PCDH19

Chr X

protocadherin 19

Also known as: DEE9, EFMR, EIEE9

NCBI Gene: 57526 ENSG00000165194 UniProt: Q8TAB3

The protein functions as a calcium-dependent cell-adhesion protein primarily expressed in the brain. Mutations cause developmental and epileptic encephalopathy 9 through X-linked inheritance, with the unusual pattern of affecting heterozygous females more severely than hemizygous males due to X-inactivation creating cellular mosaicism. The disease mechanism predominantly involves loss-of-function, consistent with the gene's extreme intolerance to such variants.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is a member of the delta-2 protocadherin subclass of the cadherin superfamily. The encoded protein is thought to be a calcium-dependent cell-adhesion protein that is primarily expressed in the brain. Mutations in this gene on human chromosome X are associated with sporadic infantile epileptic encephalopathy and to a female-restricted form of epilepsy (EFMR; also known as PCDH19RE). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDevelopmental and epileptic encephalopathy 9

Clinical highlights

Gene-disease validity (ClinGen)

X-linked complex neurodevelopmental disorder · XLDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.13

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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