PCDH19
Protocadherin 19: A Key Gene in Female-Limited Epilepsy and Neurodevelopment
Gene Information Card
| Symbol | PCDH19 |
|---|---|
| Full Name | Protocadherin 19 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq22.1 |
| NCBI Gene ID | 57526 ncbi.nlm.nih.gov/gene/57526 |
| Ensembl ID | ENSG00000165195 |
| UniProt ID | Q8TAB3 |
| OMIM ID | 300460 |
| HGNC ID | 14270 |
| Aliases | EFMR, DEE9, EIEE9, PCDH19L |
Description
PCDH19 encodes protocadherin 19, a member of the protocadherin family of calcium-dependent cell adhesion proteins. It is predominantly expressed in the brain and plays a critical role in neuronal development, synaptic function, and cell-cell interactions. Mutations in PCDH19 cause a female-limited form of epilepsy with intellectual disability (EFMR), also known as developmental and epileptic encephalopathy 9 (DEE9). The gene exhibits a unique X-linked inheritance pattern where heterozygous females are affected while hemizygous males are typically spared, likely due to cellular mosaicism from X-inactivation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Developmental and Epileptic Encephalopathy 9 (DEE9) / Epilepsy, Female-Restricted, with Mental Retardation (EFMR) | Loss-of-function mutations lead to impaired cell adhesion and disrupted neuronal network formation, with disease manifestation in females due to somatic mosaicism from X-inactivation | ClinVar, OMIM |
| Autism Spectrum Disorder (ASD) | Rare PCDH19 variants may contribute to ASD risk through altered synaptic adhesion and signaling | NCBI Gene, ClinVar |
| Intellectual Disability | Disrupted protocadherin function impairs synaptic plasticity and cognitive development | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Brain (hippocampus) | 11.8 | Medium |
| Brain (cerebellum) | 8.2 | Low |
| Heart | 0.5 | Not detected |
| Liver | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model |
| U-87 MG (glioblastoma) | 10.1 | Glial model |
| HEK293 (embryonic kidney) | 0.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339*) | Nonsense | Rare | Loss of function; premature truncation of protein |
| c.1096G>A (p.Gly366Arg) | Missense | Rare | Impaired cell adhesion and trafficking |
| c.1687C>T (p.Arg563Cys) | Missense | Rare | Altered protein stability and function |
| c.2146_2147del (p.Leu716Glufs*3) | Frameshift | Rare | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Most PCDH19 mutations result in loss of function, leading to reduced cell adhesion and disrupted neuronal network formation.
Gain of Function (GOF)
No evidence of gain-of-function mutations in PCDH19.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type protocadherin function in mosaic cells.
View complete mutation data：
Gene Ontology (GO)
| • calcium ion binding | • cell adhesion |
| • homophilic cell adhesion via plasma membrane adhesion molecules | • synaptic membrane adhesion |
| • nervous system development | • neuron projection development |
Pathways
• Cell adhesion molecules (CAMs)
• Protocadherin signaling
• Neuronal system
Protein Summary
Protocadherin 19 is a transmembrane protein with six extracellular cadherin repeats, a single transmembrane domain, and a cytoplasmic tail. It mediates calcium-dependent homophilic cell adhesion, essential for neuronal migration, synapse formation, and network maintenance. The protein is highly expressed in the developing and adult brain, particularly in the cortex and hippocampus. Mutations disrupt adhesion and signaling, leading to epilepsy and cognitive impairment.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PCDH19 Knockout HEK293 Cell Line | EDJ-KQ14701 | Human | 57526 | Details Get a Quote |
| PCDH19 Knockout HeLa Cell Line | EDJ-KQ56858 | Human | 57526 | Details Get a Quote |
| PCDH19 Knockout A-549 Cell Line | EDJ-KQ65371 | Human | 57526 | Details Get a Quote |
| PCDH19 Knockout HCT 116 Cell Line | EDJ-KQ73809 | Human | 57526 | Details Get a Quote |
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