PCDH8
protein-codingprotocadherin 8, the group of Non-clustered protocadherins
Gene summary
This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The gene encodes an integral membrane protein that is thought to function in cell adhesion in a CNS-specific manner. Unlike classical cadherins, which are generally encoded by 15-17 exons, this gene includes only 3 exons. Notable is the large first exon encoding the extracellular region, including 6 cadherin domains and a transmembrane region. Alternative splicing yields isoforms with unique cytoplasmic tails. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.8 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 PCDH8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002590.4. 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 | 4 | 3 | 7 | |||
| missense | 161 | 4 | 3 | 168 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 161 | 8 | 6 | 175 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002581.2 | 3 | MANE Select | |
| Ensembl | ENSP00000367177.3 | 3 | MANE Select | |
| RefSeq | NP_116567.1 | 3 | Standard | |
| Ensembl | ENSP00000341350.4 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| pcdh8 | Danio rerio | Structure: pronephros Quality: cystic abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- somitogenesis
- cell adhesion
- homophilic cell adhesion via plasma membrane adhesion molecules
- cell-cell signaling
- chemical synaptic transmission
Molecular Function
- calcium ion binding
Cellular Component
- plasma membrane
- integral component of plasma membrane
- cell junction
- dendrite
- presynaptic membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000377942
- Coding exons
- 3
- Length
- 4667
- Individuals with no LoFs
- 125700
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 48
- Defined
- 125748
- p
- 0.000191
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.90 | 439 | 567 | 0.775 | 0.0000293 | 6634 |
| Missense (PolyPhen) | 87 | 156.15 | 0.55714 | 1836 | ||
| Synonymous | 0.581 | 244 | 256 | 0.954 | 0.0000141 | 2383 |
| Loss of Function | 2.26 | 11 | 22.6 | 0.487 | 9.77e-7 | 260 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000063 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00013 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000054 | 0.000053 | rare |
| South Asian | 0.0012 | 0.0012 | notable |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Calcium-dependent cell-adhesion protein (By similarity). May play a role in activity-induced synaptic reorganization underlying long term memory (By similarity). Could be involved in CDH2 internalization through TAOK2/p38 MAPK pathway. In hippocampal neurons, may play a role in the down-regulation of dendritic spines, maybe through its action on CDH2 endocytosis (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.173
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.442
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |