CDH11

Summary

CDH11 (cadherin 11, HGNC:1750) is a protein-coding gene on chromosome 16q21, encoding Cadherin-11 (P55287). Cadherins are calcium-dependent cell adhesion proteins.

This gene encodes a type II classical cadherin from the cadherin superfamily, integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. Expression of this particular cadherin in osteoblastic cell lines, and its upregulation during differentiation, suggests a specific function in bone development and maintenance.

Source: NCBI Gene 1009 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Elsahy-Waters syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 49
• Clinical variants (ClinVar): 182 total — 8 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 118
• Cancer driver (intOGen): activating (oncogene-like) across 6 cancer types
• MANE Select transcript: NM_001797

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1750
Approved symbol	CDH11
Name	cadherin 11
Location	16q21
Locus type	gene with protein product
Status	Approved
Aliases	OB, CAD11
Ensembl gene	ENSG00000140937
Ensembl biotype	protein_coding
OMIM	600023
Entrez	1009

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 11 protein_coding, 8 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000268603, ENST00000394156, ENST00000562325, ENST00000562712, ENST00000562882, ENST00000562998, ENST00000563255, ENST00000563492, ENST00000564317, ENST00000564770, ENST00000565210, ENST00000566827, ENST00000567934, ENST00000568340, ENST00000569095, ENST00000569128, ENST00000569624, ENST00000569783, ENST00000619158, ENST00000871590

RefSeq mRNA: 3 — MANE Select: NM_001797 NM_001308392, NM_001330576, NM_001797

CCDS: CCDS10803, CCDS81992, CCDS81993

Canonical transcript exons

ENST00000268603 — 13 exons

Exon	Start	End
ENSE00000945666	64991768	64991935
ENSE00000945667	64988157	64988344
ENSE00000945668	64982048	64982301
ENSE00000945669	64972904	64973040
ENSE00000945672	64950767	64951018
ENSE00001350260	65053804	65053928
ENSE00001822538	65121880	65122063
ENSE00003505943	64971931	64972064
ENSE00003510398	64998562	64998856
ENSE00003576812	65004642	65005041
ENSE00003593314	64971579	64971696
ENSE00003629632	64992915	64993034
ENSE00003654772	64943753	64948099

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 99.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.7360 / max 766.7570, expressed in 1167 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157667	23.3690	1115
157668	17.7688	1117
157670	1.6571	764
157671	0.8319	509
157679	0.7493	179
157663	0.3673	189
157669	0.3132	163
157666	0.1608	65
157674	0.1158	42
157677	0.1120	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
periodontal ligament	UBERON:0008266	99.08	gold quality
stromal cell of endometrium	CL:0002255	98.26	gold quality
tibia	UBERON:0000979	98.13	gold quality
visceral pleura	UBERON:0002401	97.95	gold quality
calcaneal tendon	UBERON:0003701	97.53	gold quality
decidua	UBERON:0002450	97.38	gold quality
left ovary	UBERON:0002119	97.15	gold quality
right ovary	UBERON:0002118	96.95	gold quality
pleura	UBERON:0000977	96.87	gold quality
ovary	UBERON:0000992	96.82	gold quality
germinal epithelium of ovary	UBERON:0001304	96.76	gold quality
smooth muscle tissue	UBERON:0001135	96.48	gold quality
parietal pleura	UBERON:0002400	96.40	gold quality
gall bladder	UBERON:0002110	96.15	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.67	gold quality
lower lobe of lung	UBERON:0008949	95.67	gold quality
right coronary artery	UBERON:0001625	95.18	gold quality
placenta	UBERON:0001987	95.00	gold quality
cauda epididymis	UBERON:0004360	94.69	gold quality
lung	UBERON:0002048	94.54	gold quality
cartilage tissue	UBERON:0002418	94.52	gold quality
sural nerve	UBERON:0015488	94.48	gold quality
skin of hip	UBERON:0001554	94.44	gold quality
endometrium	UBERON:0001295	94.28	gold quality
trabecular bone tissue	UBERON:0002483	94.05	gold quality
mucosa of urinary bladder	UBERON:0001259	93.99	gold quality
colonic epithelium	UBERON:0000397	93.98	gold quality
urinary bladder	UBERON:0001255	93.84	gold quality
blood vessel layer	UBERON:0004797	93.23	gold quality
upper lobe of lung	UBERON:0008948	93.20	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	1296.77
E-GEOD-83139	yes	651.11
E-MTAB-7249	yes	430.66
E-MTAB-10287	yes	280.95
E-MTAB-9388	yes	187.60
E-MTAB-6701	yes	72.11
E-GEOD-135922	yes	57.31
E-HCAD-10	yes	54.39
E-MTAB-8410	yes	40.01
E-MTAB-6678	yes	26.75
E-CURD-112	yes	15.78
E-ANND-3	yes	15.47
E-MTAB-5061	yes	11.58
E-CURD-119	yes	10.48
E-MTAB-8271	yes	9.86

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, LRP3, SP1, TWIST1, ZEB2

Literature-anchored findings (GeneRIF, showing 40)

• The intracellular domain of cadherin-11 is not required for the induction of cell aggregation, adhesion or gap-junction formation (PMID:11775026)
• CADH11 was evaluated as a biomarker at the protein level and was found to have increased expression in xenograft tumors after S11248 treatment. (PMID:14985702)
• A 2.62 Mbp minimal region of genomic loss of chromosome 16q22 was found in retinoblastoma which contains a hotspot CDH11, implicating CDH11as a potential tumor suppressor gene in retinoblastoma. (PMID:15383628)
• primary aneurysmal bone cysts are mesenchymal neoplasms exhibiting USP6 and/or CDH11 oncogenic rearrangements (PMID:15509545)
• Review. Cadherin-11 expression confers upon cells a fundamental change in cellular behavior. Its expression on fibroblast-like synoviocytes may determine their behavior & differentiation. (PMID:15743489)
• Together, these studies implicate cadherin-11 in synovial tissue and lining layer formation and provide an in vitro system to model fibroblast-like synoviocyte behavior and function in organizing the synovial tissue. (PMID:16651616)
• Cadherin-11 is involved in the intercellular physical coupling of detrusor smooth muscle bladder cells and also of myofibroblasts. (PMID:17292535)
• Overexpression of osteoblast cadherin is associated with breast cancer cell metastatic potential (PMID:18193170)
• The results indicate that CDH11 may be useful as a prognostic marker of disease progression and survival in osteosarcoma. (PMID:18359978)
• cadherin-11 promotes homing and migration to bone and osteoclastogenesis through mediating the homophilic interactions of breast cancer cells with marrow stromal/osteoblastic cells, thereby enhancing bone metastases. (PMID:18575746)
• These findings suggest that cadherin-11 is involved in the metastasis of prostate cancer cells to bone. (PMID:18708358)
• Tumor necrosis factor alpha drives cadherin 11 expression in rheumatoid inflammation (PMID:18821672)
• Cadherin-11 and fascin might be useful markers for recurrence of pleomorphic adenomas. (PMID:19133007)
• Cadherin-11 mRNA and protein levels are regulated by the activity of GSK3beta and a significant degree of this regulation is exerted by the GSK3 target, beta-catenin, at the level of the cadherin-11 3’UTR (PMID:19274078)
• suppression of MUC1 by miR-145 causes a reduction of beta-catenin as well as the oncogenic cadherin 11 (PMID:19996288)
• cad-11 modulates synovial fibroblasts to evoke inflammatory factors that may contribute to the inflammatory process in RA. (PMID:21536877)
• CDH11 as a novel glioma invasion-associated candidate gene that likely contribute to the invasive phenotype of malignant gliomas. (PMID:21722156)
• increased expression in patients with rheumatoid arthritis (PMID:21798287)
• CDH11 expression was assessed in lung tissue from idiopathic pulmonary fibrosis patients. (PMID:21990376)
• Data indicate that CDH11 as a functional tumor suppressor and an important antagonist of Wnt/beta-catenin signaling, with frequent epigenetic inactivation in common carcinomas. (PMID:22139084)
• These results show the functional significance of cadherin-11 expression in glioblastoma multiforme. (PMID:22267545)
• The study of CDH11 5’-CpG island hypermethylation in primary tumours and lymph node metastases of cancer patients showed this epigenetic alteration to be significantly confined to the disseminated cells. (PMID:22374749)
• Results indicate the necessity of cadherin-11 for dystrophic calcific nodule formation, which proceeds through an Erk1/2-dependent pathway. (PMID:23162011)
• Data indicate that knockdown of CDH11 expression in primary human glioblastoma cells inhibits TGFbeta-stimulated migration. (PMID:23951053)
• Thus, our results indicated abnormal expression of CD44V6, CDH11, and beta-catenin in osteosarcomas and osteochondromas, which may provide important indicators for further research. (PMID:23971040)
• Data indicate that the interaction of mesenchymal stem cells (MSC) with fibroblast-like synoviocytes (FLS) via cadherin-11 may contribute to angiogenesis and chronic synovitis by enhancing the secretion of placental growth factor (PlGF). (PMID:24574497)
• Our results demonstrate that parathyroid hormone stimulates hematopoiesis through promoting the upregulation of CDH11 expression in bone marrow mesenchymal stromal cells (PMID:24648356)
• High Cadherin-11 expression is associated with breast cancer. (PMID:24681547)
• These data demonstrate that Cad-11 is a mediator of dermal fibrosis and TGFbeta production and suggest that Cad-11 may be a therapeutic target in systemic sclerosis. (PMID:24757152)
• evidence for the involvement of CDH11 in Autism Spectrum Disorder which is consistent with the association of other cadherins with Autism Spectrum Disorder and neuropsychiatric diseases (PMID:24839052)
• Cadherin 11, a miR-675 target, induces N-cadherin expression and epithelial-mesenchymal transition in melasma. (PMID:24940649)
• This study evaluated the expression of CAD11 in the peripheral blood of rheumatoid arthritis patients and normal controls. (PMID:25173800)
• Existing knowledge regarding the role of CDH2 and CDH11 during development and differentiation in vivo and in vitro is reviewed. [review] (PMID:25771201)
• Data suggest methylation status of gene promoters for CDH11 (cadherin 11) and BASP1 (brain abundant membrane attached signal protein 1) in tumor, skin, and metastatic tumor tissue may serve as prognostic biomarkers in patients with advanced melanoma. (PMID:25919928)
• Invasive cancer cells had increased expression of mesenchymal markers cadherin 2 and 11 that localized with stromal cell cadherin 11, suggesting that these molecules are involved in stromal cell engraftment. (PMID:26046821)
• High Cad-11 expression is associated with bone metastases of Ewing sarcoma. (PMID:26092671)
• Cadherin-11 may be hyper-expressed in the peripheral blood of diffuse systemic scleroderma patients. (PMID:26121083)
• that U87-p75(NTR) cells express higher levels of Cdh-11 protein and that siRNA-mediated knockdown of Cdh-11 resulted in a significant decrease in p75(NTR)-mediated glioblastoma cell migration (PMID:26476273)
• observations suggest that clathrin-mediated internalization of Cad11 regulates surface trafficking of Cad11 and that dynamic turnover of Cad11 regulates the migratory function of Cad11 in prostate cancer cells. (PMID:26519476)
• Upregulation of miR-27b significantly accelerated the proliferation, cell cycle transition from G1 to S phase, migration and invasion of C33A cells, while downregulation of miR-27b suppressed the proliferation and invasion of HeLa cells (PMID:26706910)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdh11	ENSDARG00000021442
mus_musculus	Cdh11	ENSMUSG00000031673
rattus_norvegicus	Cdh11	ENSRNOG00000013481

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), CDH13 (ENSG00000140945), CDH18 (ENSG00000145526), CDHR1 (ENSG00000148600), CDH22 (ENSG00000149654), CDH8 (ENSG00000150394), CDH12 (ENSG00000154162), PCDH1 (ENSG00000156453), DCHS1 (ENSG00000166341), PCDH7 (ENSG00000169851), CDH2 (ENSG00000170558), CDH4 (ENSG00000179242), CDH5 (ENSG00000179776), PCDH9 (ENSG00000184226), DCHS2 (ENSG00000197410), PCDH20 (ENSG00000280165)

Protein

Protein identifiers

Cadherin-11 — P55287 (reviewed: P55287)

Alternative names: OSF-4, Osteoblast cadherin

All UniProt accessions (9): P55287, A0A087X227, H3BP26, H3BPQ2, H3BQB5, H3BQH2, H3BR78, H3BSM4, H3BUU9

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. Required for proper focal adhesion assembly. Involved in the regulation of cell migration.

Subunit / interactions. Interacts with PCDH8.

Subcellular location. Cell membrane.

Tissue specificity. Expressed mainly in brain but also found in other tissues. Expressed in neuroblasts. In the embryo from 67 to 72 days of gestation, detected at high levels in facial mesenchyme including the central palatal mesenchyme, dental mesenchyme, the eye and optic muscle, and the tongue (at protein level).

Disease relevance. A chromosomal aberration involving CDH11 is a common genetic feature of aneurysmal bone cyst, a benign osseous neoplasm. Translocation t(16;17)(q22;p13) with USP6. The translocation generates a fusion gene in which the strong CDH11 promoter is fused to the entire USP6 coding sequence, resulting in USP6 transcriptional up-regulation. Elsahy-Waters syndrome (ESWS) [MIM:211380] An autosomal recessive syndrome characterized by moderate intellectual disability, hypospadias and characteristic craniofacial morphology, which includes brachycephaly, facial asymmetry, exotropia, hypertelorism, telechantus, broad nose, concave nasal ridge, underdeveloped mid-face, prognathism, and radicular dentin dysplasia. The disease is caused by variants affecting the gene represented in this entry. Teebi hypertelorism syndrome 2 (TBHS2) [MIM:619736] A form of Teebi hypertelorism syndrome, a syndrome characterized by an abnormally increased distance between ocular orbits, and facial features that can resemble craniofrontonasal dysplasia such as prominent forehead, widow’s peak, heavy and broad eyebrows, long palpebral fissures, ptosis, high and broad nasal bridge, short nose, low-set ears, natal teeth, thin upper lip and a grooved chin. Some affected individuals have limb, urogenital, umbilical and cardiac defects. Developmental delay and/or impaired intellectual development have been observed in some patients. TBHS2 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

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?
P55287-1	1	yes
P55287-2	2

RefSeq proteins (3): NP_001295321, NP_001317505, NP_001788* (*=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 (33 total): sequence variant 13, domain 5, sequence conflict 3, modified residue 2, glycosylation site 2, splice variant 2, topological domain 2, signal peptide 1, propeptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55287-F1	77.65	0.48

Functional residue map

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

Post-translational modifications (2): 788, 791

Glycosylation sites (2): 455, 540

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-418990	Adherens junctions interactions
R-HSA-9759811	Regulation of CDH11 mRNA translation by microRNAs
R-HSA-9762292	Regulation of CDH11 function
R-HSA-9833576	CDH11 homotypic and heterotypic interactions
R-HSA-9958810	SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)
R-HSA-9958825	Activation of STAT3 by cadherin engagement
R-HSA-9762293	Regulation of CDH11 gene transcription
R-HSA-1500931	Cell-Cell communication
R-HSA-421270	Cell-cell junction organization
R-HSA-446728	Cell junction organization
R-HSA-9759475	Regulation of CDH11 Expression and Function
R-HSA-9759476	Regulation of Homotypic Cell-Cell Adhesion
R-HSA-9764260	Regulation of Expression and Function of Type II Classical Cadherins

MSigDB gene sets: 573 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_FOCAL_ADHESION_ASSEMBLY, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GNF2_PTX3, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2, GOBP_NEUROGENESIS, CLASPER_LYMPHATIC_VESSELS_DURING_METASTASIS_DN, GRANDVAUX_IRF3_TARGETS_DN, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_1_DN, GOBP_CELL_CELL_SIGNALING, GOBP_CALCIUM_DEPENDENT_CELL_CELL_ADHESION, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, MODULE_66

GO Biological Process (17): cell morphogenesis (GO:0000902), skeletal system development (GO:0001501), ossification (GO:0001503), aortic valve formation (GO:0003189), cell-cell junction assembly (GO:0007043), cell adhesion (GO:0007155), homophilic cell-cell adhesion (GO:0007156), calcium-dependent cell-cell adhesion (GO:0016339), cell migration (GO:0016477), corticospinal tract morphogenesis (GO:0021957), negative regulation of cell migration (GO:0030336), cell-substrate adhesion (GO:0031589), adherens junction organization (GO:0034332), cell-cell adhesion mediated by cadherin (GO:0044331), focal adhesion assembly (GO:0048041), modulation of chemical synaptic transmission (GO:0050804), cell-cell adhesion (GO:0098609)

GO Molecular Function (4): calcium ion binding (GO:0005509), beta-catenin binding (GO:0008013), cadherin binding (GO:0045296), metal ion binding (GO:0046872)

GO Cellular Component (10): extracellular region (GO:0005576), cytoplasm (GO:0005737), plasma membrane (GO:0005886), adherens junction (GO:0005912), catenin complex (GO:0016342), extracellular exosome (GO:0070062), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978), membrane (GO:0016020), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Regulation of CDH11 Expression and Function	3
Adherens junctions interactions	2
Cell-cell junction organization	1
Regulation of CDH11 function	1
Activation of STAT3 by cadherin engagement	1
Cell junction organization	1
Cell-Cell communication	1
Regulation of Expression and Function of Type II Classical Cadherins	1
Regulation of Homotypic Cell-Cell Adhesion	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	3
cellular anatomical structure	3
cell-cell junction organization	2
cell adhesion	2
synapse	2
anatomical structure morphogenesis	1
system development	1
multicellular organismal process	1
aortic valve morphogenesis	1
heart valve formation	1
cell junction assembly	1
cellular process	1
cell motility	1
central nervous system projection neuron axonogenesis	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
cell-substrate junction assembly	1
cell-matrix adhesion	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
metal ion binding	1
protein binding	1
cell adhesion molecule binding	1
cation binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
cell-cell junction	1
extrinsic component of plasma membrane	1
plasma membrane protein complex	1
extracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

2254 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDH11	CTNNB1	P35222	947
CDH11	CDH2	P19022	863
CDH11	CTNND1	O60716	686
CDH11	CBLL1	Q75N03	662
CDH11	SNAI1	O95863	629
CDH11	NCAM1	P13591	596
CDH11	VCAM1	P19320	578
CDH11	VCL	P18206	571
CDH11	CDH3	P22223	562
CDH11	BGN	P13247	553
CDH11	CDH15	P55291	549
CDH11	LAMA4	Q16363	536
CDH11	CTNNA1	P35221	534
CDH11	BCL2	P10415	517
CDH11	DSP	P15924	513

IntAct

25 interactions, top by confidence:

A	B	Type	Score
TAX1BP3	ARVCF	psi-mi:“MI:0914”(association)	0.690
HSPA12B	EEF2K	psi-mi:“MI:0914”(association)	0.530
HUS1B	RAD1	psi-mi:“MI:0914”(association)	0.530
MAD2L1	PPIP5K2	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
SPSB4	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
CDH11	CRK	psi-mi:“MI:0915”(physical association)	0.400
	CDH11	psi-mi:“MI:0915”(physical association)	0.370
ECE1	CDH11	psi-mi:“MI:0915”(physical association)	0.370
CDH11	ATF7IP	psi-mi:“MI:0915”(physical association)	0.370
CTNNB1	IGLL5	psi-mi:“MI:0914”(association)	0.350
CTNNB1	IGSF3	psi-mi:“MI:0914”(association)	0.350
AURKB	VWA8	psi-mi:“MI:0914”(association)	0.350
CCNI2	ZNF609	psi-mi:“MI:0914”(association)	0.350
CDK20	CDH11	psi-mi:“MI:0914”(association)	0.350
DUOXA2	CHRNB1	psi-mi:“MI:0914”(association)	0.350
DYNLT4	NPR1	psi-mi:“MI:0914”(association)	0.350
MMP3	VGF	psi-mi:“MI:0914”(association)	0.350
NXPH3	NXPH4	psi-mi:“MI:0914”(association)	0.350
SRPRB	GSDME	psi-mi:“MI:0914”(association)	0.350
VSIG4	TMEM223	psi-mi:“MI:0914”(association)	0.350
ZDHHC11	NRP1	psi-mi:“MI:0914”(association)	0.350
CDH11	MTNR1B	psi-mi:“MI:0915”(physical association)	0.000
CDH11		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): CDH11 (Affinity Capture-MS), CDH11 (Two-hybrid), CDH11 (Affinity Capture-Western), CDH11 (Affinity Capture-Western), CDH11 (Co-localization), CDH11 (Affinity Capture-MS), CDH2 (Affinity Capture-MS), CDH11 (Affinity Capture-Western), PDGFRA (Affinity Capture-Western), AMOT (Affinity Capture-MS), AMOT (Reconstituted Complex), CTNNB1 (Reconstituted Complex), CTNND1 (Reconstituted Complex), AMOT (Affinity Capture-Western), CDH11 (Affinity Capture-Western)

ESM2 similar proteins: A0A8M2BIB6, F1QSQ0, F8W3X3, H2EQR6, O35902, O54800, O55111, O93319, P32926, P33545, P55280, P55285, P55286, P55287, P55288, P55289, P55292, P55849, P55850, P70407, P70408, P79995, P97291, P97326, Q01107, Q02413, Q02487, Q08554, Q08DJ5, Q13634, Q14126, Q14574, Q28060, Q3SWX5, Q5DWV1, Q5RJH3, Q61495, Q68SP4, Q6W3B0, Q7TMD7

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

5 interactions.

A	Effect	B	Mechanism
CDH11	“up-regulates activity”	α-Catenin	binding
calcium(2+)	“up-regulates activity”	CDH11	“chemical activation”
CDH11	“up-regulates activity”	CTNNB1	binding
CDH11	unknown	CTNNA1	binding
CDH11	unknown	CTNNB1	binding

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 6 cancer types — CHOL, COAD, ESCA, HCC, LUSC, STAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	5
Uncertain significance	106
Likely benign	26
Benign	10

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1339266	NM_001797.4(CDH11):c.979G>T (p.Gly327Trp)	Pathogenic
1339267	NM_001797.4(CDH11):c.164G>C (p.Trp55Ser)	Pathogenic
1339268	NM_001797.4(CDH11):c.780T>A (p.Asp260Glu)	Pathogenic
1339270	NM_001797.4(CDH11):c.1121T>A (p.Val374Glu)	Pathogenic
1339271	NM_001797.4(CDH11):c.835G>C (p.Glu279Gln)	Pathogenic
523097	NM_001797.4(CDH11):c.999+1G>T	Pathogenic
523098	NM_001797.4(CDH11):c.1116_1117delinsGATCATCAG (p.Ile372fs)	Pathogenic
523099	NM_001797.4(CDH11):c.696C>G (p.Tyr232Ter)	Pathogenic
2500121	NM_001797.4(CDH11):c.229C>T (p.Leu77Phe)	Likely pathogenic
2572369	NM_001797.4(CDH11):c.778G>C (p.Asp260His)	Likely pathogenic
2646590	NM_001797.4(CDH11):c.1096del (p.Asp366fs)	Likely pathogenic
915374	NM_001797.4(CDH11):c.1895-599A>T	Likely pathogenic
987332	NM_001797.4(CDH11):c.1639C>T (p.Arg547Ter)	Likely pathogenic

SpliceAI

3583 predictions. Top by Δscore:

Variant	Effect	Δscore
16:64948095:AATGA:A	acceptor_gain	1.0000
16:64948096:ATGA:A	acceptor_gain	1.0000
16:64948097:TGA:T	acceptor_gain	1.0000
16:64948098:GA:G	acceptor_gain	1.0000
16:64948100:C:CC	acceptor_gain	1.0000
16:64950761:CCTTA:C	donor_loss	1.0000
16:64950762:CTTAC:C	donor_loss	1.0000
16:64950763:TTA:T	donor_loss	1.0000
16:64950764:TA:T	donor_loss	1.0000
16:64950765:A:AC	donor_gain	1.0000
16:64950765:AC:A	donor_gain	1.0000
16:64950766:C:CC	donor_gain	1.0000
16:64950766:CC:C	donor_gain	1.0000
16:64971693:TTGG:T	acceptor_gain	1.0000
16:64971925:GATTA:G	donor_loss	1.0000
16:64971926:ATTAC:A	donor_loss	1.0000
16:64971927:TTACC:T	donor_loss	1.0000
16:64971928:TAC:T	donor_loss	1.0000
16:64971929:ACCT:A	donor_loss	1.0000
16:64971930:CCT:C	donor_loss	1.0000
16:64972061:TTGT:T	acceptor_gain	1.0000
16:64972062:TGT:T	acceptor_gain	1.0000
16:64972063:GT:G	acceptor_gain	1.0000
16:64972063:GTCT:G	acceptor_loss	1.0000
16:64972065:C:CC	acceptor_gain	1.0000
16:64972065:C:T	acceptor_loss	1.0000
16:64972066:T:C	acceptor_loss	1.0000
16:64972898:A:AC	donor_gain	1.0000
16:64972899:C:CC	donor_gain	1.0000
16:64972901:TA:T	donor_loss	1.0000

AlphaMissense

5277 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:64991860:T:G	D240A	1.000
16:64991861:C:G	D240H	1.000
16:64991866:G:T	A238D	1.000
16:64991867:C:G	A238P	1.000
16:64991869:T:G	Q237P	1.000
16:64991872:A:T	I236N	1.000
16:64991929:A:C	I217S	1.000
16:64991929:A:T	I217N	1.000
16:64991935:C:T	G215D	1.000
16:64992935:A:G	F208S	1.000
16:64992963:A:C	Y199D	1.000
16:64992998:T:A	D187V	1.000
16:64992999:C:G	D187H	1.000
16:64993010:G:T	A183D	1.000
16:64998608:G:C	F159L	1.000
16:64998608:G:T	F159L	1.000
16:64998609:A:G	F159S	1.000
16:64998610:A:G	F159L	1.000
16:64998615:G:T	P157Q	1.000
16:64998624:T:A	D154V	1.000
16:64998624:T:C	D154G	1.000
16:64998624:T:G	D154A	1.000
16:64998625:C:A	D154Y	1.000
16:64998625:C:G	D154H	1.000
16:64998626:A:C	N153K	1.000
16:64998626:A:T	N153K	1.000
16:64998632:G:C	D151E	1.000
16:64998632:G:T	D151E	1.000
16:64998633:T:A	D151V	1.000
16:64998633:T:C	D151G	1.000

dbSNP variants (sampled 300 via entrez): RS1000000861 (16:65014386 T>C), RS1000012180 (16:65095336 C>A,T), RS1000047729 (16:65055254 G>T), RS1000059267 (16:65064761 A>C,T), RS1000081271 (16:65104920 T>C), RS1000109781 (16:65064433 C>T), RS1000110300 (16:64967050 C>A), RS1000133981 (16:65043699 A>G), RS1000159354 (16:64957653 TAC>T,TACAC), RS1000180212 (16:64991507 A>G), RS1000184190 (16:65048376 G>C), RS1000205777 (16:65038787 G>A), RS1000207044 (16:65079512 T>C), RS1000219378 (16:65038727 G>A), RS1000241475 (16:65000141 G>A)

Disease associations

OMIM: gene MIM:600023 | disease phenotypes: MIM:211380, MIM:603463, MIM:613659, MIM:619736, MIM:157900, MIM:119530

GenCC curated gene-disease

Disease	Classification	Inheritance
Elsahy-Waters syndrome	Definitive	Autosomal recessive
Teebi hypertelorism syndrome 2	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Elsahy-Waters syndrome	Definitive	AR
Teebi hypertelorism syndrome 2	Moderate	AD

Mondo (6): Elsahy-Waters syndrome (MONDO:0008885), gastric cancer (MONDO:0001056), Teebi hypertelorism syndrome 2 (MONDO:0030674), breast ductal adenocarcinoma (MONDO:0005590), Mobius syndrome (MONDO:0008006), orofacial cleft 1 (MONDO:0007335)

Orphanet (3): Branchioskeletogenital syndrome (Orphanet:1299), Hypospadias-hypertelorism-coloboma and deafness syndrome (Orphanet:157788), Moebius syndrome (Orphanet:570)

HPO phenotypes

118 total (30 of 118 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000042	Absent external genitalia
HP:0000047	Hypospadias
HP:0000048	Bifid scrotum
HP:0000054	Micropenis
HP:0000071	Ureteral stenosis
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000179	Thick lower lip vermilion
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000233	Thin vermilion border
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000260	Wide anterior fontanel
HP:0000272	Malar flattening
HP:0000289	Broad philtrum
HP:0000303	Mandibular prognathia
HP:0000307	Pointed chin
HP:0000309	Abnormal midface morphology
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000324	Facial asymmetry
HP:0000327	Hypoplasia of the maxilla
HP:0000337	Broad forehead
HP:0000341	Narrow forehead

GWAS associations

49 associations (top):

Study	Trait	p-value
GCST002690_11	Very long-chain saturated fatty acid levels (fatty acid 20:0)	4.000000e-06
GCST003070_5	Cerebrospinal T-tau levels	8.000000e-07
GCST003818_79	Resting heart rate	4.000000e-18
GCST004068_25	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	7.000000e-06
GCST004747_13	Lung cancer in never smokers	9.000000e-06
GCST004946_62	Schizophrenia	5.000000e-08
GCST005580_12	Intraocular pressure	7.000000e-15
GCST005580_7	Intraocular pressure	2.000000e-15
GCST005830_71	Hand grip strength	5.000000e-09
GCST006394_100	Intraocular pressure	1.000000e-13
GCST006395_4	Glaucoma	2.000000e-06
GCST006412_91	Intraocular pressure	3.000000e-15
GCST006585_1493	Blood protein levels	3.000000e-101
GCST007096_224	Pulse pressure	6.000000e-14
GCST007099_185	Systolic blood pressure	5.000000e-09
GCST007656_9	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	2.000000e-12
GCST007672_16	3-month functional outcome in ischaemic stroke (modified Rankin score)	4.000000e-06
GCST009725_33	Intraocular pressure	6.000000e-13
GCST010727_35	Deep white matter hyperintensities	7.000000e-06
GCST010796_3752	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-09
GCST010796_3753	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_3754	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_3755	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-09
GCST010796_3756	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_3757	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_3758	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-09
GCST010796_3759	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-09
GCST010796_3760	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_3761	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_3762	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-09

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0004760	t-tau measurement
EFO:0004695	intraocular pressure measurement
EFO:0006941	grip strength measurement
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0009603	stroke outcome severity measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0004327	electrocardiography
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0011007	estrogen measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D020331	Mobius Syndrome	C07.465.299.825; C10.292.319.825; C10.292.562.700.375.750; C11.590.436.400.750; C16.131.077.578; C16.614.595
C537084	Brachioskeletogenital syndrome (supp.)
C566373	Hypospadias, Hypertelorism, Upper Lid Coloboma, and Mixed-Type Hearing Loss (supp.)
C566121	Orofacial Cleft 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, increases expression	6
trichostatin A	decreases expression, increases expression	3
sodium arsenite	affects methylation, decreases expression, increases expression	3
Estradiol	decreases expression, increases expression, affects cotreatment	3
methylmercuric chloride	decreases expression	2
cobaltous chloride	decreases expression	2
entinostat	decreases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	2
Tretinoin	decreases expression, increases expression	2
Aflatoxin B1	decreases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
arsenite	decreases expression	1
trimellitic anhydride	decreases expression	1
3,3’-diindolylmethane	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
afimoxifene	decreases expression	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	increases methylation	1
pentabromodiphenyl ether	decreases expression	1
azoxystrobin	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
quinocetone	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
picoxystrobin	decreases expression	1
Sevoflurane	decreases expression, decreases reaction	1
Temozolomide	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8DC	Abcam HCT 116 CDH11 KO	Cancer cell line	Male
CVCL_B8TU	Abcam MCF-7 CDH11 KO	Cancer cell line	Female
CVCL_B9FJ	Abcam A-549 CDH11 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT01038154	PHASE4	UNKNOWN	Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
NCT01234272	PHASE4	COMPLETED	Comparison of the Analgesic Effect Between Intrathecal Morphine and IV-fentanyl Patient Controlled Analgesia (ITM-IVPCA) and Epidural PCA (PCEA) in Patients Undergoing Gastrectomy -Randomized Allocation Study-
NCT01260194	PHASE4	TERMINATED	A Study of Herceptin (Trastuzumab) in Combination With Standard Chemotherapy in Patients With HER Positive Metastatic Gastric Cancer
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01401075	PHASE4	COMPLETED	RCT With Adjuvant Mistletoe Treatment in Gastric Cancer Patients
NCT01471756	PHASE4	COMPLETED	Improving Complete Endoscopic Mucosal Resection (EMR) of Colorectal Neoplasia
NCT01766765	PHASE4	UNKNOWN	Early Jejunostomy Nutrition Minimizes Time to Chemotherapy
NCT01910948	PHASE4	UNKNOWN	Perioperative Application of Omega-3 Polyunsaturated Fatty Acids in Gastric Cancer Patients
NCT01927328	PHASE4	UNKNOWN	Iron Replacement in Oesophagogastric Neoplasia
NCT01962272	PHASE4	COMPLETED	The Effect of Nutritional Counseling for Cancer Patients
NCT01962376	PHASE4	UNKNOWN	Preoperative Chemotherapy With Bevacizumab For Potentially Resectable Gastric Cancer With Liver Metastasis
NCT02047994	PHASE4	RECRUITING	Multicentric Randomized Study of H. Pylori Eradication and Pepsinogen Testing for Prevention of Gastric Cancer Mortality
NCT02235246	PHASE4	COMPLETED	The Effect of Perioperative Intravenous Magnesium on Pain After Endoscopic Submucosal Dissection for Gastric Neoplasm: Prospective Randomized Double-blind Placebo Controlled Study
NCT02366819	PHASE4	SUSPENDED	Genetic Analysis-Guided Irinotecan Hydrochloride Dosing of mFOLFIRINOX in Treating Patients With Locally Advanced Gastroesophageal or Stomach Cancer
NCT02401971	PHASE4	UNKNOWN	Irinotecan Plus Thalidomide in Second Line Advanced Gastric Cancer
NCT02458573	PHASE4	COMPLETED	Comparison of the Effects of Continuous Epidural Analgesia and Continuous Intravenous Analgesia on Postoperative Bowel Movement in Patients Undergoing Laparoscopic Gastrectomy
NCT02638584	PHASE4	COMPLETED	Effects of Ilaprazole on Ulcer Healing Rate and Prevention of Gastrointestinal Bleeding in the Patients Undergone ESD.
NCT02776527	PHASE4	UNKNOWN	A Clinical Trial of Maintenance Treatment of Apatinib in Advanced Gastric Cancer Patients Have Completed Postoprative Adjuvant Chemotherapy
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03550482	PHASE4	COMPLETED	Oncoxin® and Quality of Life in Cancer Patients
NCT03609892	PHASE4	COMPLETED	Helicobacter Rescue Therapy With Berberine Plus Amoxicillin Quadruple Therapy Versus Tetracycline Plus Furazolidone Quadruple Therapy
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03733639	PHASE4	UNKNOWN	Tisseel® as a Reinforcement of Esophagojejunal Anastomoses
NCT04168346	PHASE4	NOT_YET_RECRUITING	Preoperative Intravenous Iron Therapy in Patients With Gastric Cancer
NCT04209933	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Different Bismuth Quadruple Therapies
NCT04591028	PHASE4	WITHDRAWN	A Study to Evaluate Indocyanine Green Lymphangiography to Improve Lymphadenectomy in Gastric Cancer Patients
NCT04607057	PHASE4	UNKNOWN	Supplemental Parenteral Nutrition During Postgastrectomy in Nutritionally at Risk Patient
NCT04660123	PHASE4	COMPLETED	A Real World Study of Bismuth Colloidal Pectin Granules Quadruple Therapy for H. Pylori Eradication
NCT04678492	PHASE4	COMPLETED	Helicobacter Rescue Therapy With High-dose Esomeprazole and Amoxicillin Dual Therapy Versus Bismuth-containing Quadruple Therapy
NCT04697186	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Berberine Plus Amoxicillin Triple Therapy Versus Bismuth-containing Quadruple Therapy
NCT05029453	PHASE4	UNKNOWN	Apatinib Combined With Chemotherapy Versus Chemotherapy in Second-line Gastric Cancer Receiving Prior Anti-PD-1 Therapy
NCT05183126	PHASE4	RECRUITING	Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Cancer
NCT05354856	PHASE4	TERMINATED	The Effect of Chemoradiotherapy on Gastric Perfusion in Patients With Gastric Cancer.
NCT05410535	PHASE4	COMPLETED	To Evaluate Efficacy of Ursodeoxycholic Acid (UDCA) for the Prevention of Gallstone Formation After Gasterectomy
NCT05498766	PHASE4	NOT_YET_RECRUITING	Effect and Safety of Huaier Granule Versus SOX Regimen in Gastric Cancer Patients
NCT05518929	PHASE4	COMPLETED	Hypoxia During Gastroenterological Endoscope Procedures Sedated With Ciprofol In Overweight Or Obesity Patients