CDH4 (cadherin 4)

Gene

• Entrez ID: 1002
• Gene name: Cadherin 4
• Gene symbol: CDH4
• Synonyms (NCBI Gene): CAD4, R-CAD, RCAD
• Chromosome: 20
• Chromosome location: 20q13.33
• Summary: This gene is a classical cadherin from the cadherin superfamily. The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. B

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs765815715	G>A,C	Likely-pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT023656	hsa-miR-1-3p	Microarray	18668037
MIRT624382	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT624381	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT624380	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT624379	hsa-miR-6515-3p	HITS-CLIP	23824327
MIRT624378	hsa-miR-1236-3p	HITS-CLIP	23824327
MIRT659651	hsa-miR-570-3p	HITS-CLIP	23824327
MIRT624377	hsa-miR-623	HITS-CLIP	23824327
MIRT624376	hsa-miR-4755-5p	HITS-CLIP	23824327
MIRT624375	hsa-miR-5006-3p	HITS-CLIP	23824327
MIRT624374	hsa-miR-7111-3p	HITS-CLIP	23824327
MIRT624382	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT624381	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT624380	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT624379	hsa-miR-6515-3p	HITS-CLIP	23824327
MIRT624378	hsa-miR-1236-3p	HITS-CLIP	23824327
MIRT659651	hsa-miR-570-3p	HITS-CLIP	23824327
MIRT624377	hsa-miR-623	HITS-CLIP	23824327
MIRT624376	hsa-miR-4755-5p	HITS-CLIP	23824327
MIRT624375	hsa-miR-5006-3p	HITS-CLIP	23824327
MIRT624374	hsa-miR-7111-3p	HITS-CLIP	23824327
MIRT624382	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT624381	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT624380	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT624379	hsa-miR-6515-3p	HITS-CLIP	23824327
MIRT624378	hsa-miR-1236-3p	HITS-CLIP	23824327
MIRT624377	hsa-miR-623	HITS-CLIP	23824327
MIRT624376	hsa-miR-4755-5p	HITS-CLIP	23824327
MIRT624375	hsa-miR-5006-3p	HITS-CLIP	23824327
MIRT624374	hsa-miR-7111-3p	HITS-CLIP	23824327
MIRT624382	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT624381	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT624380	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT624379	hsa-miR-6515-3p	HITS-CLIP	23824327
MIRT624378	hsa-miR-1236-3p	HITS-CLIP	23824327
MIRT659651	hsa-miR-570-3p	HITS-CLIP	23824327
MIRT624377	hsa-miR-623	HITS-CLIP	23824327
MIRT624376	hsa-miR-4755-5p	HITS-CLIP	23824327
MIRT624375	hsa-miR-5006-3p	HITS-CLIP	23824327
MIRT624374	hsa-miR-7111-3p	HITS-CLIP	23824327
MIRT624382	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT624381	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT624380	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT624379	hsa-miR-6515-3p	HITS-CLIP	23824327
MIRT624378	hsa-miR-1236-3p	HITS-CLIP	23824327
MIRT659651	hsa-miR-570-3p	HITS-CLIP	23824327
MIRT624377	hsa-miR-623	HITS-CLIP	23824327
MIRT624376	hsa-miR-4755-5p	HITS-CLIP	23824327
MIRT624375	hsa-miR-5006-3p	HITS-CLIP	23824327
MIRT624374	hsa-miR-7111-3p	HITS-CLIP	23824327
MIRT624382	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT624381	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT624380	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT624379	hsa-miR-6515-3p	HITS-CLIP	23824327
MIRT624378	hsa-miR-1236-3p	HITS-CLIP	23824327
MIRT624377	hsa-miR-623	HITS-CLIP	23824327
MIRT624376	hsa-miR-4755-5p	HITS-CLIP	23824327
MIRT624375	hsa-miR-5006-3p	HITS-CLIP	23824327
MIRT624374	hsa-miR-7111-3p	HITS-CLIP	23824327
MIRT1921550	hsa-miR-520f	CLIP-seq
MIRT1921551	hsa-miR-548ac	CLIP-seq
MIRT1921552	hsa-miR-548ae	CLIP-seq
MIRT1921553	hsa-miR-548aj	CLIP-seq
MIRT1921554	hsa-miR-548am	CLIP-seq
MIRT1921555	hsa-miR-548d-3p	CLIP-seq
MIRT1921556	hsa-miR-548x	CLIP-seq
MIRT1921557	hsa-miR-548z	CLIP-seq
MIRT2500679	hsa-miR-148a	CLIP-seq
MIRT2500680	hsa-miR-148b	CLIP-seq
MIRT2500681	hsa-miR-152	CLIP-seq
MIRT2500682	hsa-miR-205	CLIP-seq
MIRT2500683	hsa-miR-4276	CLIP-seq
MIRT2500684	hsa-miR-515-3p	CLIP-seq
MIRT2500685	hsa-miR-519e	CLIP-seq
MIRT2500686	hsa-miR-626	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000902	Process	Cell morphogenesis	IBA
GO:0005509	Function	Calcium ion binding	IEA
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0005912	Component	Adherens junction	IBA
GO:0007043	Process	Cell-cell junction assembly	IBA
GO:0007155	Process	Cell adhesion	IEA
GO:0007155	Process	Cell adhesion	TAS	2059658
GO:0007156	Process	Homophilic cell adhesion via plasma membrane adhesion molecules	IEA
GO:0007156	Process	Homophilic cell adhesion via plasma membrane adhesion molecules	IEA
GO:0007157	Process	Heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules	IEA
GO:0007411	Process	Axon guidance	IEA
GO:0008013	Function	Beta-catenin binding	IBA
GO:0016020	Component	Membrane	IEA
GO:0016339	Process	Calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules	IBA
GO:0016342	Component	Catenin complex	IBA
GO:0016477	Process	Cell migration	IBA
GO:0034332	Process	Adherens junction organization	IBA
GO:0044331	Process	Cell-cell adhesion mediated by cadherin	IBA
GO:0045296	Function	Cadherin binding	IBA
GO:0045773	Process	Positive regulation of axon extension	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0048675	Process	Axon extension	IEA
GO:0098609	Process	Cell-cell adhesion	IEA

Other IDs

• MIM: 603006
• HGNC: 1763
• e!Ensembl: ENSG00000179242

Protein

• UniProt ID: P55283
• Protein name: Cadherin-4 (Retinal cadherin) (R-CAD) (R-cadherin)
• Protein 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. May play an important role
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08758	Cadherin_pro	30 → 120	Cadherin prodomain like	Domain
  PF00028	Cadherin	174 → 268	Cadherin domain	Domain
  PF00028	Cadherin	282 → 383	Cadherin domain	Domain
  PF00028	Cadherin	397 → 499	Cadherin domain	Domain
  PF00028	Cadherin	512 → 606	Cadherin domain	Domain
  PF01049	Cadherin_C	760 → 913	Cadherin cytoplasmic region	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed mainly in brain but also found in other tissues.
• Sequence:

  MTAGAGVLLLLLSLSGALRAHNEDLTTRETCKAGFSEDDYTALISQNILEGEKLLQVKFS
  SCVGTKGTQYETNSMDFKVGADGTVFATRELQVPSEQVAFTVTAWDSQTAEKWDAVVRLL
  VAQTSSPHSGHKPQKGKKVVALDPSPPPKDTLLPWPQHQNANGLRRRKRDWVIPPINVPE
  NSRGPFPQQLVRIRSDKDNDIPIRYSITGVGADQPPMEVFSIDSMSGRMYVTRPMDREEH
  ASYHLRAHAVDMNGNKVENPIDLYIYVIDMNDNRPEFINQVYNGSVDEGSKPGTYVMTVT
  ANDADDSTTANGMVRYRIVTQTPQSPSQNMFTINSETGDIVTVAAGLDREKVQQYTVIVQ
  ATDMEGNLNYGLSNTATAIITVTDVNDNPPEFTASTFAGEVPENRVETVVANLTVMDRDQ
  PHSPNWNAVYRIISGDPSGHFSVRTDPVTNEGMVTVVKAVDYELNRAFMLTVMVSNQAPL
  ASGIQMSFQSTAGVTISIMDINEAPYFPSNHKLIRLEEGVPPGTVLTTFSAVDPDRFMQQ
  AVRYSKLSDPASWLHINATNGQITTAAVLDRESLYTKNNVYEATFLAADNGIPPASGTGT
  LQIYLIDINDNAPELLPKEAQICEKPNLNAINITAADADVDPNIGPYVFELPFVPAAVRK
  NWTITRLNGDYAQLSLRILYLEAGMYDVPIIVTDSGNPPLSNTSIIKVKVCPCDDNGDCT
  TIGAVAAAGLGTGAIVAILICILILLTMVLLFVMWMKRREKERHTKQLLIDPEDDVRDNI
  LKYDEEGGGEEDQDYDLSQLQQPEAMGHVPSKAPGVRRVDERPVGAEPQYPIRPMVPHPG
  DIGDFINEGLRAADNDPTAPPYDSLLVFDYEGSGSTAGSVSSLNSSSSGDQDYDYLNDWG
  PRFKKLADMYGGGEED

• Sequence length: 916

Pathways

KEGG:

Cell adhesion molecules

Reactome:

Adherens junctions interactions
Myogenesis

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormal brain morphology	Likely pathogenic	rs765815715	RCV000454293	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CDH4-associated disorder of corticaldevelopment	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CDH4-related disorder	Uncertain significance; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CENTRAL NERVOUS SYSTEM CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLOR VISION DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONNECTIVE TISSUE DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GASTROESOPHAGEAL REFLUX DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOBLASTOMA MULTIFORME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL OR BEHAVIOURAL DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MIGRAINE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MIXED CONNECTIVE TISSUE DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MULTIPLE SYSTEM ATROPHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neurodevelopmental disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBSTRUCTIVE SLEEP APNEA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PEPTIC ULCER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSYCHOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RESTLESS LEGS SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Simplified gyral pattern	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TREATMENT-RESISTANT HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenoid Cystic Carcinoma	Adenocarcinoma	BEFREE	27783992		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	31489987		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	33899544	Associate	★☆☆☆☆ Found in Text Mining only
Bronchopulmonary Dysplasia	Bronchopulmonary dysplasia	Pubtator	39988826	Inhibit	★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	15548679		★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	28095912		★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	32511216	Associate	★☆☆☆☆ Found in Text Mining only
Cleft Palate	Cleft palate	Pubtator	35191549	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	24980446		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	24980446	Associate	★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	BEFREE	29924371		★☆☆☆☆ Found in Text Mining only
Darier Disease	Darier disease	Pubtator	37496039	Associate	★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	32473611	Associate	★☆☆☆☆ Found in Text Mining only
Gastrointestinal Neoplasms	Gastrointestinal Neoplasms	BEFREE	15548679		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	31426573		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	BEFREE	31426573		★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	GWASCAT_DG	26252872		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	27765630		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	28095912	Inhibit	★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	27029387	Inhibit	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	31489987		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	28095912		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	15548679		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	15548679, 27783992, 31426573		★☆☆☆☆ Found in Text Mining only
Mouth Diseases	Mouth disease	Pubtator	32473611	Associate	★☆☆☆☆ Found in Text Mining only
Multiple System Atrophy	Multiple system atrophy	Pubtator	38143373	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nasopharyngeal carcinoma	Nasopharyngeal Carcinoma	BEFREE	21665361		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	15548679, 21665361, 27783992, 28095912, 29610525		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	BEFREE	29610525, 29805751		★☆☆☆☆ Found in Text Mining only
Otofaciocervical Syndrome	Otofaciocervical syndrome	Pubtator	35191549	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	27749787	Associate	★☆☆☆☆ Found in Text Mining only
Renal Insufficiency	Renal Insufficiency	BEFREE	29873499		★☆☆☆☆ Found in Text Mining only
Sarcoidosis	Sarcoidosis	GWASDB_DG	19165924		★☆☆☆☆ Found in Text Mining only
Sleep Apnea, Obstructive	Sleep Apnea	GWASCAT_DG	26977737		★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	15548679		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	27029387	Associate	★☆☆☆☆ Found in Text Mining only
Stroke	Stroke	Pubtator	17903297	Associate	★☆☆☆☆ Found in Text Mining only