMID:12145463)
• LFA-1 integrin activation by chemokines requires cholesterol (PMID:12163503)
• role of Rap1 GTPase for Mn(2+)- and antibody-induced VLA-4-mediated cell adhesion [VLA-4] (PMID:12171996)
• Decreased stroma adhesion capacity of CD34+ progenitor cells from mobilized peripheral blood is not lineage- or stage-specific and is associated with low beta 1 and beta 2 integrin expression. (PMID:12183834)
• a modest increase in ischemic time results in conversion from a CD18-dependent to a CD18-independent muscle ischemia-reperfusion injury (PMID:12200369)
• Porphyromonas gingivalis fimbriae activate human peripheral blood monocytes utilizing TLR2, CD14 and CD11a/CD18 as cellular receptors. (PMID:12207338)
• Mac-1 (CD18) plays an essential role in establishing SIgA-Fc alpha RI interactions and subsequent neutrophil activation. (PMID:12244179)
• identification of functional segments within the beta2I-domain (PMID:12324470)
• Transition from rolling to firm adhesion is regulated by the conformation of the I domain (PMID:12368274)
• investigation of molecular basis for broad ligand recognition (PMID:12377763)
• CD18 plays a role in the migration of interstitial dendritic cells in vivo (PMID:12377933)
• iIgA promotes neutrophil apoptosis through a mechanism dependent on CD18 cooperation, which involves the activation of the respiratory burst (PMID:12377937)
• TNF-induced respiratory burst by polymorphonuclear leukocytes residing on fibronectin is mediated by alpha(L)beta(2) (PMID:12377941)
• Data suggest that calcium activation of calpain causes beta2 integrin liberation, and that this signal plays a key role in the acceleration of beta2 integrin-mediated phagocytosis. (PMID:12379807)
• The mechanism that regulates the unmasking of the integrin beta 2 cryptic binding site in the gamma C-domain of fibrinogen has been identified. (PMID:12390020)
• recognition of uPA by alpha(M)beta(2) allows for formation of a multicontact trimolecular complex, in which a single uPA ligand may bind to both uPAR and alpha(M)beta(2); interaction of uPA with each receptor influences cell adhesion and migration (PMID:12393547)
• Function of the lectin domain of Mac-1/complement receptor type 3 (CD11b/CD18) in regulating neutrophil adhesion. (PMID:12444150)
• Adhesion of dendritic cells derived from CD34+ progenitors to resting human dermal microvascular endothelial cells is down-regulated upon maturation and partially depends on CD11a-CD18, CD11b-CD18 and CD36. (PMID:12516552)
• 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)
• Level of expression of the adhesion molecule/complement receptor CD11b/CD18 and the chemokine receptor IL-8 receptor-A was also higher after vaginal delivery. (PMID:12576754)
• the expression of ICAM-1 might involve both p38 MAPK and NF-kappaB activities, whereas the regulation of CD11b, CD18, and ICAM-3 expressions might be mediated through p38 MAPK but not NF-kappaB. (PMID:12600815)
• review of activation pathways for ITGB2 and other leukocyte adhesion molecules (PMID:12617168)
• Strongly expressed in histological type II of rheumatoid arthritis. (PMID:12643440)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	itgb2	ENSDARG00000016939
mus_musculus	Itgb2	ENSMUSG00000000290
rattus_norvegicus	Itgb2	ENSRNOG00000001224
drosophila_melanogaster	mys	FBGN0004657
caenorhabditis_elegans		WBGENE00003930

Paralogs (8): ITGB5 (ENSG00000082781), ITGB8 (ENSG00000105855), ITGB6 (ENSG00000115221), ITGB4 (ENSG00000132470), ITGB7 (ENSG00000139626), ITGB1 (ENSG00000150093), ITGBL1 (ENSG00000198542), ITGB3 (ENSG00000259207)

Protein

Protein identifiers

Integrin beta-2 — P05107 (reviewed: P05107)

Alternative names: Cell surface adhesion glycoproteins LFA-1/CR3/p150,95 subunit beta, Complement receptor C3 subunit beta

All UniProt accessions (15): P05107, A0A494C0X7, A0AAA9WZN5, A8MVG7, D3DSM0, E5RFI0, E5RGK9, E5RHE6, E5RHT0, E5RIE4, E5RIG7, E5RK25, E5RK54, E7EVZ9, J3KNI6

UniProt curated annotations — full annotation on UniProt →

Function. Integrin ITGAL:ITGB2 is a receptor for ICAM1, ICAM2 and ICAM3. Integrin ITGAL:ITGB2 is also a receptor for the secreted form of ubiquitin-like protein ISG15; the interaction is mediated by ITGAL. Integrins ITGAM:ITGB2 and ITGAX:ITGB2 are receptors for the iC3b fragment of the third complement component and for fibrinogen. Integrin ITGAX:ITGB2 recognizes the sequence G-P-R in fibrinogen alpha-chain. Integrin ITGAM:ITGB2 recognizes P1 and P2 peptides of fibrinogen gamma chain. Integrin ITGAM:ITGB2 is also a receptor for factor X. Integrin ITGAD:ITGB2 is a receptor for ICAM3 and VCAM1. Contributes to natural killer cell cytotoxicity. Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils. Triggers neutrophil transmigration during lung injury through PTK2B/PYK2-mediated activation. Integrin ITGAL:ITGB2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages. In association with alpha subunit ITGAM/CD11b, required for CD177-PRTN3-mediated activation of TNF primed neutrophils. Integrins ITGAX:ITGB2 functions as a receptor of the erythrocyte-specific adhesion molecule ICAM4 and mediates erythrophagocytosis. Integrins ITGAX:ITGB2 functions as a receptor of the neuron-specific adhesion molecule ICAM5 ensuring neuron cell-leukocyte adhesion. Integrin ITGAL:ITGB2 functions as a receptor of ICAM1 by acting as a platform at the immunological synapse to translate TCR engagement and density of the ITGAL ligand ICAM1 into graded adhesion. Integrin ITGAM:ITGB2/MAC-1 complex functions as a signaling receptor for the ligand receptor ICAM1, ensuring adhesion between stimulated neutrophils and stimulated endothelial cells. Integrin ITGAL/ITGB2 that functions as a signaling receptor of ICAM2, ensuring leukocyte cell-cell adhesion on resting cells.

Subunit / interactions. Heterodimer of an alpha and a beta subunit. The ITGB2 beta subunit associates with the ITGAL, ITGAM, ITGAX or ITGAD alpha subunits. Found in a complex with CD177 and ITGAM/CD11b. Interacts with FGR. Interacts with COPS5 and RANBP9. Interacts with FLNA (via filamin repeats 4, 9, 12, 17, 19, 21, and 23). Interacts with THBD.

Subcellular location. Cell membrane. Membrane raft.

Tissue specificity. Leukocytes. Expressed in neutrophils (at protein level).

Post-translational modifications. Both Ser-745 and Ser-756 become phosphorylated when T-cells are exposed to phorbol esters. Phosphorylation on Thr-758 (but not on Ser-756) allows interaction with 14-3-3 proteins.

Disease relevance. Leukocyte adhesion deficiency 1 (LAD1) [MIM:116920] LAD1 patients have recurrent bacterial infections and their leukocytes are deficient in a wide range of adhesion-dependent functions. 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.

Similarity. Belongs to the integrin beta chain family.

RefSeq proteins (3): NP_000202, NP_001120963, NP_001290167 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002369	Integrin_bsu_VWA	Domain
IPR012896	Integrin_bsu_tail	Domain
IPR014836	Integrin_bsu_cyt_dom	Domain
IPR015439	Integrin_b-2_sf	Homologous_superfamily
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
IPR057073	EGF_integrin_2	Domain
IPR057243	Integrin_I-EGF_CS	Conserved_site

Pfam: PF00362, PF07965, PF08725, PF17205, PF23105

UniProt features (175 total): strand 57, disulfide bond 28, helix 27, sequence variant 16, binding site 13, domain 6, modified residue 6, glycosylation site 6, turn 5, sequence conflict 4, topological domain 2, signal peptide 1, chain 1, short sequence motif 1, transmembrane region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
2P26	X-RAY DIFFRACTION	1.75
5E6X	X-RAY DIFFRACTION	1.75
1YUK	X-RAY DIFFRACTION	1.8
5E6V	X-RAY DIFFRACTION	1.8
5E6S	X-RAY DIFFRACTION	2.15
2JF1	X-RAY DIFFRACTION	2.2
2P28	X-RAY DIFFRACTION	2.2
5E6W	X-RAY DIFFRACTION	2.2
2V7D	X-RAY DIFFRACTION	2.5
5E6U	X-RAY DIFFRACTION	2.5
9RM9	ELECTRON MICROSCOPY	2.6
7USL	ELECTRON MICROSCOPY	2.7
7USM	ELECTRON MICROSCOPY	2.7
9T5W	ELECTRON MICROSCOPY	2.74
4NEH	X-RAY DIFFRACTION	2.75
5E6R	X-RAY DIFFRACTION	2.9
4NEN	X-RAY DIFFRACTION	2.9
9T5V	ELECTRON MICROSCOPY	3.06
9T5Z	ELECTRON MICROSCOPY	3.1
7P2D	X-RAY DIFFRACTION	3.2
5ES4	X-RAY DIFFRACTION	3.3
9T3Y	ELECTRON MICROSCOPY	3.44
3K6S	X-RAY DIFFRACTION	3.5
3K72	X-RAY DIFFRACTION	3.7
3K71	X-RAY DIFFRACTION	3.95
1L3Y	SOLUTION NMR
5XR1	SOLUTION NMR
5ZAZ	SOLUTION NMR
9ECL	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05107-F1	86.02	0.51

Antibody-complex structures (SAbDab): 2 — 7P2D, 7USL

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 (13): 136 (in midas binding site); 138 (in admidas binding site); 138 (in midas binding site); 141 (in admidas binding site); 142 (in admidas binding site); 173 (in limbs binding site); 229 (in limbs binding site); 231 (in limbs binding site); 233 (in limbs binding site); 234 (in limbs binding site); 234 (in midas binding site); 264 (in admidas binding site and liganded-open conformation) …

Post-translational modifications (6): 23, 745, 756, 758, 759, 760

Disulfide bonds (28): 25–43, 33–447, 36–62, 46–73, 191–198, 246–286, 386–400, 420–445, 449–467, 459–470, 472–481, 483–514, 497–512, 506–517, 519–534, 536–559, 541–557, 549–562, 564–573, 575–598 …

Glycosylation sites (6): 50, 116, 212, 254, 501, 642

Mutagenesis-validated functional residues (1):

Position	Phenotype
758	abolishes phosphorylation. reduces cos cell adhesion to icam1.

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-216083	Integrin cell surface interactions
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-6798695	Neutrophil degranulation
R-HSA-109582	Hemostasis
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1280218	Adaptive Immune System
R-HSA-1474244	Extracellular matrix organization
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-449147	Signaling by Interleukins

MSigDB gene sets: 621 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, FERRANDO_TAL1_NEIGHBORS, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GNF2_MSN, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, MODULE_169, GOBP_CELL_CHEMOTAXIS, GOBP_REGULATION_OF_PHOSPHORYLATION

GO Biological Process (34): microglial cell activation (GO:0001774), leukocyte migration involved in inflammatory response (GO:0002523), receptor-mediated endocytosis (GO:0006898), phagocytosis, engulfment (GO:0006911), apoptotic process (GO:0006915), inflammatory response (GO:0006954), cell adhesion (GO:0007155), leukocyte cell-cell adhesion (GO:0007159), cell-matrix adhesion (GO:0007160), integrin-mediated signaling pathway (GO:0007229), cell-cell signaling (GO:0007267), regulation of cell shape (GO:0008360), neutrophil chemotaxis (GO:0030593), receptor internalization (GO:0031623), positive regulation of superoxide anion generation (GO:0032930), cell adhesion mediated by integrin (GO:0033627), heterotypic cell-cell adhesion (GO:0034113), endodermal cell differentiation (GO:0035987), receptor clustering (GO:0043113), positive regulation of neutrophil degranulation (GO:0043315), endothelial cell migration (GO:0043542), cellular extravasation (GO:0045123), positive regulation of nitric oxide biosynthetic process (GO:0045429), positive regulation of angiogenesis (GO:0045766), negative regulation of dopamine metabolic process (GO:0045963), regulation of peptidyl-tyrosine phosphorylation (GO:0050730), cellular response to low-density lipoprotein particle stimulus (GO:0071404), positive regulation of protein targeting to membrane (GO:0090314), amyloid-beta clearance (GO:0097242), cell-cell adhesion (GO:0098609), obsolete cell-cell adhesion via plasma-membrane adhesion molecules (GO:0098742), positive regulation of leukocyte adhesion to vascular endothelial cell (GO:1904996), neutrophil migration (GO:1990266), phagocytosis (GO:0006909)

GO Molecular Function (11): amyloid-beta binding (GO:0001540), complement component C3b binding (GO:0001851), integrin binding (GO:0005178), protein kinase binding (GO:0019901), ICAM-3 receptor activity (GO:0030369), heat shock protein binding (GO:0031072), metal ion binding (GO:0046872), cell adhesion molecule binding (GO:0050839), protein binding (GO:0005515), cargo receptor activity (GO:0038024), protein-containing complex binding (GO:0044877)

GO Cellular Component (18): plasma membrane (GO:0005886), focal adhesion (GO:0005925), integrin complex (GO:0008305), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020), integrin alphaL-beta2 complex (GO:0034687), integrin alphaM-beta2 complex (GO:0034688), integrin alphaX-beta2 complex (GO:0034689), integrin alphaD-beta2 complex (GO:0034690), specific granule membrane (GO:0035579), signaling receptor complex (GO:0043235), plasma membrane raft (GO:0044853), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821), ficolin-1-rich granule membrane (GO:0101003), extracellular vesicle (GO:1903561), membrane raft (GO:0045121)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Immune System	3
Innate Immune System	2
Toll-like Receptor Cascades	1
Adaptive Immune System	1
Hemostasis	1
Extracellular matrix organization	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
integrin complex	4
plasma membrane	3
secretory granule membrane	3
cell-cell adhesion	2
protein binding	2
binding	2
cellular anatomical structure	2
tertiary granule	2
leukocyte activation involved in inflammatory response	1
macrophage activation	1
glial cell activation	1
inflammatory response	1
leukocyte migration	1
endocytosis	1
phagocytosis	1
plasma membrane invagination	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
defense response	1
cellular process	1
cell-substrate adhesion	1
cell surface receptor signaling pathway	1
cell communication	1
signaling	1
regulation of cell morphogenesis	1
regulation of biological quality	1
granulocyte chemotaxis	1
neutrophil migration	1
receptor-mediated endocytosis	1
regulation of superoxide anion generation	1
superoxide anion generation	1
positive regulation of reactive oxygen species metabolic process	1
cell adhesion	1
endoderm formation	1
cell differentiation	1
protein localization to membrane	1
positive regulation of myeloid leukocyte mediated immunity	1
positive regulation of leukocyte degranulation	1
neutrophil degranulation	1

Protein interactions and networks

STRING

3698 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITGB2	ICAM1	P05362	999
ITGB2	ITGAL	P20701	999
ITGB2	ITGAM	P11215	999
ITGB2	ITGAX	P20702	998
ITGB2	VCAM1	P19320	997
ITGB2	ITGAD	Q13349	997
ITGB2	ICAM2	P13598	995
ITGB2	SELE	P16111	993
ITGB2	ICAM3	P32942	992
ITGB2	F11R	Q9Y624	987
ITGB2	JAM3	Q9BX67	983
ITGB2	C3	P01024	980
ITGB2	GP1BA	P07359	977
ITGB2	SELP	P16109	975
ITGB2	TLN1	Q9Y490	973

IntAct

107 interactions, top by confidence:

A	B	Type	Score
ITGB2	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.780
NOTCH2NLA	ITGB2	psi-mi:“MI:0915”(physical association)	0.780
ITGAX	ITGB2	psi-mi:“MI:0407”(direct interaction)	0.660
ITGB2	RANBP9	psi-mi:“MI:0915”(physical association)	0.610
RANBP9	ITGB2	psi-mi:“MI:0915”(physical association)	0.610
RANBP9	ITGB2	psi-mi:“MI:0407”(direct interaction)	0.610
RANBP9	ITGB2	psi-mi:“MI:0403”(colocalization)	0.610
TLN2	ITGB2	psi-mi:“MI:0915”(physical association)	0.600
ITGB2	TLN2	psi-mi:“MI:0915”(physical association)	0.600
TLN2	ITGB2	psi-mi:“MI:0407”(direct interaction)	0.600
ITGB2	MTIF3	psi-mi:“MI:0915”(physical association)	0.560
ITGB2	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
ITGB2	NOTCH2NLC	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	ITGB2	psi-mi:“MI:0915”(physical association)	0.560
ITGB2	SCML1	psi-mi:“MI:0915”(physical association)	0.560
ITGB2	APOL2	psi-mi:“MI:0915”(physical association)	0.560
ITGB2	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
ITGB2	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
ITGB2	KRT31	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (79): NOTCH2NL (Two-hybrid), ITGB2 (Two-hybrid), ITGB2 (Reconstituted Complex), GNB2L1 (Two-hybrid), ITGB2 (PCA), SHARPIN (Far Western), ITGB2 (Reconstituted Complex), FHL2 (Affinity Capture-Western), NOTCH2NL (Two-hybrid), PLAUR (Affinity Capture-Western), ITGB2 (Affinity Capture-MS), ITGB2 (Affinity Capture-Western), LCP1 (Affinity Capture-Western), ITGB2 (Affinity Capture-MS), ITGB2 (Two-hybrid)

ESM2 similar proteins: A0A8M9PFP2, A2A863, A5Z1X6, B0FYY4, B2RXS4, O13146, O15031, O73875, P05107, P05556, P07228, P09055, P09958, P11584, P11835, P12606, P12607, P16144, P18563, P18564, P23188, P23229, P23377, P26007, P26010, P26011, P29317, P32592, P49134, P53712, P53713, P53714, P97278, Q13753, Q1KL86, Q1RPR6, Q27874, Q28193, Q29052, Q2VJ42

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

23 interactions.

A	Effect	B	Mechanism
PRKCD	“up-regulates activity”	ITGB2	phosphorylation
PRKCD	up-regulates	ITGB2	phosphorylation
PRKCH	unknown	ITGB2	phosphorylation
PRKCB	unknown	ITGB2	phosphorylation
PRKCD	unknown	ITGB2	phosphorylation
PRKCA	unknown	ITGB2	phosphorylation
PTPRG	“down-regulates activity”	ITGB2
JAK2	“up-regulates activity”	ITGB2	phosphorylation
SRC	“down-regulates activity”	ITGB2	phosphorylation
ITGB1BP1	“down-regulates activity”	ITGB2	binding
DOK1	“down-regulates activity”	ITGB2	binding
ITGB2	“up-regulates activity”	PTK2
Kindlin	“up-regulates activity”	ITGB2	binding
TLN1	“up-regulates activity”	ITGB2	binding
ITGB2	“form complex”	“AL/b2 integrin”	binding
ITGB2	“form complex”	“AM/b2 integrin”	binding
ITGB2	“form complex”	“AX/b2 integrin”	binding
ITGB2	“form complex”	“AD/b2 integrin”	binding
ITGB2	“form complex”	“Av/b2 integrin”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 55 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
Signaling by Interleukins	5	9.7×	4e-03
Hemostasis	7	7.6×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
Fc-gamma receptor signaling pathway involved in phagocytosis	5	76.3×	3e-06
integrin-mediated signaling pathway	5	17.4×	2e-03
cell-cell adhesion	6	13.2×	2e-03
positive regulation of cell migration	6	8.1×	5e-03
cell adhesion	8	6.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	57
Likely pathogenic	17
Uncertain significance	344
Likely benign	353
Benign	69

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
100744	NM_000211.5(ITGB2):c.1030G>T (p.Glu344Ter)	Pathogenic
100747	NM_000211.5(ITGB2):c.1143del (p.Tyr382fs)	Pathogenic
100748	NM_000211.5(ITGB2):c.1877+2T>C	Pathogenic
100750	NM_000211.5(ITGB2):c.1907del (p.Lys636fs)	Pathogenic
100757	NM_000211.5(ITGB2):c.576dup (p.Asn193fs)	Pathogenic
100762	NM_000211.5(ITGB2):c.843del (p.Asn282fs)	Pathogenic
100764	NM_000211.5(ITGB2):c.897+1G>T	Pathogenic
1012309	NM_000211.5(ITGB2):c.1657+1G>T	Pathogenic
1064458	NM_000211.5(ITGB2):c.305_306del (p.Lys102fs)	Pathogenic
1324597	NM_000211.5(ITGB2):c.1491C>A (p.Cys497Ter)	Pathogenic
1365830	NM_000211.5(ITGB2):c.1057del (p.Val353fs)	Pathogenic
1386540	NM_000211.5(ITGB2):c.1759del (p.Arg587fs)	Pathogenic
1453796	NM_000211.5(ITGB2):c.1537_1538del (p.Val513fs)	Pathogenic
1454255	NM_000211.5(ITGB2):c.1367dup (p.Ser457fs)	Pathogenic
1455590	NM_000211.5(ITGB2):c.2036del (p.Gln679fs)	Pathogenic
1705747	NM_000211.5(ITGB2):c.616C>T (p.His206Tyr)	Pathogenic
1936220	NM_000211.5(ITGB2):c.949C>T (p.Gln317Ter)	Pathogenic
1982798	NM_000211.5(ITGB2):c.1168_1180del (p.Val390fs)	Pathogenic
1987390	NM_000211.5(ITGB2):c.239del (p.Asp80fs)	Pathogenic
2138401	NM_000211.5(ITGB2):c.59-10C>A	Pathogenic
2422587	NC_000021.8:g.(?46309171)(46310157_?)del	Pathogenic
265200	NM_000211.5(ITGB2):c.1602C>A (p.Cys534Ter)	Pathogenic
2810773	NM_000211.5(ITGB2):c.1275del (p.Phe426fs)	Pathogenic
2825893	NM_000211.5(ITGB2):c.433_436del (p.Asn145fs)	Pathogenic
2849090	NM_000211.5(ITGB2):c.851_854dup (p.Cys286fs)	Pathogenic
2860611	NM_000211.5(ITGB2):c.185del (p.Cys62fs)	Pathogenic
2910470	NM_000211.5(ITGB2):c.954del (p.Ile319fs)	Pathogenic
2982971	NM_000211.5(ITGB2):c.1471C>T (p.Gln491Ter)	Pathogenic
3248149	NC_000021.8:g.(?46308588)(46310157_?)del	Pathogenic
3652754	NM_000211.5(ITGB2):c.1125del (p.Asp376fs)	Pathogenic

SpliceAI

3049 predictions. Top by Δscore:

Variant	Effect	Δscore
21:44886731:CTTA:C	donor_loss	1.0000
21:44886732:TTA:T	donor_loss	1.0000
21:44886734:A:AC	donor_gain	1.0000
21:44886734:AC:A	donor_loss	1.0000
21:44886735:C:CA	donor_gain	1.0000
21:44886735:CA:C	donor_gain	1.0000
21:44886735:CAT:C	donor_gain	1.0000
21:44886735:CATT:C	donor_gain	1.0000
21:44886735:CATTG:C	donor_gain	1.0000
21:44886898:ACACT:A	acceptor_gain	1.0000
21:44886899:CACT:C	acceptor_gain	1.0000
21:44886899:CACTC:C	acceptor_gain	1.0000
21:44886901:CT:C	acceptor_gain	1.0000
21:44886902:TC:T	acceptor_loss	1.0000
21:44886903:C:CC	acceptor_gain	1.0000
21:44886903:CTA:C	acceptor_loss	1.0000
21:44886904:T:C	acceptor_loss	1.0000
21:44888687:CCTCA:C	donor_loss	1.0000
21:44888688:CTCAC:C	donor_loss	1.0000
21:44888689:TCA:T	donor_loss	1.0000
21:44888690:CAC:C	donor_loss	1.0000
21:44890220:CAC:C	acceptor_gain	1.0000
21:44893540:AGTTT:A	acceptor_gain	1.0000
21:44893541:GTTT:G	acceptor_gain	1.0000
21:44893542:TTT:T	acceptor_gain	1.0000
21:44893543:TT:T	acceptor_gain	1.0000
21:44894969:A:AC	donor_gain	1.0000
21:44894970:C:CC	donor_gain	1.0000
21:44899062:CTCA:C	donor_loss	1.0000
21:44899063:TCA:T	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000013297 (21:44911000 C>T), RS1000099566 (21:44904639 GCA>G), RS1000111849 (21:44898838 C>A), RS1000142643 (21:44899734 C>G), RS1000190335 (21:44924647 A>G), RS1000214927 (21:44899620 A>G), RS1000223175 (21:44924396 T>C), RS1000246667 (21:44902206 G>A), RS1000305404 (21:44894426 G>A), RS1000363706 (21:44914329 C>T), RS1000374915 (21:44890123 G>T), RS1000400543 (21:44928810 A>G,T), RS1000504699 (21:44928462 C>T), RS1000511783 (21:44888367 G>A), RS1000730565 (21:44902846 G>A,T)

Disease associations

OMIM: gene MIM:600065 | disease phenotypes: MIM:116920, MIM:612840

GenCC curated gene-disease

Disease	Classification	Inheritance
leukocyte adhesion deficiency 1	Definitive	Autosomal recessive

Mondo (2): leukocyte adhesion deficiency 1 (MONDO:0007293), leukocyte adhesion deficiency 3 (MONDO:0013016)

Orphanet (3): Leukocyte adhesion deficiency (Orphanet:2968), Leukocyte adhesion deficiency type I (Orphanet:99842), Leukocyte adhesion deficiency type III (Orphanet:99844)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000230	Gingivitis
HP:0000704	Periodontitis
HP:0001058	Poor wound healing
HP:0001974	Increased total leukocyte count
HP:0002028	Chronic diarrhea
HP:0002718	Recurrent bacterial infections
HP:0002719	Recurrent infections
HP:0002728	Chronic mucocutaneous candidiasis
HP:0002754	Osteomyelitis
HP:0003623	Neonatal onset
HP:0005224	Rectal abscess
HP:0005420	Recurrent gram-negative bacterial infections
HP:0007499	Recurrent staphylococcal infections
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0011899	Hyperfibrinogenemia
HP:0032434	Delayed umbilical cord separation
HP:0032435	Neonatal omphalitis
HP:0200042	Skin ulcer

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST006288_691	Heel bone mineral density	6.000000e-09
GCST006288_90	Heel bone mineral density	3.000000e-07
GCST011780_9	Neonatal white matter microstructure	3.000000e-06
GCST90002388_592	Lymphocyte count	6.000000e-10
GCST90002388_593	Lymphocyte count	7.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0005674	white matter microstructure measurement
EFO:0004587	lymphocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C567555	Leukocyte Adhesion Deficiency, Type III (supp.)
C535887	Leukocyte adhesion deficiency type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL2096661 (PROTEIN COMPLEX), CHEMBL2111362 (PROTEIN COMPLEX), CHEMBL2364172 (PROTEIN COMPLEX), CHEMBL3631 (SINGLE PROTEIN), CHEMBL4106121 (PROTEIN-PROTEIN INTERACTION), CHEMBL5465394 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 93,540 (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
CHEMBL2048028	LIFITEGRAST	4	1,078
CHEMBL503	LOVASTATIN	4	92,462

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Integrins

ChEMBL bioactivities

555 potent at pChembl≥5 of 618 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL336789
9.46	IC50	0.35	nM	CHEMBL488318
9.41	IC50	0.39	nM	CHEMBL4794300
9.40	IC50	0.4	nM	CHEMBL452882
9.30	IC50	0.5	nM	CHEMBL472841
9.30	IC50	0.5	nM	CHEMBL520731
9.30	IC50	0.5	nM	CHEMBL337562
9.22	IC50	0.6	nM	CHEMBL502756
9.08	IC50	0.84	nM	CHEMBL88478
9.05	IC50	0.9	nM	CHEMBL485857
9.03	IC50	0.94	nM	CHEMBL444773
8.92	IC50	1.2	nM	CHEMBL1644132
8.85	IC50	1.4	nM	CHEMBL450871
8.85	IC50	1.4	nM	CHEMBL491402
8.85	IC50	1.4	nM	CHEMBL521080
8.77	IC50	1.7	nM	CHEMBL478464
8.74	IC50	1.8	nM	CHEMBL526564
8.70	IC50	2	nM	CHEMBL2048036
8.70	IC50	2	nM	CHEMBL521708
8.70	IC50	2	nM	CHEMBL139349
8.68	IC50	2.1	nM	CHEMBL496945
8.62	IC50	2.4	nM	CHEMBL515393
8.60	IC50	2.5	nM	CHEMBL497978
8.60	IC50	2.5	nM	CHEMBL487705
8.52	IC50	3	nM	CHEMBL2048025
8.52	IC50	3	nM	CHEMBL262911
8.52	IC50	3	nM	CHEMBL502789
8.49	IC50	3.2	nM	CHEMBL500859
8.47	IC50	3.4	nM	CHEMBL446300
8.47	IC50	3.4	nM	CHEMBL443467
8.43	IC50	3.7	nM	CHEMBL524347
8.41	IC50	3.9	nM	CHEMBL495906
8.40	IC50	4	nM	CHEMBL2048402
8.40	IC50	4	nM	CHEMBL502512
8.40	IC50	4	nM	CHEMBL139068
8.40	IC50	4	nM	CHEMBL138185
8.36	IC50	4.4	nM	CHEMBL479061
8.30	IC50	5	nM	CHEMBL1222290
8.30	IC50	5	nM	CHEMBL1222288
8.30	IC50	5	nM	CHEMBL1644129
8.30	IC50	5	nM	CHEMBL423725
8.30	IC50	5	nM	CHEMBL343390
8.30	IC50	5	nM	CHEMBL369143
8.28	IC50	5.2	nM	CHEMBL88478
8.27	IC50	5.4	nM	CHEMBL489362
8.22	IC50	6	nM	CHEMBL2048024
8.22	IC50	6	nM	CHEMBL215170
8.22	IC50	6	nM	CHEMBL487702
8.22	IC50	6	nM	CHEMBL337322
8.22	IC50	6	nM	CHEMBL344897

PubChem BioAssay actives

554 with measured affinity, of 878 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
1-[(E)-3-[4-(2-methoxyphenyl)sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-enoyl]piperidine-4-carboxylic acid	94614: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range(2-8)	ic50	0.0001	uM
(E)-1-morpholin-4-yl-3-[4-[3-[(1-propan-2-ylpiperidin-4-yl)amino]phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0003	uM
2-[1-[(4-aminophenyl)methylcarbamoyl]-4-oxoazetidin-2-yl]acetic acid;2,2,2-trifluoroacetic acid	1686207: Antagonist activity at alphaLbeta2 in human Jurkat E6.1 cells assessed as reduction in cell adhesion to ICAM1 pre-incubated for 30 mins before ICAM1 and further incubated for 30 mins by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay	ic50	0.0004	uM
4-[[2-[4-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-2,3-bis(trifluoromethyl)phenyl]sulfanylphenoxy]methyl]cyclohexane-1-carboxylic acid	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0004	uM
1-[(E)-3-[4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfanyl)-2,3-bis(trifluoromethyl)phenyl]prop-2-enoyl]piperidine-4-carboxylic acid	94612: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range(0.03-0.5)	ic50	0.0005	uM
4-[3-[4-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-2,3-bis(trifluoromethyl)phenyl]sulfanylanilino]cyclohexane-1-carboxylic acid	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0005	uM
(E)-3-[4-[3-[(1-methylpiperidin-4-yl)amino]phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]-1-morpholin-4-ylprop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0005	uM
(2S)-1-[(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-4-methyl-2-[[2-[4-[(2-methylphenyl)carbamoylamino]phenyl]acetyl]amino]pentanoyl]amino]propanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carboxylic acid	1686207: Antagonist activity at alphaLbeta2 in human Jurkat E6.1 cells assessed as reduction in cell adhesion to ICAM1 pre-incubated for 30 mins before ICAM1 and further incubated for 30 mins by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay	ic50	0.0008	uM
(E)-1-morpholin-4-yl-3-[4-[3-[(1-propylpiperidin-4-yl)amino]phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0009	uM
(E)-3-[4-[3-[(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)amino]phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]-1-morpholin-4-ylprop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0009	uM
(2S)-2-[[2-(1-benzofuran-6-carbonyl)-5,7-dichloro-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(5-methylsulfonylfuran-2-yl)propanoic acid	551705: Inhibition of LFA1/ICAM1 interaction in human Hut-78 cells	ic50	0.0012	uM
4-[[3-[4-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-2,3-bis(trifluoromethyl)phenyl]sulfanylanilino]methyl]cyclohexane-1-carboxylic acid	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0014	uM
(E)-1-morpholin-4-yl-3-[4-[3-(piperidin-4-ylamino)phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0014	uM
(E)-3-[4-[3-[(1-ethylpiperidin-4-yl)amino]phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]-1-morpholin-4-ylprop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0014	uM
(E)-3-[4-(3-aminophenyl)sulfanyl-2,3-bis(trifluoromethyl)phenyl]-1-morpholin-4-ylprop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0017	uM
4-[2-[4-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-2,3-bis(trifluoromethyl)phenyl]sulfanylphenoxy]cyclohexane-1-carboxylic acid	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0018	uM
1-[(E)-3-[3-chloro-4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfanyl)-2-(trifluoromethyl)phenyl]prop-2-enoyl]piperidine-4-carboxylic acid	94603: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range (2-2)	ic50	0.0020	uM
(2S)-2-[[2-(1-benzofuran-6-carbonyl)-5,7-dichloro-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(3-ethylsulfonylphenyl)propanoic acid	669545: Antagonist activity at LFA-1/ICAM-1 in human HuT-78 T-cells assessed as inhibition of cell adhesion after 1 hr by p-nitrophenyl n-acetyl-beta-D-glucosaminide method	ic50	0.0020	uM
(E)-1-morpholin-4-yl-3-[4-(2-piperidin-4-yloxyphenyl)sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0020	uM
(E)-1-morpholin-4-yl-3-[4-[3-(thian-4-yloxy)phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0021	uM
(E)-1-morpholin-4-yl-3-[4-[2-(pyridin-3-ylmethoxy)phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0025	uM
(E)-1-morpholin-4-yl-3-[4-[2-(oxan-4-yloxy)phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0025	uM
4-[3-[4-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-2,3-bis(trifluoromethyl)phenyl]sulfanylphenoxy]cyclohexane-1-carboxylic acid	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0030	uM
4-[(5S,9R)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-7-(quinoline-6-carbonyl)-1,3,7-triazaspiro[4.4]nonan-9-yl]benzonitrile	273491: Inhibition of LFA1-mediated adhesion of T cell to HUVEC	ic50	0.0030	uM
(2S)-2-[[5,7-dichloro-2-(4-chlorobenzoyl)-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(3-methylsulfonylphenyl)propanoic acid	669545: Antagonist activity at LFA-1/ICAM-1 in human HuT-78 T-cells assessed as inhibition of cell adhesion after 1 hr by p-nitrophenyl n-acetyl-beta-D-glucosaminide method	ic50	0.0030	uM
4-[[3-[4-[(E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-2,3-bis(trifluoromethyl)phenyl]sulfanylphenoxy]methyl]cyclohexane-1-carboxylic acid	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0034	uM
(E)-1-morpholin-4-yl-3-[4-[2-(pyridin-4-ylmethoxy)phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0037	uM
(E)-1-morpholin-4-yl-3-[4-(3-piperidin-4-yloxyphenyl)sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	349037: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0039	uM
1-[(E)-3-[3-chloro-4-(2-methoxyphenyl)sulfanyl-2-(trifluoromethyl)phenyl]prop-2-enoyl]piperidine-4-carboxylic acid	94605: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range (2-9)	ic50	0.0040	uM
1-[(E)-3-[2,3-dichloro-4-(1-methylindol-5-yl)sulfanylphenyl]prop-2-enoyl]piperidine-4-carboxylic acid	94601: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range (1-10)	ic50	0.0040	uM
(2S)-2-[[2-(1-benzofuran-6-carbonyl)-5,7-dichloro-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(3-sulfamoylphenyl)propanoic acid	669545: Antagonist activity at LFA-1/ICAM-1 in human HuT-78 T-cells assessed as inhibition of cell adhesion after 1 hr by p-nitrophenyl n-acetyl-beta-D-glucosaminide method	ic50	0.0040	uM
(E)-3-[4-[3-(methylamino)phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]-1-morpholin-4-ylprop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0044	uM
1-[2-[2,3-dichloro-4-[2-[3-(2-oxopyrrolidin-1-yl)propylcarbamoyl]cyclopropyl]phenyl]sulfanylphenyl]piperidine-3-carboxylic acid	99600: Ability to block the adherence of leukocyte function-associated antigen-1 (LFA-1) expressing JY-8 cells and intercellular adhesion molecule (ICAM-1) by 50% in absence of serum	ic50	0.0050	uM
1-[(E)-3-[4-(1-methylindol-5-yl)sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-enoyl]piperidine-4-carboxylic acid	94615: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range(3-10)	ic50	0.0050	uM
(E)-3-[3-chloro-4-(2-methoxyphenyl)sulfanyl-2-(trifluoromethyl)phenyl]-1-morpholin-4-ylprop-2-en-1-one	94606: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range (3-10)	ic50	0.0050	uM
(2S)-2-[[2-(1-benzofuran-6-carbonyl)-5,7-dichloro-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(thiophene-2-carbonylamino)propanoic acid	551705: Inhibition of LFA1/ICAM1 interaction in human Hut-78 cells	ic50	0.0050	uM
(2S)-2-[[2-(1-benzofuran-2-carbonyl)-5,7-dichloro-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(thiophene-2-carbonylamino)propanoic acid	501388: Inhibition of LFA1/ICAM1 interaction in human Hut-78 cells by cell migration assay	ic50	0.0050	uM
(2S)-2-[[2-(1-benzofuran-2-carbonyl)-5,7-dichloro-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(1-propan-2-yltriazol-4-yl)propanoic acid	551705: Inhibition of LFA1/ICAM1 interaction in human Hut-78 cells	ic50	0.0050	uM
(E)-1-morpholin-4-yl-3-[4-[3-(oxan-4-ylamino)phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]prop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0054	uM
1-[(E)-3-[2,3-dichloro-4-(2,3-dihydro-1,4-benzodioxin-6-ylsulfanyl)phenyl]prop-2-enoyl]piperidine-4-carboxylic acid	94605: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range (2-9)	ic50	0.0060	uM
1-[(E)-3-[2,3-dichloro-4-(2-propan-2-ylphenyl)sulfanylphenyl]prop-2-enoyl]piperidine-4-carboxylic acid	94607: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range (3-18)	ic50	0.0060	uM
(E)-3-[2,3-dichloro-4-(2-methoxyphenyl)sulfanylphenyl]-1-morpholin-4-ylprop-2-en-1-one	94600: Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1	ic50	0.0060	uM
(2S)-2-[[5,7-dichloro-2-(4-chlorobenzoyl)-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(5-methylsulfonylfuran-2-yl)propanoic acid	669545: Antagonist activity at LFA-1/ICAM-1 in human HuT-78 T-cells assessed as inhibition of cell adhesion after 1 hr by p-nitrophenyl n-acetyl-beta-D-glucosaminide method	ic50	0.0060	uM
4-[(5S,9R)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-7-(quinolin-6-ylmethyl)-1,3,7-triazaspiro[4.4]nonan-9-yl]benzonitrile	273491: Inhibition of LFA1-mediated adhesion of T cell to HUVEC	ic50	0.0060	uM
1-[2-[2,3-dichloro-4-(2-propan-2-ylphenyl)sulfanylphenyl]cyclopropanecarbonyl]piperidine-3-carboxylic acid	99600: Ability to block the adherence of leukocyte function-associated antigen-1 (LFA-1) expressing JY-8 cells and intercellular adhesion molecule (ICAM-1) by 50% in absence of serum	ic50	0.0060	uM
(E)-3-[4-[3-[(1-methylidene-1-oxothian-4-yl)amino]phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]-1-morpholin-4-ylprop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0060	uM
2-[2,3-dichloro-4-(2-propan-2-ylphenyl)sulfanylphenyl]-N-[3-(2-oxopyrrolidin-1-yl)propyl]cyclopropane-1-carboxamide	99600: Ability to block the adherence of leukocyte function-associated antigen-1 (LFA-1) expressing JY-8 cells and intercellular adhesion molecule (ICAM-1) by 50% in absence of serum	ic50	0.0060	uM
4-[[2-[2,3-dichloro-4-(2-propan-2-ylphenyl)sulfanylphenyl]cyclopropanecarbonyl]amino]butanoic acid	99600: Ability to block the adherence of leukocyte function-associated antigen-1 (LFA-1) expressing JY-8 cells and intercellular adhesion molecule (ICAM-1) by 50% in absence of serum	ic50	0.0070	uM
(E)-3-[4-[3-[(1-acetylpiperidin-4-yl)amino]phenyl]sulfanyl-2,3-bis(trifluoromethyl)phenyl]-1-morpholin-4-ylprop-2-en-1-one	387563: Inhibition of recombinant LFA1/ICAM1-IG interaction by time-resolved fluorimetry method	ic50	0.0070	uM
(2S)-2-[[5,7-dichloro-2-(pyrazolo[1,5-a]pyridine-2-carbonyl)-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(1-propan-2-yltriazol-4-yl)propanoic acid	551705: Inhibition of LFA1/ICAM1 interaction in human Hut-78 cells	ic50	0.0070	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	increases expression, increases reaction, affects binding	5
sodium arsenite	increases expression	4
Benzo(a)pyrene	affects methylation, increases expression, decreases methylation	4
bisphenol A	affects cotreatment, increases methylation, increases expression	3
tributyltin	affects localization, decreases reaction, increases expression	2
tamibarotene	decreases expression, decreases reaction, increases expression	2
1,2-bis(2-aminophenoxy)ethane N,N,N’,N’-tetraacetic acid acetoxymethyl ester	decreases reaction, increases activity, increases expression	2
Resveratrol	decreases reaction, increases expression	2
Benzene	decreases expression	2
Estradiol	decreases expression, increases expression, affects cotreatment	2
N-Formylmethionine Leucyl-Phenylalanine	increases expression, decreases reaction	2
Progesterone	affects cotreatment, increases expression	2
Tetradecanoylphorbol Acetate	increases expression, affects localization, decreases reaction	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	increases expression, increases methylation	2
Simvastatin	affects binding, decreases reaction, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bis(tri-n-butyltin)oxide	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
sulforaphane	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
tobacco tar	decreases expression	1
ochratoxin A	increases expression	1
indirubin	increases expression	1

ChEMBL screening assays

109 unique, capped per target: 73 binding, 36 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1016754	Binding	Inhibition of LFA1/ICAM1-mediated HL60 cell aggregation	A new antimalarial quassinoid from Simaba orinocensis. — J Nat Prod
CHEMBL2051012	Functional	Antagonist activity at LFA-1/ICAM-1 in human HuT-78 T-cells assessed as inhibition of cell adhesion after 1 hr by p-nitrophenyl n-acetyl-beta-D-glucosaminide method	Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Ophthalmic Solution for Treating Dry Eye. — ACS Med Chem Lett

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1X2	Abcam A-549 ITGB2 KO	Cancer cell line	Male
CVCL_D9HH	Ubigene HEK293 ITGB2 KO	Transformed cell line	Female
CVCL_E4AH	K-562 KC/16	Cancer cell line	Female
CVCL_E4AI	K-562 KL/4	Cancer cell line	Female
CVCL_E4AJ	K-562 P/5	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05462587	PHASE3	RECRUITING	A Study to Evaluate Efficacy and Safety of AVTX-803 in Patients With Leukocyte Adhesion Deficiency Type II
NCT05754450	PHASE3	RECRUITING	An Extension Study Assessing the Safety and Efficacy of AVTX-803 in Subjects With Leukocyte Adhesion Deficiency Type II
NCT01998633	PHASE2	COMPLETED	Reduced Intensity Conditioning for Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (BMT CTN 1204)
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT03366142	PHASE1/PHASE2	COMPLETED	Ustekinumab (Anti-IL-12/23p40 Monoclonal Antibody) in Patients With Leukocyte Adhesion Deficiency Type 1 (LAD1) Who Have Inflammatory Pathology
NCT00128973	Not specified	RECRUITING	Evaluation of Patients With Immune Function Abnormalities
NCT01212055	Not specified	RECRUITING	Apheresis of Patients With Immunodeficiency
NCT01319851	Not specified	TERMINATED	Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
NCT06282432	Not specified	ACTIVE_NOT_RECRUITING	Long-Term Follow-Up (LTFU) for Gene Therapy of Leukocyte Adhesion Deficiency-I (LAD-I)