PI4K2A
phosphatidylinositol 4-kinase type 2 alpha
Basic information
Region (hg38): 10:97640671-97676434
Links
Phenotypes
GenCC
Source:
No genCC data.
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities | AR | General | 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 | Craniofacial; Musculoskeletal; Neurologic | 30564627; 32418222; 35880319 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (42 variants)
- Neurodevelopmental_disorder_with_hyperkinetic_movements,_seizures,_and_structural_brain_abnormalities (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PI4K2A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018425.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 42 | 42 | ||||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 2 | 0 | 42 | 0 | 0 |
Highest pathogenic variant AF is 0.0000020681669
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PI4K2A | protein_coding | protein_coding | ENST00000370631 | 9 | 92061 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.804 | 0.196 | 125738 | 0 | 8 | 125746 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.89 | 129 | 260 | 0.496 | 0.0000143 | 3086 |
| Missense in Polyphen | 30 | 97.665 | 0.30717 | 1194 | ||
| Synonymous | 1.97 | 77 | 102 | 0.752 | 0.00000522 | 960 |
| Loss of Function | 3.67 | 4 | 23.0 | 0.174 | 0.00000113 | 254 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000867 | 0.0000867 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.0000264 | 0.0000264 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Membrane-bound phosphatidylinositol-4 kinase (PI4- kinase) that catalyzes the phosphorylation of phosphatidylinositol (PI) to phosphatidylinositol 4-phosphate (PI4P), a lipid that plays important roles in endocytosis, Golgi function, protein sorting and membrane trafficking and is required for prolonged survival of neurons. Besides, phosphorylation of phosphatidylinositol (PI) to phosphatidylinositol 4-phosphate (PI4P) is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3). {ECO:0000269|PubMed:11279162, ECO:0000269|PubMed:16443754, ECO:0000269|PubMed:20388919, ECO:0000269|PubMed:23146885, ECO:0000269|PubMed:24675427, ECO:0000269|PubMed:25168678, ECO:0000305}.;
- Pathway
- Inositol phosphate metabolism - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;Wnt Signaling Pathway;D-<i>myo</i>-inositol (1,4,5)-trisphosphate biosynthesis;Metabolism of lipids;Metabolism;3-phosphoinositide biosynthesis;superpathway of inositol phosphate compounds;Synthesis of PIPs at the Golgi membrane;Synthesis of PIPs at the early endosome membrane;Synthesis of PIPs at the plasma membrane;PI Metabolism;Phospholipid metabolism;Canonical Wnt signaling pathway
(Consensus)
Intolerance Scores
- loftool
- 0.102
- rvis_EVS
- 0.55
- rvis_percentile_EVS
- 81.38
Haploinsufficiency Scores
- pHI
- 0.539
- hipred
- Y
- hipred_score
- 0.626
- ghis
- 0.488
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.876
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pi4k2a
- Phenotype
- growth/size/body region phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);
Gene ontology
- Biological process
- basophil degranulation;phosphatidylinositol biosynthetic process;Golgi organization;endosome organization;phosphatidylinositol phosphorylation
- Cellular component
- mitochondrion;lysosomal membrane;endosome;trans-Golgi network;cytosol;plasma membrane;integral component of plasma membrane;membrane;cell junction;dendrite;synaptic vesicle membrane;BLOC-1 complex;intrinsic component of membrane;cytoplasmic vesicle;early endosome membrane;growing cell tip;presynaptic membrane;neuron projection;neuronal cell body;perikaryon;host cell presynaptic membrane;membrane raft
- Molecular function
- magnesium ion binding;1-phosphatidylinositol 4-kinase activity;protein binding;ATP binding;AP-3 adaptor complex binding