PIK3CA
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, the group of Phosphatidylinositol 3-kinase subunits
Basic information
Region (hg38): 3:179148113-179240093
Links
Phenotypes
GenCC
Source:
- CLOVES syndrome (Definitive), mode of inheritance: Somatic mosaicism
- megalencephaly-capillary malformation-polymicrogyria syndrome (Definitive), mode of inheritance: Somatic mosaicism
- vascular malformation (Strong), mode of inheritance: AD
- megalencephaly-capillary malformation-polymicrogyria syndrome (Strong), mode of inheritance: AD
- megalencephaly-capillary malformation-polymicrogyria syndrome (Strong), mode of inheritance: AD
- Cowden disease (Supportive), mode of inheritance: AD
- CLOVES syndrome (Definitive), mode of inheritance: AD
- megalencephaly-capillary malformation-polymicrogyria syndrome (Definitive), mode of inheritance: AD
- megalencephaly-capillary malformation-polymicrogyria syndrome (Strong), mode of inheritance: AD
- Cowden syndrome 5 (Limited), mode of inheritance: AD
- familial ovarian cancer (No Known Disease Relationship), mode of inheritance: AD
- hereditary breast carcinoma (Refuted Evidence), mode of inheritance: AD
- overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cowden syndrome 5 | AD | Oncologic | Individuals have been reported with a variety of types of cancer, including breast, thyroid, renal, and endometrial cancer, and surveillance and awareness may allow early detection and management of neoplastic disease | Dermatologic; Endocrine; Oncologic | 23246288; 34496175 |
| Somatic variants can cause Cerebral cavenous malformations 4 |
ClinVar
This is a list of variants' phenotypes submitted to
- Cowden syndrome (541 variants)
- Inborn genetic diseases (508 variants)
- not provided (193 variants)
- PIK3CA related overgrowth syndrome (35 variants)
- Megalencephaly-capillary malformation-polymicrogyria syndrome (31 variants)
- Neoplasm of the large intestine (24 variants)
- Breast neoplasm (24 variants)
- Malignant neoplasm of body of uterus (23 variants)
- Cowden syndrome 5 (23 variants)
- Glioblastoma (21 variants)
- Squamous cell carcinoma of the head and neck (21 variants)
- Gastric adenocarcinoma (20 variants)
- not specified (18 variants)
- Neoplasm of uterine cervix (18 variants)
- Squamous cell lung carcinoma (16 variants)
- Transitional cell carcinoma of the bladder (15 variants)
- Lung adenocarcinoma (15 variants)
- Neoplasm of brain (15 variants)
- Prostate adenocarcinoma (15 variants)
- CLOVES syndrome (13 variants)
- Cowden syndrome 1 (13 variants)
- Uterine carcinosarcoma (12 variants)
- Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes (11 variants)
- Abnormal cardiovascular system morphology (11 variants)
- Neoplasm of ovary (11 variants)
- Hepatocellular carcinoma (10 variants)
- Hereditary cancer-predisposing syndrome (9 variants)
- Malignant melanoma of skin (9 variants)
- PIK3CA-related condition (9 variants)
- Pancreatic adenocarcinoma (8 variants)
- Brainstem glioma (8 variants)
- Carcinoma of esophagus (8 variants)
- Non-small cell lung carcinoma (8 variants)
- Papillary renal cell carcinoma type 1 (7 variants)
- CLAPO syndrome (6 variants)
- Medulloblastoma (6 variants)
- Ovarian serous cystadenocarcinoma (6 variants)
- Familial cancer of breast (5 variants)
- Small cell lung carcinoma (5 variants)
- 13 conditions (5 variants)
- Papillary renal cell carcinoma, sporadic (5 variants)
- Segmental undergrowth associated with mainly venous malformation with capillary component (4 variants)
- Adenoid cystic carcinoma (4 variants)
- Angioosteohypertrophic syndrome (4 variants)
- Capillary malformation (3 variants)
- CEREBRAL CAVERNOUS MALFORMATIONS 4, SOMATIC (3 variants)
- See cases (3 variants)
- OVARIAN CANCER, EPITHELIAL, SOMATIC (3 variants)
- Gastric cancer (3 variants)
- Carcinoma of colon (3 variants)
- Breast adenocarcinoma (3 variants)
- Nasopharyngeal neoplasm (3 variants)
- Adrenal cortex carcinoma (3 variants)
- Cerebrofacial Vascular Metameric Syndrome (CVMS) (3 variants)
- Segmental undergrowth associated with lymphatic malformation (3 variants)
- Gallbladder carcinoma (3 variants)
- Abnormal cerebral morphology (2 variants)
- PIK3CA-related disorder (2 variants)
- Thyroid tumor (2 variants)
- Seborrheic keratosis (2 variants)
- MACRODACTYLY, SOMATIC (2 variants)
- Lip and oral cavity carcinoma (2 variants)
- Multiple myeloma (2 variants)
- Colorectal cancer (2 variants)
- Neuroblastoma (2 variants)
- Hemimegalencephaly;Facial asymmetry;Overgrowth (1 variants)
- Endometrial carcinoma (1 variants)
- Keratoacanthoma (1 variants)
- Breast carcinoma (1 variants)
- Klippel-Trenaunay-like-Syndrome (1 variants)
- Lung carcinoma (1 variants)
- - (1 variants)
- Neoplasm (1 variants)
- Non-Hodgkin lymphoma (1 variants)
- Hemihypertrophy (1 variants)
- Stroke disorder;Macrodactyly of toe (1 variants)
- PIK3CA-Related Disorders (1 variants)
- Polycystic kidney disease (1 variants)
- Seizure;Focal-onset seizure;Corpus callosum, agenesis of;Ectopic tissue (1 variants)
- Megalencephaly-capillary malformation-polymicrogyria syndrome;Noonan syndrome 8 (1 variants)
- Rhabdomyosarcoma (1 variants)
- Klippel-Trénaunay syndrome (1 variants)
- Macrocephaly;Global developmental delay;Hypospadias (1 variants)
- Trabecular adenocarcinoma (1 variants)
- Sarcoma (1 variants)
- Eccrine Angiomatous Hamartoma (1 variants)
- Rosette-forming glioneuronal tumor (1 variants)
- Gallbladder cancer (1 variants)
- Epidermal nevus (1 variants)
- Malignant tumor of prostate (1 variants)
- Congenital macrodactylia (1 variants)
- Malignant tumor of floor of mouth (1 variants)
- Cerebral cavernous malformation 4 (1 variants)
- Megalencephaly, autosomal dominant;Intestinal duplication;Abnormality of the hairline;Hypertelorism;Diaphragmatic eventration (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIK3CA 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 | 371 | 379 | ||||
| missense | 31 | 25 | 373 | 434 | ||
| nonsense | 7 | |||||
| start loss | 2 | |||||
| frameshift | 9 | |||||
| inframe indel | 13 | |||||
| splice donor/acceptor (+/-2bp) | 3 | |||||
| splice region ? | 21 | 29 | 1 | 51 | ||
| non coding ? | 97 | 48 | 146 | |||
| Total | 34 | 33 | 403 | 473 | 50 |
Variants in PIK3CA
This is a list of pathogenic ClinVar variants found in the PIK3CA region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-179148542-C-T | Cowden syndrome 1 | Likely benign (May 28, 2019) | ||
| 3-179148799-G-A | Hereditary cancer-predisposing syndrome | Likely benign (Dec 01, 2015) | ||
| 3-179198547-G-T | Benign (Aug 14, 2018) | |||
| 3-179198612-A-T | Hereditary cancer-predisposing syndrome | Likely benign (Dec 01, 2015) | ||
| 3-179198716-C-G | Likely benign (Mar 16, 2019) | |||
| 3-179198731-T-C | Likely benign (Sep 04, 2018) | |||
| 3-179198826-A-G | Cowden syndrome • Epidermal nevus • Megalencephaly-capillary malformation-polymicrogyria syndrome | Uncertain significance (Oct 09, 2023) | ||
| 3-179198827-T-C | Cowden syndrome 5 | Uncertain significance (Sep 02, 2022) | ||
| 3-179198829-C-T | Inborn genetic diseases | Uncertain significance (Mar 10, 2022) | ||
| 3-179198831-T-G | Inborn genetic diseases | Likely benign (Jan 17, 2021) | ||
| 3-179198836-G-C | Uncertain significance (Jan 31, 2020) | |||
| 3-179198840-A-G | Cowden syndrome • Inborn genetic diseases | Likely benign (May 13, 2023) | ||
| 3-179198846-A-C | Inborn genetic diseases | Likely benign (Nov 19, 2020) | ||
| 3-179198846-A-G | Inborn genetic diseases | Likely benign (May 11, 2020) | ||
| 3-179198852-ACTGTGGGGCATCCACTTGATGCCCC-A | Cowden syndrome | Uncertain significance (May 22, 2018) | ||
| 3-179198854-T-C | Uncertain significance (Oct 31, 2022) | |||
| 3-179198855-G-A | Cowden syndrome • Inborn genetic diseases | Likely benign (Mar 17, 2023) | ||
| 3-179198856-TGGGGCATCCACTTGATGCCCC-T | Likely pathogenic (Aug 20, 2021) | |||
| 3-179198862-A-G | Cowden syndrome | Uncertain significance (May 07, 2021) | ||
| 3-179198865-C-T | Cowden syndrome | Uncertain significance (Nov 18, 2018) | ||
| 3-179198867-C-G | Inborn genetic diseases | Uncertain significance (Dec 07, 2023) | ||
| 3-179198867-C-T | Inborn genetic diseases • Cowden syndrome | Likely benign (Apr 11, 2023) | ||
| 3-179198869-T-G | Inborn genetic diseases | Uncertain significance (Dec 07, 2023) | ||
| 3-179198870-G-C | Inborn genetic diseases • Cowden syndrome | Uncertain significance (Jan 14, 2023) | ||
| 3-179198876-C-A | Inborn genetic diseases | Likely benign (Jan 10, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PIK3CA | protein_coding | protein_coding | ENST00000263967 | 20 | 91980 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 4.14e-9 | 124789 | 0 | 5 | 124794 | 0.0000200 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 5.60 | 191 | 566 | 0.338 | 0.0000285 | 7098 |
| Missense in Polyphen | 31 | 200.84 | 0.15435 | 2490 | ||
| Synonymous | 2.36 | 144 | 185 | 0.779 | 0.00000879 | 1924 |
| Loss of Function | 7.21 | 3 | 66.4 | 0.0452 | 0.00000431 | 710 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000291 | 0.0000291 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000464 | 0.0000464 |
| European (Non-Finnish) | 0.0000266 | 0.0000265 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| 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. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. Also has serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS. Plays a role in the positive regulation of phagocytosis and pinocytosis (By similarity). {ECO:0000250|UniProtKB:P42337, ECO:0000269|PubMed:21708979, ECO:0000269|PubMed:26593112}.;
- Disease
- DISEASE: Note=PIK3CA mutations are involved in various type of cancer. Most of the cancer-associated mutations are missense mutations and map to one of the three hotspots: Glu-542; Glu-545 and His-1047. Mutated isoforms participate in cellular transformation and tumorigenesis induced by oncogenic receptor tyrosine kinases (RTKs) and HRAS/KRAS. Interaction with HRAS/KRAS is required for Ras-driven tumor formation. Mutations increasing the lipid kinase activity are required for oncogenic signaling. The protein kinase activity may not be required for tumorigenesis. {ECO:0000269|PubMed:15016963, ECO:0000269|PubMed:15289301, ECO:0000269|PubMed:15520168, ECO:0000269|PubMed:15712344, ECO:0000269|PubMed:15784156, ECO:0000269|PubMed:15924253, ECO:0000269|PubMed:15930273, ECO:0000269|PubMed:15994075, ECO:0000269|PubMed:16114017, ECO:0000269|PubMed:16322209, ECO:0000269|PubMed:16353168, ECO:0000269|PubMed:16432179, ECO:0000269|PubMed:16533766, ECO:0000269|PubMed:17673550, ECO:0000269|PubMed:19805105, ECO:0000269|PubMed:21708979, ECO:0000269|PubMed:22658544, ECO:0000269|PubMed:22729224}.; DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:15930273, ECO:0000269|PubMed:15994075}. Note=The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:16353168}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. {ECO:0000269|PubMed:15520168}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Hepatocellular carcinoma (HCC) [MIM:114550]: A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. {ECO:0000269|PubMed:15608678}. Note=The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Keratosis, seborrheic (KERSEB) [MIM:182000]: A common benign skin tumor. Seborrheic keratoses usually begin with the appearance of one or more sharply defined, light brown, flat macules. The lesions may be sparse or numerous. As they initially grow, they develop a velvety to finely verrucous surface, followed by an uneven warty surface with multiple plugged follicles and a dull or lackluster appearance. {ECO:0000269|PubMed:17673550}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) [MIM:602501]: A syndrome characterized by a spectrum of anomalies including primary megalencephaly, prenatal overgrowth, brain and body asymmetry, cutaneous vascular malformations, digital anomalies consisting of syndactyly with or without postaxial polydactyly, connective tissue dysplasia involving the skin, subcutaneous tissue, and joints, and cortical brain malformations, most distinctively polymicrogyria. {ECO:0000269|PubMed:22729224, ECO:0000269|PubMed:26593112}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE) [MIM:612918]: A sporadically occurring, non-hereditary disorder characterized by asymmetric somatic hypertrophy and anomalies in multiple organs. It is defined by four main clinical findings: congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal/spinal abnormalities. The presence of truncal overgrowth and characteristic patterned macrodactyly at birth differentiates CLOVE from other syndromic forms of overgrowth. {ECO:0000269|PubMed:22658544}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cowden syndrome 5 (CWS5) [MIM:615108]: A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid. {ECO:0000269|PubMed:23246288}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- 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);MicroRNAs in cancer - 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;Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;Fc Epsilon Receptor I Signaling in Mast Cells;Phosphatidylinositol Phosphate Metabolism;Joubert syndrome;Inositol Metabolism;AMP-activated Protein Kinase (AMPK) Signaling;Regulation of toll-like receptor signaling pathway;Angiogenesis;MicroRNAs in cardiomyocyte hypertrophy;Sterol Regulatory Element-Binding Proteins (SREBP) signalling;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Prolactin Signaling Pathway;Regulation of Microtubule Cytoskeleton;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;Signaling Pathways in Glioblastoma;Androgen Receptor Network in Prostate Cancer;JAK-STAT;IL1 and megakaryocytes in obesity;nerve growth factor pathway (ngf);Transcriptional activation by NRF2;Focal Adhesion;Signaling of Hepatocyte Growth Factor Receptor;Copper homeostasis;Rac1-Pak1-p38-MMP-2 pathway;Pathways Affected in Adenoid Cystic Carcinoma;PI3K-AKT-mTOR signaling pathway and therapeutic opportunities;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;IL-4 Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Chemokine signaling pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Microglia Pathogen Phagocytosis Pathway;PDGFR-beta pathway;miRNA regulation of prostate cancer signaling pathways;PI3K-AKT-mTOR - VitD3 Signalling;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);Estrogen signaling pathway;Serotonin HTR1 Group and FOS Pathway;Toll-like Receptor Signaling Pathway;Signaling by GPCR;Signaling by FGFR2;PI-3K cascade:FGFR2;Downstream signaling of activated FGFR2;PI-3K cascade:FGFR4;PI-3K cascade:FGFR3;Downstream signaling of activated FGFR3;Disease;Signaling by FGFR3;Signal Transduction;Downstream signaling of activated FGFR4;Signaling by Interleukins;DAP12 signaling;DAP12 interactions;Signaling by FGFR4;Signaling by FGFR;inhibition of cellular proliferation by gleevec;mtor signaling pathway;bioactive peptide induced signaling pathway;role of erk5 in neuronal survival pathway;the co-stimulatory signal during t-cell activation;erk and pi-3 kinase are necessary for collagen binding in corneal epithelia;role of pi3k subunit p85 in regulation of actin organization and cell migration;human cytomegalovirus and map kinase pathways;influence of ras and rho proteins on g1 to s transition;egf signaling pathway;trefoil factors initiate mucosal healing;transcription factor creb and its extracellular signals;tumor suppressor arf inhibits ribosomal biogenesis;regulation of eif-4e and p70s6 kinase;il-7 signal transduction;il-2 receptor beta chain in t cell activation;akt signaling pathway;phospholipase c signaling pathway;ras signaling pathway;cxcr4 signaling pathway;corticosteroids and cardioprotection;phospholipids as signalling intermediaries;regulation of bad phosphorylation;multiple antiapoptotic pathways from igf-1r signaling lead to bad phosphorylation;pten dependent cell cycle arrest and apoptosis;vegf hypoxia and angiogenesis;b cell survival pathway;VEGFA-VEGFR2 Pathway;nfat and hypertrophy of the heart ;thrombin signaling and protease-activated receptors;ras-independent pathway in nk cell-mediated cytotoxicity;skeletal muscle hypertrophy is regulated via akt-mtor pathway;trka receptor signaling pathway;insulin signaling pathway;t cell receptor signaling pathway;rac1 cell motility signaling pathway;role of erbb2 in signal transduction and oncology;ctcf: first multivalent nuclear factor;Metabolism of lipids;Cytokine Signaling in Immune system;Alpha6Beta4Integrin;B cell receptor signaling;Downstream TCR signaling;TCR signaling;CD28 dependent PI3K/Akt signaling;CD28 co-stimulation;PI3K Cascade;Costimulation by the CD28 family;IRS-mediated signalling;Insulin receptor signalling cascade;Signaling by Insulin receptor;Signaling by PDGF;igf-1 signaling pathway;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;IL5-mediated signaling events;Signaling by FGFR2 in disease;Adaptive Immune System;superpathway of inositol phosphate compounds;KitReceptor;insulin Mam;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;ErbB4 signaling events;actions of nitric oxide in the heart;pdgf signaling pathway;GPVI-mediated activation cascade;Signaling by EGFR;Platelet activation, signaling and aggregation;IL-7 signaling;Phosphatidylinositol phosphate metabolism;tpo signaling pathway;Signaling by NTRK1 (TRKA);TGF_beta_Receptor;role of nicotinic acetylcholine receptors in the regulation of apoptosis;fc epsilon receptor i signaling in mast cells;control of skeletal myogenesis by hdac and calcium/calmodulin-dependent kinase (camk);Signaling by NTRKs;EGFR1;SHP2 signaling;Tie2 Signaling;growth hormone signaling pathway;CXCR4-mediated signaling events;ErbB1 downstream signaling;Cell surface interactions at the vascular wall;Hemostasis;GAB1 signalosome;the igf-1 receptor and longevity;PI3K/AKT activation;BCR signaling pathway;Signaling events mediated by TCPTP;PIP3 activates AKT signaling;PDGF;IL2;VEGFR3 signaling in lymphatic endothelium;E-cadherin signaling in keratinocytes;EPO signaling;Signaling events regulated by Ret tyrosine kinase;a6b1 and a6b4 Integrin signaling;IL2-mediated signaling events;Downstream signal transduction;Ephrin B reverse signaling;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 EGFRvIII in Cancer;Signaling by EGFR in Cancer;IFN-gamma pathway;Signaling by VEGF;Angiopoietin receptor Tie2-mediated signaling;PI Metabolism;IL4;Signaling by FGFR3 point mutants in cancer;Phospholipid metabolism;Signaling by FGFR4 in disease;Signaling by FGFR3 fusions in cancer;Signaling by FGFR3 in disease;G alpha (12/13) signalling events;Signaling by SCF-KIT;Signaling by FGFR in disease;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K events in ERBB2 signaling;Signaling by ERBB2;PI3K/AKT Signaling in Cancer;PI3K events in ERBB4 signaling;Signaling by ERBB4;IRS-related events triggered by IGF1R;IGF1R signaling cascade;MET activates PI3K/AKT signaling;Signaling by cytosolic FGFR1 fusion mutants;FGFR1 mutant receptor activation;Signaling by FGFR1 in disease;Signaling by MET;Constitutive Signaling by EGFRvIII;Signaling by Receptor Tyrosine Kinases;VEGF;Nephrin family interactions;Cell-Cell communication;G alpha (q) signalling events;G beta:gamma signalling through PI3Kgamma;G-protein beta:gamma signalling;GPCR downstream signalling;Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants;Signaling by Ligand-Responsive EGFR Variants in Cancer;ErbB2/ErbB3 signaling events;Intracellular signaling by second messengers;Osteopontin-mediated events;IL23-mediated signaling events;GMCSF-mediated signaling events;IL2 signaling events mediated by STAT5;Insulin Pathway;PAR1-mediated thrombin signaling events;Nectin adhesion pathway;Neurotrophic factor-mediated Trk receptor signaling;CD40/CD40L signaling;TRAIL signaling pathway;Diseases of signal transduction;CDC42 signaling events;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Fc-epsilon receptor I signaling in mast cells;Internalization of ErbB1;Netrin-mediated signaling events;N-cadherin signaling events;Signaling events mediated by focal adhesion kinase;IL2 signaling events mediated by PI3K;Reelin signaling pathway;CXCR3-mediated signaling events;p75(NTR)-mediated signaling;EPHB forward signaling;IGF1 pathway;Signaling events mediated by Stem cell factor receptor (c-Kit);Plasma membrane estrogen receptor signaling;FAS (CD95) signaling pathway;Nongenotropic Androgen signaling;Trk receptor signaling mediated by PI3K and PLC-gamma;PDGFR-beta signaling pathway;IL1-mediated signaling events;IL4-mediated signaling events;Signaling events mediated by PTP1B;Downstream signaling of activated FGFR1;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);EPHA2 forward signaling;Signaling events mediated by the Hedgehog family;IL6-mediated signaling events;FGF signaling pathway;Signaling events mediated by VEGFR1 and VEGFR2;Nephrin/Neph1 signaling in the kidney podocyte;PDGFR-alpha signaling pathway;IL3-mediated signaling events;Integrins in angiogenesis;Atypical NF-kappaB pathway;E-cadherin signaling in the nascent adherens junction;S1P2 pathway;VEGFR1 specific signals;CD4 T cell receptor signaling-NFkB cascade;Role of LAT2/NTAL/LAB on calcium mobilization;insulin;PI-3K cascade:FGFR1;Signaling by FGFR1;CD4 T cell receptor signaling;Regulation of signaling by CBL;Interleukin-3, 5 and GM-CSF signaling
(Consensus)
Recessive Scores
- pRec
- 0.851
Intolerance Scores
- loftool
- 0.268
- rvis_EVS
- -0.45
- rvis_percentile_EVS
- 24.19
Haploinsufficiency Scores
- pHI
- 0.954
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.622
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- H
- 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
- Pik3ca
- Phenotype
- adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland 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; cellular phenotype; homeostasis/metabolism 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); muscle phenotype; neoplasm; 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); reproductive 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype;
Zebrafish Information Network
- Gene name
- pik3ca
- Affected structure
- retinal ganglion cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased branchiness
Gene ontology
- Biological process
- angiogenesis;liver development;vasculature development;glucose metabolic process;protein phosphorylation;epidermal growth factor receptor signaling pathway;G protein-coupled receptor signaling pathway;axon guidance;regulation of gene expression;phosphatidylinositol 3-kinase signaling;positive regulation of phosphatidylinositol 3-kinase signaling;negative regulation of macroautophagy;phosphorylation;cell migration;cytokine-mediated signaling pathway;platelet activation;T cell costimulation;positive regulation of TOR signaling;activation of protein kinase activity;positive regulation of peptidyl-serine phosphorylation;phosphatidylinositol-3-phosphate biosynthetic process;insulin receptor signaling pathway via phosphatidylinositol 3-kinase;Fc-epsilon receptor signaling pathway;Fc-gamma receptor signaling pathway involved in phagocytosis;ERBB2 signaling pathway;regulation of multicellular organism growth;anoikis;regulation of cellular respiration;protein kinase B signaling;negative regulation of neuron apoptotic process;endothelial cell migration;hypomethylation of CpG island;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;cardiac muscle contraction;adipose tissue development;cellular response to glucose stimulus;energy homeostasis;negative regulation of fibroblast apoptotic process;regulation of genetic imprinting;negative regulation of anoikis
- Cellular component
- cytoplasm;cytosol;plasma membrane;phosphatidylinositol 3-kinase complex;phosphatidylinositol 3-kinase complex, class IA;membrane;lamellipodium
- Molecular function
- protein serine/threonine kinase activity;protein binding;ATP binding;kinase activity;1-phosphatidylinositol-3-kinase activity;protein kinase activator activity;phosphatidylinositol 3-kinase activity;1-phosphatidylinositol-4-phosphate 3-kinase activity;insulin receptor substrate binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity