AKT1
AKT serine/threonine kinase 1, the group of Pleckstrin homology domain containing|AKT kinases
Basic information
Region (hg38): 14:104769348-104795751
Links
Phenotypes
GenCC
Source:
- Proteus syndrome (Definitive), mode of inheritance: Somatic mosaicism
- Cowden disease (Supportive), mode of inheritance: AD
- Proteus syndrome (Definitive), mode of inheritance: AD
- Proteus syndrome (Strong), mode of inheritance: AD
- Cowden syndrome 6 (Limited), mode of inheritance: Unknown
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cowden syndrome 6; Proteus syndrome | AD | Cardiovascular; Hematologic; Oncologic; Pulmonary | In Cowden syndrome, individuals have been described with manifestations including breast, renal, and thyroid cancer, and surveillance may allow early detection and management of neoplasms; In Proteus syndrome, individuals may be at risk for a variety of manifestations, some of which may be occult; Surveillance for hematologic/vascular manifestations (eg, deep vein thrombosis and pulmonary embolism) can allow early detection and treatment; Surveillance for pulmonary disease (as patients are at risk for restrictive lung disease) can allow early detection and treatment; As individuals may be at increased risk for neoplastic processes, routine monitoring by history and physical examination (without separate imaging) may allow early detection of neoplasms | Cardiovascular; Dermatologic; Craniofacial; Hematologic; Musculoskeletal; Neurologic; Oncologic; Pulmonary | 21793738; 22876373; 23246288 |
| In Proteus syndrome, variants may be found on peripheral blood testing, but affected tissue must typically be tested for molecular diagnosis |
ClinVar
This is a list of variants' phenotypes submitted to
- Cowden syndrome 6 (441 variants)
- Inborn genetic diseases (322 variants)
- not provided (88 variants)
- not specified (14 variants)
- AKT1-related condition (3 variants)
- Familial cancer of breast (2 variants)
- Lung adenocarcinoma (2 variants)
- Proteus syndrome (2 variants)
- Squamous cell carcinoma (2 variants)
- Transitional cell carcinoma of the bladder (1 variants)
- Hereditary cancer (1 variants)
- Neoplasm of uterine cervix (1 variants)
- Hepatocellular carcinoma (1 variants)
- Neoplasm of the large intestine (1 variants)
- Prostate neoplasm (1 variants)
- Carcinoma of colon (1 variants)
- Endometrial Endometrioid Adenocarcinoma, Variant with Squamous Differentiation (1 variants)
- Bone osteosarcoma (1 variants)
- Small cell lung carcinoma (1 variants)
- Neoplasm of ovary;Cowden syndrome 6;Familial cancer of breast;Proteus syndrome;Colorectal cancer (1 variants)
- Breast adenocarcinoma (1 variants)
- Non-small cell lung carcinoma (1 variants)
- Gastric adenocarcinoma (1 variants)
- Thyroid tumor (1 variants)
- Prostate adenocarcinoma (1 variants)
- Squamous cell carcinoma of the head and neck (1 variants)
- Hemihypertrophy (1 variants)
- Squamous cell lung carcinoma (1 variants)
- Tumor of meninges (1 variants)
- Neoplasm of ovary (1 variants)
- Malignant melanoma of skin (1 variants)
- Breast neoplasm (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the AKT1 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 | 243 | 250 | ||||
| missense | 225 | 229 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 2 | |||||
| inframe indel | 5 | |||||
| splice donor/acceptor (+/-2bp) | 3 | |||||
| splice region ? | 25 | 33 | 2 | 60 | ||
| non coding ? | 83 | 51 | 139 | |||
| Total | 2 | 1 | 244 | 327 | 55 |
Variants in AKT1
This is a list of pathogenic ClinVar variants found in the AKT1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 14-104770335-G-A | Benign (Jul 01, 2022) | |||
| 14-104770344-G-C | Cowden syndrome 6 | Uncertain significance (Jun 29, 2020) | ||
| 14-104770347-C-A | Cowden syndrome 6 | Likely benign (May 15, 2021) | ||
| 14-104770347-C-T | Cowden syndrome 6 • Inborn genetic diseases | Likely benign (May 30, 2022) | ||
| 14-104770348-G-A | Cowden syndrome 6 | Uncertain significance (Sep 15, 2020) | ||
| 14-104770352-C-T | Cowden syndrome 6 | Uncertain significance (May 31, 2023) | ||
| 14-104770353-G-A | Cowden syndrome 6 • Inborn genetic diseases | Likely benign (Oct 16, 2023) | ||
| 14-104770356-G-A | Inborn genetic diseases | Likely benign (Mar 12, 2021) | ||
| 14-104770359-C-T | Inborn genetic diseases • Cowden syndrome 6 • AKT1-related disorder | Conflicting classifications of pathogenicity (Nov 29, 2022) | ||
| 14-104770362-G-A | Inborn genetic diseases | Likely benign (Aug 11, 2023) | ||
| 14-104770364-A-G | Uncertain significance (Dec 12, 2022) | |||
| 14-104770365-G-C | Cowden syndrome 6 • Inborn genetic diseases | Likely benign (Mar 07, 2020) | ||
| 14-104770368-G-A | Cowden syndrome 6 • Inborn genetic diseases • AKT1-related disorder | Likely benign (Oct 03, 2023) | ||
| 14-104770380-G-A | Inborn genetic diseases | Likely benign (Feb 03, 2024) | ||
| 14-104770385-G-A | Cowden syndrome 6 | Uncertain significance (Nov 01, 2022) | ||
| 14-104770387-C-T | Cowden syndrome 6 | Uncertain significance (Apr 08, 2022) | ||
| 14-104770388-T-C | Inborn genetic diseases | Uncertain significance (Aug 03, 2023) | ||
| 14-104770389-G-C | Cowden syndrome 6 • Inborn genetic diseases | Likely benign (May 14, 2023) | ||
| 14-104770390-C-T | Cowden syndrome 6 | Conflicting classifications of pathogenicity (Jun 01, 2023) | ||
| 14-104770391-G-A | Cowden syndrome 6 | Uncertain significance (Dec 13, 2023) | ||
| 14-104770394-C-T | Cowden syndrome 6 | Uncertain significance (Sep 23, 2022) | ||
| 14-104770395-G-A | Cowden syndrome 6 | Benign (Jan 27, 2024) | ||
| 14-104770396-C-A | Inborn genetic diseases | Uncertain significance (Feb 27, 2023) | ||
| 14-104770396-C-T | Inborn genetic diseases | Uncertain significance (Nov 21, 2023) | ||
| 14-104770397-T-C | Inborn genetic diseases • Cowden syndrome 6 | Uncertain significance (Jan 26, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| AKT1 | protein_coding | protein_coding | ENST00000554581 | 13 | 26403 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.976 | 0.0241 | 125732 | 0 | 8 | 125740 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.48 | 152 | 330 | 0.461 | 0.0000223 | 3175 |
| Missense in Polyphen | 34 | 128.93 | 0.26371 | 1379 | ||
| Synonymous | -0.424 | 138 | 132 | 1.05 | 0.00000974 | 882 |
| Loss of Function | 4.31 | 4 | 29.1 | 0.138 | 0.00000150 | 311 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.000141 | 0.000139 |
| European (Non-Finnish) | 0.0000355 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000164 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: AKT1 is one of 3 closely related serine/threonine- protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)- response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development. Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3. Phosphorylates STK3/MST2 at 'Thr- 117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation. Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation. Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity. Phosphorylation of BAD stimulates its pro- apoptotic activity. Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53.;
- Disease
- 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:17611497}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; 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. Note=The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Note=Genetic variations in AKT1 may play a role in susceptibility to ovarian cancer.; DISEASE: Proteus syndrome (PROTEUSS) [MIM:176920]: A highly variable, severe disorder of asymmetric and disproportionate overgrowth of body parts, connective tissue nevi, epidermal nevi, dysregulated adipose tissue, and vascular malformations. Many features of Proteus syndrome overlap with other overgrowth syndromes. {ECO:0000269|PubMed:18954143, ECO:0000269|PubMed:21793738}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cowden syndrome 6 (CWS6) [MIM:615109]: 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);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);Adipocytokine signaling pathway - 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);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);Dopaminergic synapse - Homo sapiens (human);Melanoma - 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);AMPK signaling pathway - Homo sapiens (human);Glucagon 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);Adrenergic signaling in cardiomyocytes - 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);Apelin 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);Tuberculosis - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);cGMP-PKG signaling pathway - 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);Progesterone-mediated oocyte maturation - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics;Pathway_PA165959425;Sorafenib Pharmacodynamics;VEGF Signaling Pathway;Intracellular Signalling Through Adenosine Receptor A2b and Adenosine;Intracellular Signalling Through Adenosine Receptor A2a and Adenosine;Fc Epsilon Receptor I Signaling in Mast Cells;Leucine Stimulation on Insulin Signaling;Insulin Signalling;IGF-Core;WNT-Core;HH-Core;TGF-Core;IL-5 Signaling Pathway;Androgen receptor signaling pathway;AMP-activated Protein Kinase (AMPK) Signaling;Regulation of toll-like receptor signaling pathway;Target Of Rapamycin (TOR) Signaling;Angiogenesis;MicroRNAs in cardiomyocyte hypertrophy;TFs Regulate miRNAs related to cardiac hypertrophy;IL-1 signaling pathway;Sterol Regulatory Element-Binding Proteins (SREBP) signalling;Angiogenesis overview;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Integrin-mediated Cell Adhesion;Leptin signaling pathway;Human Thyroid Stimulating Hormone (TSH) signaling pathway;Follicle Stimulating Hormone (FSH) signaling pathway;TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;Prolactin Signaling Pathway;Regulation of Microtubule Cytoskeleton;IL-7 Signaling Pathway;IL17 signaling pathway;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;Signaling Pathways in Glioblastoma;B Cell Receptor Signaling Pathway;TNF alpha Signaling Pathway;AGE-RAGE pathway;Interleukin-11 Signaling Pathway;Corticotropin-releasing hormone signaling pathway;Oncostatin M Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Alpha 6 Beta 4 signaling pathway;Apoptosis;Primary Focal Segmental Glomerulosclerosis FSGS;T-Cell Receptor and Co-stimulatory Signaling;JAK-STAT;Signal Transduction of S1P Receptor;Cardiac Hypertrophic Response;IL-3 Signaling Pathway;Apoptosis-related network due to altered Notch3 in ovarian cancer;Extracellular vesicle-mediated signaling in recipient cells;Kit receptor signaling pathway;Focal Adhesion;Copper homeostasis;Rac1-Pak1-p38-MMP-2 pathway;MECP2 and Associated Rett Syndrome;Wnt Signaling Pathway;Apoptotic Signaling Pathway;IL-6 signaling pathway;Hepatitis C and Hepatocellular Carcinoma;Pathways Affected in Adenoid Cystic Carcinoma;Wnt-beta-catenin Signaling Pathway in Leukemia;TGF-beta Signaling Pathway;BDNF-TrkB Signaling;Association Between Physico-Chemical Features and Toxicity Associated Pathways;MAPK Signaling Pathway;PI3K-AKT-mTOR signaling pathway and therapeutic opportunities;Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling;TGF-B Signaling in Thyroid Cells for Epithelial-Mesenchymal Transition;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;Regulation of Apoptosis by Parathyroid Hormone-related Protein;4-hydroxytamoxifen, Dexamethasone, and Retinoic Acids Regulation of p27 Expression;IL-4 Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Chemokine signaling pathway;ESC Pluripotency Pathways;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Leptin Insulin Overlap;Lipid Metabolism Pathway;Steatosis AOP;Pathways in clear cell renal cell carcinoma;Interleukin-4 and 13 signaling;apoptotic signaling in response to dna damage;Fibrin Complement Receptor 3 Signaling Pathway;PI3K-AKT-mTOR - VitD3 Signalling;Endometrial cancer;PI3K-Akt Signaling Pathway;Ebola Virus Pathway on Host;Somatroph axis (GH) and its relationship to dietary restriction and aging;Caloric restriction and aging;MET in type 1 papillary renal cell carcinoma;Chromosomal and microsatellite instability in colorectal cancer;Ebola Virus Pathway on Host;Ras Signaling;EMT transition in Colorectal Cancer;EGF-EGFR Signaling Pathway;Endochondral Ossification;Insulin Signaling;IL-2 Signaling Pathway;EPO Receptor Signaling;Notch Signaling Pathway;T-Cell antigen Receptor (TCR) Signaling Pathway;DNA Damage Response (only ATM dependent);Estrogen signaling pathway;Toll-like Receptor Signaling Pathway;Developmental Biology;Signaling by PTK6;Signaling by GPCR;RAGE;TWEAK;RUNX2 regulates genes involved in cell migration;Transcriptional regulation by RUNX2;Notch;Disease;Signaling by WNT;Signal Transduction;Gene expression (Transcription);hypoxia and p53 in the cardiovascular system;inhibition of cellular proliferation by gleevec;mtor signaling pathway;role of erk5 in neuronal survival pathway;Vesicle-mediated transport;Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA;telomeres telomerase cellular aging and immortality;human cytomegalovirus and map kinase pathways;influence of ras and rho proteins on g1 to s transition;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-2 receptor beta chain in t cell activation;akt signaling pathway;ras signaling pathway;corticosteroids and cardioprotection;phospholipids as signalling intermediaries;ion channels and their functional role in vascular endothelium;il 4 signaling pathway;regulation of 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 ;phosphoinositides and their downstream targets;skeletal muscle hypertrophy is regulated via akt-mtor pathway;trka receptor signaling pathway;Membrane Trafficking;role of erbb2 in signal transduction and oncology;Generic Transcription Pathway;Prolactin;Regulation of PTEN stability and activity;Alpha6Beta4Integrin;Metabolism of nitric oxide;KSRP (KHSRP) binds and destabilizes mRNA;CD28 dependent PI3K/Akt signaling;CD28 co-stimulation;CTLA4 inhibitory signaling;Costimulation by the CD28 family;RNA Polymerase II Transcription;Activation of BAD and translocation to mitochondria ;mTOR signalling;Integrin alphaIIb beta3 signaling;Activation of BH3-only proteins;Metabolism of RNA;Intrinsic Pathway for Apoptosis;TCR;eNOS activation;eNOS activation and regulation;Oncostatin_M;IGF signaling;Immune System;Metabolism;Apoptosis;Ghrelin;Programmed Cell Death;Adaptive Immune System;Cyclin E associated events during G1/S transition ;Fibroblast growth factor-1;AKT phosphorylates targets in the nucleus;insulin Mam;PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;Mitotic G1-G1/S phases;Cyclin A:Cdk2-associated events at S phase entry;BCR;AndrogenReceptor;CRH;TP53 Regulates Metabolic Genes;actions of nitric oxide in the heart;Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation;Metabolism of cofactors;Metabolism of vitamins and cofactors;Aurora A signaling;S Phase;Platelet Aggregation (Plug Formation);Deactivation of the beta-catenin transactivating complex;Downregulation of ERBB2:ERBB3 signaling;Downregulation of ERBB2 signaling;IL1;Platelet activation, signaling and aggregation;IL-7 signaling;TGF_beta_Receptor;role of nicotinic acetylcholine receptors in the regulation of apoptosis;control of skeletal myogenesis by hdac and calcium/calmodulin-dependent kinase (camk);BDNF;EGFR1;Integrin signaling;Glucocorticoid receptor regulatory network;CXCR4-mediated signaling events;ErbB1 downstream signaling;Hemostasis;Coregulation of Androgen receptor activity;the igf-1 receptor and longevity;Rab regulation of trafficking;Regulation of TP53 Degradation;Regulation of TP53 Expression and Degradation;BCR signaling pathway;Thromboxane A2 receptor signaling;PTEN Regulation;PIP3 activates AKT signaling;JAK STAT pathway and regulation;PDGF;IL2;VEGFR3 signaling in lymphatic endothelium;IL11;E-cadherin signaling in keratinocytes;Signaling by Non-Receptor Tyrosine Kinases;G1/S Transition;EPO signaling;Regulation of TP53 Activity through Association with Co-factors;IL3;a6b1 and a6b4 Integrin signaling;Gastrin;Regulation of TP53 Activity through Acetylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;IFN-gamma pathway;Signaling by VEGF;Angiopoietin receptor Tie2-mediated signaling;IL4;Leptin;Signaling by ERBB2;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;RAB GEFs exchange GTP for GDP on RABs;Cell Cycle;IL6;Wnt;TNFalpha;Regulation of mRNA stability by proteins that bind AU-rich elements;IL-7;Integrin-linked kinase signaling;Signaling by Receptor Tyrosine Kinases;AKT phosphorylates targets in the cytosol;VEGF;Cell Cycle, Mitotic;G beta:gamma signalling through PI3Kgamma;G-protein beta:gamma signalling;GPCR downstream signalling;ErbB2/ErbB3 signaling events;Intracellular signaling by second messengers;Caspase Cascade in Apoptosis;mTOR signaling pathway;Insulin Pathway;CD40/CD40L signaling;LPA receptor mediated events;Diseases of signal transduction;Insulin-mediated glucose transport;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Fc-epsilon receptor I signaling in mast cells;IL8- and CXCR1-mediated signaling events;Regulation of Telomerase;Retinoic acid receptors-mediated signaling;Regulation of beta-cell development;IL2 signaling events mediated by PI3K;TCR signaling in naïve CD8+ T cells;Reelin signaling pathway;S1P3 pathway;TCF dependent signaling in response to WNT;CXCR3-mediated signaling events;p75(NTR)-mediated signaling;HIF-1-alpha transcription factor network;IGF1 pathway;Signaling events mediated by Stem cell factor receptor (c-Kit);Plasma membrane estrogen receptor signaling;FAS (CD95) signaling pathway;Nongenotropic Androgen signaling;FoxO family signaling;Class I PI3K signaling events mediated by Akt;Trk receptor signaling mediated by PI3K and PLC-gamma;IL4-mediated signaling events;Signaling events mediated by PTP1B;FOXA2 and FOXA3 transcription factor networks;Hedgehog signaling events mediated by Gli proteins;Signaling events mediated by the Hedgehog family;Regulation of nuclear SMAD2/3 signaling;IL6-mediated signaling events;Endothelins;IL8- and CXCR2-mediated signaling events;FGF signaling pathway;Signaling events mediated by VEGFR1 and VEGFR2;TCR signaling in naïve CD4+ T cells;Nephrin/Neph1 signaling in the kidney podocyte;Ceramide signaling pathway;Integrins in angiogenesis;E-cadherin signaling in the nascent adherens junction;p53 pathway;VEGFR1 specific signals;CD4 T cell receptor signaling-NFkB cascade;VEGFR2 mediated vascular permeability;TSLP;AKT-mediated inactivation of FOXO1A;Regulation of gene expression in beta cells;insulin;CD4 T cell receptor signaling
(Consensus)
Recessive Scores
- pRec
- 1.00
Intolerance Scores
- loftool
- 0.357
- rvis_EVS
- -1
- rvis_percentile_EVS
- 8.32
Haploinsufficiency Scores
- pHI
- 0.996
- hipred
- Y
- hipred_score
- 0.765
- ghis
- 0.638
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Akt1
- 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); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); neoplasm; endocrine/exocrine gland 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); immune system phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary 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); hematopoietic 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); normal phenotype; reproductive system phenotype;
Zebrafish Information Network
- Gene name
- akt1
- Affected structure
- neuron
- Phenotype tag
- abnormal
- Phenotype quality
- apoptotic
Gene ontology
- Biological process
- obsolete protein import into nucleus, translocation;osteoblast differentiation;maternal placenta development;positive regulation of protein phosphorylation;positive regulation of endothelial cell proliferation;cell migration involved in sprouting angiogenesis;glycogen biosynthetic process;regulation of glycogen biosynthetic process;glucose metabolic process;translation;regulation of translation;cellular protein modification process;protein phosphorylation;negative regulation of protein kinase activity;nitric oxide biosynthetic process;activation-induced cell death of T cells;inflammatory response;cellular response to DNA damage stimulus;response to oxidative stress;signal transduction;epidermal growth factor receptor signaling pathway;G protein-coupled receptor signaling pathway;I-kappaB kinase/NF-kappaB signaling;germ cell development;aging;cell population proliferation;positive regulation of cell population proliferation;insulin receptor signaling pathway;apoptotic mitochondrial changes;carbohydrate transport;response to heat;negative regulation of autophagy;positive regulation of gene expression;negative regulation of gene expression;negative regulation of plasma membrane long-chain fatty acid transport;positive regulation of fibroblast migration;positive regulation of sodium ion transport;positive regulation of glucose metabolic process;positive regulation of mitochondrial membrane potential;negative regulation of endopeptidase activity;regulation of neuron projection development;phosphatidylinositol 3-kinase signaling;negative regulation of macroautophagy;phosphorylation;protein ubiquitination;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;cytokine-mediated signaling pathway;spinal cord development;cell projection organization;cell differentiation;protein catabolic process;hyaluronan metabolic process;positive regulation of cell growth;regulation of cell migration;endocrine pancreas development;T cell costimulation;negative regulation of protein ubiquitination;regulation of myelination;lipopolysaccharide-mediated signaling pathway;TOR signaling;negative regulation of fatty acid beta-oxidation;positive regulation of endodeoxyribonuclease activity;negative regulation of protein binding;response to food;activation of protein kinase B activity;positive regulation of cellular protein metabolic process;peripheral nervous system myelin maintenance;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;cellular response to insulin stimulus;positive regulation of peptidyl-serine phosphorylation;response to fluid shear stress;cellular response to reactive oxygen species;intracellular signal transduction;interleukin-18-mediated signaling pathway;cellular response to vascular endothelial growth factor stimulus;NIK/NF-kappaB signaling;glucose homeostasis;regulation of apoptotic process;positive regulation of apoptotic process;negative regulation of apoptotic process;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;anoikis;regulation of mRNA stability;protein kinase B signaling;positive regulation of blood vessel endothelial cell migration;positive regulation of nitric oxide biosynthetic process;positive regulation of fat cell differentiation;positive regulation of glycogen biosynthetic process;positive regulation of epidermal growth factor receptor signaling pathway;negative regulation of Notch signaling pathway;negative regulation of cell size;negative regulation of proteolysis;positive regulation of transcription, DNA-templated;positive regulation of vasoconstriction;positive regulation of transcription by RNA polymerase II;positive regulation of glucose import;negative regulation of JNK cascade;positive regulation of organ growth;protein autophosphorylation;positive regulation of lipid biosynthetic process;insulin-like growth factor receptor signaling pathway;positive regulation of smooth muscle cell proliferation;regulation of nitric-oxide synthase activity;positive regulation of nitric-oxide synthase activity;positive regulation of DNA-binding transcription factor activity;striated muscle cell differentiation;cofactor metabolic process;negative regulation of protein kinase B signaling;excitatory postsynaptic potential;response to growth hormone;mammary gland epithelial cell differentiation;glycogen cell differentiation involved in embryonic placenta development;labyrinthine layer blood vessel development;response to UV-A;cellular response to mechanical stimulus;cellular response to cadmium ion;cellular response to tumor necrosis factor;cellular response to epidermal growth factor stimulus;cellular response to prostaglandin E stimulus;cellular response to organic cyclic compound;cellular response to hypoxia;negative regulation of protein serine/threonine kinase activity;establishment of protein localization to mitochondrion;maintenance of protein location in mitochondrion;negative regulation of release of cytochrome c from mitochondria;cellular response to granulocyte macrophage colony-stimulating factor stimulus;execution phase of apoptosis;negative regulation of protein kinase activity by protein phosphorylation;cellular response to oxidised low-density lipoprotein particle stimulus;positive regulation of protein localization to nucleus;negative regulation of neuron death;regulation of signal transduction by p53 class mediator;negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway;negative regulation of leukocyte cell-cell adhesion;positive regulation of protein localization to plasma membrane;positive regulation of I-kappaB phosphorylation;cellular response to nerve growth factor stimulus;response to insulin-like growth factor stimulus;positive regulation of protein localization to cell surface;negative regulation of lymphocyte migration;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
- Cellular component
- nucleus;nucleoplasm;cytoplasm;mitochondrion;spindle;cytosol;plasma membrane;cell-cell junction;microtubule cytoskeleton;vesicle;protein-containing complex;ciliary basal body;postsynapse
- Molecular function
- protein kinase activity;protein serine/threonine kinase activity;protein serine/threonine/tyrosine kinase activity;protein kinase C binding;protein binding;ATP binding;phosphatidylinositol-3,4,5-trisphosphate binding;kinase activity;enzyme binding;nitric-oxide synthase regulator activity;GTPase activating protein binding;identical protein binding;protein homodimerization activity;phosphatidylinositol-3,4-bisphosphate binding;protein phosphatase 2A binding;14-3-3 protein binding