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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PCDH19
protocadherin 19
Chromosome X · Xq22.1
NCBI Gene: 57526Ensembl: ENSG00000165194.16HGNC: HGNC:14270UniProt: B3KU71
87PubMed Papers
21Diseases
0Drugs
438Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cell adhesion molecule bindingplasma membranecell adhesionhomophilic cell-cell adhesiondevelopmental and epileptic encephalopathy, 9genetic developmental and epileptic encephalopathygenetic disorderSeizure
✦AI Summary

PCDH19 encodes protocadherin 19, a calcium-dependent cell adhesion protein belonging to the δ2 subgroup of non-clustered protocadherins 1. The protein is expressed predominantly in the nervous system with spatiotemporally diverse patterns, particularly in cortical regions during early postnatal development and in the caudate putamen and hippocampal formation of mature brains, suggesting roles in neural circuit formation and maintenance 1. PCDH19 exhibits unique X-linked inheritance patterns where pathogenic variants cause developmental and epileptic encephalopathy 9 (DEE9) in heterozygous females but not in hemizygous males 23. The disorder manifests as childhood-onset epilepsy with brief clusters of febrile and afebrile seizures before age three, cognitive impairment, autistic traits, and behavioral abnormalities 2. The pathogenic mechanism involves cellular interference due to random X chromosome X creating somatic mosaicism, where coexistence of wild-type and variant PCDH19-expressing cells disrupts normal cellular function 34. Additional pathogenic mechanisms include allopregnanolone deficiency, altered steroid gene expression, decreased GABAA receptor function, and blood-brain barrier dysfunction 4. Treatment approaches include clobazam, bromide, and experimental ganaxolone therapy 52.

Sources cited
1
PCDH19 belongs to δ2 subgroup of non-clustered protocadherins and is expressed predominantly in nervous system
PMID: 21173574
2
PCDH19 variants cause childhood-onset epilepsy syndrome with seizures, cognitive impairment, and behavioral abnormalities
PMID: 32057594
3
PCDH19-CE manifests in heterozygous females but not hemizygous males due to cellular mosaicism
PMID: 32726744
4
Multiple pathogenic mechanisms include cellular interference, allopregnanolone deficiency, and GABAA dysfunction
PMID: 38521028
5
Treatment options include clobazam, bromide, and experimental ganaxolone therapy
PMID: 36004035
Disease Associationsⓘ21
developmental and epileptic encephalopathy, 9Open Targets
0.85Strong
genetic developmental and epileptic encephalopathyOpen Targets
0.67Moderate
genetic disorderOpen Targets
0.55Moderate
SeizureOpen Targets
0.54Moderate
X-linked intellectual disability - epilepsyOpen Targets
0.50Moderate
Bilateral tonic-clonic seizureOpen Targets
0.44Moderate
glycine encephalopathyOpen Targets
0.40Moderate
Dravet syndromeOpen Targets
0.39Weak
early-infantile DEEOpen Targets
0.37Weak
X-linked complex neurodevelopmental disorderOpen Targets
0.37Weak
Intellectual disabilityOpen Targets
0.36Weak
epilepsyOpen Targets
0.36Weak
Global developmental delayOpen Targets
0.34Weak
Neurodevelopmental delayOpen Targets
0.34Weak
Delayed speech and language developmentOpen Targets
0.34Weak
Frontal cortical atrophyOpen Targets
0.34Weak
Generalized non-motor (absence) seizureOpen Targets
0.34Weak
Prominent fingertip padsOpen Targets
0.34Weak
StrabismusOpen Targets
0.34Weak
Temporal cortical atrophyOpen Targets
0.34Weak
Developmental and epileptic encephalopathy 9UniProt
Pathogenic Variants438
NM_001184880.2(PCDH19):c.799G>T (p.Glu267Ter)Pathogenic
not provided|Developmental and epileptic encephalopathy, 9
★★☆☆2025→ Residue 267
NM_001184880.2(PCDH19):c.2656C>T (p.Arg886Ter)Pathogenic
not provided|Inborn genetic diseases|Developmental and epileptic encephalopathy, 9
★★☆☆2025→ Residue 886
NM_001184880.2(PCDH19):c.1183C>T (p.Arg395Ter)Pathogenic
Developmental and epileptic encephalopathy, 9|not provided|Inborn genetic diseases
★★☆☆2025→ Residue 395
NM_001184880.2(PCDH19):c.1091dup (p.Tyr366fs)Pathogenic
Developmental and epileptic encephalopathy, 9|not provided|11 conditions
★★☆☆2025→ Residue 366
NM_001184880.2(PCDH19):c.706C>T (p.Pro236Ser)Pathogenic
not provided|Developmental and epileptic encephalopathy, 9
★★☆☆2025→ Residue 236
NM_001184880.2(PCDH19):c.1091del (p.Pro364fs)Pathogenic
Developmental and epileptic encephalopathy, 9|Inborn genetic diseases|Seizure
★★☆☆2025→ Residue 364
NM_001184880.2(PCDH19):c.1671C>G (p.Asn557Lys)Pathogenic
Developmental and epileptic encephalopathy, 9|not provided
★★☆☆2025→ Residue 557
NM_001184880.2(PCDH19):c.593G>T (p.Arg198Leu)Pathogenic
not provided|developmental delay with seizures|Developmental and epileptic encephalopathy, 9|Seizure
★★☆☆2025→ Residue 198
NM_001184880.2(PCDH19):c.1019A>G (p.Asn340Ser)Pathogenic
not provided|Developmental and epileptic encephalopathy, 9|Inborn genetic diseases|Epilepsy|PCDH19-related epilepsy syndrome
★★☆☆2025→ Residue 340
NM_001184880.2(PCDH19):c.695A>G (p.Asn232Ser)Pathogenic
not provided|Developmental and epileptic encephalopathy, 9|Inborn genetic diseases
★★☆☆2025→ Residue 232
NM_001184880.2(PCDH19):c.1241A>G (p.Glu414Gly)Likely pathogenic
Developmental and epileptic encephalopathy, 9
★★☆☆2025→ Residue 414
NM_001184880.2(PCDH19):c.1031C>T (p.Pro344Leu)Pathogenic
not provided|Developmental and epileptic encephalopathy, 9
★★☆☆2025→ Residue 344
NM_001184880.2(PCDH19):c.361G>A (p.Asp121Asn)Likely pathogenic
not provided|Developmental and epileptic encephalopathy, 9
★★☆☆2025→ Residue 121
NM_001184880.2(PCDH19):c.1855C>T (p.Gln619Ter)Pathogenic
not provided|Developmental and epileptic encephalopathy, 9
★★☆☆2025→ Residue 619
NM_001184880.2(PCDH19):c.98_102del (p.Gln33fs)Pathogenic
Developmental and epileptic encephalopathy, 9|Inborn genetic diseases
★★☆☆2025→ Residue 33
NM_001184880.2(PCDH19):c.2675+2T>CPathogenic
Developmental and epileptic encephalopathy, 9|not provided
★★☆☆2025
NM_001184880.2(PCDH19):c.810C>G (p.Asn270Lys)Pathogenic
Developmental and epileptic encephalopathy, 9
★★☆☆2025→ Residue 270
NM_001184880.2(PCDH19):c.1682C>T (p.Pro561Leu)Pathogenic
Developmental and epileptic encephalopathy, 9|not provided
★★☆☆2024→ Residue 561
NM_001184880.2(PCDH19):c.1031C>G (p.Pro344Arg)Pathogenic
Developmental and epileptic encephalopathy, 9|not provided
★★☆☆2024→ Residue 344
NM_001184880.2(PCDH19):c.369C>G (p.Asn123Lys)Pathogenic
not provided|Developmental and epileptic encephalopathy, 9|Seizure
★★☆☆2024→ Residue 123
View on ClinVar ↗
Related Genes
PCDH7Shared pathway100%PCDH11XShared pathway100%CDHR4Shared pathway100%PCDH11YShared pathway100%PCDH20Shared pathway100%KCNQ2Protein interaction94%
Tissue Expression6 tissues
Brain
100%
Ovary
31%
Heart
20%
Liver
3%
Lung
2%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
PCDH19PCDH7PCDH11XCDHR4PCDH11YPCDH20KCNQ2
PROTEIN STRUCTURE
Preparing viewer…
PDB6VFU · 3.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.26Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.13 [0.07–0.26]
RankingsWhere PCDH19 stands among ~20K protein-coding genes
  • #5,501of 20,598
    Most Researched87
  • #122of 5,498
    Most Pathogenic Variants438 · top 5%
  • #810of 17,882
    Most Constrained (LOEUF)0.26 · top 5%
Genes detectedPCDH19
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PCDH19-Related Epilepsy Syndrome: A Comprehensive Clinical Review.
PMID: 32057594
Pediatr Neurol · 2020
1.00
2
X-Linked Epilepsies: A Narrative Review.
PMID: 38612920
Int J Mol Sci · 2024
0.90
3
PCDH19-clustering epilepsy, pathophysiology and clinical significance.
PMID: 38521028
Epilepsy Behav · 2024
0.80
4
Deriving early single-rosette brain organoids from human pluripotent stem cells.
PMID: 37995702
Stem Cell Reports · 2023
0.70
5
Non-clustered protocadherin.
PMID: 21173574
Cell Adh Migr · 2011
0.60