PIK3CG
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma, the group of Phosphatidylinositol 3-kinase subunits
Basic information
Region (hg38): 7:106865278-106908980
Links
Phenotypes
GenCC
Source:
- immunodeficiency 97 with autoinflammation (Limited), mode of inheritance: Unknown
- immunodeficiency 97 with autoinflammation (Moderate), mode of inheritance: AR
- immunodeficiency 97 with autoinflammation (Moderate), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Immunodeficiency 97 with autoinflammation | AR | Allergy/Immunology/Infectious | Antiinfectious prophylaxis, early and aggressive treatment of infections, and medical management (eg, treatment with anakinra has been described) may be beneficial | Allergy/Immunology/Infectious | 31554793; 33054089 |
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 PIK3CG 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 | 10 | 15 | ||||
| missense | 51 | 59 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 3 | |||||
| Total | 0 | 0 | 53 | 15 | 11 |
Variants in PIK3CG
This is a list of pathogenic ClinVar variants found in the PIK3CG region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 7-106867579-T-C | Likely benign (Apr 13, 2018) | |||
| 7-106867617-G-A | Inborn genetic diseases | Uncertain significance (Aug 02, 2021) | ||
| 7-106867646-G-C | Inborn genetic diseases | Uncertain significance (Nov 14, 2024) | ||
| 7-106867658-T-C | Inborn genetic diseases | Uncertain significance (Jun 25, 2024) | ||
| 7-106867664-A-G | Inborn genetic diseases | Uncertain significance (Mar 02, 2023) | ||
| 7-106867696-C-T | Likely benign (Feb 01, 2023) | |||
| 7-106867706-C-A | Immunodeficiency 97 with autoinflammation | Pathogenic (Apr 04, 2022) | ||
| 7-106867721-C-G | Inborn genetic diseases | Uncertain significance (Jan 29, 2024) | ||
| 7-106867738-G-C | Likely benign (Feb 01, 2023) | |||
| 7-106867766-C-G | Inborn genetic diseases | Uncertain significance (Jan 08, 2024) | ||
| 7-106867796-C-A | Inborn genetic diseases | Uncertain significance (Apr 07, 2022) | ||
| 7-106867819-C-T | Benign (Jul 04, 2018) | |||
| 7-106867883-G-C | Inborn genetic diseases | Uncertain significance (May 24, 2023) | ||
| 7-106867892-G-C | Inborn genetic diseases | Uncertain significance (Mar 02, 2023) | ||
| 7-106867929-G-A | Inborn genetic diseases | Uncertain significance (Aug 23, 2021) | ||
| 7-106867947-ACCGGAGC-A | - | no classification for the single variant (-) | ||
| 7-106867951-G-C | Benign/Likely benign (Dec 01, 2023) | |||
| 7-106867958-G-A | Inborn genetic diseases | Uncertain significance (Aug 18, 2023) | ||
| 7-106867973-G-A | Inborn genetic diseases | Uncertain significance (Aug 23, 2021) | ||
| 7-106867982-C-A | Inborn genetic diseases | Uncertain significance (Oct 12, 2022) | ||
| 7-106868013-AGCGGCAGCTCACG-A | - | no classification for the single variant (-) | ||
| 7-106868035-T-G | Inborn genetic diseases | Uncertain significance (Jan 24, 2023) | ||
| 7-106868074-T-A | Inborn genetic diseases | Uncertain significance (Oct 25, 2024) | ||
| 7-106868089-G-T | Likely benign (Apr 01, 2022) | |||
| 7-106868118-C-A | Inborn genetic diseases | Uncertain significance (Mar 24, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PIK3CG | protein_coding | protein_coding | ENST00000359195 | 10 | 41868 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00000141 | 1.00 | 125696 | 0 | 52 | 125748 | 0.000207 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.97 | 514 | 656 | 0.784 | 0.0000406 | 7276 |
| Missense in Polyphen | 120 | 203.12 | 0.59078 | 2312 | ||
| Synonymous | 0.115 | 273 | 275 | 0.991 | 0.0000197 | 2129 |
| Loss of Function | 3.72 | 18 | 44.9 | 0.401 | 0.00000216 | 514 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000121 | 0.000121 |
| Ashkenazi Jewish | 0.0000994 | 0.0000992 |
| East Asian | 0.000381 | 0.000272 |
| Finnish | 0.000193 | 0.000185 |
| European (Non-Finnish) | 0.000278 | 0.000273 |
| Middle Eastern | 0.000381 | 0.000272 |
| South Asian | 0.000196 | 0.000196 |
| Other | 0.000164 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Phosphoinositide-3-kinase (PI3K) that phosphorylates 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. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin- based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B- lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis. {ECO:0000269|PubMed:12163475, ECO:0000269|PubMed:15294162, ECO:0000269|PubMed:16094730, ECO:0000269|PubMed:21393242, ECO:0000269|PubMed:7624799}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Platelet activation - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Inositol phosphate metabolism - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics;Sorafenib Pharmacodynamics;Leucine Stimulation on Insulin Signaling;Insulin Signalling;EGF-Core;IGF-Core;IL-5 Signaling Pathway;AMP-activated Protein Kinase (AMPK) Signaling;Regulation of toll-like receptor signaling pathway;MicroRNAs in cardiomyocyte hypertrophy;Prolactin Signaling Pathway;Signaling Pathways in Glioblastoma;B Cell Receptor Signaling Pathway;JAK-STAT;BDNF-TrkB Signaling;Amplification and Expansion of Oncogenic Pathways as Metastatic Traits;Association Between Physico-Chemical Features and Toxicity Associated Pathways;PI3K-AKT-mTOR signaling pathway and therapeutic opportunities;Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling;Regulation of Apoptosis by Parathyroid Hormone-related Protein;Angiopoietin Like Protein 8 Regulatory Pathway;Chemokine signaling pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Leptin Insulin Overlap;Microglia Pathogen Phagocytosis Pathway;PI3K-Akt Signaling Pathway;Insulin Signaling;Regulation of Actin Cytoskeleton;EPO Receptor Signaling;DNA Damage Response (only ATM dependent);Toll-like Receptor Signaling Pathway;Signaling by GPCR;Signal Transduction;Metabolism of lipids;Alpha6Beta4Integrin;Inositol phosphate metabolism;Metabolism;3-phosphoinositide biosynthesis;superpathway of inositol phosphate compounds;BCR;GPVI-mediated activation cascade;Platelet activation, signaling and aggregation;Phosphatidylinositol phosphate metabolism;EGFR1;CXCR4-mediated signaling events;Hemostasis;Thromboxane A2 receptor signaling;IL2;Class IB PI3K non-lipid kinase events;Synthesis of PIPs at the plasma membrane;Class I PI3K signaling events;PI Metabolism;Phospholipid metabolism;IL5;G beta:gamma signalling through PI3Kgamma;G-protein beta:gamma signalling;GPCR downstream signalling;CD40/CD40L signaling;IL8- and CXCR1-mediated signaling events;PDGFR-beta signaling pathway;IL8- and CXCR2-mediated signaling events;EPHA forward signaling
(Consensus)
Recessive Scores
- pRec
- 0.760
Intolerance Scores
- loftool
- 0.490
- rvis_EVS
- -0.81
- rvis_percentile_EVS
- 12.05
Haploinsufficiency Scores
- pHI
- 0.960
- hipred
- Y
- hipred_score
- 0.756
- ghis
- 0.570
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pik3cg
- Phenotype
- immune system phenotype; skeleton phenotype; 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); 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); endocrine/exocrine gland phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region 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);
Gene ontology
- Biological process
- angiogenesis;cytokine production;adaptive immune response;dendritic cell chemotaxis;positive regulation of acute inflammatory response;respiratory burst involved in defense response;protein phosphorylation;endocytosis;inflammatory response;G protein-coupled receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;T cell chemotaxis;negative regulation of triglyceride catabolic process;phosphatidylinositol 3-kinase signaling;positive regulation of phosphatidylinositol 3-kinase signaling;phosphorylation;cell migration;platelet activation;neutrophil chemotaxis;secretory granule localization;regulation of cell adhesion mediated by integrin;natural killer cell chemotaxis;phosphatidylinositol-3-phosphate biosynthetic process;T cell proliferation;T cell activation;mast cell degranulation;positive regulation of MAP kinase activity;innate immune response;phosphatidylinositol phosphorylation;phosphatidylinositol-mediated signaling;positive regulation of protein kinase B signaling;negative regulation of cardiac muscle contraction;platelet aggregation;cellular response to cAMP;neutrophil extravasation;hepatocyte apoptotic process;regulation of calcium ion transmembrane transport;negative regulation of fibroblast apoptotic process
- Cellular component
- cytoplasm;cytosol;plasma membrane;phosphatidylinositol 3-kinase complex;phosphatidylinositol 3-kinase complex, class IB;membrane;mast cell granule
- Molecular function
- protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;kinase activity;1-phosphatidylinositol-3-kinase activity;phosphatidylinositol 3-kinase activity;1-phosphatidylinositol-4-phosphate 3-kinase activity;identical protein binding;ephrin receptor binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity