PIP5K1A
phosphatidylinositol-4-phosphate 5-kinase type 1 alpha
Basic information
Region (hg38): 1:151197948-151249536
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIP5K1A gene is commonly pathogenic or not.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 4 | |||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 1 | 4 | 0 | 0 |
Variants in PIP5K1A
This is a list of pathogenic ClinVar variants found in the PIP5K1A region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-151199055-C-T | not specified | Uncertain significance (Nov 09, 2021) | ||
| 1-151234467-C-T | not specified | Uncertain significance (Oct 06, 2021) | ||
| 1-151236729-G-T | not specified | Uncertain significance (Jun 18, 2021) | ||
| 1-151236732-C-T | Intellectual developmental disorder 60 with seizures | Likely pathogenic (Mar 17, 2024) | ||
| 1-151239973-C-T | not specified | Uncertain significance (Jul 13, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PIP5K1A | protein_coding | protein_coding | ENST00000368888 | 15 | 51588 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00209 | 0.998 | 125719 | 0 | 27 | 125746 | 0.000107 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.58 | 199 | 331 | 0.602 | 0.0000187 | 3650 |
| Missense in Polyphen | 25 | 78.946 | 0.31667 | 951 | ||
| Synonymous | 0.743 | 110 | 120 | 0.914 | 0.00000646 | 1109 |
| Loss of Function | 3.61 | 11 | 33.6 | 0.328 | 0.00000182 | 387 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000442 | 0.000431 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000163 | 0.000163 |
| Finnish | 0.000277 | 0.000277 |
| European (Non-Finnish) | 0.0000704 | 0.0000703 |
| Middle Eastern | 0.000163 | 0.000163 |
| South Asian | 0.0000987 | 0.0000980 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Catalyzes the phosphorylation of phosphatidylinositol 4- phosphate (PtdIns4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). PtdIns(4,5)P2 is involved in a variety of cellular processes and is the substrate to form phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), another second messenger. The majority of PtdIns(4,5)P2 is thought to occur via type I phosphatidylinositol 4-phosphate 5-kinases given the abundance of PtdIns4P. Participates in a variety of cellular processes such as actin cytoskeleton organization, cell adhesion, migration and phagocytosis. Required for membrane ruffling formation, actin organization and focal adhesion formation during directional cell migration by controlling integrin-induced translocation of RAC1 to the plasma membrane. Together with PIP5K1C is required for phagocytosis, but they regulate different types of actin remodeling at sequential steps. Promotes particle ingestion by activating WAS that induces Arp2/3 dependent actin polymerization at the nascent phagocytic cup. Together with PIP5K1B is required after stimulation of G-protein coupled receptors for stable platelet adhesion. Plays a role during calcium-induced keratinocyte differentiation. Recruited to the plasma membrane by the E-cadherin/beta-catenin complex where it provides the substrate PtdIns(4,5)P2 for the production of PtdIns(3,4,5)P3, diacylglycerol and inositol 1,4,5-trisphosphate that mobilize internal calcium and drive keratinocyte differentiation. Together with PIP5K1C have a role during embryogenesis. Functions also in the nucleus where acts as an activator of TUT1 adenylyltransferase activity in nuclear speckles, thereby regulating mRNA polyadenylation of a select set of mRNAs (PubMed:18288197, PubMed:19158393, PubMed:20660631). Positively regulates insulin-induced translocation of SLC2A4 to the cell membrane in adipocytes (By similarity). {ECO:0000250|UniProtKB:P70182, ECO:0000269|PubMed:18288197, ECO:0000269|PubMed:19158393, ECO:0000269|PubMed:20660631}.;
- Pathway
- Fc gamma R-mediated phagocytosis - Homo sapiens (human);Inositol phosphate metabolism - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Endocytosis - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Phosphatidylinositol Phosphate Metabolism;Joubert syndrome;B Cell Receptor Signaling Pathway;Regulation of Actin Cytoskeleton;D-<i>myo</i>-inositol (1,4,5)-trisphosphate biosynthesis;Signal Transduction;rho cell motility signaling pathway;Metabolism of lipids;Inositol phosphate metabolism;Metabolism;3-phosphoinositide biosynthesis;superpathway of inositol phosphate compounds;BCR;Phosphatidylinositol phosphate metabolism;PIP3 activates AKT signaling;E-cadherin signaling in keratinocytes;Arf1 pathway;Synthesis of PIPs at the plasma membrane;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;PI Metabolism;Phospholipid metabolism;Intracellular signaling by second messengers;Osteopontin-mediated events;RAC1 signaling pathway;Arf6 downstream pathway;RhoA signaling pathway
(Consensus)
Recessive Scores
- pRec
- 0.128
Intolerance Scores
- loftool
- rvis_EVS
- -0.51
- rvis_percentile_EVS
- 21.41
Haploinsufficiency Scores
- pHI
- 0.120
- hipred
- Y
- hipred_score
- 0.704
- ghis
- 0.658
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.989
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pip5k1a
- Phenotype
- cellular phenotype; endocrine/exocrine gland 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;
Gene ontology
- Biological process
- glycerophospholipid metabolic process;phosphatidylinositol biosynthetic process;phagocytosis;signal transduction;phospholipid biosynthetic process;fibroblast migration;regulation of phosphatidylinositol 3-kinase signaling;cell migration;keratinocyte differentiation;actin cytoskeleton reorganization;phosphatidylinositol phosphorylation;focal adhesion assembly;cell chemotaxis;protein localization to plasma membrane;activation of GTPase activity;ruffle assembly
- Cellular component
- nucleus;nucleoplasm;cytosol;mRNA cleavage and polyadenylation specificity factor complex;plasma membrane;focal adhesion;nuclear speck;lamellipodium;ruffle membrane
- Molecular function
- 1-phosphatidylinositol-3-phosphate 5-kinase activity;protein binding;ATP binding;1-phosphatidylinositol-4-phosphate 5-kinase activity;kinase binding;1-phosphatidylinositol-5-kinase activity;1-phosphatidylinositol-3-phosphate 4-kinase activity;phosphatidylinositol-3,4-bisphosphate 5-kinase activity