PCDHA8
protein-codingprotocadherin alpha 8, the group of Clustered protocadherins
Gene summary
This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [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 ~171.2 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 PCDHA8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018911.3. 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 | 5 | 1 | 6 | |||
| missense | 168 | 18 | 186 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 168 | 23 | 1 | 192 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_061734.1 | 4 | MANE Select | |
| Ensembl | ENSP00000434655.1 | 4 | MANE Select | |
| RefSeq | NP_114062.1 | 1 | Standard | |
| Ensembl | ENSP00000367363.3 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cell adhesion
- homophilic cell adhesion via plasma membrane adhesion molecules
- nervous system development
Molecular Function
- calcium ion binding
Cellular Component
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000531613
- Coding exons
- 4
- Length
- 171023
- Individuals with no LoFs
- 125192
- Homozygous LoFs
- 10
- Heterozygous LoFs
- 546
- Defined
- 125748
- p
- 0.00221
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.40 | 689 | 593 | 1.16 | 0.0000434 | 6081 |
| Missense (PolyPhen) | 125 | 131.25 | 0.95235 | 1436 | ||
| Synonymous | -1.01 | 310 | 288 | 1.08 | 0.0000255 | 2069 |
| Loss of Function | 0.151 | 28 | 28.9 | 0.970 | 0.00000159 | 324 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00058 | 0.00055 | rare |
| Latino/Admixed American | 0.0011 | 0.0011 | notable |
| Ashkenazi Jewish | 0.0019 | 0.0018 | notable |
| East Asian | 0.0016 | 0.0016 | notable |
| Finnish | 0.0026 | 0.0026 | notable |
| European (Non-Finnish) | 0.0031 | 0.0030 | notable |
| South Asian | 0.0016 | 0.0016 | notable |
| Other | 0.0025 | 0.0023 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.;
Intolerance Scores
- LoFtool
- 0.904
- RVIS EVS
- 1.88
- RVIS percentile EVS
- 97.23
Essentials
- Essential (CRISPR)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.117
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |