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VCAM1

gene
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Also known as CD106

Summary

VCAM1 (vascular cell adhesion molecule 1, HGNC:12663) is a protein-coding gene on chromosome 1p21.2, encoding Vascular cell adhesion protein 1 (P19320). Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation.

This gene is a member of the Ig superfamily and encodes a cell surface sialoglycoprotein expressed by cytokine-activated endothelium. This type I membrane protein mediates leukocyte-endothelial cell adhesion and signal transduction, and may play a role in the development of artherosclerosis and rheumatoid arthritis. Three alternatively spliced transcripts encoding different isoforms have been described for this gene.

Source: NCBI Gene 7412 — RefSeq curated summary.

At a glance

  • GWAS associations: 8
  • Clinical variants (ClinVar): 101 total
  • GTEx eGene: eQTL in 23 tissues, sQTL in 1 (q < 0.05)
  • ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
  • Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.84 (unconstrained)
  • MANE Select transcript: NM_001078
  • Interaction hub: 4,000 STRING partners (top 1% of genes corpus-wide)
  • Notable: 101 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:12663
Approved symbolVCAM1
Namevascular cell adhesion molecule 1
Location1p21.2
Locus typegene with protein product
StatusApproved
AliasesCD106
Ensembl geneENSG00000162692
Ensembl biotypeprotein_coding
OMIM192225
Entrez7412

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 5 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000294728

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 5: 1

ENST00000294728, ENST00000347652, ENST00000370115, ENST00000370119, ENST00000603679, ENST00000650339, ENST00000855907, ENST00000949395, ENST00000949396, ENST00000988852, ENST00001011558, ENST00001011559, ENST00001112640, ENST00001120419, ENST00001125052, ENST00001143533

RefSeq mRNA: 3 — MANE Select: NM_001078 NM_001078, NM_001199834, NM_080682

CCDS: CCDS55617, CCDS773, CCDS774

Canonical transcript exons

ENST00000294728 — 9 exons

ExonStartEnd
ENSE00001067751100734502100734768
ENSE00001067753100731198100731518
ENSE00001067755100723020100723340
ENSE00001067756100729107100729382
ENSE00001067757100720476100720751
ENSE00001067758100724624100724890
ENSE00001067759100732418100732684
ENSE00001167786100719742100719924
ENSE00004803124100738123100739045

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 99.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.7029 / max 910.3466, expressed in 928 samples.

Highest expression (Bgee): cartilage tissue, trabecular bone tissue, parietal pleura, vena cava, tendon of biceps brachii.

Genetic regulation across tissues (GTEx eQTL / sQTL)

VCAM1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 23 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 24 significant tissue × QTL associations:

TissueQTLq-valueSlopeLead variant
Cells Cultured fibroblastseqtl6.9e-42-0.681:100725310:A:C
Skin Sun Exposed Lower legeqtl7.7e-15-0.281:100725310:A:C
Skin Not Sun Exposed Suprapubiceqtl8.7e-10-0.241:100721765:C:T
Breast Mammary Tissueeqtl1.6e-07+0.251:100695695:G:A
Esophagus Mucosaeqtl1.9e-07-0.191:100725310:A:C
Thyroideqtl2.5e-07-0.231:100721765:C:T
Nerve Tibialeqtl6.7e-07-0.281:100691849:C:T
Whole Bloodeqtl1.2e-05-0.191:100698224:G:A
Adipose Subcutaneouseqtl1.3e-05-0.231:100721765:C:T
Colon Transverseeqtl9.5e-05+0.161:100589446:G:A
Pituitaryeqtl2.2e-04-0.271:100725310:A:C
Minor Salivary Glandeqtl4.7e-04-0.401:100603549:C:T
Pancreaseqtl7.3e-04+0.181:100669621:A:G
Esophagus Musculariseqtl3.3e-03-0.161:100525823:C:T
Brain Putamen basal gangliaeqtl3.7e-03+0.271:100571457:G:GTGGTA
Colon Sigmoideqtl7.9e-03-0.151:100623936:A:C
Heart Left Ventricleeqtl9.8e-03+0.201:100300140:T:C
Spleeneqtl1.3e-02-0.171:101224714:A:G
Brain Caudate basal gangliaeqtl1.3e-02-0.261:100605485:A:C
Prostateeqtl1.8e-02-0.231:100703651:A:G

FANTOM5 promoters

1 alternative TSS:

Promoter IDTPM avgSamples expressed
424814.7029928

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
cartilage tissueUBERON:000241899.13gold quality
trabecular bone tissueUBERON:000248398.99gold quality
parietal pleuraUBERON:000240098.23gold quality
vena cavaUBERON:000408798.08gold quality
tendon of biceps brachiiUBERON:000818898.08gold quality
spleenUBERON:000210697.98gold quality
adrenal tissueUBERON:001830397.94gold quality
renal glomerulusUBERON:000007497.91gold quality
metanephric glomerulusUBERON:000473697.80gold quality
synovial jointUBERON:000221797.38gold quality
nephron tubuleUBERON:000123197.34gold quality
pleuraUBERON:000097797.21gold quality
kidney epitheliumUBERON:000481997.14gold quality
lymph nodeUBERON:000002996.63gold quality
deciduaUBERON:000245096.19gold quality
layer of synovial tissueUBERON:000761695.41gold quality
visceral pleuraUBERON:000240195.40gold quality
epithelium of nasopharynxUBERON:000195195.16gold quality
nasopharynxUBERON:000172895.15gold quality
germinal epithelium of ovaryUBERON:000130495.05gold quality
choroid plexus epitheliumUBERON:000391194.62gold quality
kidneyUBERON:000211393.36gold quality
metanephrosUBERON:000008193.25gold quality
adult mammalian kidneyUBERON:000008293.20gold quality
vermiform appendixUBERON:000115493.11gold quality
adrenal glandUBERON:000236992.76gold quality
mucosa of urinary bladderUBERON:000125992.64gold quality
cortex of kidneyUBERON:000122592.43gold quality
colonic epitheliumUBERON:000039792.33gold quality
ventricular zoneUBERON:000305392.26gold quality
left adrenal glandUBERON:000123491.97gold quality
right adrenal glandUBERON:000123391.96gold quality
gall bladderUBERON:000211091.60gold quality
pericardiumUBERON:000240791.52gold quality
adrenal cortexUBERON:000123591.22gold quality
right adrenal gland cortexUBERON:003582791.11gold quality
caecumUBERON:000115391.06gold quality
tibiaUBERON:000097991.00gold quality
left adrenal gland cortexUBERON:003582590.74gold quality
tonsilUBERON:000237290.62gold quality
epithelial cell of pancreasCL:000008390.52gold quality
placentaUBERON:000198790.11gold quality
tendonUBERON:000004389.62gold quality
rectumUBERON:000105289.59gold quality
metanephros cortexUBERON:001053388.93gold quality
mucosa of sigmoid colonUBERON:000499388.84gold quality
islet of LangerhansUBERON:000000688.69gold quality
omental fat padUBERON:001041488.53gold quality
peritoneumUBERON:000235888.48gold quality
right ovaryUBERON:000211888.39gold quality
calcaneal tendonUBERON:000370188.33gold quality
adipose tissue of abdominal regionUBERON:000780887.90gold quality
superficial temporal arteryUBERON:000161487.70gold quality
left ovaryUBERON:000211987.29gold quality
ovaryUBERON:000099287.13gold quality
urethraUBERON:000005786.37gold quality
thoracic mammary glandUBERON:000520086.36gold quality
mammary glandUBERON:000191186.18gold quality
urinary bladderUBERON:000125585.67gold quality
thymusUBERON:000237085.59gold quality
ileal mucosaUBERON:000033185.49gold quality
epithelium of mammary glandUBERON:000324485.42gold quality
periodontal ligamentUBERON:000826685.41gold quality
mammary ductUBERON:000176585.31gold quality
mucosa of paranasal sinusUBERON:000503085.00gold quality
colonic mucosaUBERON:000031784.87gold quality
trigeminal ganglionUBERON:000167584.68gold quality
right coronary arteryUBERON:000162584.59gold quality
liverUBERON:000210784.36gold quality
connective tissueUBERON:000238484.18gold quality
adipose tissueUBERON:000101383.81gold quality
pylorusUBERON:000116683.55gold quality
endothelial cellCL:000011583.52silver quality
cranial nerve IIUBERON:000094183.26gold quality
bone elementUBERON:000147483.13gold quality
pancreasUBERON:000126483.12gold quality
renal medullaUBERON:000036283.08gold quality
coronary arteryUBERON:000162182.98gold quality
descending thoracic aortaUBERON:000234582.86gold quality
saphenous veinUBERON:000731882.82gold quality
ascending aortaUBERON:000149682.81gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047382.62gold quality
thoracic aortaUBERON:000151582.51gold quality
skin of hipUBERON:000155482.51gold quality
left coronary arteryUBERON:000162682.44gold quality
cauda epididymisUBERON:000436082.26gold quality
subcutaneous adipose tissueUBERON:000219082.22gold quality
jejunal mucosaUBERON:000039982.07gold quality
ganglionic eminenceUBERON:000402381.51gold quality
dorsal motor nucleus of vagus nerveUBERON:000287081.41gold quality
olfactory segment of nasal mucosaUBERON:000538681.23gold quality
duodenumUBERON:000211481.09gold quality
sigmoid colonUBERON:000115980.47gold quality
aortaUBERON:000094780.34gold quality
type B pancreatic cellCL:000016980.15silver quality
left uterine tubeUBERON:000130379.93gold quality
tibial nerveUBERON:000132379.60gold quality
oral cavityUBERON:000016779.56gold quality
seminal vesicleUBERON:000099879.43gold quality
arteryUBERON:000163779.24gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

ExperimentMarker?Max mean expression
E-MTAB-8322yes1536.75
E-MTAB-7407yes597.59
E-ANND-5yes582.58
E-GEOD-135922yes33.99
E-HCAD-4yes24.46
E-MTAB-10553yes23.55
E-ANND-3yes23.25
E-HCAD-9yes19.88
E-GEOD-93593yes14.84
E-GEOD-83139yes13.16
E-CURD-112yes11.19
E-GEOD-124858no807.76

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cellAxisnTPMProtein (IHC)
Spleentissue366.8medium
Lymph nodetissue90.1low
Spinal cordtissue84.0
Tonsiltissue71.2medium
Substantia nigratissue69.4
Urinary bladdertissue67.7not detected
Thalamustissue63.7
Medulla oblongatatissue59.9
Midbraintissue58.0
Ponstissue57.8
Periaqueductal graytissue55.9
Superior colliculitissue55.8
Kidneytissue55.4high
Hypothalamustissue55.1
Septumtissue52.9
Ovarytissue50.4not detected
Corpus callosumtissue46.3
Hippocampal formationtissue42.4
Livertissue40.8not detected
Adrenal glandtissue40.8not detected
Placentatissue40.6not detected
Putamentissue39.3
Ventral forebraintissue35.7
Amygdalatissue35.0
Prefrontal cortextissue33.2
Cerebral cortextissue33.2not detected
Entorhinal cortextissue33.1
Appendixtissue32.8low
Caudate putamentissue32.6
Motor cortextissue32.5
Retrosplenial cortextissue31.5
Basal gangliatissue29.7not detected
Retrosplenial and cingulate cortextissue29.7
Temporal cortextissue29.5
Insular cortextissue29.0
Gallbladdertissue27.7not detected
Frontal cortextissue27.4
Occipital cortextissue27.0
Somatosensory cortextissue26.3
Thymustissue22.9
Rectumtissue22.1not detected
Olfactory bulbtissue20.7
Adipose tissuetissue20.4not detected
Parathyroid glandtissue17.3not detected
Duodenumtissue14.5not detected
Breasttissue14.1not detected
Colontissue14.0not detected
Stomach 1tissue13.6not detected
Small intestinetissue13.5not detected
Pancreastissue12.5not detected
Cerebellumtissue11.7not detected
Lungtissue10.7not detected
Smooth muscletissue10.3not detected
Choroid plexustissue10.3
Locus coeruleustissue9.2
Prostatetissue9.1not detected
Endometrium 1tissue8.8not detected
Salivary glandtissue8.2not detected
Bone marrowtissue7.9not detected
Esophagustissue7.2not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Ventral spinal cord (84.0), Dorsal spinal cord (74.1), White matter (46.3), Dorsal hippocampus (42.4), Subiculum (38.6).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, APLNR, AR, CLOCK, CREB1, EP300, EPAS1, FLCN, FOS, FOXC1, FOXO1, GATA2, GATA3, GATA4, GATA6, HDAC4, HOXA9, ID3, IKBKB, IL1B, IRF1, IRF2, IRF6, JUN, KLF4, MYC, NFATC1, NFE2L2, NFKB1, NFKB2, NFKB, NFKBIA, NFKBID, NR4A3, PARP1, PGR, POU2F1, PPARA, PPARD, PPARG

miRNA regulators (miRDB)

Targeting VCAM1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 49 miRNAs:

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3163100.0077.238605
HSA-MIR-4692100.0067.322066
HSA-MIR-3925-3P100.0069.951237
HSA-MIR-4262100.0073.263931
HSA-MIR-428299.9975.366408
HSA-MIR-451499.9967.101870
HSA-MIR-1185-1-3P99.9871.042593
HSA-MIR-1185-2-3P99.9871.042593
HSA-LET-7F-2-3P99.9870.982588
HSA-MIR-477599.9875.006394
HSA-MIR-50799.9770.111915
HSA-MIR-590-3P99.9674.346478
HSA-MIR-55799.9670.011640
HSA-MIR-545-3P99.9570.742783
HSA-LET-7C-3P99.9573.422862
HSA-MIR-990299.8969.152250
HSA-MIR-95-5P99.8972.173973
HSA-MIR-7845-5P99.8864.88771
HSA-MIR-450399.8571.451869
HSA-MIR-202-3P99.8471.411290
HSA-MIR-3180-5P99.8269.122422
HSA-MIR-4799-5P99.8270.602663
HSA-MIR-3121-3P99.8271.963630
HSA-MIR-6739-5P99.8067.872806
HSA-MIR-4766-5P99.7569.232662
HSA-MIR-6733-5P99.7467.942759
HSA-MIR-1212999.7267.451311
HSA-MIR-5580-3P99.7069.412052
HSA-MIR-548AU-3P99.7068.221373
HSA-MIR-128499.6773.561353

Functional genomics

gnomAD constraint: pLI 4.18e-09, LOEUF 0.837, missense Z 1.45 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000294728 — one region, missense o/e 0.91.

Literature-anchored findings (GeneRIF, showing 40)

  • Premature labor is associated with up-regulation of adhesion molecules in the lower uterine segment (PMID:11776680)
  • Soluble VCAM-1 is a very early marker of endothelial cell activation in cardiopulmonary bypass. (PMID:11817523)
  • 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)
  • Testosterone attenuates expression of vascular cell adhesion molecule-1 by conversion to estradiol by aromatase in endothelial cells: implications in atherosclerosis (PMID:11904449)
  • Elevated soluble CD40 ligand is related to the endothelial adhesion molecules in patients with acute coronary syndrome. (PMID:11922919)
  • Human mast cell progenitors use alpha4-integrin, VCAM-1, and PSGL-1, E-selectin for adhesive interactions with human vascular endothelium under flow conditions (PMID:11929779)
  • relation between glycemic control, hyperinsulinism and plasma concentration in patients with glucosse intolerance or NIDDM (PMID:11935152)
  • Results suggest that exogenous NO inhibits VCAM-1 expression via suppression of NF-kappaB through a cGMP-independent pathway. (PMID:11961404)
  • women with stage III and IV endometriosis had higher serum concentrations of soluble VCAM-1, lower serum concentration of soluble ICAM-1 (PMID:11963839)
  • The tumor necrosis factor-alpha-stimulated redox-sensitive vascular cell adhesion molecule-1 selective signaling pathway in endothelial cells depends upon isoprenylcysteine carboxyl methyltransferase as a critical component. (PMID:12006387)
  • 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 VCAM-1 on the endothelium of femoral and iliac arteries in thromboangiitis obliterans (PMID:12086338)
  • VCAM-1/alpha4 integrin interactions mediate monocyte adhesion to human saphenous vein (PMID:12097820)
  • signal transduction pathways involved in rheumatoid arthritis synovial fibroblast interleukin-18-induced vascular cell adhesion molecule-1 expression (PMID:12105209)
  • VCAM-1 expression via effects on interferon regulatory factor-1 expression and activity (PMID:12115600)
  • 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 vcam-1 is associated with nodal metastasis in breast cancer (PMID:12172576)
  • Synchronized human hematopoietic progenitor cell adhesion fluctuates reversibly during cell cycle transit in ex vivo culture (PMID:12351381)
  • induction by tumor necrosis factor alpha (PMID:12387879)
  • Of the 10 candidate SNPs analyzed in this pilot study, the variant allele of the nonsynonymous SNP, VCAM1 G1238C, may be associated with protection from stroke. (PMID:12393616)
  • Relationship between pathological changes and the expression of vascular cell adhesion molecule-1 in the placenta of patients with pregnancy-induced hypertension complicated by intrauterine growth retardation (PMID:12433638)
  • VCAM1 stimulation by thrombin in endothelial cells is mediated by protein kinase C-delta-NF-kappa B and PKC-zeta-GATA signaling pathways (PMID:12493764)
  • VCAM1 expression is induced by p38-mediated TNFalpha and suppressed by JNK in human cells (PMID:12587980)
  • In adults with sickle cell disease, steady-state serum sVCAM-1 levels do not seem to reflect clinical disease severity, but may reflect bone marrow activity in SCD, underlying the pleiotropic nature of adhesion molecules in vivo. (PMID:12601490)
  • Strongly expressed in histological type II of rheumatoid arthritis. (PMID:12643440)
  • Crosslinking of CD44 on osteoblastic cells with specific antibodies augmented the expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 (PMID:12650924)
  • Endothelial cells have increased expression of VCAM-1, E-selectin, and ICAM-1 when exposed to sickle blood cells. (PMID:12673844)
  • VCAM-1-induced, Rac-dependent signaling plays a key role in the modulation of vascular-endothelial cadherin-mediated endothelial cell-cell adhesion and leukocyte extravasation. (PMID:12700137)
  • regulation of expression in osteoblasts by interleukin 13 (PMID:12704784)
  • a novel role for the P2Y2 receptor in the p38- and Rho kinase-dependent expression of VCAM-1 that mediates the recruitment of monocytes by vascular endothelium associated with the development of atherosclerosis (PMID:12714597)
  • Soluble VCAM-1 markedly enhances phosphorylation of both p38 and focal adhesion kinase, but not ERK1/2, in endothelial cells, endothelial cell migration activity in vitro, and neovascularization in Matrigel in vivo. (PMID:12759453)
  • Extravasated and oxidized LDL in xanthoma adds to foam cell recruitment by activating tyrosine kinase and inducing adhesion of monocytes to dermal microvascular endothelial cells through VCAM-1 and E-selectin. (PMID:12788528)
  • Blood levels do not differ in normal and coronary artery disease patients. (PMID:12940514)
  • During infusion of triacylglycerol, PAI-1 increased to approximately 2.6 fold higher levels while tPA and adipsin were unaffected; changes in sVCAM-1 were significantly correlated with those seen for PAI-1. (PMID:12958610)
  • presence of vascular cell adhesion molecule (VCAM-1) in placental villi is specific to developmental stage, and it is decreased in fetal growth restriction which could be attributed to the uteroplacental deficiency (PMID:12969778)
  • Adrenomedullin and ACTH induce cell surface expression of adhesion molecules E-selectin, VCAM-1, and ICAM-1 on human umbilical vein endothelial cells. (PMID:14534081)
  • 11,12-EET analogues were synthesized and compared using a human endothelial cell based TNF-alpha-induced VCAM-1 expression assay. (PMID:14592496)
  • Novel androgen receptor/NF-kappaB mediated mechanism for VCAM-1 expression and monocyte adhesion operating in male endothelial cells that may represent an important unrecognized mechanism for the male predisposition to atherosclerosis. (PMID:14684616)
  • study demonstrates that overexpression of RORalpha1 and RORalpha4 inhibits TNF-alpha induced expression of VCAM-1 and ICAM-1 in human umbilical vein endothelial cells by inhibiting the NF-B signaling pathway (PMID:14741380)
  • sVCAM-1 was associated with dengue disease severity and the time post infection; a significant difference was found in the plasma levels of sVCAM-1 between dengue shock syndrome and dengue fever patients (PMID:14748068)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriovcam1bENSDARG00000062479
mus_musculusVcam1ENSMUSG00000027962
rattus_norvegicusVcam1ENSRNOG00000014333
caenorhabditis_elegansWBGENE00007736
caenorhabditis_elegansWBGENE00011418

Paralogs (36): CNTN1 (ENSG00000018236), CDON (ENSG00000064309), NEO1 (ENSG00000067141), SDK2 (ENSG00000069188), IGSF9B (ENSG00000080854), IGSF9 (ENSG00000085552), NRCAM (ENSG00000091129), MXRA5 (ENSG00000101825), IGDCC4 (ENSG00000103742), CNTN3 (ENSG00000113805), IGSF21 (ENSG00000117154), CNTN6 (ENSG00000134115), CHL1 (ENSG00000134121), PTPRQ (ENSG00000139304), CNTN4 (ENSG00000144619), BOC (ENSG00000144857), SDK1 (ENSG00000146555), HMCN2 (ENSG00000148357), NCAM1 (ENSG00000149294), CNTN5 (ENSG00000149972), IGSF10 (ENSG00000152580), ROBO4 (ENSG00000154133), ROBO3 (ENSG00000154134), NCAM2 (ENSG00000154654), NFASC (ENSG00000163531), PRTG (ENSG00000166450), ROBO1 (ENSG00000169855), DSCAM (ENSG00000171587), IGDCC3 (ENSG00000174498), VSIG10 (ENSG00000176834), DSCAML1 (ENSG00000177103), CNTN2 (ENSG00000184144), ROBO2 (ENSG00000185008), VSIG10L (ENSG00000186806), DCC (ENSG00000187323), L1CAM (ENSG00000198910)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:98926) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 44 distinct phenotype terms.

Mouse phenotype (MP)Records
increased leukocyte cell number3
decreased bone marrow cell number3
abnormal interventricular septum morphology2
decreased embryo size2
disorganized myocardium2
abnormal bone marrow cell morphology/development2
abnormal blood cell morphology/development2
abnormal chorioallantoic fusion2
increased B cell number2
decreased B cell number2
pericardial effusion2
increased immature B cell number2
thin ventricle myocardium compact layer2
embryonic lethality during organogenesis, complete penetrance2
increased monocyte cell number1
spleen hyperplasia1
decreased body weight1
abnormal allantois morphology1
abnormal humoral immune response1
postnatal lethality1
abnormal extraembryonic tissue morphology1
abnormal cardiovascular system morphology1
abnormal epicardium morphology1
abnormal lymphocyte physiology1
abnormal CD8-positive, alpha-beta T cell physiology1

+19 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

OrganismUniProtIdentityMethod
Canis lupus familiarisQ2826081.1%Diamond
Bos taurusQ29RR675.2%Diamond
Gallus gallusQ0369650.0%Diamond
Drosophila melanogasterQ9I7U437.4%Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

SymbolTypeEntrez
LINC01349ncRNA100128787
DPH5-DTncRNA102606465
SLC30A7protein-coding148867
EXTL2protein-coding2135
DPH5protein-coding51611

Protein

Protein identifiers

Vascular cell adhesion protein 1 — P19320 (reviewed: P19320)

Alternative names: INCAM-100

All UniProt accessions (3): P19320, A0A3B3ISS8, E9PDD2

UniProt curated annotations — full annotation on UniProt →

Function. Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation. Acts as a major regulator of leukocyte adhesion to the endothelium through interaction with different types of integrins. During inflammatory responses, binds ligands on the surface of activated endothelial cells to initiate the activation of calcium channels and the plasma membrane-associated small GTPase RAC1 leading to leukocyte transendothelial migration. Also serves as a quality-control checkpoint for entry into bone marrow by providing a ‘don’t-eat-me’ stamping in the context of major histocompatibility complex (MHC) class-I presentation.

Subcellular location. Cell membrane Secreted.

Tissue specificity. Expressed on inflamed vascular endothelium, as well as on macrophage-like and dendritic cell types in both normal and inflamed tissue.

Post-translational modifications. Cleaved by the metalloproteinase ADAM17 to generate the soluble form. Sialoglycoprotein. Ubiquitinated by TRIM65 via ‘Lys-48’-linked ubiquitination; leading to proteasomal degradation.

Domain organisation. Either the first or the fourth Ig-like C2-type domain is required for VLA4-dependent cell adhesion.

Induction. By pro-inflammatory cytokines, including TNFalpha, and also by ROS, oxidized low density lipoprotein, high glucose concentration, toll-like receptor agonists, and shear stress.

Miscellaneous. Major isoform.

Isoforms (3)

UniProt IDNamesCanonical?
P19320-11, Long, VCAM-7Dyes
P19320-22, Short, VCAM-6D
P19320-33

RefSeq proteins (3): NP_001069, NP_001186763, NP_542413 (=MANE)

Domains & families (InterPro)

IDNameType
IPR003598Ig_sub2Domain
IPR003599Ig_subDomain
IPR003987ICAM_VCAM_NDomain
IPR003989VCAM-1Family
IPR007110Ig-like_domDomain
IPR008424Ig_C2-setDomain
IPR013098Ig_I-setDomain
IPR013106Ig_V-setDomain
IPR013151Immunoglobulin_domDomain
IPR013783Ig-like_foldHomologous_superfamily
IPR036179Ig-like_dom_sfHomologous_superfamily
IPR047012ICAM_VCAMFamily

Pfam: PF00047, PF05790, PF07679, PF13927

UniProt features (57 total): strand 15, domain 7, sequence variant 7, glycosylation site 6, disulfide bond 6, sequence conflict 3, helix 3, chain 2, splice variant 2, topological domain 2, mutagenesis site 2, signal peptide 1, transmembrane region 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDBTitleMethodResolution (Å)
1VCACRYSTAL STRUCTURE OF AN INTEGRIN-BINDING FRAGMENT OF VASCULAR CELL ADHESION MOLECULE-1 AT …X-RAY DIFFRACTION1.8
1VSCVCAM-1X-RAY DIFFRACTION1.9
1IJ9Highly Hydrated Human VCAM-1 FragmentX-RAY DIFFRACTION3

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P19320-F184.240.50

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, Predicted secreted proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cell junctions

Antibody reliability (HPA): IH enhanced · IF approved

Functional residue map

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

Disulfide bonds (6)

TypePositions
Disulfide bond47–95, 52–99, 137–195, 246–291, 335–383, 534–579

Glycosylation sites (6)

TypePositions
N-linked (glcnac…) asparagine273, 365, 417, 463, 531, 561

Mutagenesis-validated functional residues (2)

PositionPhenotype
730loss of rac1 activation and subsequent leukocyte transmigration.
737loss of rac1 activation and subsequent leukocyte transmigration.

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

IDPathwayEvidence
R-HSA-198933Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cellcurated
R-HSA-216083Integrin cell surface interactionscurated
R-HSA-877300Interferon gamma signalingcurated
R-HSA-6785807Interleukin-4 and Interleukin-13 signalingcurated
R-HSA-1280218Adaptive Immune System—
R-HSA-9938027Affinity selection of immunoglobulinselectronic
R-HSA-1280215Cytokine Signaling in Immune system—
R-HSA-1474244Extracellular matrix organization—
R-HSA-168256Immune System—
R-HSA-913531Interferon Signaling—
R-HSA-449147Signaling by Interleukins—

MSigDB gene sets: 416 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_RESPONSE_TO_ETHANOL, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_RESPONSE_TO_ZINC_ION, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, MCLACHLAN_DENTAL_CARIES_UP, GOBP_CELL_CHEMOTAXIS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE

GO Biological Process (27): response to hypoxia (GO:0001666), chronic inflammatory response (GO:0002544), inflammatory response (GO:0006954), cell adhesion (GO:0007155), heterophilic cell-cell adhesion (GO:0007157), leukocyte cell-cell adhesion (GO:0007159), cell-matrix adhesion (GO:0007160), response to nutrient (GO:0007584), amine metabolic process (GO:0009308), response to zinc ion (GO:0010043), response to ionizing radiation (GO:0010212), membrane to membrane docking (GO:0022614), B cell differentiation (GO:0030183), response to lipopolysaccharide (GO:0032496), cell-cell adhesion mediated by integrin (GO:0033631), heterotypic cell-cell adhesion (GO:0034113), response to nicotine (GO:0035094), cellular response to vascular endothelial growth factor stimulus (GO:0035924), positive regulation of T cell proliferation (GO:0042102), response to ethanol (GO:0045471), leukocyte tethering or rolling (GO:0050901), cell chemotaxis (GO:0060326), innervation (GO:0060384), cardiac neuron differentiation (GO:0060945), cellular response to tumor necrosis factor (GO:0071356), cellular response to amyloid-beta (GO:1904646), cell-cell adhesion (GO:0098609)

GO Molecular Function (4): integrin binding (GO:0005178), primary methylamine oxidase activity (GO:0008131), cell adhesion molecule binding (GO:0050839), cell adhesion mediator activity (GO:0098631)

GO Cellular Component (15): podosome (GO:0002102), early endosome (GO:0005769), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), microvillus (GO:0005902), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), filopodium (GO:0030175), sarcolemma (GO:0042383), apical part of cell (GO:0045177), extracellular exosome (GO:0070062), alpha9-beta1 integrin-vascular cell adhesion molecule-1 complex (GO:0071065), extracellular region (GO:0005576), membrane (GO:0016020)

Reactome top-level categories

7 top-level categories:

CategoryPathways
Immune System2
Cytokine Signaling in Immune system2
Adaptive Immune System1
Extracellular matrix organization1
Signaling by Interleukins1
Interferon Signaling1
Immunoglobulin maturation1

GO top-level categories

45 GO namespaces:

CategoryTerms
cell-cell adhesion4
cellular anatomical structure4
actin-based cell projection3
response to chemical2
cell adhesion molecule binding2
cytoplasm2
endomembrane system2
intracellular membrane-bounded organelle2
plasma membrane2
response to stress1
response to decreased oxygen levels1
inflammatory response1
defense response1
cellular process1
cell-substrate adhesion1
response to nutrient levels1
metabolic process1
response to metal ion1
response to radiation1
membrane docking1
lymphocyte differentiation1
B cell activation1
response to molecule of bacterial origin1
response to lipid1
response to oxygen-containing compound1
cell adhesion mediated by integrin1
cellular response to growth factor stimulus1
T cell proliferation1
regulation of T cell proliferation1
positive regulation of lymphocyte proliferation1
positive regulation of T cell activation1
response to alcohol1
signaling receptor binding1
protein-containing complex binding1
monoamine oxidase activity1
protein binding1
cell adhesion1
endosome1
membrane1
cell periphery1
actin filament bundle1
cell surface1
side of membrane1
extracellular vesicle1
plasma membrane protein complex1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 27 of 47 annotations. The rest are phylogenetic / computational / electronic (IEA).

27 experimentally-supported GO terms:

GO termNSEvidence
amine metabolic processBPdirect assay
cell adhesionBPdirect assay
cell-cell adhesion mediated by integrinBPgenetic interaction
cell-matrix adhesionBPdirect assay
cellular response to amyloid-betaBPgenetic interaction
heterophilic cell-cell adhesionBPdirect assay
heterotypic cell-cell adhesionBPgenetic interaction
inflammatory responseBPdirect assay
leukocyte cell-cell adhesionBPdirect assay
leukocyte tethering or rollingBPdirect assay
membrane to membrane dockingBPexpression pattern
positive regulation of T cell proliferationBPdirect assay
Golgi apparatusCCdirect assay
alpha9-beta1 integrin-vascular cell adhesion molecule-1 complexCCdirect assay
apical part of cellCCdirect assay
cell surfaceCCdirect assay
early endosomeCCdirect assay
endoplasmic reticulumCCdirect assay
external side of plasma membraneCCdirect assay
extracellular exosomeCChigh-throughput assay
filopodiumCCdirect assay
microvillusCCdirect assay
podosomeCCdirect assay
cell adhesion mediator activityMFdirect assay
cell adhesion molecule bindingMFdirect assay
integrin bindingMFdirect assay
primary methylamine oxidase activityMFdirect assay

Protein interactions and networks

STRING

showing 15 of 4,000 interactions by confidence (×1000):

Protein AProtein BPartner UniProtScore
VCAM1ICAM1P05362978
VCAM1SELEP16111946
VCAM1SELPP16109914
VCAM1TNFP01375909
VCAM1IL6P05231898
VCAM1CCL2P13500867
VCAM1IL1BP01584867
VCAM1IFNGP01579832
VCAM1IL1AP01583829
VCAM1ITGA4P13612820
VCAM1ITGB2P05107819
VCAM1ITGB1P05556806
VCAM1VWFP04275801
VCAM1NFKB1P19838791
VCAM1IL4P05112790

IntAct

Human interaction partners of VCAM1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

PartnerInteraction typeMIscoreRecords
ITGB1association0.6603
PSMD11association0.5301
APOA1association0.3501
ATP1A3association0.3501
ATP2A1association0.3501

BioGRID (494 interactions; top human partners by supporting records): MSN (Affinity Capture-Western; 4 records), TRIM65 (Affinity Capture-Western; 3 records), ACTB (Affinity Capture-MS; 2 records), BCS1L (Affinity Capture-MS; 2 records), EZR (Affinity Capture-Western; 2 records), ITGA4 (Affinity Capture-MS; 2 records), LGALS1 (Affinity Capture-MS; 2 records), NCL (Affinity Capture-MS; 2 records), PARP1 (Proximity Label-MS; 2 records), PODXL2 (Affinity Capture-MS; 2 records), PRKDC (Affinity Capture-MS; 2 records), SEMA4D (Affinity Capture-MS; 2 records), TUBA4A (Affinity Capture-MS; 2 records), VCP (Affinity Capture-Western; 2 records), VDAC1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

3 signaling interactions:

AEffectBMechanism
VCAM1“up-regulates activity”“A4/b1 integrin”binding
“AD/b2 integrin”“up-regulates activity”VCAM1binding
hsa-mir-126-5p“down-regulates quantity by repression”VCAM1“post transcriptional regulation”

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

ComplexSubunitsMembers
★ ITGA4-ITGB1-VCAM1 complex3ITGA4, ITGB1, VCAM1
★ ITGA9-ITGB1-VCAM1 complex3ITGB1, VCAM1, ITGA9
★ ITGA4-ITGAB7-VCAM1 complex3ITGB7, VCAM1, ITGA4

Ligand–receptor pairs (CellPhoneDB) (4)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

4 ligand–receptor pairs:

PartnerThis gene’s roleSignaling class
ITGB2;ITGADligandAdhesion by VCAM
ITGB1;ITGA9ligandAdhesion by VCAM
ITGB7;ITGA4ligandAdhesion by VCAM
ITGB1;ITGA4ligandAdhesion by VCAM

Disease & clinical

Genetic variants

Variant evidence for VCAM1: 101 ClinVar records (0 pathogenic / likely pathogenic); 8 GWAS associations.

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance81
Likely benign13
Benign1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 41 predictions of 687):

Position(s)EffectΔscoreSites
1:100734769–100734770donor_loss1.00005
1:100720474–100720475acceptor_loss0.99004
1:100723214donor_gain0.9900
1:100723341–100723342donor_loss0.99006
1:100723345donor_loss0.9900
1:100724622–100724623acceptor_loss0.99006
1:100729095acceptor_gain0.9900
1:100731196–100731197acceptor_loss0.99006
1:100731519–100731520donor_loss0.99005
1:100734500–100734501acceptor_loss0.99006

AlphaMissense

577 missense substitutions predicted likely pathogenic (of 4,860 scored), across 200 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

ResidueLikely-pathogenic substitutionsMean am_pathogenicityMax am_pathogenicity
C9570.9690.990
W5970.9610.994
C29170.9560.981
C4770.9540.979
W34770.9450.989
C48370.9420.977
C57970.9410.972
C19570.9380.979
C42570.9380.968
C24670.9330.979
C66870.9310.977
C13770.9300.986
C62370.9290.970
W25870.9140.982
C53470.9040.967
C38370.8970.960
C33570.8910.964
C5270.8720.924
C9970.8200.888
C34070.7960.863

HPA cancer prognostics

RNA cancer specificity: Group enriched (Kidney Renal Clear Cell Carcinoma, Kidney Renal Papillary Cell Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

CancerPrognosticp-value
Kidney Renal Clear Cell Carcinoma (TCGA)favorable0.000186
Head and Neck Squamous Cell Carcinoma (TCGA)favorable0.000257

Disease associations

OMIM: gene MIM:192225 | disease phenotypes:

GWAS associations

8 associations:

StudyTraitp-value
GCST009597_229Multiple sclerosis1e-22
GCST005531_104Multiple sclerosis2e-16
GCST90002388_492Lymphocyte count3e-13
GCST001198_27Multiple sclerosis3e-10
GCST90002389_341Lymphocyte percentage of white cells1e-9
GCST90002399_94Neutrophil percentage of white cells6e-9
GCST001198_77Multiple sclerosis4e-8
GCST005532_3Sjögren’s syndrome4e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO IDTrait name
EFO:0004587lymphocyte count
EFO:0007993lymphocyte percentage of leukocytes
EFO:0007990neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3735 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 251 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

MoleculeNamePhasePatents
CHEMBL83626SUCCINOBUCOL3251

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

206 measured of 228 human assays (229 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
4-(4-Trifluoromethyl-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC500.7 nM
4-(4-Vinyl-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid amideIC501 nM
4-(4-Imidazol-1-yl-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC502 nM
4-[4-(Tetrahydro-pyran-2-yloxymethyl)-phenoxy]-thieno[2,3-c]pyridine-2-carboxylic acid amideIC502 nM
4-(4-Cyano-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC502.8 nM
4-{4-[2-(2-Methoxy-ethoxy)-ethoxymethyl]-phenoxy}-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC504 nM
4-(4-Bromo-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid amideIC504 nM
4-(4-Pyrazol-1-yl-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC504 nM
4-(4-Bromo-phenylsulfanyl)-thieno[2,3-c]pyridine-2-carboxylic acid amideIC505 nM
4-(4-Thiophen-2-yl-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC505 nM
4-[4-(2-Methoxy-ethoxymethyl)-phenoxy]-thieno[2,3-c]pyridine-2-carboxylic acid amideIC505 nM
4-(4-Furan-2-yl-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC505 nM
4-{4-[2-(2-Methoxy-ethoxy)-ethoxymethyl]-phenoxy}-thieno[2,3-c]pyridine-2-carboxylic acid amideIC505 nM
4-(4-Cyano-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid amideIC505.1 nM
4-p-Tolyloxy-thieno[2,3-c]pyridine-2-carboxylic acid amideIC506 nM
4-(4-Iodo-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid amideIC506 nM
4-(4-Imidazol-1-yl-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid amideIC506 nM
4-(4-Chloro-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid amideIC506.2 nM
4-(4-Bromo-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC507 nM
4-[4-(2-Methoxy-ethoxymethyl)-phenoxy]-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC507 nM
4-(4-Chloro-3-fluoro-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid amideIC508 nM
4-(4-Chloro-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC508.2 nM
4-(Biphenyl-4-yloxy)-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC509 nM
4-(4-Chloro-phenylsulfanyl)-thieno[2,3-c]pyridine-2-carboxylic acid amideIC5012 nM
(2S)-2-[[2,6-difluoro-4-[[5-(1,2,4-triazol-1-yl)-2-pyridinyl]sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4aH-pyrido[3,4-d]pyrimidin-1-ium-3-yl)phenyl]propanoic acidIC5013 nMUS-9533985: Sulfonamide derivative and medicinal use thereof
4-(3,4-Dimethyl-phenylsulfanyl)-thieno[2,3-c]pyridine-2-carboxylic acid amideIC5013 nM
4-[4-(N-Hydroxycarbamimidoyl)-phenoxy]-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC5013 nM
4-(4-Methoxymethyl-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC5013 nM
4-(4-Chloro-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid ethylamideIC5016 nM
4-(4-Methoxymethyl-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid amideIC5016 nM
(2S)-2-[[2,6-difluoro-4-[(5-pyrimidin-5-yl-2-pyridinyl)sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4a,5,6,7,8,8a-hexahydropyrido[3,4-d]pyrimidin-3-yl)phenyl]propanoic acidIC5018 nMUS-9533985: Sulfonamide derivative and medicinal use thereof
4-(4-Cyano-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC5018 nM
4-(4-Trifluoromethyl-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid amideIC5019 nM
4-Phenylsulfanyl-thieno[2,3-c]pyridine-2-carboxylic acid amideIC5020 nM
4-(2-Carbamoyl-thieno[2,3-c]pyridin-4-yloxy)-benzoic acid ethyl esterIC5020 nM
4-(4-Acetyl-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC5021 nM
(2S)-2-[[2,6-difluoro-4-[[5-(1,3-thiazol-2-yl)-2-pyridinyl]sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4aH-pyrido[3,4-d]pyrimidin-1-ium-3-yl)phenyl]propanoic acidIC5022 nMUS-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[5-(triazol-1-yl)-2-pyridinyl]sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4a,5,6,7,8,8a-hexahydropyrido[3,4-d]pyrimidin-3-yl)phenyl]propanoic acidIC5022 nMUS-9533985: Sulfonamide derivative and medicinal use thereof
4-(4-Hydroxymethyl-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC5025 nM
4-[4-(3-Morpholin-4-yl-3-oxo-propenyl)-phenoxy]-thieno[2,3-c]pyridine-2-carboxylic acid amideIC5025 nM
4-(4-Methoxy-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid amideIC5025 nM
4-(4-Hydroxymethyl-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid amideIC5028 nM
4-[4-(5-Trifluoromethyl-[1,2,4]oxadiazol-3-yl)-phenoxy]-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC5028 nM
4-(4-Acetylamino-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid amideIC5029 nM
4-(4-Ethyl-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid amideIC5030 nM
(2S)-2-[[2,6-difluoro-4-[[4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl]sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4aH-pyrido[3,4-d]pyrimidin-1-ium-3-yl)phenyl]propanoic acidIC5031 nMUS-9533985: Sulfonamide derivative and medicinal use thereof
4-[4-(1-Hydroxymethyl-cyclopropyl)-phenoxy]-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC5031 nM
4-p-Tolylsulfanyl-thieno[2,3-c]pyridine-2-carboxylic acid hydrazideIC5032 nM
4-{4-[2-(2-Morpholin-4-yl-ethylcarbamoyl)-vinyl]-phenoxy}-thieno[2,3-c]pyridine-2-carboxylic acid amideIC5034 nM
4-(4-Morpholin-4-yl-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid methylamideIC5035 nM

ChEMBL bioactivities

68 potent at pChembl≥5 of 107 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
8.30IC505nMCHEMBL119039
8.22IC506nMCHEMBL117894
8.15IC507nMCHEMBL116070
8.10IC508nMCHEMBL116070
7.77IC5017nMCHEMBL326120
7.72IC5019nMCHEMBL325184
7.70IC5020nMCHEMBL117279
7.70IC5020nMCHEMBL116070
7.64IC5023nMCHEMBL119183
7.52IC5030nMCHEMBL117279
7.32IC5048nMCHEMBL116070
7.19IC5064nMCHEMBL117936
7.16IC5070nMCHEMBL118074
7.13IC5074nMCHEMBL118089
7.10IC5079nMCHEMBL115637
7.07IC5085nMCHEMBL117198
7.04IC5091nMCHEMBL115971
6.92IC50120nMCHEMBL117279
6.89IC50130nMCHEMBL324133
6.85IC50140nMCHEMBL119732
6.77IC50170nMCHEMBL115431
6.76IC50175nMCHEMBL6248
6.72IC50191nMCHEMBL118022
6.70IC50200nMCHEMBL118074
6.62IC50240nMCHEMBL119705
6.48IC50330nMCHEMBL119599
6.43IC50370nMCHEMBL118300
6.38IC50420nMCHEMBL115960
6.33IC50470nMCHEMBL324824
6.11IC50770nMCHEMBL6830
6.11IC50780nMCHEMBL325286
6.07IC50850nMCHEMBL325893
6.06IC50880nMCHEMBL119523
6.03IC50930nMCHEMBL115462
5.89IC501300nMCHEMBL6257
5.68IC502100nMCHEMBL266572
5.64IC502300nMCHEMBL266197
5.60IC502500nMCHEMBL4166467
5.60IC502500nMCHEMBL6229
5.57IC502700nMCHEMBL6371
5.52IC503000nMCHEMBL53269
5.46IC503500nMCHEMBL267127
5.46IC503500nMCHEMBL6249
5.41IC503900nMCHEMBL118518
5.40IC504000nMCHEMBL298775
5.35IC504500nMCHEMBL4166036
5.30IC505000nMCHEMBL53082
5.30IC505000nMCHEMBL52799
5.30IC505000nMCHEMBL51654
5.30IC505000nMCHEMBL53475

PubChem BioAssay actives

68 with measured affinity, of 212 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.

CompoundAssayTypeValueUnit
N-methyl-4-(4-pyrazol-1-ylphenoxy)thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.0050uM
N-methyl-4-(4-thiophen-2-ylphenoxy)thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.0060uM
4-(4-bromophenoxy)thieno[2,3-c]pyridine-2-carboxamide216486: In vitro inhibitory potency compared to IL1-beta induced VCAM-1 in human endothelial cells (ELISA assay)ic500.0070uM
4-(4-imidazol-1-ylphenoxy)thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.0170uM
4-(4-imidazol-1-ylphenoxy)-N-methylthieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.0190uM
4-[4-[2-(2-methoxyethoxy)ethoxymethyl]phenoxy]-N-methylthieno[2,3-c]pyridine-2-carboxamide216486: In vitro inhibitory potency compared to IL1-beta induced VCAM-1 in human endothelial cells (ELISA assay)ic500.0200uM
4-[4-(methoxymethyl)phenoxy]thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.0230uM
4-(4-aminophenoxy)thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.0640uM
4-(4-chlorophenoxy)-N-methylthieno[2,3-c]pyridine-2-carboxamide216485: In vitro inhibitory potency compared to IL1-beta induced VCAM-1 expression in human endothelial cells (ELISA assay)ic500.0700uM
4-[4-[1-(hydroxymethyl)cyclopropyl]phenoxy]-N-methylthieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.0740uM
N-methyl-4-(4-phenylphenoxy)thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.0790uM
4-(4-cyanophenoxy)thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.0850uM
4-(4-cyanophenoxy)-N-methylthieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.0910uM
4-(4-chlorophenoxy)-N,N-dimethylthieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.1300uM
4-(4-ethylphenoxy)thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.1400uM
4-[4-[2-[2-(2-ethoxyethoxy)ethoxy]-1,1-difluoroethyl]phenoxy]-N-methylthieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.1700uM
5-methoxy-3-propan-2-yloxy-1-benzothiophene-2-carboxamide216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assayic500.1750uM
4-[4-(hydroxymethyl)phenoxy]thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.1910uM
N-methyl-4-[4-(1,2,4-triazol-1-yl)phenoxy]thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.2400uM
4-(2-bromo-4-chlorophenoxy)thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.3300uM
N-methyl-4-[4-(trifluoromethoxy)phenoxy]thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.3700uM
4-[4-[1-[2-(2-ethoxyethoxy)ethoxymethyl]cyclopropyl]phenoxy]-N-methylthieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.4200uM
4-[4-(1,1-difluoro-2-hydroxyethyl)phenoxy]-N-methylthieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.4700uM
4-(2,4-dimethylphenyl)sulfanylthieno[2,3-c]pyridine-2-carboxamide216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assayic500.7700uM
4-(2-prop-2-enylphenoxy)thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.7800uM
4-(3-chlorophenoxy)thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.8500uM
4-(4-chlorophenoxy)-N-(2-hydroxyethyl)thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.8800uM
4-[4-(1,2-dihydroxyethyl)phenoxy]thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic500.9300uM
4-chlorothieno[2,3-c]pyridine-2-carboxamide216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assayic501.3000uM
4-(4-methylphenyl)sulfanylthieno[2,3-c]pyridine216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assayic502.1000uM
2-ethyl-4-(4-methylphenyl)sulfanylthieno[2,3-c]pyridine216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assayic502.3000uM
2-[3-(10H-pyrazino[2,3-b][1,4]benzothiazin-8-ylmethyl)-3-azabicyclo[3.3.1]nonan-9-yl]acetic acid1508013: Inhibition of VCAM1 (unknown origin)ic502.5000uM
5-(6-ethylthieno[2,3-d]pyrimidin-4-yl)sulfanyl-1,3,4-thiadiazol-2-amine216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assayic502.5000uM
[4-(4-methylphenyl)sulfanylthieno[2,3-c]pyridin-2-yl]-phenylmethanone216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assayic502.7000uM
4-chloro-N,N-diethyl-3-nitrobenzenesulfonamide216481: Ability to inhibit expression of Vascular cell adhesion molecule 1ic503.0000uM
(E)-1-[4-(4-methylphenyl)sulfanylthieno[2,3-c]pyridin-2-yl]-N-phenoxymethanimine216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assayic503.5000uM
6-ethyl-4-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]thieno[2,3-d]pyrimidine216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assayic503.5000uM
4-(4-chlorophenoxy)thieno[2,3-c]pyridine-2-carboxamide216483: Inhibition of VCAM-1 in human endothelial cellsic503.9000uM
1-(4-chloro-3-nitrophenyl)sulfonylpyrrolidine216481: Ability to inhibit expression of Vascular cell adhesion molecule 1ic504.0000uM
8-[[4-(dimethylsulfamoylamino)piperidin-1-yl]methyl]-10H-pyrazino[2,3-b][1,4]benzothiazine1508013: Inhibition of VCAM1 (unknown origin)ic504.5000uM
bis(4-chloro-3-nitrophenyl)methanone216481: Ability to inhibit expression of Vascular cell adhesion molecule 1ic505.0000uM
4-chloro-N,N-bis(2-methoxyethyl)-3-nitrobenzenesulfonamide216481: Ability to inhibit expression of Vascular cell adhesion molecule 1ic505.0000uM
methyl 4-methylsulfonyl-3-nitrobenzoate216481: Ability to inhibit expression of Vascular cell adhesion molecule 1ic505.0000uM
4-chloro-2-nitrobenzonitrile216481: Ability to inhibit expression of Vascular cell adhesion molecule 1ic505.0000uM
4-[2,6-ditert-butyl-4-[2-(3,5-ditert-butyl-4-hydroxyphenyl)sulfanylpropan-2-ylsulfanyl]phenoxy]-4-oxobutanoic acid216494: Inhibition of TNF-alpha inducible Vascular cell adhesion molecule-1 expression.ic506.0000uM
4-chloro-N-[3-[(4-chloro-3-nitrophenyl)sulfonyl-methylamino]propyl]-N-methyl-3-nitrobenzenesulfonamide216481: Ability to inhibit expression of Vascular cell adhesion molecule 1ic506.0000uM
4-chloro-N-(4-chloro-3-nitrophenyl)sulfonyl-3-nitro-N-phenylbenzenesulfonamide216481: Ability to inhibit expression of Vascular cell adhesion molecule 1ic507.0000uM
4-chloro-3-nitro-N,N-dipentylbenzenesulfonamide216481: Ability to inhibit expression of Vascular cell adhesion molecule 1ic507.0000uM
1-fluoro-4-(4-fluoro-3-nitrophenyl)sulfonyl-2-nitrobenzene216481: Ability to inhibit expression of Vascular cell adhesion molecule 1ic507.0000uM
1-(4-chloro-3-nitrophenyl)sulfonyl-4-methylpiperazine216481: Ability to inhibit expression of Vascular cell adhesion molecule 1ic508.0000uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Lipopolysaccharidesincreases expression, increases reaction, increases secretion, affects reaction, decreases reaction18
Particulate Matterdecreases expression, decreases reaction, increases expression, increases abundance, affects expression (+1 more)12
Vehicle Emissionsincreases expression, increases reaction, affects expression, decreases expression, decreases reaction (+1 more)9
Glucosedecreases reaction, increases expression, affects cotreatment, increases secretion8
Valproic Acidaffects cotreatment, decreases expression, affects expression, increases expression8
Simvastatinincreases expression, affects cotreatment, decreases expression, increases reaction, decreases reaction8
Quercetinaffects cotreatment, decreases reaction, increases expression, increases reaction6
bisphenol Adecreases expression, affects cotreatment, decreases reaction, increases expression5
3-(4-methylphenylsulfonyl)-2-propenenitrileincreases reaction, increases abundance, decreases reaction, increases expression, affects binding5
lipopolysaccharide, Escherichia coli O111 B4decreases reaction, increases expression, affects reaction5
Resveratroldecreases reaction, increases expression, decreases expression5
Acetylcysteinedecreases reaction, increases expression5
Hydrogen Peroxidedecreases reaction, increases secretion, increases expression, decreases expression5
Ascorbic Acidaffects binding, affects cotreatment, increases expression, decreases reaction, decreases expression4
Plant Extractsdecreases reaction, increases expression, increases reaction, decreases expression4
titanium dioxidedecreases reaction, increases expression3
acetovanillonedecreases reaction, increases expression3
SB 203580decreases reaction, increases expression3
lipopolysaccharide, E coli O55-B5decreases reaction, increases expression, affects cotreatment3
Air Pollutantsincreases expression, affects reaction, affects expression3
Arsenicincreases expression, increases secretion3
Dexamethasonedecreases reaction, increases expression, decreases expression, affects cotreatment3
Estradiolaffects cotreatment, decreases expression, decreases reaction, increases expression3
Ethinyl Estradiolaffects cotreatment, decreases expression, increases reaction3
Formaldehydedecreases expression, increases expression3
Hydrocortisoneaffects cotreatment, increases expression, decreases reaction3
Sulfasalazinedecreases reaction, increases expression, decreases expression3
Smokedecreases reaction, increases expression3
Tetrachlorodibenzodioxinaffects expression, decreases expression, increases expression3
Sootincreases expression3

ChEMBL screening assays

16 unique, capped per target: 15 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1176151BindingInhibition of VCAM1 in TNF-alpha/IL4-stimulated HUVEC assessed as inhibition of cell adhesion between HUVEC and Ramos cells at 8 uM after 20 hrs incubation relative to untreated controlSymbiopolyol, a VCAM-1 inhibitor from a symbiotic dinoflagellate of the jellyfish Mastigias papua. — *J Nat Prod*
CHEMBL815903FunctionalInhibition of TNF-alpha inducible Vascular cell adhesion molecule-1 expression.Novel phenolic antioxidants as multifunctional inhibitors of inducible VCAM-1 expression for use in atherosclerosis. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

CellosaurusNameCategorySex
CVCL_B1IGAbcam A-549 VCAM1 KOCancer cell lineMale

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for VCAM1 across ~30M SureChEMBL compounds — explore on Sugi Predict.

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): multiple sclerosis, Sjogren syndrome