CDH5
protein-codingcadherin 5, the group of CD molecules|Type II classical cadherins
Gene summary
This gene encodes a classical cadherin of the cadherin superfamily. The encoded preproprotein is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion molecule is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Functioning as a classical cadherin by imparting to cells the ability to adhere in a homophilic manner, this protein plays a role in endothelial adherens junction assembly and maintenance. This gene is located in a gene cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. [provided by RefSeq, Nov 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~38.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CDH5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001795.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 140 | 11 | 151 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 140 | 12 | 1 | 153 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001786.2 | 11 | MANE Select | |
| Ensembl | ENSP00000344115.3 | 11 | MANE Select | |
| Ensembl | ENSP00000461880.1 | 2 | Standard | |
| Ensembl | ENSP00000461880.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cdh5 | Danio rerio | Structure: nucleate erythrocyte Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
- Fluid shear stress and atherosclerosis - Homo sapiens (human)
- Leukocyte transendothelial migration - Homo sapiens (human)
- VEGFA-VEGFR2 Signaling Pathway
- Signal Transduction
Biological Process
- cell morphogenesis
- blood vessel maturation
- cell-cell junction assembly
- homophilic cell adhesion via plasma membrane adhesion molecules
- transforming growth factor beta receptor signaling pathway
Molecular Function
- signaling receptor binding
- calcium ion binding
- protein binding
- beta-catenin binding
- cytoskeletal protein binding
Cellular Component
- plasma membrane
- cell-cell junction
- cell-cell adherens junction
- bicellular tight junction
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000341529
- Coding exons
- 11
- Length
- 38154
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 125748
- p
- 0.0000756
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.518 | 479 | 512 | 0.936 | 0.0000344 | 5138 |
| Missense (PolyPhen) | 155 | 184.65 | 0.8394 | 1984 | ||
| Synonymous | -0.515 | 240 | 230 | 1.04 | 0.0000184 | 1567 |
| Loss of Function | 4.15 | 7 | 32.6 | 0.215 | 0.00000184 | 345 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00013 | 0.00012 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. This cadherin may play a important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions. It associates with alpha-catenin forming a link to the cytoskeleton. Acts in concert with KRIT1 to establish and maintain correct endothelial cell polarity and vascular lumen. These effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for activation of PRKCZ and for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction. {ECO:0000269|PubMed:20332120, ECO:0000269|PubMed:21269602}.;
Recessive Scores
- pRec
- 0.222
Intolerance Scores
- LoFtool
- 0.498
- RVIS EVS
- -1.06
- RVIS percentile EVS
- 7.58
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.713
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |