CDH6
protein-codingcadherin 6, the group of Type II classical cadherins
Gene summary
This gene encodes a member of the cadherin superfamily. Cadherins are membrane glycoproteins that mediate homophilic cell-cell adhesion and play critical roles in cell differentiation and morphogenesis. The encoded protein is a type II cadherin and may play a role in kidney development as well as endometrium and placenta formation. Decreased expression of this gene may be associated with tumor growth and metastasis. [provided by RefSeq, May 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~135.5 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 CDH6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004932.4. 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 | ||||
| missense | 71 | 2 | 73 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 78 | 2 | 0 | 80 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004923.1 | 11 | MANE Select | |
| Ensembl | ENSP00000265071.2 | 11 | MANE Select | |
| RefSeq | NP_001349364.1 | 10 | Standard | |
| Ensembl | ENSP00000424843.1 | 10 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cdh6 | Danio rerio | Structure: eye photoreceptor cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neural Crest Differentiation
- Ectoderm Differentiation
- TGF-B Signaling in Thyroid Cells for Epithelial-Mesenchymal Transition
- Cell-cell junction organization
- Adherens junctions interactions
Biological Process
- cell morphogenesis
- cell-cell junction assembly
- cell adhesion
- homophilic cell adhesion via plasma membrane adhesion molecules
- Notch signaling pathway
Molecular Function
- calcium ion binding
- cytoskeletal protein binding
- protein homodimerization activity
- cadherin binding
Cellular Component
- plasma membrane
- cell-cell adherens junction
- cell surface
- integral component of membrane
- catenin complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000265071
- Coding exons
- 11
- Length
- 135397
- Individuals with no LoFs
- 125736
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125747
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.39 | 308 | 451 | 0.684 | 0.0000249 | 5185 |
| Missense (PolyPhen) | 128 | 192.39 | 0.66532 | 2169 | ||
| Synonymous | 0.583 | 171 | 181 | 0.945 | 0.0000116 | 1552 |
| Loss of Function | 4.74 | 7 | 38.9 | 0.180 | 0.00000252 | 404 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0 | 0.0 | absent |
| 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.;
Recessive Scores
- pRec
- 0.0817
Intolerance Scores
- LoFtool
- 0.386
- RVIS EVS
- -1.31
- RVIS percentile EVS
- 4.85
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.668
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |