PCDH19
protocadherin 19, the group of Non-clustered protocadherins
Basic information
Region (hg38): X:100291644-100410273
Previous symbols: [ "EFMR" ]
Links
Phenotypes
GenCC
Source:
- developmental and epileptic encephalopathy, 9 (Definitive), mode of inheritance: XL
- Dravet syndrome (Supportive), mode of inheritance: AD
- developmental and epileptic encephalopathy, 9 (Supportive), mode of inheritance: Unknown
- developmental and epileptic encephalopathy, 9 (Definitive), mode of inheritance: XL
- developmental and epileptic encephalopathy, 9 (Strong), mode of inheritance: XL
- X-linked complex neurodevelopmental disorder (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Epileptic encephalopathy, early infantile, 9 | XL | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Neurologic | 18469813; 19214208; 19752159; 20830798; 20713952; 21519002; 21777234; 22050978; 22267240; 22633638; 22848613; 22949144 |
| As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection |
ClinVar
This is a list of variants' phenotypes submitted to
- Developmental and epileptic encephalopathy, 9 (221 variants)
- not provided (67 variants)
- Inborn genetic diseases (13 variants)
- Seizure (7 variants)
- Focal-onset seizure (1 variants)
- Epilepsy (1 variants)
- 11 conditions (1 variants)
- Neurodevelopmental delay (1 variants)
- Complex febrile seizure (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCDH19 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 266 | 276 | ||||
| missense | 34 | 64 | 475 | 19 | 593 | |
| nonsense | 73 | 10 | 84 | |||
| start loss | 1 | |||||
| frameshift | 156 | 15 | 178 | |||
| inframe indel | 17 | 22 | ||||
| splice donor/acceptor (+/-2bp) | 13 | |||||
| splice region | 1 | 4 | 5 | 10 | ||
| non coding | 23 | 31 | ||||
| Total | 274 | 95 | 509 | 308 | 12 |
Variants in PCDH19
This is a list of pathogenic ClinVar variants found in the PCDH19 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| X-100296269-A-G | not specified | Benign (May 22, 2014) | ||
| X-100296285-C-G | Developmental and epileptic encephalopathy, 9 | Uncertain significance (Jul 12, 2022) | ||
| X-100296285-C-T | not specified • Developmental and epileptic encephalopathy, 9 • Inborn genetic diseases | Conflicting classifications of pathogenicity (Oct 22, 2023) | ||
| X-100296285-CG-C | Developmental and epileptic encephalopathy, 9 | Uncertain significance (Jan 13, 2022) | ||
| X-100296287-A-G | Developmental and epileptic encephalopathy, 9 • Inborn genetic diseases | Uncertain significance (Jun 20, 2023) | ||
| X-100296286-G-GAT | Developmental and epileptic encephalopathy, 9 | Uncertain significance (Jun 16, 2021) | ||
| X-100296287-A-ATATCCT | Developmental and epileptic encephalopathy, 9 | Uncertain significance (Dec 05, 2022) | ||
| X-100296292-C-G | Uncertain significance (Nov 14, 2022) | |||
| X-100296293-T-C | Uncertain significance (Jan 21, 2020) | |||
| X-100296300-G-A | Developmental and epileptic encephalopathy, 9 | Uncertain significance (Dec 24, 2021) | ||
| X-100296302-T-C | Developmental and epileptic encephalopathy, 9 | Uncertain significance (Jun 13, 2022) | ||
| X-100296303-T-C | Developmental and epileptic encephalopathy, 9 | Uncertain significance (Apr 18, 2024) | ||
| X-100296308-C-T | Developmental and epileptic encephalopathy, 9 | Uncertain significance (Jul 18, 2023) | ||
| X-100296309-C-T | not specified • Developmental and epileptic encephalopathy, 9 • PCDH19-related disorder | Likely benign (Jan 14, 2023) | ||
| X-100296312-G-A | Developmental and epileptic encephalopathy, 9 • not specified • Inborn genetic diseases • PCDH19-related disorder | Benign/Likely benign (Jan 17, 2024) | ||
| X-100296318-CTT-C | Developmental and epileptic encephalopathy, 9 | Uncertain significance (Oct 04, 2023) | ||
| X-100296319-T-C | not specified • Developmental and epileptic encephalopathy, 9 | Conflicting classifications of pathogenicity (Nov 10, 2022) | ||
| X-100296324-T-G | not specified • Developmental and epileptic encephalopathy, 9 • Inborn genetic diseases • PCDH19-related disorder | Benign (Jan 26, 2024) | ||
| X-100296326-C-T | Developmental and epileptic encephalopathy, 9 | Uncertain significance (Nov 08, 2022) | ||
| X-100296331-T-C | Developmental and epileptic encephalopathy, 9 | Likely benign (Dec 27, 2023) | ||
| X-100296340-A-C | Developmental and epileptic encephalopathy, 9 | Uncertain significance (Jan 31, 2020) | ||
| X-100296345-G-A | Developmental and epileptic encephalopathy, 9 | Uncertain significance (Jan 17, 2024) | ||
| X-100296354-C-G | Developmental and epileptic encephalopathy, 9 | Uncertain significance (Mar 06, 2020) | ||
| X-100296357-G-A | not specified | Uncertain significance (Dec 20, 2017) | ||
| X-100296360-T-G | Developmental and epileptic encephalopathy, 9 | Uncertain significance (Nov 24, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PCDH19 | protein_coding | protein_coding | ENST00000373034 | 6 | 118630 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000250 | 124794 | 1 | 3 | 124798 | 0.0000160 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.59 | 336 | 499 | 0.673 | 0.0000422 | 7525 |
| Missense in Polyphen | 95 | 201.52 | 0.47142 | 2998 | ||
| Synonymous | -0.225 | 222 | 218 | 1.02 | 0.0000195 | 2390 |
| Loss of Function | 4.51 | 0 | 23.7 | 0.00 | 0.00000178 | 381 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000738 | 0.0000556 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000256 | 0.0000177 |
| Middle Eastern | 0.0000738 | 0.0000556 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000225 | 0.000165 |
dbNSFP
Source:
- Function
- FUNCTION: Potential calcium-dependent cell-adhesion protein.;
- Disease
- DISEASE: Epileptic encephalopathy, early infantile, 9 (EIEE9) [MIM:300088]: A condition characterized by seizure with onset in infancy or early childhood, cognitive impairment, and delayed development of variable severity in some patients. Additional features include autistic signs and psychosis. The disorder is sex-limited, with the phenotype being restricted to females. {ECO:0000269|PubMed:18469813, ECO:0000269|PubMed:19214208, ECO:0000269|PubMed:19752159, ECO:0000269|PubMed:20713952, ECO:0000269|PubMed:20830798, ECO:0000269|PubMed:21053371, ECO:0000269|PubMed:21480887, ECO:0000269|PubMed:21519002, ECO:0000269|PubMed:22050978, ECO:0000269|PubMed:22267240, ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26993267}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- loftool
- 0.0992
- rvis_EVS
- -0.89
- rvis_percentile_EVS
- 10.43
Haploinsufficiency Scores
- pHI
- 0.380
- hipred
- Y
- hipred_score
- 0.809
- ghis
- 0.572
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.296
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pcdh19
- Phenotype
- cellular phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- pcdh19
- Affected structure
- ethmoid cartilage
- Phenotype tag
- abnormal
- Phenotype quality
- decreased size
Gene ontology
- Biological process
- cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;brain development
- Cellular component
- integral component of plasma membrane
- Molecular function
- calcium ion binding