PI4KA
Chr 22ARphosphatidylinositol 4-kinase alpha
Also known as: GIDID2, PI4K-ALPHA, PIK4CA, PMGYCHA, SPG84, pi4K230
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.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Highly missense-constrained (top ~0.1%)
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
300 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 0 | 21 | 0 | 22 |
Likely Pathogenic | 8 | 4 | 0 | 0 | 12 |
VUS | 5 | 107 | 16 | 0 | 128 |
Likely Benign | 0 | 10 | 9 | 52 | 71 |
Benign | 0 | 1 | 4 | 2 | 7 |
Conflicting | — | 1 | |||
| Total | 14 | 122 | 50 | 54 | 241 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PI4KA · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools