PI4KA

Chr 22AR

phosphatidylinositol 4-kinase alpha

Also known as: GIDID2, PI4K-ALPHA, PIK4CA, PMGYCHA, SPG84, pi4K230

NCBI Gene: 5297 ENSG00000241973 UniProt: P42356 OMIM: 600286

This protein catalyzes the phosphorylation of phosphatidylinositol to produce phosphatidylinositol 4-phosphate, the first committed step in generating the second messenger inositol-1,4,5-trisphosphate. Autosomal recessive mutations cause a spectrum of disorders including gastrointestinal defects with immunodeficiency, perisylvian polymicrogyria with cerebellar hypoplasia and arthrogryposis, and spastic paraplegia. Loss of function disrupts phosphoinositide signaling pathways critical for normal development and cellular function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a phosphatidylinositol (PI) 4-kinase which catalyzes the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. The mammalian PI 4-kinases have been classified into two types, II and III, based on their molecular mass, and modulation by detergent and adenosine. The protein encoded by this gene is a type III enzyme that is not inhibited by adenosine. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2018]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Gastrointestinal defects and immunodeficiency syndrome 2MIM #619708

Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposisMIM #616531

Spastic paraplegia 84, autosomal recessiveMIM #619621

UniProtNeurodevelopmental disorder with spasticity, hypomyelinating leukodystrophy, and brain abnormalities

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.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

0.46

LOEUF

LOF

Mechanism· G2P

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GeneReview available — PI4KA