PI4KA
protein-codingphosphatidylinositol 4-kinase alpha, the group of Armadillo like helical domain containing|PI4KA lipid kinase complex
Gene summary
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]
- PIK4CA
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~151.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014679
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014679
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014679
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PI4KA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_058004.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 91 | 5 | 101 | ||
| missense | 4 | 10 | 166 | 8 | 188 | |
| nonsense | 5 | 10 | 2 | 17 | ||
| start loss | 1 | 1 | ||||
| frameshift | 7 | 11 | 18 | |||
| splice donor/acceptor (+/-2bp) | 1 | 8 | 10 | 19 | ||
| Total | 17 | 39 | 184 | 99 | 5 | 344 |
Highest pathogenic variant AF is 0.00039111817
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_477352.3 | 55 | MANE Select | |
| Ensembl | ENSP00000255882.6 | 55 | MANE Select | |
| RefSeq | NP_001349791.1 | 54 | Standard | |
| RefSeq | NP_001349792.1 | 54 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| pi4kaa | Danio rerio | Structure: pectoral fin Quality: aplastic abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Inositol phosphate metabolism - Homo sapiens (human)
- Phosphatidylinositol signaling system - Homo sapiens (human)
- Phosphatidylinositol Phosphate Metabolism
- Joubert syndrome
- Inositol Metabolism
Biological Process
- phosphatidylinositol biosynthetic process
- signal transduction
- phosphorylation
- viral RNA genome replication
- multi-organism membrane organization
Molecular Function
- 1-phosphatidylinositol 4-kinase activity
- protein binding
- ATP binding
- kinase activity
- cadherin binding
Cellular Component
- cytoplasm
- cytosol
- plasma membrane
- focal adhesion
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000255882
- Coding exons
- 55
- Length
- 151727
- Individuals with no LoFs
- 125613
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 134
- Defined
- 125748
- p
- 0.000537
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.53 | 883 | 1.23e+3 | 0.717 | 0.0000752 | 13738 |
| Missense (PolyPhen) | 190 | 350.99 | 0.54132 | 3933 | ||
| Synonymous | -0.243 | 505 | 498 | 1.01 | 0.0000332 | 4037 |
| Loss of Function | 6.53 | 43 | 120 | 0.357 | 0.00000651 | 1342 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00049 | 0.00049 | rare |
| Latino/Admixed American | 0.0013 | 0.0013 | notable |
| Ashkenazi Jewish | 0.00060 | 0.00060 | rare |
| East Asian | 0.00065 | 0.00065 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00041 | 0.00040 | rare |
| South Asian | 0.00043 | 0.00039 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts on phosphatidylinositol (PtdIns) in the first committed step in the production of the second messenger inositol- 1,4,5,-trisphosphate. {ECO:0000269|PubMed:10101268, ECO:0000269|PubMed:23229899}.;
Recessive Scores
- pRec
- 0.182
Intolerance Scores
- LoFtool
- 0.684
- RVIS EVS
- -4.02
- RVIS percentile EVS
- 0.18
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |