GeneBe

PCDH19

protocadherin 19, the group of Non-clustered protocadherins

Basic information

Region (hg38): X:100291644-100410273

Previous symbols: [ "EFMR" ]

Links

ENSG00000165194 ∙ NCBI:57526 ∙ OMIM:300460 ∙ HGNC:14270 ∙ Uniprot:Q8TAB3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • 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: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Epileptic encephalopathy, early infantile, 9XLGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic18469813; 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 ClinVar and linked to the PCDH19 gene.

  • Developmental_and_epileptic_encephalopathy,_9 (1176 variants)
  • not_provided (400 variants)
  • Inborn_genetic_diseases (143 variants)
  • not_specified (102 variants)
  • PCDH19-related_disorder (28 variants)
  • Seizure (13 variants)
  • Glycine_encephalopathy (11 variants)
  • Intellectual_disability (4 variants)
  • Bilateral_tonic-clonic_seizure (3 variants)
  • Abnormal_cerebral_morphology (2 variants)
  • Neurodevelopmental_disorder_with_epilepsy (2 variants)
  • sporadic_NAFE (2 variants)
  • Developmental_and_epileptic_encephalopathy,_1 (2 variants)
  • Periventricular_nodular_heterotopia_and_epilepsy (1 variants)
  • PCDH19-related_epilespy (1 variants)
  • Prominent_fingertip_pads (1 variants)
  • Non-lesional_parietal_lobe_epilepsy (1 variants)
  • Self-limited_epilepsy_with_centrotemporal_spikes (1 variants)
  • Epilepsy (1 variants)
  • Autism_spectrum_disorder (1 variants)
  • Complex_cortical_dysplasia_with_other_brain_malformations_7 (1 variants)
  • Delayed_speech_and_language_development (1 variants)
  • Generalized-onset_seizure (1 variants)
  • developmental_delay_with_seizures (1 variants)
  • Long_palpebral_fissure (1 variants)
  • Hand_tremor (1 variants)
  • PCDH19-related_epilepsy (1 variants)
  • Strabismus (1 variants)
  • Refractory_epilepsy_with_Lennox_Gastaut_syndrome (1 variants)
  • Epileptic_encephalopathy (1 variants)
  • Temporal_cortical_atrophy (1 variants)
  • Familial_GGE (1 variants)
  • Frontal_cortical_atrophy (1 variants)
  • Global_developmental_delay (1 variants)
  • Neurodevelopmental_delay (1 variants)
  • Complex_febrile_seizure (1 variants)
  • See_cases (1 variants)
  • Focal-onset_seizure (1 variants)
  • Generalized_non-motor_(absence)_seizure (1 variants)
  • PCDH19-related_epilepsy_syndrome (1 variants)
  • Intractable_status_epilepticus (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. These statistics are base on transcript: NM_001184880.2. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
3
clinvar
307
clinvar
2
clinvar
 313
missense
44
clinvar
91
clinvar
567
clinvar
48
clinvar
2
clinvar
 752
nonsense
82
clinvar
13
clinvar
1
clinvar
 96
start loss
1
 1
frameshift
175
clinvar
17
clinvar
7
clinvar
 199
splice donor/acceptor (+/-2bp)
10
clinvar
4
clinvar
1
clinvar
 15
Total 313 125 579 355 4

Highest pathogenic variant AF is 0.000011848428

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PCDH19protein_codingprotein_codingENST00000373034 6118630
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.000.000250124794131247980.0000160
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.593364990.6730.00004227525
Missense in Polyphen95201.520.471422998
Synonymous-0.2252222181.020.00001952390
Loss of Function4.51023.70.000.00000178381

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.00007380.0000556
Finnish0.000.00
European (Non-Finnish)0.00002560.0000177
Middle Eastern0.00007380.0000556
South Asian0.000.00
Other0.0002250.000165

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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