CDH2

Summary

CDH2 (cadherin 2, HGNC:1759) is a protein-coding gene on chromosome 18q12.1, encoding Cadherin-2 (P19022). Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell.

This gene encodes a classical cadherin and member of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein is proteolytically processed to generate a calcium-dependent cell adhesion molecule and glycoprotein. This protein plays a role in the establishment of left-right asymmetry, development of the nervous system and the formation of cartilage and bone.

Source: NCBI Gene 1000 — RefSeq curated summary.

At a glance

• Gene–disease (curated): agenesis of corpus callosum, cardiac, ocular, and genital syndrome (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 77 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 1,206 total — 9 pathogenic, 12 likely-pathogenic (top 2% of genes corpus-wide)
• Regional missense constraint (gnomAD): 2 of 5 regions constrained (≈8% of expected missense variation)
• GTEx eGene: eQTL in 21 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 63
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.34 (highly constrained)
• MANE Select transcript: NM_001792
• Interaction hub: 4,854 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1759
Approved symbol	CDH2
Name	cadherin 2
Location	18q12.1
Locus type	gene with protein product
Status	Approved
Aliases	CDHN, CD325
Ensembl gene	ENSG00000170558
Ensembl biotype	protein_coding
OMIM	114020
Entrez	1000

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 17 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000269141

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 4: 2, TSL 5: 1

ENST00000269141, ENST00000399380, ENST00000413878, ENST00000418492, ENST00000430882, ENST00000674998, ENST00000675173, ENST00000675688, ENST00000675708, ENST00000676041, ENST00000676445, ENST00000876838, ENST00000876839, ENST00000967815, ENST00000967816, ENST00000967818, ENST00000967819, ENST00001023182, ENST00001023187, ENST00001110464, ENST00001114452, ENST00001131119, ENST00001131989

RefSeq mRNA: 2 — MANE Select: NM_001792 NM_001308176, NM_001792

CCDS: CCDS11891, CCDS77172

Canonical transcript exons

ENST00000269141 — 16 exons

Exon	Start	End
ENSE00001103818	28009717	28009872
ENSE00001103869	28011846	28011992
ENSE00001158044	27963357	27963521
ENSE00001158081	27990097	27990350
ENSE00001158160	27985000	27985233
ENSE00001162393	28005849	28005993
ENSE00001169137	28002997	28003169
ENSE00001199798	27982944	27983083
ENSE00001199810	27985528	27985761
ENSE00001199819	27988524	27988666
ENSE00001199832	27992655	27992840
ENSE00001235865	27950966	27952359
ENSE00001235868	28176963	28177130
ENSE00001610614	27993500	27993637
ENSE00003584242	28147673	28147784
ENSE00003649734	28013683	28013909

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 99.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.7118 / max 1034.5312, expressed in 1242 samples.

Highest expression (Bgee): heart right ventricle, ventricular zone, stromal cell of endometrium, myocardium, cortical plate.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CDH2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 21 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 23 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	3.6e-12	-0.22	18:28083495:A:T
Testis	eqtl	8.3e-09	-0.20	18:28035830:C:G
Testis	sqtl	1.4e-08	-0.59	18:28035830:C:G
Brain Cerebellar Hemisphere	eqtl	1.0e-07	-0.24	18:27859305:G:A
Whole Blood	eqtl	1.0e-07	-0.35	18:28172618:A:G
Artery Aorta	eqtl	1.1e-07	+0.27	18:28703747:G:T
Pancreas	eqtl	7.5e-07	-0.48	18:28085642:T:C
Adipose Visceral Omentum	eqtl	4.8e-06	-0.41	18:28148255:A:G
Cells Cultured fibroblasts	eqtl	1.9e-05	-0.18	18:28177084:A:C
Brain Cerebellum	eqtl	6.0e-05	+0.25	18:27872993:T:C
Artery Coronary	eqtl	1.2e-04	-0.19	18:28137225:A:C
Esophagus Muscularis	eqtl	2.4e-03	-0.19	18:28101928:C:G
Pituitary	eqtl	4.9e-03	+0.14	18:28033475:T:G
Heart Atrial Appendage	sqtl	6.0e-03	-1.10	18:27964258:T:C
Artery Tibial	eqtl	1.0e-02	-0.15	18:28719300:C:T
Cells EBV-transformed lymphocytes	eqtl	2.6e-02	-0.72	18:28114748:C:A
Colon Transverse	eqtl	3.4e-02	-0.21	18:27649378:T:C
Brain Spinal cord cervical c-1	eqtl	3.4e-02	-0.23	18:28048124:C:A
Brain Frontal Cortex BA9	eqtl	3.4e-02	+0.17	18:27957721:T:A
Stomach	eqtl	3.6e-02	+0.13	18:28111495:C:T

FANTOM5 promoters

showing 10 of 20 alternative TSS:

Promoter ID	TPM avg	Samples expressed
171524	18.2794	1134
171522	8.8597	1097
171528	4.0920	877
171494	3.5513	753
171501	0.7265	323
171527	0.4437	256
171503	0.4273	214
171502	0.4090	155
171495	0.3594	162
171523	0.2976	166

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	99.31	gold quality
ventricular zone	UBERON:0003053	99.00	gold quality
stromal cell of endometrium	CL:0002255	98.74	gold quality
myocardium	UBERON:0002349	98.55	gold quality
cortical plate	UBERON:0005343	98.40	gold quality
left ventricle myocardium	UBERON:0006566	98.39	gold quality
endothelial cell	CL:0000115	98.13	silver quality
ganglionic eminence	UBERON:0004023	98.01	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.94	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.92	gold quality
middle temporal gyrus	UBERON:0002771	97.77	gold quality
embryo	UBERON:0000922	97.47	gold quality
cardiac ventricle	UBERON:0002082	97.39	gold quality
heart left ventricle	UBERON:0002084	97.32	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.99	gold quality
inferior olivary complex	UBERON:0002127	96.44	gold quality
periodontal ligament	UBERON:0008266	96.41	gold quality
heart	UBERON:0000948	96.28	gold quality
cardiac atrium	UBERON:0002081	96.09	gold quality
right atrium auricular region	UBERON:0006631	95.87	gold quality
vena cava	UBERON:0004087	95.64	gold quality
right adrenal gland cortex	UBERON:0035827	95.32	gold quality
right adrenal gland	UBERON:0001233	95.27	gold quality
medial globus pallidus	UBERON:0002477	95.25	gold quality
cranial nerve II	UBERON:0000941	95.24	gold quality
Brodmann (1909) area 10	UBERON:0013541	95.20	gold quality
left adrenal gland	UBERON:0001234	95.02	gold quality
apex of heart	UBERON:0002098	94.95	gold quality
adrenal cortex	UBERON:0001235	94.89	gold quality
frontal pole	UBERON:0002795	94.87	gold quality
globus pallidus	UBERON:0001875	94.73	gold quality
CA1 field of hippocampus	UBERON:0003881	94.67	gold quality
entorhinal cortex	UBERON:0002728	94.60	gold quality
left adrenal gland cortex	UBERON:0035825	94.46	gold quality
medulla oblongata	UBERON:0001896	94.41	gold quality
adrenal gland	UBERON:0002369	94.38	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.19	gold quality
primary visual cortex	UBERON:0002436	94.18	gold quality
middle frontal gyrus	UBERON:0002702	94.03	gold quality
right coronary artery	UBERON:0001625	93.90	gold quality
occipital lobe	UBERON:0002021	93.88	gold quality
ventral tegmental area	UBERON:0002691	93.59	gold quality
nephron tubule	UBERON:0001231	93.45	gold quality
superior vestibular nucleus	UBERON:0007227	93.42	gold quality
adrenal tissue	UBERON:0018303	93.40	gold quality
superior frontal gyrus	UBERON:0002661	92.80	gold quality
lateral globus pallidus	UBERON:0002476	92.79	gold quality
orbitofrontal cortex	UBERON:0004167	92.79	gold quality
urethra	UBERON:0000057	92.62	gold quality
parietal lobe	UBERON:0001872	92.60	gold quality
paraflocculus	UBERON:0005351	92.38	gold quality
inferior vagus X ganglion	UBERON:0005363	92.29	gold quality
cerebellar vermis	UBERON:0004720	92.27	gold quality
postcentral gyrus	UBERON:0002581	92.12	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.12	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.91	gold quality
temporal lobe	UBERON:0001871	91.62	gold quality
liver	UBERON:0002107	91.60	gold quality
corpus callosum	UBERON:0002336	91.11	gold quality
subthalamic nucleus	UBERON:0001906	91.07	gold quality
cerebral cortex	UBERON:0000956	90.77	gold quality
substantia nigra pars reticulata	UBERON:0001966	90.71	gold quality
prefrontal cortex	UBERON:0000451	90.61	gold quality
substantia nigra pars compacta	UBERON:0001965	90.58	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.48	gold quality
neocortex	UBERON:0001950	90.44	gold quality
frontal cortex	UBERON:0001870	90.25	gold quality
pons	UBERON:0000988	90.18	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.15	gold quality
telencephalon	UBERON:0001893	90.13	gold quality
tibia	UBERON:0000979	89.96	gold quality
right testis	UBERON:0004534	89.75	gold quality
dorsal root ganglion	UBERON:0000044	89.71	gold quality
testis	UBERON:0000473	89.66	gold quality
Ammon’s horn	UBERON:0001954	89.47	gold quality
kidney epithelium	UBERON:0004819	89.43	silver quality
amygdala	UBERON:0001876	89.33	gold quality
cingulate cortex	UBERON:0003027	89.23	gold quality
anterior cingulate cortex	UBERON:0009835	89.22	gold quality
forebrain	UBERON:0001890	89.19	gold quality
left testis	UBERON:0004533	89.06	gold quality
hypothalamus	UBERON:0001898	88.79	gold quality
coronary artery	UBERON:0001621	88.75	gold quality
brain	UBERON:0000955	88.52	gold quality
nucleus accumbens	UBERON:0001882	88.46	gold quality
central nervous system	UBERON:0001017	88.36	gold quality
caudate nucleus	UBERON:0001873	88.26	gold quality
trigeminal ganglion	UBERON:0001675	88.21	gold quality
ascending aorta	UBERON:0001496	87.97	gold quality
left coronary artery	UBERON:0001626	87.90	gold quality
renal glomerulus	UBERON:0000074	87.81	gold quality
thoracic aorta	UBERON:0001515	87.78	gold quality
right lobe of liver	UBERON:0001114	87.74	gold quality
secondary oocyte	CL:0000655	87.41	gold quality
putamen	UBERON:0001874	87.37	gold quality
midbrain	UBERON:0001891	87.06	gold quality
metanephric glomerulus	UBERON:0004736	86.78	silver quality
right frontal lobe	UBERON:0002810	86.62	gold quality
saphenous vein	UBERON:0007318	86.52	gold quality
substantia nigra	UBERON:0002038	86.42	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	265.76
E-CURD-11	yes	91.57
E-HCAD-10	yes	18.72
E-CURD-112	yes	17.37
E-MTAB-9388	yes	11.76
E-GEOD-83139	no	103.80
E-ANND-3	no	5.73
E-MTAB-9543	no	1.22

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Heart muscle	tissue	183.5	high
Hippocampal formation	tissue	63.0
Adrenal gland	tissue	62.8	high
Hypothalamus	tissue	58.6
Frontal cortex	tissue	57.0
Prefrontal cortex	tissue	56.1
Cerebral cortex	tissue	56.1	medium
Retina	tissue	55.9
Postcentral gyrus	tissue	55.0
Liver	tissue	53.5	high
Hippocampus	tissue	51.8	not detected
Somatosensory cortex	tissue	51.8
Entorhinal cortex	tissue	51.3
Thalamus	tissue	50.5
Occipital cortex	tissue	50.4
Midbrain	tissue	48.3
Retrosplenial and cingulate cortex	tissue	48.2
Olfactory bulb	tissue	48.2
Temporal cortex	tissue	48.0
Amygdala	tissue	47.7
Insular cortex	tissue	47.7
Motor cortex	tissue	47.4
Caudate putamen	tissue	47.4
Pons	tissue	45.6
Nucleus accumbens	tissue	45.4
Locus coeruleus	tissue	45.4
Septum	tissue	44.7
Superior colliculi	tissue	44.1
Periaqueductal gray	tissue	44.1
Retrosplenial cortex	tissue	41.8
Testis	tissue	41.5	high
Medulla oblongata	tissue	41.5
Spinal cord	tissue	41.1
Ventral forebrain	tissue	35.5
Basal ganglia	tissue	32.3	not detected
Cerebellum	tissue	29.7	high
Corpus callosum	tissue	28.2
Parathyroid gland	tissue	28.0	not detected
Substantia nigra	tissue	27.9
Putamen	tissue	26.9
Choroid plexus	tissue	19.2
Kidney	tissue	16.9	high
Ovary	tissue	14.3	not detected
Spleen	tissue	12.7	not detected
Seminal vesicle	tissue	10.1	not detected
Fallopian tube	tissue	9.9	medium
Pituitary gland	tissue	7.7
Smooth muscle	tissue	6.4	not detected
Cervix	tissue	6.2	not detected
Endometrium 1	tissue	5.8	low
Thyroid gland	tissue	5.8	low
Stomach 1	tissue	5.5	medium
Thymus	tissue	3.6
Gallbladder	tissue	2.9	not detected
Vagina	tissue	2.6	not detected
Appendix	tissue	2.5	not detected
Prostate	tissue	2.3	not detected
Tongue	tissue	2.0
Lymph node	tissue	1.8	not detected
Tonsil	tissue	1.5	not detected

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Ventromedial nucleus (72.3), Arcuate nucleus (69.4), Perirhinal gyrus (64.8), Orbitofrontal gyrus, anterior (64.4), Habenula (63.6).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, CUX1, EHMT2, GATA3, HNRNPK, JUN, KLF4, KLF8, MARK1, MSX1, MSX2, MTA3, MYC, MZF1, NFKB, NOTCH1, OVOL1, OVOL2, PAWR, PAX6, PPARG, RBPJ, SATB2, SMAD4, SMAD7, SNAI1, SNAI2, SOX4, SOX5, SOX9, SP1, SP3, STAT3, TWIST1, TWIST2, WT1, ZEB1, ZEB2, ZNF77

miRNA regulators (miRDB)

Targeting CDH2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 129 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-548BB-3P	99.86	70.58	4354

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.336, missense Z 2.87 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000269141 splits into 5 regions with different missense tolerance; 2 are missense-constrained (≈8% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
18:27,952,156–27,963,490	114 / 144.8	0.79	no
18:27,963,491–27,982,986	4 / 27.1	0.15	yes (p 8.9e-06)
18:27,982,987–28,009,806	564 / 722.2	0.78	no
18:28,009,807–28,011,938	21 / 61.8	0.34	yes (p 2.1e-07)
18:28,011,939–28,177,022	159 / 177.2	0.90	no

Literature-anchored findings (GeneRIF, showing 40)

• Cadherin-mediated cell sorting not determined by binding or adhesion specificity (PMID:11790800)
• Expression of beta1-integrins and N-cadherin in bladder cancer and melanoma cell lines (PMID:11996105)
• expression patterns of E- and N-cadherins in both embryonic and adult (healthy, injured, carious) human teeth (PMID:12057916)
• N-cadherin signal transduction upregulates Bcl-2 (PMID:12095980)
• Protection of the FGFR-1 from fgf-2-induced downregulation by N-cadherin enhances receptor signaling and provides a mechanism by which tumor cells can acquire metastatic properties (PMID:12398894)
• carbohydrate profile of this protein synthesized in human melanoma cell lines. N-glycans of N-cadherin are altered in metastatic melanomas in a way characteristic for invasive tumor cells. (PMID:12545205)
• N-cadherin cleavage by presenilin 1 is regulated by NMDA receptor (PMID:13678586)
• Presenilin-1-mediated delivery of N-cadherin to the plasma membrane is important for N-cadherin to exert its physiological function, and it may control the state of cell-cell contact. (PMID:14515347)
• the comparable region of N-cadherin can substitute for this required region in E-cadherin and is required for suppression by the mutant form of N-cadherin that is capable of suppressing (PMID:14559901)
• In human melanocytic tumors, a causative role of (loss of ) E-cadherin or (gain of ) N-cadherin for melanocytic tumor progression still remains to be proven. (PMID:14675278)
• E- to N-cadherin switching in epithelial carcinomas has a potential impact on metastatic progression. (PMID:15153430)
• N-cadherin may have a role in the epithelial-mesenchymal transition in pancreatic carcinoma (PMID:15217949)
• N-cadherin involved in primary colon cancer progression, promoting tumor invasiveness (PMID:15252840)
• a subset of integrin signaling molecules, namely Fak and paxillin, but not p130 Crk-associated substrate or proline-rich tyrosine kinase 2, participate in processes regulating N-cadherin-based cell-cell adhesion (PMID:15263022)
• Data show that N-cadherin, expressed at the tips of filopodia in colon cancer-derived myofibroblasts invading extracellular matrices in vitro, is upregulated by TGF-beta. (PMID:15331629)
• High expression of N-cadherin is associated with esophageal carcinoma invasiveness (PMID:15355896)
• Decreased expression of N-cadherin correlated with a dramatic increase in invasive behavior of glioma cells (PMID:15527101)
• Sp1/Sp3 and MZF1 are important transcription factors regulating N-cadherin promoter activity and expression in osteoblasts. (PMID:15541732)
• The topics discussed in this review point to N-cadherin as an important player in tumor development and, therefore, a potential target for novel therapeutic approaches. (PMID:15648948)
• regulation of N-cadherin is a crucial event and it has a role in controlling the survival capability of human ovarian surface epithelial cells (PMID:15701645)
• cadherin switching (downregulation of E-cadherin and upregulation of N-cadherin) is necessary for increased motility but is not required for the morphological changes that accompany the epithelium-to-mesenchyme transition (PMID:15713751)
• cleaved by Porphyromonas gingivalis gingipains in endothelial cells (PMID:15731052)
• vascular smooth muscle cell survival is dependent on N-cadherin-mediated cell-cell contacts, which could be important in the context of plaque instability (PMID:15774907)
• Co-localization of ZO-1 with N-cadherin. Zonula occludens protein-1 has role in N-cadherin-based adhesion. (PMID:15855653)
• N-cadherin plays a key role in the transendothelial migration of melanoma cells (PMID:15987741)
• Data suggest that a vimentin-based N-cadherin complex functions together with an actin-based complex to promote strong cell-cell adhesion in fibroblasts. (PMID:16091424)
• ERK activation and p21 and N-cadherin upregulation are required for genistein-induced neuronal differentiation (PMID:16149052)
• demonstrated for the first time that N-cadherin switching occurs in higher grade prostate cancer and correlates significantly with increasing Gleason patterns; N-cadherin may be a useful biomarker of aggressive PC (PMID:16173043)
• N-cadherin is associated with tumor aggressiveness and metastatic potential and may contribute to tumor progression (PMID:16258702)
• The data suggest a novel role for tyrosine phosphorylation of N-cadherin by Src family kinases in the regulation of beta-catenin association during transendothelial migration of melanoma cells. (PMID:16371504)
• N-cadherin up-regulation is associated with recurrent hepatocellular carcinomas (PMID:16596172)
• N-cadherin acts in an invasive mode in bladder cancer, but whether it has a primary role in urothelial neoplastic progression has yet to be investigated. (PMID:16675571)
• beta-catenin is regulated via epsilon-cleavage of N-cadherin (PMID:16707106)
• N-cadherin was selectively expressed on epithelial cells of the thymus, pituitary, pancreas, liver, adrenal, endometrium of the uterus, ovary, and stomach as well as in neuronal tissues. (PMID:16819153)
• N-cadherin and beta3 integrin expression correlates with progression to advanced-stage melanoma. (PMID:16969099)
• These results indicate that N-cadherin may be a critical cell-to-cell adhesion molecule between corneal epithelial stem/progenitor cells and their corresponding niche cells in the limbal epithelium. (PMID:17008425)
• Reduced E-cadherin expression was found in pseudomyxoma peritonei. (PMID:17031402)
• engagement of N-cadherin provides a stop signal for breast carcinoma cell migration (PMID:17171299)
• JNK1 is activated in response to collagen I, which increases tumorigenesis by up-regulating N-cadherin expression and by increasing motility. (PMID:17178870)
• N-cadherin and beta-catenin play role in cell migration via PDGF-Rbeta-mediated signaling through the scaffolding molecule NHERF2 (PMID:17229887)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdh2	ENSDARG00000018693
mus_musculus	Cdh2	ENSMUSG00000024304
rattus_norvegicus	Cdh2	ENSRNOG00000015602

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), CDH4 (ENSG00000179242), CDH5 (ENSG00000179776), PCDH9 (ENSG00000184226), DCHS2 (ENSG00000197410), PCDH20 (ENSG00000280165)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88355) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 65 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal heart tube morphology	2
abnormal myocardial fiber morphology	2
abnormal somite shape	2
enlarged heart	1
abnormal heart shape	1
distended pericardium	1
abnormal nervous system tract morphology	1
abnormal cerebral cortex morphology	1
thickened cerebral cortex	1
abnormal brain development	1
wavy neural tube	1
abnormal spinal cord morphology	1
hyperactivity	1
decreased exploration in new environment	1
increased startle reflex	1
abnormal cardiovascular system physiology	1
abnormal embryo turning	1
abnormal visceral yolk sac morphology	1
pericardial edema	1
impaired synaptic plasticity	1
premature death	1
abnormal cardiovascular system morphology	1
abnormal CNS synaptic transmission	1
increased heart rate	1
abnormal sensorimotor gating	1

+40 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.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R9X1	99.4%	Diamond
Callithrix jacchus	B0KW95	99.0%	Diamond
Cricetulus griseus	O55075	98.3%	Diamond
Otolemur garnettii	B4USZ0	98.1%	Diamond
Rhinolophus ferrumequinum	B2KI42	97.6%	Diamond
Bos taurus	P19534	97.6%	Diamond
Xenopus laevis	P20310	95.9%	Diamond
Gallus gallus	P24503	94.6%	Diamond
Sus scrofa	O18926	92.4%	Diamond
Canis lupus familiaris	F1PAA9	82.9%	Diamond
Drosophila melanogaster	O15943	74.9%	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).

Symbol	Type	Entrez
CDH2-AS1	ncRNA	139281654

Protein

Protein identifiers

Cadherin-2 — P19022 (reviewed: P19022)

Alternative names: CDw325, Neural cadherin

All UniProt accessions (7): A0A6Q8PF58, A0A6Q8PG20, A0A6Q8PHJ8, C9J126, C9J8J8, C9JMH2, P19022

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heterogeneous cell types. Acts as a regulator of neural stem cells quiescence by mediating anchorage of neural stem cells to ependymocytes in the adult subependymal zone: upon cleavage by MMP24, CDH2-mediated anchorage is affected, leading to modulate neural stem cell quiescence. Plays a role in cell-to-cell junction formation between pancreatic beta cells and neural crest stem (NCS) cells, promoting the formation of processes by NCS cells. Required for proper neurite branching. Required for pre- and postsynaptic organization. CDH2 may be involved in neuronal recognition mechanism. In hippocampal neurons, may regulate dendritic spine density. May promote axon outgrowth and motor fiber repair via DSP-mediated recruitment to outgrowth tips.

Subunit / interactions. Homodimer (via extracellular region). Can also form heterodimers with other cadherins (via extracellular region). Dimerization occurs in trans, i.e. with a cadherin chain from another cell. Identified in a complex containing at least DSP, JUP, VIM and CDH2; the complex is more abundant following crush injury in regenerating motor neurons and may promote axon outgrowth and motor fiber repair. Interacts with CDCP1. Interacts with PCDH8; this complex may also include TAOK2. The interaction with PCDH8 may lead to internalization through TAOK2/p38 MAPK pathway. Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. May interact with OBSCN (via protein kinase domain 2). Interacts with FBXO45.

Subcellular location. Cell membrane. Sarcolemma. Cell junction. Cell surface. Desmosome. Adherens junction. Cell projection. Axon.

Post-translational modifications. Cleaved by MMP24. Ectodomain cleavage leads to the generation of a soluble 90 kDa N-terminal soluble fragment and a 45 kDa membrane-bound C-terminal fragment 1 (CTF1), which is further cleaved by gamma-secretase into a 35 kDa. Cleavage in neural stem cells by MMP24 affects CDH2-mediated anchorage of neural stem cells to ependymocytes in the adult subependymal zone, leading to modulate neural stem cell quiescence. May be phosphorylated by OBSCN.

Disease relevance. Arrhythmogenic right ventricular dysplasia, familial, 14 (ARVD14) [MIM:618920] A congenital heart disease characterized by infiltration of adipose and fibrous tissue into the right ventricle and loss of myocardial cells, resulting in ventricular and supraventricular arrhythmias. The disease may be caused by variants affecting the gene represented in this entry. Agenesis of corpus callosum, cardiac, ocular, and genital syndrome (ACOGS) [MIM:618929] An autosomal dominant, syndromic neurodevelopmental disorder characterized by global developmental delay and/or intellectual disability, corpus callosum agenesis or hypoplasia, mirror movements, dysmorphic features, and ocular, cardiac, and genital anomalies. The disease is caused by variants affecting the gene represented in this entry. Attention deficit-hyperactivity disorder 8 (ADHD8) [MIM:619957] A form of attention deficit-hyperactivity disorder, a neurobehavioral developmental condition primarily characterized by the coexistence of attentional problems and hyperactivity, with each feature occurring infrequently alone. ADHD8 is an autosomal recessive form with onset in early childhood, usually by age 3 years. ADHD8 patients may manifest mild developmental delay with autism. 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. Calcium-binding sites are occupied sequentially in the order of site 3, then site 2 and site 1.

Isoforms (2)

UniProt ID	Names	Canonical?
P19022-1	1	yes
P19022-2	2

RefSeq proteins (2): NP_001295105, NP_001783* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000233	Cadherin_Y-type_LIR	Domain
IPR002126	Cadherin-like_dom	Domain
IPR014868	Cadherin_pro_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, PF08758

UniProt features (65 total): sequence variant 19, binding site 15, sequence conflict 8, glycosylation site 7, domain 5, modified residue 2, topological domain 2, signal peptide 1, propeptide 1, region of interest 1, compositionally biased region 1, chain 1, splice variant 1, transmembrane region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19022-F1	79.68	0.51

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes, Congenital malformations, Other congenital malformations

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; cell junctions

Antibody reliability (HPA): IH enhanced · IF supported

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 (15)

Position	Role
170	Ca(2+)
226	Ca(2+)
228	Ca(2+)
259	Ca(2+)
260	Ca(2+)
261	Ca(2+)
262	Ca(2+)
263	Ca(2+)
293	Ca(2+)
295	Ca(2+)
301	Ca(2+)
353	Ca(2+)

Post-translational modifications (2)

Type	Positions
Phosphoserine	96, 135

Glycosylation sites (7)

Type	Positions
N-linked (glcnac…) asparagine	190, 273, 325, 402, 572, 651, 692

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 13; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

13 pathways:

ID	Pathway	Evidence
R-HSA-418990	Adherens junctions interactions	curated
R-HSA-8957275	Post-translational protein phosphorylation	curated
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	curated
R-HSA-9926550	Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition	curated
R-HSA-446728	Cell junction organization	—
R-HSA-1500931	Cell-Cell communication	—
R-HSA-421270	Cell-cell junction organization	—
R-HSA-1266738	Developmental Biology	—
R-HSA-9856651	MITF-M-dependent gene expression	—
R-HSA-9730414	MITF-M-regulated melanocyte development	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-525793	Myogenesis	electronic
R-HSA-597592	Post-translational protein modification	—

MSigDB gene sets: 571 (showing top): GOBP_SYNAPTIC_VESICLE_LOCALIZATION, MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EPITHELIUM_DEVELOPMENT, HORIUCHI_WTAP_TARGETS_DN, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, GOBP_RESPONSE_TO_MUSCLE_STRETCH, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, GOBP_VESICLE_LOCALIZATION, GOBP_SYNAPSE_ASSEMBLY, GOBP_MEMBRANE_BIOGENESIS, GOBP_EPITHELIAL_CELL_DEVELOPMENT, TTTGTAG_MIR520D, GOBP_TYPE_B_PANCREATIC_CELL_DEVELOPMENT

GO Biological Process (21): cell morphogenesis (GO:0000902), type B pancreatic cell development (GO:0003323), cell-cell junction assembly (GO:0007043), cell adhesion (GO:0007155), homophilic cell-cell adhesion (GO:0007156), synapse assembly (GO:0007416), glial cell differentiation (GO:0010001), neural crest cell development (GO:0014032), calcium-dependent cell-cell adhesion (GO:0016339), cell migration (GO:0016477), adherens junction organization (GO:0034332), detection of muscle stretch (GO:0035995), cell-cell adhesion mediated by cadherin (GO:0044331), synaptic vesicle clustering (GO:0097091), neuroligin clustering involved in postsynaptic membrane assembly (GO:0097118), neuronal stem cell population maintenance (GO:0097150), cell-cell adhesion (GO:0098609), regulation of postsynaptic density protein 95 clustering (GO:1902897), positive regulation of synaptic vesicle clustering (GO:2000809), positive regulation of axon extension (GO:0045773), positive regulation of protein localization (GO:1903829)

GO Molecular Function (12): RNA binding (GO:0003723), calcium ion binding (GO:0005509), beta-catenin binding (GO:0008013), protein kinase binding (GO:0019901), protein phosphatase binding (GO:0019903), identical protein binding (GO:0042802), alpha-catenin binding (GO:0045294), gamma-catenin binding (GO:0045295), cadherin binding (GO:0045296), protein binding (GO:0005515), enzyme binding (GO:0019899), metal ion binding (GO:0046872)

GO Cellular Component (27): cytoplasm (GO:0005737), endoplasmic reticulum lumen (GO:0005788), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), adherens junction (GO:0005912), fascia adherens (GO:0005916), focal adhesion (GO:0005925), cell surface (GO:0009986), intercalated disc (GO:0014704), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), apicolateral plasma membrane (GO:0016327), catenin complex (GO:0016342), lamellipodium (GO:0030027), cell junction (GO:0030054), desmosome (GO:0030057), axon (GO:0030424), extracellular matrix (GO:0031012), sarcolemma (GO:0042383), neuron projection (GO:0043005), plasma membrane raft (GO:0044853), apical part of cell (GO:0045177), presynapse (GO:0098793), membrane (GO:0016020), cortical actin cytoskeleton (GO:0030864), synapse (GO:0045202), anchoring junction (GO:0070161)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Metabolism of proteins	2
Developmental Biology	2
Cell-cell junction organization	1
Post-translational protein modification	1
MITF-M-dependent gene expression	1
Cell junction organization	1
Cell-Cell communication	1
MITF-M-regulated melanocyte development	1

GO top-level categories

showing 60 of 62 GO namespaces:

Category	Terms
protein binding	5
cell-cell adhesion	3
cellular anatomical structure	3
cell-cell junction	3
plasma membrane region	3
cell junction assembly	2
cell-cell junction organization	2
plasma membrane bounded cell projection	2
anatomical structure morphogenesis	1
epithelial cell development	1
type B pancreatic cell differentiation	1
cellular process	1
nervous system development	1
synapse organization	1
cell differentiation	1
gliogenesis	1
neural crest cell differentiation	1
stem cell development	1
cell motility	1
response to muscle stretch	1
detection of mechanical stimulus	1
synaptic vesicle localization	1
synaptic vesicle cycle	1
receptor clustering	1
postsynaptic membrane assembly	1
stem cell population maintenance	1
cell adhesion	1
postsynaptic density protein 95 clustering	1
regulation of protein localization to membrane	1
regulation of postsynaptic density organization	1
positive regulation of transport	1
synaptic vesicle clustering	1
regulation of synaptic vesicle clustering	1
positive regulation of cell growth	1
regulation of axon extension	1
positive regulation of developmental growth	1
axon extension	1
positive regulation of axonogenesis	1
nucleic acid binding	1
metal ion binding	1
kinase binding	1
phosphatase binding	1
cell adhesion molecule binding	1
binding	1
cation binding	1
intracellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
anchoring junction	1
intercalated disc	1
cell-substrate junction	1
cell-cell contact zone	1
basal plasma membrane	1
apical part of cell	1
extrinsic component of plasma membrane	1
plasma membrane protein complex	1
cell leading edge	1
neuron projection	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 13 of 60 annotations. The rest are phylogenetic / computational / electronic (IEA).

13 experimentally-supported GO terms:

GO term	NS	Evidence
cell-cell adhesion	BP	mutant phenotype
adherens junction	CC	direct assay
catenin complex	CC	direct assay
cell junction	CC	direct assay
cell-cell junction	CC	direct assay
cytoplasm	CC	direct assay
extracellular matrix	CC	high-throughput assay
focal adhesion	CC	high-throughput assay
lamellipodium	CC	direct assay
plasma membrane	CC	direct assay
alpha-catenin binding	MF	physical interaction
beta-catenin binding	MF	physical interaction
gamma-catenin binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 4,854 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDH2	CTNNB1	P35222	925
CDH2	SNAI1	O95863	918
CDH2	SNAI2	O43623	882
CDH2	ZEB1	P37275	881
CDH2	FN1	P02751	803
CDH2	TGFB1	P01137	795
CDH2	TWIST1	Q15672	793
CDH2	GAPDH	P00354	776
CDH2	VIM	P08670	770
CDH2	MMP9	P14780	770
CDH2	ZEB2	O60315	769
CDH2	CDH1	P12830	760
CDH2	TJP1	Q07157	760
CDH2	AKT1	P31749	757
CDH2	ACTB	P02570	755

IntAct

Human interaction partners of CDH2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

20 partners by confidence:

Partner	Interaction type	MIscore	Records
CTNNB1	physical association	0.930	6
FCER2	direct interaction	0.600	3
JUP	association	0.560	2
CTNND1	physical association	0.560	1
FAM20C	phosphorylation reaction	0.440	1
EXOC5	physical association	0.370	1
ARVCF	association	0.350	1
LRRC8B	association	0.350	1
PRKAR1A	physical association	0.000	1
PTPN12	dephosphorylation reaction	0.000	1
PTPN22	dephosphorylation reaction	0.000	1
PTPN6	dephosphorylation reaction	0.000	1
PTPN7	dephosphorylation reaction	0.000	1
PTPRB	dephosphorylation reaction	0.000	1
PTPRC	dephosphorylation reaction	0.000	1
PTPRG	dephosphorylation reaction	0.000	1
PTPRJ	dephosphorylation reaction	0.000	1
PTPRK	dephosphorylation reaction	0.000	1
PTPRO	dephosphorylation reaction	0.000	1
PTPRR	dephosphorylation reaction	0.000	1

BioGRID (190 interactions; top human partners by supporting records): CTNNB1 (Affinity Capture-Western; 18 records), CTNND1 (Affinity Capture-MS; 7 records), CTNNA1 (Affinity Capture-MS; 6 records), FBXO45 (Affinity Capture-MS; 4 records), JUP (Affinity Capture-MS; 4 records), DDR2 (Affinity Capture-Western; 3 records), EGFR (Affinity Capture-Western; 3 records), ERBB2 (Affinity Capture-Western; 3 records), CDH11 (Affinity Capture-MS; 2 records), CLEC4D (Affinity Capture-MS; 2 records), CREBBP (Affinity Capture-Western; 2 records), CTNNA3 (Affinity Capture-MS; 2 records), DPP4 (Affinity Capture-MS; 2 records), FGFR1 (Affinity Capture-Western; 2 records), HPCAL1 (Affinity Capture-Western; 2 records)

SIGNOR signaling

showing 17 of 20 signaling interactions:

A	Effect	B	Mechanism
SRC	down-regulates	CDH2	phosphorylation
CDH2	up-regulates	CDON	binding
CDH2	up-regulates	CDON/SPAG9	binding
CTNND1	“up-regulates quantity by stabilization”	CDH2	binding
ARVCF	“up-regulates quantity by stabilization”	CDH2	binding
CTNND2	“up-regulates quantity by stabilization”	CDH2	binding
calcium(2+)	“up-regulates activity”	CDH2	“chemical activation”
CDH2	“up-regulates activity”	CTNNB1	binding
hsa-mir-494-3p	“down-regulates quantity by repression”	CDH2	“post transcriptional regulation”
hsa-miR-338-3p	“down-regulates quantity by repression”	CDH2	“post transcriptional regulation”
hsa-miR-148a-3p	“down-regulates quantity by repression”	CDH2	“post transcriptional regulation”
TWIST1	“up-regulates quantity by expression”	CDH2	“transcriptional regulation”
CDH2	up-regulates	Epithelial-mesenchymal_transition
LEF1	“up-regulates quantity by expression”	CDH2	“transcriptional regulation”
TCF7	“up-regulates quantity by expression”	CDH2	“transcriptional regulation”
CDH4	“down-regulates quantity by repression”	CDH2
NEXMIF	“up-regulates quantity by expression”	CDH2	“transcriptional regulation”

Protein complexes (CORUM) (1)

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

1 complexes by size:

Complex	Subunits	Members
DLL1-CTNNB1-CDH2 complex	3	CDH2, CTNNB1, DLL1

Ligand–receptor pairs (CellPhoneDB) (2)

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

2 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
FCER2	ligand	Adhesion by Cadherin
CDH2	ligand	Adhesion by Cadherin

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neutrophil degranulation	5	6.8×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein dephosphorylation	8	88.7×	6e-12
negative regulation of cell population proliferation	5	10.5×	3e-03

Disease & clinical

Genetic variants

Variant evidence for CDH2: 1,206 ClinVar records (21 pathogenic / likely pathogenic); 2 PharmGKB clinical annotations; 77 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,206 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	12
Uncertain significance	630
Likely benign	430
Benign	37

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 21 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
804251	NM_001792.5(CDH2):c.2027A>G (p.Tyr676Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
805762	NM_001792.5(CDH2):c.1839C>G (p.Cys613Trp)	Pathogenic	criteria provided, single submitter	2
2663233	NM_001792.5(CDH2):c.1208_1209dup (p.Thr404Ter)	Pathogenic	criteria provided, single submitter	1
3075674	NM_001792.5(CDH2):c.1159-1G>A	Pathogenic	criteria provided, single submitter	1
3342458	NM_001792.5(CDH2):c.1344+1G>C	Pathogenic	criteria provided, single submitter	1
805765	NM_001792.5(CDH2):c.2564_2567dup (p.Leu856fs)	Likely pathogenic	criteria provided, single submitter	4
805758	NM_001792.5(CDH2):c.1057G>A (p.Asp353Asn)	Likely pathogenic	criteria provided, single submitter	3
1695977	NM_001792.5(CDH2):c.448C>T (p.His150Tyr)	Likely pathogenic	criteria provided, single submitter	2
545108	NM_001792.5(CDH2):c.2075A>G (p.Asn692Ser)	Likely pathogenic	criteria provided, single submitter	1
1723671	NM_001792.5(CDH2):c.1344+5G>A	Likely pathogenic	criteria provided, single submitter	1
2443606	NM_001792.5(CDH2):c.345G>A (p.Trp115Ter)	Likely pathogenic	criteria provided, single submitter	1
2446624	NM_001792.5(CDH2):c.172+2T>C	Likely pathogenic	criteria provided, single submitter	1
2683877	NM_001792.5(CDH2):c.1805C>G (p.Ala602Gly)	Likely pathogenic	criteria provided, single submitter	1
3378101	NM_001792.5(CDH2):c.1321G>T (p.Asp441Tyr)	Likely pathogenic	criteria provided, single submitter	1
4755526	NM_001792.5(CDH2):c.1879G>C (p.Asp627His)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CDH2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 1,699):

Position(s)	Effect	Δscore	Sites
18:27963522	acceptor_gain	1.0000
18:27963522–27963523	acceptor_loss	1.0000	4
18:27982942–27982943	donor_loss	1.0000	5
18:27983085	acceptor_loss	1.0000	3
18:27983088	acceptor_gain	1.0000
18:27984998–27984999	donor_loss	1.0000	4
18:27985234–27985235	acceptor_loss	1.0000	4
18:27985238	acceptor_gain	1.0000
18:27985526–27985527	donor_loss	1.0000	5
18:27985762–27985763	acceptor_loss	1.0000	6

AlphaMissense

2,627 missense substitutions predicted likely pathogenic (of 5,972 scored), across 592 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:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D853	8	0.999	1.000
N261	8	0.998	1.000
D262	8	0.998	1.000
D782	8	0.998	1.000
D259	8	0.997	0.999
D293	8	0.997	0.998
D295	8	0.997	0.999
D684	8	0.997	0.999
D768	8	0.997	1.000
D786	8	0.997	1.000
D353	8	0.995	0.999
D629	8	0.995	0.999
D409	8	0.994	0.999
D627	8	0.994	0.998
D859	8	0.994	0.999
F894	8	0.994	1.000
D846	8	0.992	0.999
F858	8	0.991	1.000
D407	8	0.990	0.998
D784	8	0.990	0.998

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme)

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	7.16e-05

Disease associations

OMIM: gene MIM:114020 | disease phenotypes: MIM:618920, MIM:618929, MIM:619957, MIM:609129, MIM:108010, MIM:217990

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
arrhythmogenic right ventricular dysplasia, familial, 14	Strong	Autosomal dominant	3
agenesis of corpus callosum, cardiac, ocular, and genital syndrome	Strong	Autosomal dominant	3
arrhythmogenic right ventricular cardiomyopathy	Limited	Autosomal dominant	2

ClinGen Gene-Disease Validity

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

3 validity classifications:

Disease	Classification	Inheritance
agenesis of corpus callosum, cardiac, ocular, and genital syndrome	Definitive	AD
dilated cardiomyopathy	Limited	AD
arrhythmogenic right ventricular cardiomyopathy	Limited	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (15 panels, 11 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

15 panels:

Panel	Rating
Cerebral malformation	green
DDG2P	green
Dilated and arrhythmogenic cardiomyopathy	green
Fetal anomalies	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Malformations of cortical development	green
Paediatric disorders	green
Paediatric disorders - additional genes	green
Paediatric or syndromic cardiomyopathy	green
Arrhythmogenic right ventricular cardiomyopathy	amber
Structural eye disease	amber
Sudden unexplained death or survivors of a cardiac event	amber
Unexplained death in infancy and sudden unexplained death in childhood	amber

Mondo (7): arrhythmogenic right ventricular dysplasia, familial, 14 (MONDO:0030062), agenesis of corpus callosum, cardiac, ocular, and genital syndrome (MONDO:0030065), attention deficit-hyperactivity disorder 8 (MONDO:0859261), auditory neuropathy (MONDO:0021944), arteriovenous malformations of the brain (MONDO:0007154), corpus callosum, agenesis of (MONDO:0009022), arrhythmogenic right ventricular cardiomyopathy (MONDO:0016587)

Orphanet (2): Brain arteriovenous malformation (Orphanet:46724), Isolated corpus callosum agenesis (Orphanet:200)

HPO phenotypes

showing 60 of 63 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000256	Macrocephaly
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000391	Thickened helices
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0000659	Peters anomaly
HP:0000664	Synophrys
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000912	Sprengel anomaly
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001335	Bimanual synkinesia
HP:0001651	Dextrocardia
HP:0001680	Coarctation of aorta
HP:0001962	Palpitations
HP:0002007	Frontal bossing
HP:0002162	Low posterior hairline
HP:0002194	Delayed gross motor development
HP:0002280	Enlarged cisterna magna
HP:0002384	Focal impaired awareness seizure
HP:0002558	Supernumerary nipple
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0004756	Ventricular tachycardia
HP:0005133	Right ventricular dilatation
HP:0005180	Tricuspid regurgitation
HP:0005280	Depressed nasal bridge
HP:0006682	Premature ventricular contraction
HP:0006695	Atrioventricular canal defect
HP:0007018	Attention deficit hyperactivity disorder
HP:0007165	Periventricular heterotopia
HP:0008765	Auditory hallucination
HP:0008936	Axial hypotonia
HP:0010862	Delayed fine motor development
HP:0011220	Prominent forehead
HP:0011342	Mild global developmental delay
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0011713	Left bundle branch block
HP:0012469	Infantile spasms
HP:0031972	Presyncope
HP:0032327	Interhemispheric cyst
HP:0033105	Interhypothalamic adhesion

GWAS associations

showing 30 of 77 associations:

Study	Trait	p-value
GCST010796_3620	Electrocardiogram morphology (amplitude at temporal datapoints)	7e-21
GCST010796_3440	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-20
GCST010796_2226	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-20
GCST010796_2230	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-20
GCST010796_2235	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-20
GCST010796_3442	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-20
GCST010796_2231	Electrocardiogram morphology (amplitude at temporal datapoints)	7e-20
GCST010796_2229	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-19
GCST010796_2232	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-19
GCST010796_2234	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-19
GCST010796_2227	Electrocardiogram morphology (amplitude at temporal datapoints)	8e-19
GCST010796_2237	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-18
GCST010796_2228	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-18
GCST010796_2233	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-18
GCST010796_2238	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-18
GCST010796_2240	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-18
GCST010796_2239	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-18
GCST010796_2236	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-17
GCST010796_3434	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-17
GCST010796_3435	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-17
GCST010796_3438	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-17
GCST010796_3437	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-17
GCST010796_2241	Electrocardiogram morphology (amplitude at temporal datapoints)	9e-17
GCST010796_3432	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-16
GCST010796_3431	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-16
GCST010796_3436	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-16
GCST010796_2242	Electrocardiogram morphology (amplitude at temporal datapoints)	5e-16
GCST010796_3439	Electrocardiogram morphology (amplitude at temporal datapoints)	7e-16
GCST010796_2243	Electrocardiogram morphology (amplitude at temporal datapoints)	9e-16
GCST010002_362	Refractive error	2e-15

EFO canonical traits (from GWAS)

11 canonical traits:

EFO ID	Trait name
EFO:0004365	personality trait
EFO:0004730	hormone measurement
EFO:0004312	vital capacity
EFO:0004337	intelligence
EFO:0004645	response to vaccine
EFO:0007778	urinary albumin to creatinine ratio
EFO:0010517	oxalate measurement
EFO:0009695	household income
EFO:0004462	PR interval
EFO:0004327	electrocardiography
EFO:0007828	daytime rest measurement

MeSH disease descriptors

4 disease descriptors:

Descriptor	Name	Tree numbers
D061085	Agenesis of Corpus Callosum	C10.500.034; C16.131.666.034; C23.300.008
D019571	Arrhythmogenic Right Ventricular Dysplasia	C14.240.400.145; C14.280.238.028; C14.280.400.145; C16.131.240.400.145
D002538	Intracranial Arteriovenous Malformations	C10.228.140.300.520; C10.500.190.500; C14.240.850.750.295; C14.240.850.875.500; C14.907.150.295; C14.907.253.560.400; C16.131.240.850.750.295; C16.131.240.850.875.500; C16.131.666.190.500
C538268	Auditory neuropathy *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1697669 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

2 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs17446819	Efficacy	3	methadone
rs8094439	Efficacy	3	methadone

PharmGKB variants

2 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs8094439	CDH2	3	2.25	1	methadone
rs17446819	CDH2	3	2.25	1	methadone

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

3 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs8094439	methadone	Efficacy	Genotype AA is associated with increased response to methadone as compared to genotypes AG + GG.	PMID:28358908
rs17446819	methadone	Efficacy	Genotype CC is associated with increased response to methadone as compared to genotypes AA + AC.	PMID:28358908
rs1944294	glucocorticoids, methotrexate, radiotherapy	Toxicity	Genotypes AT + TT is associated with decreased bone density when exposed to glucocorticoids, methotrexate and radiotherapy in children with Precursor Cell Lymphoblastic Leukemia-Lymphoma as compared to genotype AA.	PMID:30983502

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
N-Ac-CHAVDC-NH2	IC50	5000 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.30	IC50	5000	nM	CHEMBL1689350

PubChem BioAssay actives

1 with measured affinity, of 7 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4R,7S,10S,13S,16S,19R)-19-acetamido-4-carbamoyl-16-(1H-imidazol-5-ylmethyl)-13-methyl-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicos-7-yl]acetic acid	587333: Antagonist activity at N-cadherin	ic50	5.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases reaction, increases expression, affects localization, decreases expression, increases methylation (+2 more)	14
sodium arsenite	decreases reaction, increases abundance, increases expression, decreases expression, increases reaction (+1 more)	10
Particulate Matter	increases expression, increases abundance, decreases reaction	7
Cadmium Chloride	affects localization, increases abundance, increases expression	6
Fulvestrant	decreases reaction, increases expression	5
Quercetin	affects expression, decreases expression, increases expression, decreases reaction, affects reaction	5
Valproic Acid	affects cotreatment, decreases expression, decreases methylation	5
Resveratrol	decreases expression, decreases reaction, increases expression, affects cotreatment	4
Arsenic Trioxide	decreases expression, increases expression, increases reaction, affects reaction, decreases reaction	4
Cadmium	increases expression, decreases reaction, increases abundance	4
Doxorubicin	affects cotreatment, decreases expression, increases response to substance, affects expression	4
Estradiol	decreases reaction, increases expression, affects cotreatment	4
Tobacco Smoke Pollution	decreases reaction, increases expression, increases reaction, decreases expression	4
trichostatin A	affects cotreatment, decreases expression	3
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	increases expression, increases abundance, decreases expression, decreases reaction	3
bisphenol S	increases expression, decreases reaction, affects reaction	3
Arsenic	decreases reaction, increases abundance, increases expression, affects expression, affects response to substance	3
Benzo(a)pyrene	affects cotreatment, increases expression, decreases methylation	3
Cisplatin	affects cotreatment, decreases expression, decreases response to substance, increases expression	3
Tamoxifen	affects expression, affects reaction, affects cotreatment, increases expression, decreases expression	3
Tretinoin	increases expression, decreases reaction, affects expression, decreases expression	3
Cyclosporine	decreases expression	3
Lithium Chloride	decreases reaction, increases expression, decreases expression	3
aristolochic acid I	decreases expression, increases expression	2
thymoquinone	decreases reaction, increases reaction, decreases expression	2
arsenite	increases abundance, increases expression, increases methylation, affects reaction	2
cobaltous chloride	decreases expression, increases expression	2
dictamnine	affects cotreatment, decreases expression, decreases reaction, increases expression, affects expression (+1 more)	2
andrographolide	increases expression, decreases expression, increases reaction, decreases reaction	2
cordycepin	decreases expression, affects cotreatment, increases reaction	2

ChEMBL screening assays

4 unique, capped per target: 3 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1694377	Functional	Antagonist activity at N-cadherin	Tripeptide motifs in biology: targets for peptidomimetic design. — *J Med Chem*
CHEMBL3822107	Binding	Inhibition of recombinant N-cadherin-Fc chimeric protein (unknown origin) homodimerization at 10 uM preincubated for 30 mins followed by N-cadherin-Fc addition by surface plasmon resonance analysis relative to control	Crystal Structure of Human E-Cadherin-EC1EC2 in Complex with a Peptidomimetic Competitive Inhibitor of Cadherin Homophilic Interaction. — *J Med Chem*

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2TY	Abcam HEK293T CDH2 KO	Transformed cell line	Female
CVCL_F0XP	BT-20N	Cancer cell line	Female
CVCL_SI14	HAP1 CDH2 (-) 1	Cancer cell line	Male
CVCL_XM67	HAP1 CDH2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

showing 60 of 284 trials:

NCT	Phase	Status	Title
NCT00374465	Phase 4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	Phase 4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	Phase 4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	Phase 4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	Phase 4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	Phase 4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00083772	Phase 4	TERMINATED	Use of Nesiritide in the Management of Acute Diastolic Heart Failure
NCT00146848	Phase 4	COMPLETED	PEGASUS CRT Study: Atrial Support Study in Cardiac Resynchronization Therapy
NCT00154115	Phase 4	COMPLETED	Levosimendan in High Risk Heart Valve Surgery
NCT00170313	Phase 4	TERMINATED	CORE: Study to Evaluate the Conducted AF-Response-Algorithm in Patients Suffering From Heart Failure and Atrial Fibrillation
NCT00180596	Phase 4	COMPLETED	PACMAN - PAcing for CardioMyopathies, a EuropeAN Study
NCT00187200	Phase 4	COMPLETED	Response of Cardiac Resynchronization Therapy Optimization With Ventricle to Ventricle Timing in Heart Failure Patients
NCT00206232	Phase 4	COMPLETED	Novel Treatment for Diastolic Heart Failure in Women
NCT00206856	Phase 4	TERMINATED	Rapid Assessment of Bedside BNP In Treatment of Heart Failure (RABBIT)
NCT00219388	Phase 4	COMPLETED	Efficacy and Safety of Treatment With Simdax® Versus Dobutrex® in Decompensated Heart Failure Patients.
NCT00288587	Phase 4	COMPLETED	Extracorporeal Ultrafiltration (UF) vs. Usual and Customary Care for Patients With Severe Heart Failure (HF)
NCT00305526	Phase 4	TERMINATED	REBEAT Resynchronisation and Beta-Blocker European Trial
NCT00324766	Phase 4	COMPLETED	Levosimendan in Acute Heart Failure Following Acute Myocardial Infarction.
NCT00347087	Phase 4	COMPLETED	Effect of Irbesartan on Insulin Sensitivity in Chronic Heart Failure
NCT00371085	Phase 4	COMPLETED	Congestive Heart Failure Outreach Program
NCT00384566	Phase 4	WITHDRAWN	A Comparison of the Effect of Carvedilol and Metoprolol on Airways Tone in Patients With Heart Failure
NCT00391846	Phase 4	COMPLETED	Evaluation of Heart Failure Treatment Guided by N-terminal Pro B-type Natriuretic Peptide (NTproBNP) vs Clinical Symptoms and Signs Alone
NCT00400582	Phase 4	COMPLETED	A Pharmacogenomic Study of Candesartan in Heart Failure
NCT00402376	Phase 4	TERMINATED	Evaluation of Myocardial Improvement in Patients Supported by Ventricular Assist Device Under Optimal Pharmacological Therapy
NCT00418119	Phase 4	UNKNOWN	Erythropoietin Treatment in Patients With Systolic Left Ventricular Dysfunction, Mild Anemia and Normal Renal Function
NCT00422318	Phase 4	COMPLETED	Treatment of Hyperuricemia in Patients With Heart Failure
NCT00477789	Phase 4	COMPLETED	Effects of Allopurinol on Diastolic Function in Chronic Heart Failure Patients
NCT00480077	Phase 4	TERMINATED	Diagnostic Outcome Trial in Heart Failure (DOT-HF Trial)
NCT00489177	Phase 4	COMPLETED	Optimal Programming to Improve Mechanical Indices, Symptoms and Exercise in Cardiac Resynchronization Therapy.
NCT00491907	Phase 4	TERMINATED	Effect of Folic Acid on Endothelial and Baroreceptor Function in Patients With Heart Failure
NCT00497900	Phase 4	COMPLETED	The Effect of Calcium and Vitamin D in Patients With Heart Failure
NCT00498472	Phase 4	COMPLETED	NT-proBNP in the Optimization of Treatment After Recent Acute Heart Failure Trial
NCT00512759	Phase 4	COMPLETED	Goal-directed Afterload Reduction in Acute Congestive Cardiac Decompensation Study
NCT00517426	Phase 4	COMPLETED	Effects of Acetazolamide and CO2 Inhalation on Exercise-induced Periodic Breathing in Heart Failure
NCT00517725	Phase 4	COMPLETED	Nebivolol Versus Bisoprolol Versus Carvedilol in Heart Failure
NCT00527059	Phase 4	UNKNOWN	Renal Effects of Levosimendan in Patients Admitted With Acute Decompensated Heart Failure
NCT00551499	Phase 4	COMPLETED	Cardiac Resynchronisation Therapy in Combination With Overdrive Pacing in the Treatment of Central Sleep Apnea in CHF
NCT00552851	Phase 4	UNKNOWN	Changes of Left Ventricular Mass and Cardiac Function in Patients With Active Acromegaly During Treatment With the Growth Hormone Receptor Antagonist Pegvisomant
NCT00574119	Phase 4	COMPLETED	Effect of Aldosterone on Energy Starvation in Heart Failure
NCT00613964	Phase 4	TERMINATED	The Effects of Carperitide on Short and Long-term Prognosis in Patients With Both Cardiac and Renal Failure
NCT00643188	Phase 4	COMPLETED	Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF
NCT00652652	Phase 4	COMPLETED	Evaluation of Combined Action Between Natrecor and Furosemide on Kidney and Neurohormone Responses in Chronic Heart Failure: A Phase-IV study704.351 / DSS
NCT00658203	Phase 4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00663377	Phase 4	COMPLETED	Effects of Losartan on Insulin Resistance in Patients With Heart Failure
NCT00664339	Phase 4	COMPLETED	Flu Vaccination in Congestive Heart Failure
NCT00668408	Phase 4	UNKNOWN	LTOT in COPD Patients With Moderate Chronic Hypoxemia and Chronic Heart Failure
NCT00677014	Phase 4	COMPLETED	Comparison of AV Optimization Methods Used in Cardiac Resynchronization Therapy (CRT)
NCT00692718	Phase 4	UNKNOWN	N-3 Fatty Acids for the Prevention of Atrial Fibrillation in Patients With Acute Heart Failure
NCT00701285	Phase 4	COMPLETED	South Korean Pitavastatin Heart Failure Study
NCT00711360	Phase 4	COMPLETED	Monitoring of Fluid Status in Heart Failure Patients by Intrathoracic Impedance Measurement (HomeCARE II)
NCT00729911	Phase 4	COMPLETED	Ablation vs Amiodarone for Treatment of AFib in Patients With CHF and an ICD
NCT00769457	Phase 4	COMPLETED	OptiLink HF Study: Optimization of Heart Failure Management Using Medtronic OptiVol Fluid Status Monitoring and CareLink Network
NCT00781508	Phase 4	COMPLETED	Effects of Viagra on Heart Function in Patients With Heart Failure
NCT00793338	Phase 4	WITHDRAWN	Evaluation of Sildenafil for the Treatment of Moderate Congestive Heart Failure
NCT00795912	Phase 4	COMPLETED	A Study Of The Usage Of Statins In A Community Heart Failure Population
NCT00802230	Phase 4	COMPLETED	Pharmacodynamic Study of Carvedilol Versus Metoprolol in Heart Failure
NCT00804349	Phase 4	COMPLETED	Treatment of Sleep Disordered Breathing In Acute Decompensated Heart Failure Patients
NCT00806910	Phase 4	WITHDRAWN	Diuretic and Renal Effects of Vaprisol When Administered Along With Furosemide and Nesiritide Continuous Infusion
NCT00821938	Phase 4	COMPLETED	Cardiac Resynchronization Therapy (CRT)-Narrow-dp/Dt-Study
NCT00839566	Phase 4	TERMINATED	PAF-HEFT (Permanent Atrial Fibrillation in Heart Failure Trial)