CDH4 cadherin 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CDH4provided by HGNC
Official Full Name: cadherin 4provided by HGNC
Primary source: HGNC:HGNC:1763
See related: Ensembl:ENSG00000179242 MIM:603006; AllianceGenome:HGNC:1763
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CAD4; RCAD; R-CAD
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. Based on studies in chicken and mouse, this cadherin is thought to play an important role during brain segmentation and neuronal outgrowth. In addition, a role in kidney and muscle development is indicated. Of particular interest are studies showing stable cis-heterodimers of cadherins 2 and 4 in cotransfected cell lines. Previously thought to interact in an exclusively homophilic manner, this is the first evidence of cadherin heterodimerization. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
Expression: Biased expression in spleen (RPKM 3.2), brain (RPKM 3.1) and 6 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 20q13.33

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	20	NC_000020.11 (61252261..61940617)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	20	NC_060944.1 (63037438..63731679)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	20	NC_000020.10 (59827317..60515673)

Chromosome 20 - NC_000020.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Cytosolic Cadherin 4 promotes angiogenesis and metastasis in papillary thyroid cancer by suppressing the ubiquitination/degradation of beta-catenin.
Title: Cytosolic Cadherin 4 promotes angiogenesis and metastasis in papillary thyroid cancer by suppressing the ubiquitination/degradation of β-catenin.
Understanding the Role of CDH4 in Multiple System Atrophy Brain.
Title: Understanding the Role of CDH4 in Multiple System Atrophy Brain.
CDH4 inhibits ferroptosis in oral squamous cell carcinoma cells.
Title: CDH4 inhibits ferroptosis in oral squamous cell carcinoma cells.
Alu Deletions in LAMA2 and CDH4 Genes Are Key Components of Polygenic Predictors of Longevity.
Title: Alu Deletions in LAMA2 and CDH4 Genes Are Key Components of Polygenic Predictors of Longevity.
Cadherin switches during epithelial-mesenchymal transition: CDH4/RCAD downregulation reduces bladder cancer progression.
Title: Cadherin switches during epithelial-mesenchymal transition: CDH4/RCAD downregulation reduces bladder cancer progression.
Regulatory CDH4 Genetic Variants Associate With Risk to Develop Capecitabine-Induced Hand-Foot Syndrome.
Title: Regulatory CDH4 Genetic Variants Associate With Risk to Develop Capecitabine-Induced Hand-Foot Syndrome.
Expression and Prognostic Significance of Cadherin 4 (CDH4) in Renal Cell Carcinoma.
Title: Expression and Prognostic Significance of Cadherin 4 (CDH4) in Renal Cell Carcinoma.
Cdh4 regulates cell proliferation, cell migration and tumorigenic potential of patient derived glioblastoma cells.
Title: Cdh4 Down-Regulation Impairs in Vivo Infiltration and Malignancy in Patients Derived Glioblastoma Cells.
High CDH4 expression is associated with triple-negative breast cancer.
Title: Identification of CHD4-β1 integrin axis as a prognostic marker in triple-negative breast cancer using next-generation sequencing and bioinformatics.
CDH4 overexpression activates c-Jun via the JNK pathway, while CDH4 knockdown suppresses both tumor xenograft growth and lung colonization.
Title: CDH4 is a novel determinant of osteosarcoma tumorigenesis and metastasis.

Submit: New GeneRIF Correction See all GeneRIFs (23)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham Study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic determinants of plasma &#x003b2;&#x02082;-glycoprotein I levels: a genome-wide association study in extended pedigrees from Spain. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association reveals genetic effects on human A&#x003b2;42 and &#x003c4; protein levels in cerebrospinal fluids: a case control study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of a heart failure related metabolomic profile among African Americans in the Atherosclerosis Risk in Communities (ARIC) study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of bipolar disorder accounting for effect of body mass index identifies a new risk allele in TCF7L2. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies new susceptibility loci for migraine. EBI GWAS Catalog EBI GWAS CatalogPubMed
GWAS for discovery and replication of genetic loci associated with sudden cardiac arrest in patients with coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Joint influence of small-effect genetic variants on human longevity. EBI GWAS Catalog EBI GWAS CatalogPubMed
Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Z94692 (e-PCR)
- UniSTS:16659

Z94350 (e-PCR)
- UniSTS:75050

Z94484 (e-PCR)
- UniSTS:69935

GDB:314889 (e-PCR)
- UniSTS:156498

SHGC-149017 (e-PCR)
- UniSTS:176743

RH76588 (e-PCR)
- UniSTS:83832

Z94494 (e-PCR)
- UniSTS:54396

Z94317 (e-PCR)
- UniSTS:12415

D1S513 (e-PCR)
- UniSTS:13953

SHGC-106055 (e-PCR)
- UniSTS:169607

G13391 (e-PCR)
- UniSTS:61066

SHGC-148162 (e-PCR)
- UniSTS:172942

RH65523 (e-PCR)
- UniSTS:75414

SHGC-146884 (e-PCR)
- UniSTS:172707

SHGC-147401 (e-PCR)
- UniSTS:175791

D13S707 (e-PCR)
- UniSTS:43219

SHGC-148547 (e-PCR)
- UniSTS:173023

Z94541 (e-PCR)
- UniSTS:75237

Z94684 (e-PCR)
- UniSTS:12775

SHGC-84661 (e-PCR)
- UniSTS:103148

Clone Names

FLJ22202, FLJ40547, MGC126700, MGC138355

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables beta-catenin binding	IBA Inferred from Biological aspect of Ancestor more info
enables cadherin binding	IBA Inferred from Biological aspect of Ancestor more info
enables calcium ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in adherens junction organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in axon extension	IEA Inferred from Electronic Annotation more info
involved_in axon guidance	IEA Inferred from Electronic Annotation more info
involved_in calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell adhesion	TAS Traceable Author Statement more info	PubMed
involved_in cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-cell adhesion mediated by cadherin	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell-cell junction assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules	IEA Inferred from Electronic Annotation more info
involved_in homophilic cell adhesion via plasma membrane adhesion molecules	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of axon extension	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in adherens junction	IBA Inferred from Biological aspect of Ancestor more info
part_of catenin complex	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: cadherin-4

Names: R-cadherin; cadherin 4, type 1, R-cadherin (retinal); cadherin 4, type 1, preproprotein; retinal cadherin

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001252338.2 → NP_001239267.1 cadherin-4 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) has an alternate exon in place of the first two exons compared to variant 1, and the alternate exon has an in-frame translation start site. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 1.

Source sequence(s)

AA213385, AK308345, AL109911, AL162457, KF511320

UniProtKB/TrEMBL

B2RCN5

Conserved Domains (4) summary

cd11304
Location:244 → 351

Cadherin_repeat; Cadherin tandem repeat domain

pfam01049
Location:732 → 874

Cadherin_C; Cadherin cytoplasmic region

cl07391
Location:20 → 82

Cadherin_pro; Cadherin prodomain like

cl09101
Location:136 → 236

E_set; Early set domain associated with the catalytic domain of sugar utilizing enzymes at either the N or C terminus
NM_001252339.3 → NP_001239268.1 cadherin-4 isoform 3

See identical proteins and their annotated locations for NP_001239268.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) has an alternate exon in place of the first two exons compared to variant 1, but the alternate exon does not have an in-frame translation start site. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AA213385, AK124724, AL109911, AL162457, DC330816, KF511320

Consensus CDS

CCDS58784.1

UniProtKB/TrEMBL

A0A087WX99

Related

ENSP00000443301.1, ENST00000543233.2

Conserved Domains (4) summary

cd11304
Location:207 → 314

Cadherin_repeat; Cadherin tandem repeat domain

pfam01049
Location:695 → 837

Cadherin_C; Cadherin cytoplasmic region

cl07391
Location:2 → 45

Cadherin_pro; Cadherin prodomain like

cl09101
Location:99 → 199

E_set; Early set domain associated with the catalytic domain of sugar utilizing enzymes at either the N or C terminus
NM_001794.5 → NP_001785.2 cadherin-4 isoform 1 preproprotein

See identical proteins and their annotated locations for NP_001785.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AA213385, AL109911, AL365229, BC101651, KF511320

Consensus CDS

CCDS13488.1

UniProtKB/Swiss-Prot

B3KWB8, G3V1P8, P55283, Q2M208, Q5VZ44, Q9BZ05

UniProtKB/TrEMBL

B2RCN5

Related

ENSP00000484928.1, ENST00000614565.5

Conserved Domains (4) summary

cd11304
Location:281 → 388

Cadherin_repeat; Cadherin tandem repeat domain

pfam01049
Location:769 → 911

Cadherin_C; Cadherin cytoplasmic region

pfam08758
Location:30 → 119

Cadherin_pro; Cadherin prodomain like

cl09101
Location:173 → 273

E_set; Early set domain associated with the catalytic domain of sugar utilizing enzymes at either the N or C terminus