ICAM1

Summary

ICAM1 (intercellular adhesion molecule 1, HGNC:5344) is a protein-coding gene on chromosome 19p13.2, encoding Intercellular adhesion molecule 1 (P05362). Cell adhesion molecule that functions as a receptor ligand of the signaling receptor ITGAL:ITGB2/LFA-1 (lymphocyte-function associated (LFA) molecule 1) ensuring leukocyte cell-cell adhesion, by providing a calibrated system to namely adjust T-cell killing to the antigen stimula….

This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by Rhinovirus as a receptor.

Source: NCBI Gene 3383 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 106 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000201

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5344
Approved symbol	ICAM1
Name	intercellular adhesion molecule 1
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	BB2, CD54
Ensembl gene	ENSG00000090339
Ensembl biotype	protein_coding
OMIM	147840
Entrez	3383

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000264832, ENST00000423829, ENST00000585443, ENST00000588645, ENST00000592686, ENST00000902798, ENST00000935832

RefSeq mRNA: 1 — MANE Select: NM_000201 NM_000201

CCDS: CCDS12231

Canonical transcript exons

ENST00000264832 — 7 exons

Exon	Start	End
ENSE00000576130	10274765	10275028
ENSE00000676100	10283481	10283786
ENSE00000676102	10284033	10284320
ENSE00000676105	10284403	10284657
ENSE00000676106	10284783	10285028
ENSE00000872752	10285115	10286615
ENSE00002860912	10271120	10271226

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 192.2938 / max 6356.0772, expressed in 1629 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173757	191.6269	1629
173763	0.4418	237
173762	0.2251	142

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vena cava	UBERON:0004087	98.73	gold quality
upper lobe of left lung	UBERON:0008952	98.15	gold quality
upper lobe of lung	UBERON:0008948	97.74	gold quality
cartilage tissue	UBERON:0002418	97.27	gold quality
right lung	UBERON:0002167	97.19	gold quality
type B pancreatic cell	CL:0000169	96.69	gold quality
gall bladder	UBERON:0002110	95.93	gold quality
lung	UBERON:0002048	94.79	gold quality
olfactory bulb	UBERON:0002264	94.55	silver quality
lower lobe of lung	UBERON:0008949	93.73	gold quality
spleen	UBERON:0002106	93.39	gold quality
omental fat pad	UBERON:0010414	92.87	gold quality
peritoneum	UBERON:0002358	92.84	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.50	gold quality
monocyte	CL:0000576	90.93	gold quality
lymph node	UBERON:0000029	90.91	gold quality
left uterine tube	UBERON:0001303	90.90	gold quality
vermiform appendix	UBERON:0001154	90.61	gold quality
mononuclear cell	CL:0000842	90.57	gold quality
leukocyte	CL:0000738	90.42	gold quality
tendon of biceps brachii	UBERON:0008188	90.10	gold quality
caecum	UBERON:0001153	89.98	gold quality
pancreatic ductal cell	CL:0002079	89.64	silver quality
mucosa of stomach	UBERON:0001199	89.19	gold quality
granulocyte	CL:0000094	89.13	gold quality
islet of Langerhans	UBERON:0000006	88.90	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.59	gold quality
colonic epithelium	UBERON:0000397	88.45	gold quality
stromal cell of endometrium	CL:0002255	88.32	gold quality
smooth muscle tissue	UBERON:0001135	88.29	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	2756.24
E-MTAB-8142	yes	2222.67
E-MTAB-9221	yes	23.59
E-HCAD-1	yes	18.44
E-CURD-112	yes	13.69
E-GEOD-130148	yes	7.18
E-MTAB-10137	no	3898.49
E-CURD-10	no	1029.01
E-MTAB-4850	no	344.99
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPA, CEBPB, CEBPG, CLOCK, CNOT7, CREB1, CUX1, DLX4, EGR1, ELF1, ERG, ESR1, ETS2, ETV5, EZR, FEV, FOS, FOXC1, GATA2, HDAC1, HR, HSF1, IFI16, IRF1, IRF6, JUN, KLF5, LDLR, MSN, MYADM, MYB, MYC, NFATC1, NFKB1, NFKB, NFKBIA, NFKBID, NFKBIE, NR1H4

miRNA regulators (miRDB)

57 targeting ICAM1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-7106-5P	99.53	67.47	3574

Literature-anchored findings (GeneRIF, showing 40)

• A defective expression of ICAM-1 (CD54) on secretory endometrial cells is associated with endometriosis. (PMID:11716965)
• IFN-gamma activates PLC-gamma2 via an upstream tyrosine kinase to induce activation of PKC-alpha and c-Src or Lyn, resulting in activation of STAT1alpha, and GAS in the ICAM-1 promoter, followed by initiation of ICAM-1 expression and monocyte adhesion. (PMID:11751911)
• Premature labor is associated with up-regulation of adhesion molecules in the lower uterine segment (PMID:11776680)
• Role of ICAM-1 in the aggregation and adhesion of human alveolar macrophages in response to TNF-alpha and INF-gamma. (PMID:11817671)
• Transient exposure of human bronchial epithelial cells to cytokines IFNG and TNFA, but not IL1B, leads to persistent increased expression of ICAM-1. (PMID:11831440)
• Incubation of endothelial cells with conditioned media derived from stimulated macrophages modulates ICAM1 mRNA expression. Results suggest TNF-alpha and activation of the NF-kB pathway are involved. (PMID:11831864)
• heat shock decreases endothelial cell ICAM-1 expression via inhibition of IKK activity (PMID:11837795)
• Down-regulation of cell adhesion molecules LFA-1 and ICAM-1 after in vitro treatment with the anti-TNF-alpha agent thalidomide. (PMID:11838958)
• significant increase in plasma levels between day 1 and day 5 of G-CSF-induced stem cell mobilization; possible effect on leukocyte-endothelial cell interactions (PMID:11847011)
• oncogenic transformation by BCR-ABL may increase susceptibility of leukemic progenitors to NK cell cytotoxicity by a mechanism involving overexpression of ICAM-1 (PMID:11877286)
• ICAM-1 participated in cell attachment to X- and Y-fragments, rather than to intact fibrinogen or late degradation products, fragments D and E. (PMID:11881155)
• Intercellular adhesion molecule-1 gene polymorphisms in isolated polymyalgia rheumatica. (PMID:11911111)
• raised sICAM-1 in breast cancer, like the acute phase response, reflects inflammation (PMID:11914659)
• Elevated soluble CD40 ligand is related to the endothelial adhesion molecules in patients with acute coronary syndrome. (PMID:11922919)
• Dynamic regulation of LFA-1 activation and neutrophil arrest on intercellular adhesion molecule 1 in shear flow (PMID:11929876)
• Relation between glycemic control, hyperinsulinaemia and plasma concentration in patients with glucose intolerance or niddm (PMID:11935152)
• colocalization of ICAM-1 and B7.1 molecules was demonstrated in Hashomoto’s thyroiditis whereas no B7.1 expression was observed in Graves’ disease (PMID:11936473)
• CD54 may play an important role in pathogenic process (in COPD) (PMID:11953106)
• expression of ICAM1 in colorectal cancer (PMID:11956618)
• women with stage III and IV endometriosis had higher serum concentrations of soluble VCAM-1, lower serum concentration of soluble ICAM-1 (PMID:11963839)
• Prolonged, low dose alpha-tocopherol therapy counteracts intercellular cell adhesion molecule-1 activation (PMID:11983194)
• Blood levels of ICAM1 are low in non-Hodgkin’s lymphoma patients (PMID:12011765)
• X-ray doses of < or =5 Gy did not induce ICAM-1 expression, or modulate TNFalpha-induced ICAM-1 expression. (PMID:12020443)
• polymorphism is associated with diabetic retinopathy in type 2 diabetes mellitus (PMID:12027924)
• pregnancy-induced hypertension is accompanied by overexpression of intercellular adhesion molecule-1 (ICAM-1) on peripheral blood and decidual lymphocytes studied “in vitro” (PMID:12039084)
• During leukocyte adhesion VCAM-1, ICAM-1, and activated moesin and ezrin clustered in an endothelial actin-rich docking structure that anchored and partially embraced the leukocyte containing other cytoskeletal components (PMID:12082081)
• the preferential expression of ICAM-1 on the endothelium of femoral and iliac arteries in thromboangiitis obliterans (PMID:12086338)
• that genetic polymorphisms of ICAM-1 might be clinically important in the development and progression of neurodegenerative diseases (PMID:12095649)
• In endothelial cells, ICAM-1 stimulates c-fos and rhoA transcription and up-regulates rhoA expression by a positive feedback pathway after RhoA activation. (PMID:12097408)
• ICAM-1/beta2 integrin interactions mediate monocyte adhesion to human saphenous vein (PMID:12097820)
• infection with cagA+ Helicobacter pylori induces homotypic aggregation of macrophage-like cell by up-regulation and recruitment of intracellular adhesion molecule 1 to the cell surface and mediates the aggregation via LFA-1 (PMID:12117984)
• The TT and TC genotype of the ICAM-1 gene polymorphism in codon 469 is a genetic factor that may determine an individual’s susceptibility for CHD and MI. (PMID:12127369)
• modulation of expression in endothelial cells by glucosyltransfease inhibitor (PMID:12147222)
• E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1) were measured in serum from hypertensive patients with LV hypertrophy (PMID:12172318)
• Downregulation of icam-1 is associated with nodal metastasis in breast cancer (PMID:12172576)
• Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), ceruloplasmin (Cp), and transferrin (Tf) in rheumatoid arthritis. Serum Tf levels were significantly diminished and serum levels of sICAM-1 and Cp were significantly increased. (PMID:12175089)
• Depletion of intracellular GTP results in nuclear factor-kappaB activation and intercellular adhesion molecule-1 expression in human endothelial cells. (PMID:12181421)
• may play a role in the development of nephropathy in patients with type 2 diabetes mellitus (PMID:12207164)
• B. pertussis FHA up-regulates ICAM-1 expression on respiratory epithelial cells through interaction of its RGD site with host cell VLA-5 integrin, and that PT impairs this response (PMID:12220988)
• Increased expression in Mycobacterium tuberculosis-infected human macrophages exhibiting enhanced cellular adhesion (PMID:12368450)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Icam1	ENSMUSG00000037405
rattus_norvegicus	Icam1	ENSRNOG00000020679

Paralogs (4): ICAM3 (ENSG00000076662), ICAM4 (ENSG00000105371), ICAM5 (ENSG00000105376), ICAM2 (ENSG00000108622)

Protein

Protein identifiers

Intercellular adhesion molecule 1 — P05362 (reviewed: P05362)

Alternative names: Major group rhinovirus receptor

All UniProt accessions (4): P05362, A0A384MEK5, E7ESS4, K7EKL8

UniProt curated annotations — full annotation on UniProt →

Function. Cell adhesion molecule that functions as a receptor ligand of the signaling receptor ITGAL:ITGB2/LFA-1 (lymphocyte-function associated (LFA) molecule 1) ensuring leukocyte cell-cell adhesion, by providing a calibrated system to namely adjust T-cell killing to the antigen stimulation strength. Also functions as a ligand receptor of the signaling receptor ITGAM:ITGB2/MAC-1 ensuring adhesion between stimulated neutrophils and stimulated endothelial cells. During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups through ARHGEF26/SGEF and RHOG activation. Promotes cell aggregation in epithelial cells through interaction with MUC1. (Microbial infection) Acts as a receptor for major receptor group rhinovirus A-B capsid proteins. (Microbial infection) Acts as a receptor for Coxsackievirus A21 capsid proteins. (Microbial infection) Upon Kaposi’s sarcoma-associated herpesvirus/HHV-8 infection, is degraded by viral E3 ubiquitin ligase MIR2, presumably to prevent lysis of infected cells by cytotoxic T-lymphocytes and NK cell.

Subunit / interactions. Homodimer. Interacts with MUC1 and promotes cell aggregation in epithelial cells. Interacts with ARHGEF26/SGEF. Interacts (on T cell side) with CD81, CD247 and CD9 at immunological synapses between antigen-presenting cells and T cells. (Microbial infection) Interacts with major receptor group rhinovirus A-B capsid proteins. (Microbial infection) Interacts with Coxsackievirus A21 capsid proteins.

Subcellular location. Cell membrane.

Tissue specificity. Expressed on non-hematopoietic cells such as vascular endothelial cells, thymic epithelial cells, certain other epithelial cells, and fibroblasts, and on hematopoietic cells such as tissue macrophages, mitogen-stimulated T lymphocyte blasts, and germinal center dendritic cells in tonsils, lymph nodes, and Peyer’s patches. Expressed in low amounts on peripheral blood leukocytes.

Post-translational modifications. Monoubiquitinated, which is promoted by MARCH9 and leads to endocytosis.

Induction. Up-regulated by coagulation factor Xa (F10) in atrial tissues. Up-regulated in atrial tissues by rapid pacing resembling atrial fibrillation. Induced by either inflammatory cytokines.

Polymorphism. Variant p.Lys56Met, known as ICAM1-Kilifi, may influence susceptibility to cerebral malaria [MIM:611162].

Similarity. Belongs to the immunoglobulin superfamily. ICAM family.

RefSeq proteins (1): NP_000192* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR003987	ICAM_VCAM_N	Domain
IPR003988	ICAM	Domain
IPR013768	ICAM_N	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR047012	ICAM_VCAM	Family
IPR048679	ICAM1_3_5_D2	Domain

Pfam: PF03921, PF13895, PF21146

UniProt features (90 total): strand 41, glycosylation site 8, sequence variant 8, helix 8, disulfide bond 7, domain 5, sequence conflict 3, modified residue 2, topological domain 2, turn 2, signal peptide 1, chain 1, short sequence motif 1, transmembrane region 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
1IAM	X-RAY DIFFRACTION	2.1
7BG7	ELECTRON MICROSCOPY	2.4
2OZ4	X-RAY DIFFRACTION	2.7
5MZA	X-RAY DIFFRACTION	2.78
1IC1	X-RAY DIFFRACTION	3
1P53	X-RAY DIFFRACTION	3.06
1D3L	X-RAY DIFFRACTION	3.25
1MQ8	X-RAY DIFFRACTION	3.3
3TCX	X-RAY DIFFRACTION	3.6
6S8U	X-RAY DIFFRACTION	3.67
6EIT	ELECTRON MICROSCOPY	3.9
1Z7Z	ELECTRON MICROSCOPY	8
1D3I	ELECTRON MICROSCOPY	26
1D3E	ELECTRON MICROSCOPY	28

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05362-F1	88.66	0.76

Antibody-complex structures (SAbDab): 1 — 2OZ4

Functional residue map

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

Post-translational modifications (2): 521, 530

Disulfide bonds (7): 48–92, 52–96, 135–186, 237–290, 332–371, 403–419, 431–457

Glycosylation sites (8): 130, 145, 183, 202, 267, 296, 385, 406

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-216083	Integrin cell surface interactions
R-HSA-6783783	Interleukin-10 signaling
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-877300	Interferon gamma signaling

MSigDB gene sets: 625 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, CREL_01, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, MCLACHLAN_DENTAL_CARIES_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_EPITHELIAL_CELL_DEVELOPMENT, BROWNE_HCMV_INFECTION_8HR_UP, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE

GO Biological Process (28): regulation of leukocyte mediated cytotoxicity (GO:0001910), T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell (GO:0002291), T cell antigen processing and presentation (GO:0002457), positive regulation of cellular extravasation (GO:0002693), cell adhesion (GO:0007155), heterophilic cell-cell adhesion (GO:0007157), leukocyte cell-cell adhesion (GO:0007159), membrane to membrane docking (GO:0022614), cell-cell adhesion mediated by integrin (GO:0033631), adhesion of symbiont to host (GO:0044406), receptor-mediated virion attachment to host cell (GO:0046813), leukocyte migration (GO:0050900), establishment of endothelial barrier (GO:0061028), leukocyte adhesion to vascular endothelial cell (GO:0061756), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to glucose stimulus (GO:0071333), T cell extravasation (GO:0072683), regulation of ruffle assembly (GO:1900027), negative regulation of extrinsic apoptotic signaling pathway via death domain receptors (GO:1902042), cellular response to amyloid-beta (GO:1904646), cellular response to leukemia inhibitory factor (GO:1990830), negative regulation of endothelial cell apoptotic process (GO:2000352), immune effector process (GO:0002252), immune response (GO:0006955), cell adhesion mediated by integrin (GO:0033627), symbiont entry into host cell (GO:0046718), cell-cell adhesion (GO:0098609), cellular response to oxygen-containing compound (GO:1901701)

GO Molecular Function (6): virus receptor activity (GO:0001618), transmembrane signaling receptor activity (GO:0004888), integrin binding (GO:0005178), signaling receptor activity (GO:0038023), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (10): immunological synapse (GO:0001772), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), focal adhesion (GO:0005925), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020), extracellular matrix (GO:0031012), membrane raft (GO:0045121), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Signaling by Interleukins	2
Adaptive Immune System	1
Extracellular matrix organization	1
Interferon Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	3
signaling receptor binding	3
cellular anatomical structure	3
cellular extravasation	2
plasma membrane	2
leukocyte mediated cytotoxicity	1
regulation of leukocyte mediated immunity	1
regulation of cell killing	1
T cell activation involved in immune response	1
T cell mediated immunity	1
antigen processing and presentation	1
positive regulation of leukocyte migration	1
regulation of cellular extravasation	1
cellular process	1
membrane docking	1
cell adhesion mediated by integrin	1
biological process involved in interaction with host	1
virion attachment to host cell	1
immune system process	1
cell migration	1
endothelial cell development	1
leukocyte cell-cell adhesion	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
intracellular glucose homeostasis	1
response to glucose	1
cellular response to hexose stimulus	1
T cell migration	1
ruffle assembly	1
regulation of plasma membrane bounded cell projection assembly	1
extrinsic apoptotic signaling pathway via death domain receptors	1
regulation of extrinsic apoptotic signaling pathway via death domain receptors	1
negative regulation of extrinsic apoptotic signaling pathway	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
response to amyloid-beta	1
symbiont entry into host cell	1
exogenous protein binding	1
signaling receptor activity	1

Protein interactions and networks

STRING

4864 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ICAM1	ITGB2	P05107	999
ICAM1	VCAM1	P19320	999
ICAM1	CD80	P33681	997
ICAM1	ITGAL	P20701	997
ICAM1	ITGAM	P11215	996
ICAM1	CD58	P19256	996
ICAM1	CD44	P16070	995
ICAM1	CD2	P06729	992
ICAM1	SELPLG	Q14242	991
ICAM1	MUC1	P13931	988
ICAM1	ITGA4	P13612	985
ICAM1	EZR	P15311	980
ICAM1	ITGAX	P20702	980
ICAM1	CD28	P10747	977
ICAM1	SPN	P16150	977

IntAct

81 interactions, top by confidence:

A	B	Type	Score
RAD51D	RAD51B	psi-mi:“MI:0914”(association)	0.850
EGFR	GAPDH	psi-mi:“MI:0914”(association)	0.790
ITGAL	ICAM1	psi-mi:“MI:0407”(direct interaction)	0.730
ICAM1	ITGAL	psi-mi:“MI:0407”(direct interaction)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
TEPSIN	AP4M1	psi-mi:“MI:0914”(association)	0.700
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
NAT1	ICAM1	psi-mi:“MI:0915”(physical association)	0.590
CYSRT1	ICAM1	psi-mi:“MI:0915”(physical association)	0.560
ICAM1	KEAP1	psi-mi:“MI:0915”(physical association)	0.560
ICAM1	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
ICAM1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
ICAM1	CIB1	psi-mi:“MI:0915”(physical association)	0.560
PELO	ICAM1	psi-mi:“MI:0915”(physical association)	0.560
CLIC4	CLIC2	psi-mi:“MI:0914”(association)	0.530
AREG	ADCY9	psi-mi:“MI:0914”(association)	0.530
CCN5	ICAM1	psi-mi:“MI:0914”(association)	0.530
EDA2R	ICAM1	psi-mi:“MI:0914”(association)	0.530
TUBA4A	PLD2	psi-mi:“MI:0914”(association)	0.530
NCS1	NMT2	psi-mi:“MI:0914”(association)	0.530

BioGRID (303): ICAM1 (Affinity Capture-MS), ICAM1 (Affinity Capture-MS), ICAM1 (Affinity Capture-MS), FGG (Co-localization), PAK1 (Affinity Capture-MS), GIT1 (Affinity Capture-MS), ARHGEF7 (Affinity Capture-MS), ICAM1 (Affinity Capture-MS), ARHGEF6 (Affinity Capture-MS), GIT2 (Affinity Capture-MS), ICAM1 (Affinity Capture-MS), ICAM1 (Affinity Capture-MS), NCS1 (Affinity Capture-MS), NT5C1A (Affinity Capture-MS), WDFY3 (Affinity Capture-MS)

ESM2 similar proteins: A6NMB1, A7LCJ3, G1T7E7, G1TR84, M3XWH1, O15389, O43699, O70540, P04217, P05362, P0DP72, P13597, P20138, P32942, P33729, Q00238, Q08ET2, Q14773, Q28125, Q28730, Q28806, Q2KJF1, Q5NKT8, Q5NKU6, Q5NKV4, Q5NKV6, Q5NKV9, Q60625, Q62230, Q64JA4, Q6DN72, Q7L513, Q80ZE3, Q91Y57, Q920A9, Q920G3, Q92154, Q95132, Q95LH0, Q96A28

Diamond homologs: P05362, P13597, P13598, P32942, P33729, P35330, Q00238, Q14773, Q28125, Q28730, Q28806, Q5NKT8, Q5NKU6, Q5NKV1, Q5NKV2, Q5NKV4, Q5NKV6, Q5NKV9, Q60625, Q95132, Q9UMF0, Q290N5, Q9ERM2, A2ASS6, P13688, Q00888, Q00889, Q13046, Q1WIM1, Q4VA61, Q86VR7, Q8NFZ8, Q8R464, Q8TD84, D3ZB51, O00533, O15146, Q26474, Q61006, Q62838

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
FEV	“down-regulates quantity by repression”	ICAM1	“transcriptional regulation”
ERG	“down-regulates quantity by repression”	ICAM1	“transcriptional regulation”
ITGAL	up-regulates	ICAM1	binding
ITGAM	up-regulates	ICAM1	binding
ICAM1	up-regulates	Chemotaxis
TWIST2	“up-regulates quantity by expression”	ICAM1	“transcriptional regulation”
TWIST1	“up-regulates quantity by expression”	ICAM1	“transcriptional regulation”
MARCHF9	“down-regulates quantity by destabilization”	ICAM1	ubiquitination
ICAM1	up-regulates	ITGAX	binding
“AL/b2 integrin”	“up-regulates activity”	ICAM1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 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.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of protein localization to plasma membrane	5	17.9×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	15
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

640 predictions. Top by Δscore:

Variant	Effect	Δscore
19:10271223:CCAGG:C	donor_loss	1.0000
19:10271224:CAGG:C	donor_loss	1.0000
19:10271227:GT:G	donor_loss	1.0000
19:10274753:C:CA	acceptor_gain	1.0000
19:10274761:CTA:C	acceptor_loss	1.0000
19:10274762:TAGG:T	acceptor_loss	1.0000
19:10274763:A:AG	acceptor_gain	1.0000
19:10274763:A:AT	acceptor_loss	1.0000
19:10274764:G:GC	acceptor_loss	1.0000
19:10274764:G:GG	acceptor_gain	1.0000
19:10275024:GTACT:G	donor_gain	1.0000
19:10275029:G:GG	donor_gain	1.0000
19:10283479:A:AG	acceptor_gain	1.0000
19:10283480:G:GG	acceptor_gain	1.0000
19:10283787:G:GG	donor_gain	1.0000
19:10284029:CTA:C	acceptor_loss	1.0000
19:10284030:TA:T	acceptor_loss	1.0000
19:10284031:A:AC	acceptor_loss	1.0000
19:10284031:A:AG	acceptor_gain	1.0000
19:10284032:G:GG	acceptor_gain	1.0000
19:10284032:GTC:G	acceptor_gain	1.0000
19:10284032:GTCC:G	acceptor_gain	1.0000
19:10284032:GTCCT:G	acceptor_gain	1.0000
19:10284268:A:AG	donor_gain	1.0000
19:10284269:G:GG	donor_gain	1.0000
19:10284316:CTACA:C	donor_gain	1.0000
19:10284317:TACA:T	donor_gain	1.0000
19:10284318:ACA:A	donor_gain	1.0000
19:10284319:CA:C	donor_gain	1.0000
19:10284319:CAG:C	donor_loss	1.0000

AlphaMissense

3376 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:10284971:T:A	C457S	0.993
19:10284972:G:C	C457S	0.993
19:10284857:T:A	C419S	0.991
19:10284858:G:C	C419S	0.991
19:10284893:T:A	C431S	0.987
19:10284894:G:C	C431S	0.987
19:10274971:T:A	C92S	0.986
19:10274972:G:C	C92S	0.986
19:10283552:T:A	C135S	0.985
19:10283553:G:C	C135S	0.985
19:10283705:T:A	C186S	0.981
19:10283706:G:C	C186S	0.981
19:10284893:T:C	C431R	0.980
19:10284809:T:A	C403S	0.979
19:10284810:G:C	C403S	0.979
19:10274839:T:A	C48S	0.977
19:10274840:G:C	C48S	0.977
19:10284471:T:A	C332S	0.977
19:10284472:G:C	C332S	0.977
19:10284857:T:C	C419R	0.977
19:10283552:T:C	C135R	0.976
19:10284588:T:A	C371S	0.976
19:10284589:G:C	C371S	0.976
19:10284971:T:C	C457R	0.975
19:10274971:T:C	C92R	0.974
19:10284965:T:G	Y455D	0.974
19:10284471:T:C	C332R	0.973
19:10283705:T:C	C186R	0.972
19:10284869:G:T	G423W	0.971
19:10283586:T:C	L146P	0.969

dbSNP variants (sampled 300 via entrez): RS1000328583 (19:10269839 G>A,T), RS1000391834 (19:10284240 A>G), RS1000675984 (19:10285576 G>A,C), RS1000785397 (19:10279708 G>A), RS1000903705 (19:10280046 A>G), RS1000951974 (19:10281048 T>G), RS1001130557 (19:10285254 C>T), RS1001150652 (19:10269371 C>T), RS1001438031 (19:10269638 G>C,T), RS1001657948 (19:10275403 A>G), RS1002156881 (19:10281364 A>C), RS1002288516 (19:10285542 T>C), RS1002443579 (19:10280882 T>A), RS1002459833 (19:10281152 C>T), RS1002582178 (19:10285907 C>T)

Disease associations

OMIM: gene MIM:147840 | disease phenotypes: MIM:611162

GenCC curated gene-disease

Mondo (1): malaria, susceptibility to (MONDO:0021024)

Orphanet (1): Malaria (Orphanet:673)

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000210_1	Soluble ICAM-1	4.000000e-47
GCST000210_2	Soluble ICAM-1	5.000000e-25
GCST000210_3	Soluble ICAM-1	3.000000e-10
GCST000879_7	Crohn’s disease	1.000000e-12
GCST001047_1	Soluble ICAM-1	1.000000e-120
GCST001047_3	Soluble ICAM-1	6.000000e-89
GCST001725_60	Inflammatory bowel disease	2.000000e-18
GCST004627_183	Lymphocyte count	7.000000e-30
GCST005578_10	Low white blood cell count (conditioned on rs2814778)	2.000000e-06
GCST006585_483	Blood protein levels	0.000000e+00
GCST007096_89	Pulse pressure	4.000000e-08
GCST008210_2	Soluble ICAM-1	8.000000e-40
GCST008210_3	Soluble ICAM-1	1.000000e-16
GCST008839_214	Height	5.000000e-11
GCST90002388_36	Lymphocyte count	1.000000e-50
GCST90002393_641	Monocyte count	7.000000e-10
GCST90002407_360	White blood cell count	1.000000e-15
GCST90013407_117	Liver enzyme levels (gamma-glutamyl transferase)	3.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004520	ICAM-1 measurement
EFO:0004587	lymphocyte count
EFO:0005763	pulse pressure measurement
EFO:0005091	monocyte count
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2096661 (PROTEIN COMPLEX), CHEMBL3070 (SINGLE PROTEIN)

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)

Binding affinities (BindingDB)

2 measured of 2 human assays (2 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4161090	IC50	420 nM
CHEMBL4166467	IC50	3000 nM

ChEMBL bioactivities

701 potent at pChembl≥5 of 762 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
9.40	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
9.05	IC50	0.9	nM	CHEMBL485857
9.03	IC50	0.94	nM	CHEMBL444773
9.00	IC50	1	nM	CHEMBL119501
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
8.85	IC50	1.4	nM	CHEMBL118113
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	CHEMBL117198
8.70	IC50	2	nM	CHEMBL119733
8.70	IC50	2	nM	CHEMBL117279
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
8.53	IC50	2.98	nM	LIFITEGRAST
8.52	IC50	3	nM	CHEMBL2048025
8.52	IC50	3	nM	CHEMBL262911
8.52	IC50	3	nM	CHEMBL502789
8.52	IC50	3	nM	CHEMBL116070
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
8.42	IC50	3.8	nM	CHEMBL119335
8.41	IC50	3.9	nM	CHEMBL495906
8.40	IC50	4	nM	CHEMBL2048402
8.40	IC50	4	nM	CHEMBL502512
8.40	IC50	4	nM	CHEMBL117746
8.40	IC50	4	nM	CHEMBL119039
8.40	IC50	4	nM	CHEMBL116152
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	CHEMBL118034
8.30	IC50	5	nM	CHEMBL326271
8.30	IC50	5	nM	CHEMBL1222288

PubChem BioAssay actives

700 with measured affinity, of 1019 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
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
(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
N-methyl-4-[4-(trifluoromethyl)phenoxy]thieno[2,3-c]pyridine-2-carboxamide	91867: Inhibition of intercellular adhesion molecule-1 (ICAM1) in human endothelial cells	ic50	0.0010	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-[4-(oxan-2-yloxymethyl)phenoxy]thieno[2,3-c]pyridine-2-carboxamide	91867: Inhibition of intercellular adhesion molecule-1 (ICAM1) in human endothelial cells	ic50	0.0014	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
4-(4-cyanophenoxy)thieno[2,3-c]pyridine-2-carboxamide	91867: Inhibition of intercellular adhesion molecule-1 (ICAM1) in human endothelial cells	ic50	0.0020	uM
4-[4-[2-(2-methoxyethoxy)ethoxymethyl]phenoxy]-N-methylthieno[2,3-c]pyridine-2-carboxamide	91869: In vitro inhibitory potency compared to IL1-beta induced Intercellular adhesion molecule-1 in human endothelial cells (ELISA assay)	ic50	0.0020	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
4-(4-ethenylphenoxy)thieno[2,3-c]pyridine-2-carboxamide	91867: Inhibition of intercellular adhesion molecule-1 (ICAM1) in human endothelial cells	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
Lifitegrast	669552: Inhibition of human recombinant ICAM-1 adhesion into human Jurkat cells after 1 hr	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-(4-bromophenoxy)thieno[2,3-c]pyridine-2-carboxamide	91869: In vitro inhibitory potency compared to IL1-beta induced Intercellular adhesion molecule-1 in human endothelial cells (ELISA assay)	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
4-[4-[3-hydroxy-3-[4-[2-(methylcarbamoyl)thieno[2,3-c]pyridin-4-yl]oxyphenyl]butanoyl]phenoxy]-N-methylthieno[2,3-c]pyridine-2-carboxamide	91867: Inhibition of intercellular adhesion molecule-1 (ICAM1) in human endothelial cells	ic50	0.0038	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
4-(4-iodophenoxy)thieno[2,3-c]pyridine-2-carboxamide	91867: Inhibition of intercellular adhesion molecule-1 (ICAM1) in human endothelial cells	ic50	0.0040	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
N-methyl-4-(4-pyrazol-1-ylphenoxy)thieno[2,3-c]pyridine-2-carboxamide	91867: Inhibition of intercellular adhesion molecule-1 (ICAM1) in human endothelial cells	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
4-[4-[2-(2-methoxyethoxy)ethoxymethyl]phenoxy]thieno[2,3-c]pyridine-2-carboxamide	91867: Inhibition of intercellular adhesion molecule-1 (ICAM1) in human endothelial cells	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
4-(4-bromophenoxy)-N-methylthieno[2,3-c]pyridine-2-carboxamide	91867: Inhibition of intercellular adhesion molecule-1 (ICAM1) in human endothelial cells	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
4-[4-(furan-2-yl)phenoxy]-N-methylthieno[2,3-c]pyridine-2-carboxamide	91867: Inhibition of intercellular adhesion molecule-1 (ICAM1) in human endothelial cells	ic50	0.0050	uM
4-(4-imidazol-1-ylphenoxy)thieno[2,3-c]pyridine-2-carboxamide	91867: Inhibition of intercellular adhesion molecule-1 (ICAM1) in human endothelial cells	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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	affects cotreatment, decreases reaction, increases reaction, increases secretion, affects response to substance (+3 more)	34
Particulate Matter	decreases reaction, increases abundance, decreases methylation, increases secretion, increases expression (+3 more)	23
sodium arsenite	decreases reaction, affects reaction, affects cotreatment, decreases expression, increases abundance (+3 more)	13
Air Pollutants	affects expression, decreases methylation, decreases expression, increases abundance, increases expression (+1 more)	13
Quercetin	affects cotreatment, decreases reaction, increases expression, decreases expression, decreases phosphorylation	13
Glucose	increases secretion, affects localization, decreases reaction, increases expression	12
Acetylcysteine	affects expression, affects reaction, decreases reaction, increases expression	11
3-(4-methylphenylsulfonyl)-2-propenenitrile	decreases expression, decreases reaction, increases expression, increases abundance	10
Resveratrol	affects reaction, increases reaction, affects localization, decreases expression, decreases reaction (+1 more)	10
Vehicle Emissions	decreases reaction, increases abundance, increases expression, affects cotreatment, increases reaction (+1 more)	9
bisphenol A	decreases methylation, affects expression, decreases reaction, increases expression, decreases expression	8
Arsenic Trioxide	decreases expression, increases expression, increases reaction, affects cotreatment	8
Simvastatin	decreases reaction, increases expression, increases reaction, affects expression, affects secretion (+1 more)	8
lipopolysaccharide, Escherichia coli O111 B4	decreases reaction, increases expression, affects cotreatment, affects reaction	7
Arsenic	affects expression, increases expression, increases secretion, affects cotreatment, increases abundance	7
Dinitrochlorobenzene	affects expression, affects reaction, decreases reaction, increases expression	7
Nickel	decreases activity, decreases reaction, increases expression, affects cotreatment, increases abundance (+1 more)	7
Tretinoin	affects cotreatment, increases expression, increases reaction, decreases reaction	7
lipopolysaccharide, E coli O55-B5	decreases reaction, increases expression, affects cotreatment	6
Benzo(a)pyrene	affects cotreatment, increases expression, affects methylation, affects expression, affects reaction	6
Hydrogen Peroxide	decreases reaction, increases secretion, increases expression, affects cotreatment, affects expression	6
Silicon Dioxide	decreases reaction, increases expression	6
Smoke	affects reaction, increases expression, decreases expression, decreases nitrosation, increases abundance	6
Ascorbic Acid	increases expression, affects cotreatment, decreases reaction	5
Curcumin	decreases reaction, increases expression	5
Estradiol	affects cotreatment, decreases expression, increases expression, affects reaction	5
Glucosamine	decreases reaction, increases expression, increases reaction, affects cotreatment	5
Plant Extracts	decreases reaction, increases expression, increases reaction, decreases expression	5
Tobacco Smoke Pollution	affects response to substance, affects expression, increases expression	5
titanium dioxide	decreases reaction, increases expression, increases secretion	4

ChEMBL screening assays

111 unique, capped per target: 73 binding, 38 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

12 cell lines: 8 cancer cell line, 2 spontaneously immortalized cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_8849	CHO-ICAM-1	Spontaneously immortalized cell line	Female
CVCL_AS85	CHO-ICAM-1Fc	Spontaneously immortalized cell line	Female
CVCL_B1U3	Abcam HeLa ICAM1 KO	Cancer cell line	Female
CVCL_B8HP	Abcam HCT 116 ICAM1 KO	Cancer cell line	Male
CVCL_B9JZ	Abcam A-549 ICAM1 KO	Cancer cell line	Male
CVCL_C4TS	L14-hICAM1(10)	Transformed cell line	Male
CVCL_D2FM	Abcam MCF-7 ICAM1 KO	Cancer cell line	Female
CVCL_D7RM	Ubigene A-549 ICAM1 KO	Cancer cell line	Male
CVCL_D8FG	Ubigene Calu-1 ICAM1 KO	Cancer cell line	Male
CVCL_D9GJ	Ubigene HEK293 ICAM1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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