CDH5

Summary

CDH5 (cadherin 5, HGNC:1764) is a protein-coding gene on chromosome 16q21, encoding Cadherin-5 (P33151). Cadherins are calcium-dependent cell adhesion proteins.

This gene encodes a classical cadherin of the cadherin superfamily. The encoded preproprotein is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion molecule is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Functioning as a classical cadherin by imparting to cells the ability to adhere in a homophilic manner, this protein plays a role in endothelial adherens junction assembly and maintenance. This gene is located in a gene cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer.

Source: NCBI Gene 1003 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 156 total
• MANE Select transcript: NM_001795

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1764
Approved symbol	CDH5
Name	cadherin 5
Location	16q21
Locus type	gene with protein product
Status	Approved
Aliases	7B4, CD144
Ensembl gene	ENSG00000179776
Ensembl biotype	protein_coding
OMIM	601120
Entrez	1003

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 nonsense_mediated_decay

ENST00000341529, ENST00000539168, ENST00000562048, ENST00000563425, ENST00000565334, ENST00000568023, ENST00000568155, ENST00000649567, ENST00000894863, ENST00000894864

RefSeq mRNA: 1 — MANE Select: NM_001795 NM_001795

CCDS: CCDS10804

Canonical transcript exons

ENST00000341529 — 12 exons

Exon	Start	End
ENSE00001284556	66386809	66387097
ENSE00001304636	66389358	66389522
ENSE00001326240	66388324	66388440
ENSE00001327551	66390403	66390590
ENSE00001385723	66379319	66379547
ENSE00001811497	66402652	66404784
ENSE00001913675	66366691	66366758
ENSE00003462548	66398456	66398561
ENSE00003493816	66400771	66401016
ENSE00003504261	66397982	66398106
ENSE00003624896	66392136	66392383
ENSE00003672095	66396059	66396201

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 97.35.

FANTOM5 (CAGE): breadth broad, TPM avg 23.9568 / max 974.9515, expressed in 549 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154490	17.4146	477
154488	3.8571	324
154489	1.7368	304
154503	0.3146	128
154493	0.1693	31
154495	0.1401	25
154504	0.1179	64
154497	0.1088	78
154496	0.0727	24
154494	0.0107	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	97.35	gold quality
upper lobe of left lung	UBERON:0008952	96.44	gold quality
upper lobe of lung	UBERON:0008948	96.36	gold quality
omental fat pad	UBERON:0010414	95.93	gold quality
peritoneum	UBERON:0002358	95.87	gold quality
apex of heart	UBERON:0002098	95.78	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.77	gold quality
lower lobe of lung	UBERON:0008949	95.60	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.38	gold quality
lung	UBERON:0002048	95.31	gold quality
placenta	UBERON:0001987	94.66	gold quality
adipose tissue	UBERON:0001013	94.38	gold quality
pericardium	UBERON:0002407	94.21	gold quality
vena cava	UBERON:0004087	94.08	gold quality
heart left ventricle	UBERON:0002084	93.82	gold quality
cardiac ventricle	UBERON:0002082	93.79	gold quality
connective tissue	UBERON:0002384	93.65	gold quality
right lobe of thyroid gland	UBERON:0001119	92.94	gold quality
heart	UBERON:0000948	92.08	gold quality
left lobe of thyroid gland	UBERON:0001120	91.71	gold quality
gall bladder	UBERON:0002110	91.39	gold quality
thyroid gland	UBERON:0002046	91.31	gold quality
myocardium	UBERON:0002349	91.09	gold quality
cardiac atrium	UBERON:0002081	90.83	gold quality
right atrium auricular region	UBERON:0006631	90.83	gold quality
heart right ventricle	UBERON:0002080	90.73	gold quality
adult organism	UBERON:0007023	90.64	gold quality
left ventricle myocardium	UBERON:0006566	90.18	gold quality
superficial temporal artery	UBERON:0001614	89.99	gold quality
tibial nerve	UBERON:0001323	89.92	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	1691.95
E-MTAB-6678	yes	882.98
E-HCAD-10	yes	44.16
E-GEOD-135922	yes	43.30
E-HCAD-11	yes	43.17
E-HCAD-1	yes	39.65
E-MTAB-8410	yes	33.14
E-CURD-46	yes	25.96
E-MTAB-8271	yes	15.63
E-MTAB-6701	yes	15.19
E-CURD-112	yes	13.25
E-GEOD-130148	yes	5.01
E-MTAB-10137	yes	4.43
E-MTAB-7303	no	7.95
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
CLDN5	Activation
ID1	Activation

Upstream regulators (CollecTRI, top): E2F1, EGR1, EPAS1, ERG, ETS1, GATA5, GSC, HIF1A, HOXA9, ID2, KLF4, LMO2, MYCN, NOTCH1, RAMP2, RBPJ, SNAI1, SNAI2, SOX7, SOX9, SP1, SP3, SRF, TAL1, TCF3, TWIST1, WT1, ZEB1

miRNA regulators (miRDB)

75 targeting CDH5, 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-4481	100.00	66.42	1669
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-4498	99.47	67.42	2360

Literature-anchored findings (GeneRIF, showing 40)

• Imaging studies of VE-cadherin in a flow model show neutrophil and monocyte transmigration occurring exclusively at the cell borders through formation of transient gaps in VE-cad distribution, as well as through preexisting gaps. (PMID:11490021)
• Loss of vascular endothelial cadherin-mediated cell-cell adhesion increases the permeability of bone marrow endothelial cell monolayers and stimulates the transendothelial migration of CD34+ cells in response to stromal cell-derived factor-1 alpha. (PMID:11777950)
• An octapeptide in the juxtamembrane domain of VE-cadherin is important for p120ctn binding and cell proliferation. (PMID:11855855)
• results suggest that the inadequate trophoblastic invasion, induced by antiphospholipid antibodies, can be the result of decreased alpha1 integrin and VE-cadherin and increased alpha5 integrin and E-cadherin expression in the trophoblast (PMID:11937138)
• VEC may influence the constitutive organization of the actin cytoskeleton. (PMID:11950930)
• TNF-alpha affects VE-cadherin gene expression on the transcriptional level, inducing a downregulation of the VE-cadherin expression. (PMID:12010652)
• Results show that P2X4 and P2X6 receptors are associated with VE-cadherin at HUVEC adherens junctions. (PMID:12088286)
• TNFalpha significantly increased permeability and induced p38 and ERK MAPK activation compared with controls (P < 0.05). These changes were associated with a loss of membrane-associated VE cadherin (PMID:12095140)
• tyrosine phosphorylation of VE cadherin is an important regulatory pathway associated with TNF-induced endothelial barrier dysfunction. (PMID:12219009)
• ADAM15 colocalizes with vascular endothelial (VE)-cadherin, which mediates endothelial cell adherens junction formation (PMID:12243749)
• During transmigration of neutrophils through umbilical vein endothelium, VE-cadherin moved away to different ends of the transmigration site so that VE-cadherin-containing adherent junctions were relocated aside. (PMID:12393634)
• Data show that VE-cadherin and beta-catenin are only weakly associated with the actin-based cytoskeleton in cultured human vascular endothelial cells. (PMID:12413882)
• cleavage of VE cadherin by neutrophil surface-bound proteases induces formation of gaps through which neutrophils transmigrate (PMID:12584200)
• VE-cadherin actively participates in inside-out signaling at the plasma membrane, leading to the development of endothelial membrane protrusions. (PMID:12595527)
• results provide new insights into the mechanisms of VE-cadherin processing and degradation in microvascular endothelial cells (PMID:12626512)
• Human Schlemm’s canal cells express the endothelial adherens proteins, VE-cadherin and PECAM-1. (PMID:12658549)
• Modification by protein kinase C contributes to vascular endothelium barrier dysregulation induced by thrombin (PMID:12740216)
• the intracellular association of VE-cadherin with beta-catenin-linked cytoskeleton is essential to the maintenance of endothelial junctional integrity and microvascular permeability. (PMID:14678493)
• elevated plasma levels in coronary artherossclerosis (PMID:14695457)
• interacts with p120 catenin to mediate cell locomotion and proliferation (PMID:14699141)
• Histamine interrupts cadherin adhesion and this effect on cadherin adhesion is independent of capacitive calcium flux. (PMID:15220112)
• Serum VE-cadherin decreases significantly in both estradiol and raloxifene treated postmenopausal women. (PMID:15374707)
• VE-cadherin is involved in transendothelial migration of TCs, and replacement of DECs by TCs is not the result of apoptosis. (PMID:15572031)
• cAMP-Epac-Rap1 signaling promotes decreased cell permeability by enhancing VE-cadherin-mediated adhesion lined by the rearranged cortical actin (PMID:15601837)
• cleaved by Porphyromonas gingivalis gingipains in endothelial cells (PMID:15731052)
• promoter is subjected to bFGF induction, silencer elements may be located elsewhere in the gene (PMID:15735710)
• upregulation of MIP-1beta and downregulation of VE-cadherin may strongly participate in human acute heart rejection. (PMID:15897346)
• G alpha12 interaction with alphaSNAP induces VE-cadherin localization at endothelial junctions and regulates barrier function (PMID:15980433)
• A single phosphorylation event within the VE-cadherin cytoplasmic tail is sufficient to maintain cells in a mesenchymal state. (PMID:16027153)
• Results suggest that in human umbilical vein endothelial cells Epac1 controls VE-cadherin-mediated cell junction formation and induces reorganization of the actin cytoskeleton. (PMID:16115630)
• Cdc42 regulates AJ permeability by controlling the binding of alpha-catenin with beta-catenin and the consequent interaction of the VE-cadherin/catenin complex with the actin cytoskeleton. (PMID:16322481)
• VE-cadherin and EphA2 act in a coordinated manner as a key regulatory element in the process of melanoma vasculogenic mimicry. (PMID:16481735)
• Thus, VEC limits cell proliferation by retaining VEGFR-2 at the membrane and preventing its internalization into signaling compartments. (PMID:16893970)
• Tyrosine phosphorylation mediated by Src kinase on cadherin 5 residue Tyr685 is a process that appears to be critical for vascular endothelial growth factor (VEGF)-induced endothelial cell migration. (PMID:16909109)
• Surprisingly, the VE-cadherin-associated PAR protein complex lacks aPKC. Ectopic expression of VE-cadherin in epithelial cells affects tight junction formation. (PMID:17057644)
• Here, we show that, in some transformed lines, cadherin adhesion molecules exhibit a flow-like movement in a basal-apical direction at the cell junction and that this flow is associated with reorganizing actin filaments. (PMID:17159998)
• OxidizedLDL downregulated VE Cadherin on endothelial junctions in an in vitro model of transendothelial monocyte migration (PMID:17194459)
• Strategies targeting signals in the marrow microenvironment that amplify the Bcr-abl/VE-cadherin/beta-catenin axis may have utility in sensitizing drug-resistant leukemic stem cells. (PMID:17638851)
• basal Rho kinase activity was essential for proper expression of the adhesion molecule VE-cadherin in human vascular endothelial cells (PMID:17761936)
• Endothelial cell junctional proteins respond to flow transiently by increasing the strength of intercellular attachments early after flow onset, supporting the view on the active role of intercellular adhesions in mechanotransduction. (PMID:18163230)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cdh5	ENSMUSG00000031871
rattus_norvegicus	Cdh5	ENSRNOG00000013324

Paralogs (33): CDH1 (ENSG00000039068), CDH10 (ENSG00000040731), CDH3 (ENSG00000062038), CDH19 (ENSG00000071991), CDHR2 (ENSG00000074276), CDH17 (ENSG00000079112), CDH7 (ENSG00000081138), PCDH11Y (ENSG00000099715), CDHR5 (ENSG00000099834), CDH20 (ENSG00000101542), PCDH11X (ENSG00000102290), CDH23 (ENSG00000107736), CDH9 (ENSG00000113100), CDH6 (ENSG00000113361), CDH26 (ENSG00000124215), CDHR3 (ENSG00000128536), CDH15 (ENSG00000129910), CDH24 (ENSG00000139880), CDH11 (ENSG00000140937), CDH13 (ENSG00000140945), CDH18 (ENSG00000145526), CDHR1 (ENSG00000148600), CDH22 (ENSG00000149654), CDH8 (ENSG00000150394), CDH12 (ENSG00000154162), PCDH1 (ENSG00000156453), DCHS1 (ENSG00000166341), PCDH7 (ENSG00000169851), CDH2 (ENSG00000170558), CDH4 (ENSG00000179242), PCDH9 (ENSG00000184226), DCHS2 (ENSG00000197410), PCDH20 (ENSG00000280165)

Protein

Protein identifiers

Cadherin-5 — P33151 (reviewed: P33151)

Alternative names: 7B4 antigen, Vascular endothelial cadherin

All UniProt accessions (7): B4DTR2, P33151, H3BPG1, H3BQ82, H3BR11, H3BR64, I3L1J2

UniProt curated annotations — full annotation on UniProt →

Function. Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. This cadherin may play a important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions. It associates with alpha-catenin forming a link to the cytoskeleton. Plays a role in coupling actin fibers to cell junctions in endothelial cells, via acting as a cell junctional complex anchor for AMOTL2 and MAGI1. Acts in concert with KRIT1 and PALS1 to establish and maintain correct endothelial cell polarity and vascular lumen. These effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Positively regulates reorientation of actin stress fibers and endothelial cell reorientation in response to cellular mechantransduction. Required for activation of PRKCZ and for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction. Associates with CTNND1/p120-catenin to control CADH5 endocytosis.

Subunit / interactions. Part of a complex composed of AMOTL2, MAGI1 and CDH5, within the complex AMOTL2 acts as a scaffold protein for the interaction of MAGI1 with CDH5. The complex is required for coupling actin fibers to cell junctions in endothelial cells. Within the complex AMOTL2 (via its N-terminus) interacts with CDH5. Interacts (via cadherin 5 domain) with PTPRB. Interacts with TRPC4. Interacts with KRIT1. Interacts with PARD3. Interacts with RTN4 (isoform B). Interacts with PALS1; the interaction promotes PALS1 localization to cell junctions and is required for CDH5-mediated vascular lumen formation and endothelial cell. Interacts with CTNND1/p120-catenin; the interaction controls CADH5 endocytosis.

Subcellular location. Cell junction. Adherens junction. Cell membrane. Cytoplasm.

Tissue specificity. Expressed in endothelial cells (at protein level). Expressed in the brain.

Post-translational modifications. Phosphorylated on tyrosine residues by KDR/VEGFR-2. Dephosphorylated by PTPRB. O-glycosylated.

Domain organisation. Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.

Isoforms (2)

UniProt ID	Names	Canonical?
P33151-1	1	yes
P33151-2	2

RefSeq proteins (1): NP_001786* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000233	Cadherin_Y-type_LIR	Domain
IPR002126	Cadherin-like_dom	Domain
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR020894	Cadherin_CS	Conserved_site
IPR027397	Catenin-bd_sf	Homologous_superfamily
IPR039808	Cadherin	Family

Pfam: PF00028, PF01049

UniProt features (40 total): binding site 17, glycosylation site 7, domain 5, topological domain 2, sequence variant 2, signal peptide 1, propeptide 1, region of interest 1, chain 1, splice variant 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P33151-F1	78.46	0.46

Functional residue map

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

Ligand- & substrate-binding residues (17): 58; 58; 59; 109; 111; 111; 143; 144; 145; 146; 146; 147 …

Glycosylation sites (7): 61, 112, 157, 362, 442, 523, 535

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-418990	Adherens junctions interactions
R-HSA-5218920	VEGFR2 mediated vascular permeability
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-1500931	Cell-Cell communication
R-HSA-162582	Signal Transduction
R-HSA-194138	Signaling by VEGF
R-HSA-421270	Cell-cell junction organization
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-446728	Cell junction organization
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9855142	Cellular responses to mechanical stimuli
R-HSA-9860931	Response of endothelial cells to shear stress

MSigDB gene sets: 356 (showing top): GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, RNGTGGGC_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, HORIUCHI_WTAP_TARGETS_DN, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, MYOGENIN_Q6, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_CIRCULATORY_SYSTEM_PROCESS, MODULE_255, GOBP_INFLAMMATORY_RESPONSE, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION

GO Biological Process (32): cell morphogenesis (GO:0000902), endothelial cell morphogenesis (GO:0001886), blood vessel maturation (GO:0001955), cell migration involved in sprouting angiogenesis (GO:0002042), intracellular calcium ion homeostasis (GO:0006874), cell-cell junction assembly (GO:0007043), homophilic cell-cell adhesion (GO:0007156), cell surface receptor signaling pathway (GO:0007166), transforming growth factor beta receptor signaling pathway (GO:0007179), negative regulation of cell population proliferation (GO:0008285), positive regulation of gene expression (GO:0010628), calcium-dependent cell-cell adhesion (GO:0016339), cell migration (GO:0016477), positive regulation of cell migration (GO:0030335), positive regulation of BMP signaling pathway (GO:0030513), negative regulation of microtubule polymerization (GO:0031115), positive regulation of protein-containing complex assembly (GO:0031334), adherens junction organization (GO:0034332), maintenance of blood-brain barrier (GO:0035633), regulation of vascular permeability (GO:0043114), blood vessel endothelial cell migration (GO:0043534), cell-cell adhesion mediated by cadherin (GO:0044331), positive regulation of angiogenesis (GO:0045766), negative regulation of inflammatory response (GO:0050728), bicellular tight junction assembly (GO:0070830), cell-cell adhesion (GO:0098609), protein localization to bicellular tight junction (GO:1902396), positive regulation of intracellular signal transduction (GO:1902533), positive regulation of establishment of endothelial barrier (GO:1903142), regulation of establishment of cell polarity (GO:2000114), negative regulation of endothelial cell apoptotic process (GO:2000352), cell adhesion (GO:0007155)

GO Molecular Function (14): signaling receptor binding (GO:0005102), calcium ion binding (GO:0005509), beta-catenin binding (GO:0008013), protein phosphatase binding (GO:0019903), signaling receptor complex adaptor activity (GO:0030159), vascular endothelial growth factor receptor 2 binding (GO:0043184), transmembrane transporter binding (GO:0044325), cadherin binding (GO:0045296), fibrinogen binding (GO:0070051), BMP receptor binding (GO:0070700), cell-cell adhesion mediator activity (GO:0098632), protein tyrosine kinase binding (GO:1990782), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (14): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), adherens junction (GO:0005912), bicellular tight junction (GO:0005923), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020), catenin complex (GO:0016342), cell junction (GO:0030054), nuclear membrane (GO:0031965), anchoring junction (GO:0070161), cell periphery (GO:0071944)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Cell-cell junction organization	1
VEGFA-VEGFR2 Pathway	1
Response of endothelial cells to shear stress	1
Signaling by Receptor Tyrosine Kinases	1
Cell junction organization	1
Signaling by VEGF	1
Cell-Cell communication	1
Signal Transduction	1
Cellular responses to stimuli	1
Cellular responses to mechanical stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cell-cell adhesion	3
protein binding	3
cell-cell junction organization	2
anatomical structure morphogenesis	1
endothelial cell development	1
epithelial cell morphogenesis	1
blood vessel development	1
anatomical structure maturation	1
sprouting angiogenesis	1
blood vessel endothelial cell migration	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
cell junction assembly	1
signal transduction	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cell motility	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule polymerization	1
negative regulation of protein polymerization	1
microtubule polymerization	1
negative regulation of supramolecular fiber organization	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
tissue homeostasis	1

Protein interactions and networks

STRING

3530 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDH5	PECAM1	P16284	999
CDH5	KDR	P35968	998
CDH5	CTNNB1	P35222	995
CDH5	CTNND1	O60716	994
CDH5	TJP1	Q07157	993
CDH5	CLDN5	O00501	989
CDH5	OCLN	Q16625	980
CDH5	SELE	P16111	977
CDH5	CDH1	P12830	969
CDH5	VCL	P18206	965
CDH5	PTPRB	P23467	949
CDH5	FLT4	P35916	943
CDH5	TEK	Q02763	870
CDH5	ANGPTL4	Q9BY76	867
CDH5	ENG	P17813	848

IntAct

35 interactions, top by confidence:

A	B	Type	Score
CDH5	CTNNB1	psi-mi:“MI:0914”(association)	0.930
CTNNB1	CDH5	psi-mi:“MI:0915”(physical association)	0.930
CDH5	CTNNB1	psi-mi:“MI:0403”(colocalization)	0.930
CDH5	CTNNB1	psi-mi:“MI:0915”(physical association)	0.930
CDH5	CTNNB1	psi-mi:“MI:0407”(direct interaction)	0.930
CDH5	WARS1	psi-mi:“MI:0915”(physical association)	0.650
CDH5	WARS1	psi-mi:“MI:0407”(direct interaction)	0.650
CDH5	PARD6A	psi-mi:“MI:0915”(physical association)	0.590
PARD6A	CDH5	psi-mi:“MI:0915”(physical association)	0.590
PARD3	CDH5	psi-mi:“MI:0403”(colocalization)	0.560
CDH5	PARD3	psi-mi:“MI:0915”(physical association)	0.560
KDR	CDH5	psi-mi:“MI:0915”(physical association)	0.560
CDH5	SHC1	psi-mi:“MI:0407”(direct interaction)	0.540
SHC1	CDH5	psi-mi:“MI:0915”(physical association)	0.540
CDH5	AFDN	psi-mi:“MI:0915”(physical association)	0.470
CDH5	PARD6G	psi-mi:“MI:0915”(physical association)	0.400
CDH5	Ctnnd1	psi-mi:“MI:0915”(physical association)	0.400
CTNNBIP1	CDH5	psi-mi:“MI:0915”(physical association)	0.400
CDH5	ARVCF	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CDH5	NBAS	psi-mi:“MI:0914”(association)	0.350

BioGRID (176): CTNNB1 (Affinity Capture-Western), CDH5 (Two-hybrid), CDH5 (Synthetic Lethality), CDH5 (PCA), ARVCF (Affinity Capture-MS), PKP4 (Affinity Capture-MS), SCML1 (Affinity Capture-MS), CTNNA2 (Affinity Capture-MS), CTNNB1 (Affinity Capture-MS), RBFA (Affinity Capture-MS), CTNNA1 (Affinity Capture-MS), SARAF (Affinity Capture-MS), PLD1 (Affinity Capture-MS), TMTC3 (Affinity Capture-MS), ZMYM1 (Affinity Capture-MS)

ESM2 similar proteins: B0KW95, B2KI42, B4USZ0, F1PAA9, O02840, O60330, P08641, P09803, P10287, P10288, P12830, P15116, P19022, P19534, P19535, P20310, P22223, P24503, P26009, P33145, P33147, P33148, P33150, P33151, P33152, P39038, P53708, P55283, P55284, P79883, Q08174, Q5DRB7, Q5DRB8, Q5DRC0, Q5DRC2, Q5R9X1, Q5RAX1, Q6R8F2, Q6URK6, Q90275

Diamond homologs: A0A8M9PFP2, B0S5G3, F1R520, O02840, O55111, O88278, O94985, P30944, P33151, P55287, P55288, Q0VCN6, Q14517, Q5DRC8, Q5R9Q9, Q63418, Q6Q0N0, Q6URK6, Q6V1P9, Q86UP0, Q8BNA6, Q8R553, Q8VDA1, Q96JQ0, Q99JH7, Q9BQT9, Q9EPL2, Q9ER65, Q9H4D0, Q9HCU4, Q9NYQ6, Q9R0M0, A0A8M2BIB6, B0KW95, B2KI42, B4USZ0, F1PAA9, F1QSQ0, O35902, O54800

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
SRC	up-regulates	CDH5	phosphorylation
CTNND1	“up-regulates quantity by stabilization”	CDH5	binding
ARVCF	“up-regulates quantity by stabilization”	CDH5	binding
CTNND2	“up-regulates quantity by stabilization”	CDH5	binding
ERG	“up-regulates quantity by expression”	CDH5	“transcriptional regulation”
calcium(2+)	“up-regulates activity”	CDH5	“chemical activation”
CDH5	“up-regulates activity”	CTNNB1	binding
PTPRB	“up-regulates activity”	CDH5	dephosphorylation
SRC	“down-regulates activity”	CDH5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 17 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
cell adhesion	6	14.0×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	137
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2037 predictions. Top by Δscore:

Variant	Effect	Δscore
16:66366755:CACGG:C	donor_loss	1.0000
16:66366756:ACGGT:A	donor_loss	1.0000
16:66366757:CGGTG:C	donor_loss	1.0000
16:66366759:G:C	donor_loss	1.0000
16:66366759:G:GG	donor_gain	1.0000
16:66379315:CCAG:C	acceptor_loss	1.0000
16:66379316:CAG:C	acceptor_loss	1.0000
16:66379317:A:AG	acceptor_gain	1.0000
16:66379317:AGATC:A	acceptor_loss	1.0000
16:66379318:G:GA	acceptor_gain	1.0000
16:66379318:GAT:G	acceptor_gain	1.0000
16:66379318:GATC:G	acceptor_gain	1.0000
16:66379318:GATCT:G	acceptor_gain	1.0000
16:66386806:TA:T	acceptor_loss	1.0000
16:66386807:A:AG	acceptor_gain	1.0000
16:66386807:A:AT	acceptor_loss	1.0000
16:66386808:G:GA	acceptor_gain	1.0000
16:66386808:G:GC	acceptor_loss	1.0000
16:66386808:GATC:G	acceptor_gain	1.0000
16:66386808:GATCA:G	acceptor_gain	1.0000
16:66387094:GTGG:G	donor_gain	1.0000
16:66387096:GG:G	donor_gain	1.0000
16:66387097:GG:G	donor_gain	1.0000
16:66387097:GGTA:G	donor_loss	1.0000
16:66387098:G:C	donor_loss	1.0000
16:66387098:G:GG	donor_gain	1.0000
16:66387099:T:A	donor_loss	1.0000
16:66388413:A:T	donor_gain	1.0000
16:66388416:GA:G	donor_gain	1.0000
16:66388418:G:GG	donor_gain	1.0000

AlphaMissense

5168 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:66386927:G:C	R110P	0.998
16:66387008:T:C	F137S	0.998
16:66387035:A:C	D146A	0.998
16:66386876:T:C	F93S	0.997
16:66386957:C:A	A120D	0.997
16:66387020:T:A	V141D	0.997
16:66379484:G:C	W49C	0.996
16:66379484:G:T	W49C	0.996
16:66386876:T:G	F93C	0.996
16:66386930:A:T	E111V	0.996
16:66386951:T:C	L118P	0.996
16:66387014:T:A	I139N	0.996
16:66386842:T:G	Y82D	0.995
16:66386897:G:A	G100E	0.995
16:66386897:G:T	G100V	0.995
16:66386903:T:A	V102E	0.995
16:66387025:G:C	D143H	0.995
16:66387026:A:T	D143V	0.995
16:66387034:G:C	D146H	0.995
16:66387035:A:T	D146V	0.995
16:66387044:C:A	P149H	0.995
16:66389489:G:C	D250H	0.995
16:66396169:T:C	L443P	0.995
16:66386875:T:C	F93L	0.994
16:66386877:C:A	F93L	0.994
16:66386877:C:G	F93L	0.994
16:66387026:A:C	D143A	0.994
16:66387027:C:A	D143E	0.994
16:66387027:C:G	D143E	0.994
16:66388348:C:A	A175E	0.994

dbSNP variants (sampled 300 via entrez): RS1000009724 (16:66401799 C>G), RS1000052307 (16:66390433 C>A,T), RS1000110191 (16:66397240 A>G), RS1000140788 (16:66384600 A>G), RS1000278513 (16:66384317 C>T), RS1000378265 (16:66372803 C>T), RS1000385307 (16:66398174 C>A,T), RS1000486715 (16:66378669 C>G,T), RS1000487484 (16:66375288 G>T), RS1000551039 (16:66390248 C>A,T), RS1000558459 (16:66404807 CA>C,CAA), RS1000609365 (16:66385664 G>A), RS1000732232 (16:66378821 G>A), RS1000787798 (16:66392709 A>C), RS1000838694 (16:66393004 G>A)

Disease associations

OMIM: gene MIM:601120 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002114_3	Molar-incisor hypomineralization	3.000000e-06
GCST004573_4	Iron status biomarkers (ferritin levels)	2.000000e-07
GCST006482_10	Lung function (FEV1/FVC)	5.000000e-09
GCST010396_62	Gut microbiota (bacterial taxa, hurdle binary method)	8.000000e-06
GCST010989_13	Body size at age 10	3.000000e-08
GCST012484_10	Cerebral amyloid angiopathy x APOEe4 status interaction in Alzheimer’s disease	2.000000e-06
GCST90002385_79	High light scatter reticulocyte count	2.000000e-09
GCST90002405_309	Reticulocyte count	7.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005321	molar-incisor hypomineralization
EFO:0004459	ferritin measurement
EFO:0004713	FEV/FVC ratio
EFO:0007874	gut microbiome measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0007659	APOE carrier status
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, affects splicing, decreases expression	4
Oxygen	affects cotreatment, decreases expression, decreases reaction, increases degradation, increases reaction (+4 more)	3
Valproic Acid	affects cotreatment, increases expression	3
Particulate Matter	increases abundance, increases expression, decreases expression, decreases reaction, affects reaction (+1 more)	3
kaempferol	decreases expression, decreases reaction	2
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	affects cotreatment, decreases reaction, increases degradation, increases reaction, decreases expression	2
Resveratrol	affects localization	2
Arsenic Trioxide	decreases expression, affects localization, increases degradation, decreases reaction, increases reaction	2
Vehicle Emissions	affects localization, affects binding, decreases reaction	2
Benzo(a)pyrene	decreases reaction, decreases methylation, increases methylation, affects cotreatment, decreases expression	2
Glucose	affects cotreatment, affects localization, decreases expression, increases localization, decreases reaction	2
Lipopolysaccharides	decreases reaction, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Nanotubes, Carbon	decreases expression, affects localization	2
N-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide	decreases expression, decreases reaction	1
2-methoxy-5-((3,4,5-trimethosyphenyl)seleninyl)phenol	decreases expression	1
bis(1-chloro-2-propyl)phosphate	increases abundance, affects expression	1
nonachlor	decreases expression, decreases reaction	1
nuciferine	affects cotreatment, decreases reaction, increases localization, affects localization	1
titanium dioxide	increases expression, affects binding	1
tris(2-butoxyethyl) phosphate	affects expression	1
lycorine	decreases expression	1
sulforaphane	decreases expression	1
cobaltous chloride	decreases expression	1
sodium bisulfide	decreases expression, decreases reaction	1
aflatoxin B2	decreases methylation	1
tert-butylphenyl diphenyl phosphate	affects cotreatment, decreases expression, decreases reaction	1
methyllycaconitine	decreases expression, decreases reaction	1
columbamine	increases expression	1
jasplakinolide	decreases reaction, increases uptake	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1VP	Abcam A-549 CDH5 KO	Cancer cell line	Male
CVCL_D2A9	Abcam HCT 116 CDH5 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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