PIK3CB
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta, the group of Phosphatidylinositol 3-kinase subunits
Basic information
Region (hg38): 3:138652697-138834928
Previous symbols: [ "PIK3C1" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (29 variants)
- not provided (21 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIK3CB 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 | 12 | |||||
| missense | 28 | 31 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 1 | 1 | ||||
| non coding ? | 6 | |||||
| Total | 0 | 0 | 28 | 14 | 7 |
Variants in PIK3CB
This is a list of pathogenic ClinVar variants found in the PIK3CB region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-138655397-T-G | Benign (Dec 31, 2019) | |||
| 3-138655414-G-A | not specified | Uncertain significance (Jun 12, 2023) | ||
| 3-138656179-G-C | not specified | Uncertain significance (Apr 04, 2023) | ||
| 3-138656200-A-C | not specified | Uncertain significance (Feb 07, 2023) | ||
| 3-138656202-C-G | Likely benign (Dec 14, 2018) | |||
| 3-138656222-G-C | not specified | Uncertain significance (Feb 26, 2024) | ||
| 3-138656225-T-A | not specified | Uncertain significance (Nov 05, 2021) | ||
| 3-138656256-C-A | NK-cell enteropathy | Likely pathogenic (Jul 31, 2019) | ||
| 3-138656283-G-A | Likely benign (Apr 04, 2018) | |||
| 3-138657732-A-G | not specified | Uncertain significance (Jan 03, 2024) | ||
| 3-138663898-C-A | Likely benign (Jul 06, 2018) | |||
| 3-138664015-C-A | Likely benign (Oct 23, 2018) | |||
| 3-138665026-A-G | Likely benign (Jun 21, 2018) | |||
| 3-138665052-T-C | not specified | Uncertain significance (Dec 03, 2021) | ||
| 3-138665168-C-T | not specified | Uncertain significance (Aug 21, 2023) | ||
| 3-138681982-G-A | not specified | Uncertain significance (Apr 22, 2022) | ||
| 3-138682017-T-C | Likely benign (Dec 31, 2019) | |||
| 3-138682038-T-C | Benign (Jan 02, 2019) | |||
| 3-138683669-A-C | Likely benign (Dec 31, 2019) | |||
| 3-138684641-T-A | not specified | Uncertain significance (Oct 03, 2022) | ||
| 3-138684790-T-C | Likely benign (Dec 31, 2019) | |||
| 3-138688912-C-T | not specified | Uncertain significance (Jan 31, 2022) | ||
| 3-138691056-T-C | Likely benign (Apr 20, 2018) | |||
| 3-138691104-T-C | Benign (Dec 31, 2019) | |||
| 3-138694795-C-T | not specified | Uncertain significance (Nov 13, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PIK3CB | protein_coding | protein_coding | ENST00000477593 | 22 | 180921 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000359 | 125730 | 0 | 12 | 125742 | 0.0000477 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.09 | 357 | 564 | 0.633 | 0.0000290 | 7059 |
| Missense in Polyphen | 76 | 195.46 | 0.38882 | 2530 | ||
| Synonymous | 0.622 | 186 | 197 | 0.944 | 0.00000971 | 1973 |
| Loss of Function | 6.27 | 9 | 62.4 | 0.144 | 0.00000382 | 718 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000906 | 0.0000906 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000465 | 0.0000462 |
| European (Non-Finnish) | 0.0000711 | 0.0000703 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000328 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4- phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5- bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Involved in the activation of AKT1 upon stimulation by G-protein coupled receptors (GPCRs) ligands such as CXCL12, sphingosine 1-phosphate, and lysophosphatidic acid. May also act downstream receptor tyrosine kinases. Required in different signaling pathways for stable platelet adhesion and aggregation. Plays a role in platelet activation signaling triggered by GPCRs, alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) and ITAM (immunoreceptor tyrosine-based activation motif)-bearing receptors such as GP6. Regulates the strength of adhesion of ITGA2B/ ITGB3 activated receptors necessary for the cellular transmission of contractile forces. Required for platelet aggregation induced by F2 (thrombin) and thromboxane A2 (TXA2). Has a role in cell survival. May have a role in cell migration. Involved in the early stage of autophagosome formation. Modulates the intracellular level of PtdIns3P (Phosphatidylinositol 3-phosphate) and activates PIK3C3 kinase activity. May act as a scaffold, independently of its lipid kinase activity to positively regulate autophagy. May have a role in insulin signaling as scaffolding protein in which the lipid kinase activity is not required. May have a kinase-independent function in regulating cell proliferation and in clathrin-mediated endocytosis. Mediator of oncogenic signal in cell lines lacking PTEN. The lipid kinase activity is necessary for its role in oncogenic transformation. Required for the growth of ERBB2 and RAS driven tumors. {ECO:0000269|PubMed:18594509, ECO:0000269|PubMed:18755892, ECO:0000269|PubMed:21030680, ECO:0000269|PubMed:21383062}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Non-small cell lung cancer - Homo sapiens (human);Platelet activation - Homo sapiens (human);Chronic myeloid leukemia - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Focal adhesion - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Regulation of lipolysis in adipocytes - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Renal cell carcinoma - Homo sapiens (human);Inositol phosphate metabolism - Homo sapiens (human);VEGF signaling pathway - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Melanoma - Homo sapiens (human);Type II diabetes mellitus - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Longevity regulating pathway - multiple species - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Influenza A - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);Breast cancer - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Carbohydrate digestion and absorption - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Axon guidance - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Glioma - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Aldosterone-regulated sodium reabsorption - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Apoptosis - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Human papillomavirus infection - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics;Sorafenib Pharmacodynamics;AMP-activated Protein Kinase (AMPK) Signaling;Regulation of toll-like receptor signaling pathway;MicroRNAs in cardiomyocyte hypertrophy;Prolactin Signaling Pathway;Signaling Pathways in Glioblastoma;JAK-STAT;Focal Adhesion;PI3K-AKT-mTOR signaling pathway and therapeutic opportunities;Angiopoietin Like Protein 8 Regulatory Pathway;Chemokine signaling pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Microglia Pathogen Phagocytosis Pathway;Endometrial cancer;PI3K-Akt Signaling Pathway;MET in type 1 papillary renal cell carcinoma;Ras Signaling;EMT transition in Colorectal Cancer;Insulin Signaling;Regulation of Actin Cytoskeleton;G13 Signaling Pathway;DNA Damage Response (only ATM dependent);Toll-like Receptor Signaling Pathway;Signaling by GPCR;Disease;Signal Transduction;Signaling by Interleukins;DAP12 signaling;DAP12 interactions;VEGFA-VEGFR2 Pathway;Metabolism of lipids;Cytokine Signaling in Immune system;Alpha6Beta4Integrin;B cell receptor signaling;Downstream TCR signaling;TCR signaling;PI3K Cascade;IRS-mediated signalling;Insulin receptor signalling cascade;Signaling by Insulin receptor;Signaling by PDGF;Inositol phosphate metabolism;Role of phospholipids in phagocytosis;Fcgamma receptor (FCGR) dependent phagocytosis;HGF;Fc epsilon receptor (FCERI) signaling;IGF signaling;Innate Immune System;Immune System;Metabolism;3-phosphoinositide biosynthesis;FGF;Interleukin receptor SHC signaling;Interleukin-2 family signaling;Adaptive Immune System;superpathway of inositol phosphate compounds;insulin Mam;ErbB4 signaling events;GPVI-mediated activation cascade;Platelet activation, signaling and aggregation;IL-7 signaling;Phosphatidylinositol phosphate metabolism;Signaling by NTRK1 (TRKA);Signaling by NTRKs;EGFR1;Tie2 Signaling;CXCR4-mediated signaling events;ErbB1 downstream signaling;Cell surface interactions at the vascular wall;Hemostasis;PI3K/AKT activation;Signaling events mediated by TCPTP;PIP3 activates AKT signaling;PDGF;IL2;EPO signaling;Downstream signal transduction;Synthesis of PIPs at the plasma membrane;Class I PI3K signaling events;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Signaling by VEGF;PI Metabolism;Phospholipid metabolism;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K/AKT Signaling in Cancer;IRS-related events triggered by IGF1R;IGF1R signaling cascade;Signaling by Receptor Tyrosine Kinases;VEGF;Nephrin family interactions;Cell-Cell communication;G beta:gamma signalling through PI3Kgamma;G-protein beta:gamma signalling;GPCR downstream signalling;ErbB2/ErbB3 signaling events;Intracellular signaling by second messengers;CD40/CD40L signaling;TRAIL signaling pathway;LPA receptor mediated events;Diseases of signal transduction;Internalization of ErbB1;CXCR3-mediated signaling events;FAS (CD95) signaling pathway;PDGFR-beta signaling pathway;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);Nephrin/Neph1 signaling in the kidney podocyte;CD4 T cell receptor signaling-NFkB cascade;Role of LAT2/NTAL/LAB on calcium mobilization;insulin;CD4 T cell receptor signaling;Regulation of signaling by CBL;Interleukin-3, 5 and GM-CSF signaling
(Consensus)
Recessive Scores
- pRec
- 0.362
Intolerance Scores
- loftool
- 0.313
- rvis_EVS
- -1.42
- rvis_percentile_EVS
- 4.1
Haploinsufficiency Scores
- pHI
- 0.998
- hipred
- Y
- hipred_score
- 0.758
- ghis
- 0.591
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pik3cb
- Phenotype
- integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; skeleton phenotype; embryo phenotype; respiratory system 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); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm;
Gene ontology
- Biological process
- activation of MAPK activity;endothelial cell proliferation;regulation of cell-matrix adhesion;protein phosphorylation;cellular calcium ion homeostasis;autophagy;chemotaxis;homophilic cell adhesion via plasma membrane adhesion molecules;signal transduction;transmembrane receptor protein tyrosine kinase signaling pathway;G protein-coupled receptor signaling pathway;axon guidance;positive regulation of autophagy;positive regulation of gene expression;phosphatidylinositol 3-kinase signaling;positive regulation of phosphatidylinositol 3-kinase signaling;phosphorylation;cell migration;cytokine-mediated signaling pathway;platelet activation;positive regulation of neutrophil apoptotic process;phosphatidylinositol-3-phosphate biosynthetic process;Fc-epsilon receptor signaling pathway;Fc-gamma receptor signaling pathway involved in phagocytosis;embryonic cleavage;phosphatidylinositol phosphorylation;vascular endothelial growth factor receptor signaling pathway;phosphatidylinositol-mediated signaling;T cell receptor signaling pathway;leukocyte migration;positive regulation of protein kinase B signaling;angiogenesis involved in wound healing;platelet aggregation;regulation of clathrin-dependent endocytosis
- Cellular component
- nucleus;nucleolus;cytoplasm;cytosol;plasma membrane;phosphatidylinositol 3-kinase complex;membrane;midbody
- Molecular function
- protein binding;ATP binding;kinase activity;1-phosphatidylinositol-3-kinase activity;phosphatidylinositol 3-kinase activity;1-phosphatidylinositol-4-phosphate 3-kinase activity;insulin receptor substrate binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity