Gene: AKT1

Alternate names for this Gene: AKT|PKB|PKB-ALPHA|PRKBA|RAC|RAC-ALPHA

Gene Summary: This gene encodes one of the three members of the human AKT serine-threonine protein kinase family which are often referred to as protein kinase B alpha, beta, and gamma. These highly similar AKT proteins all have an N-terminal pleckstrin homology domain, a serine/threonine-specific kinase domain and a C-terminal regulatory domain. These proteins are phosphorylated by phosphoinositide 3-kinase (PI3K). AKT/PI3K forms a key component of many signalling pathways that involve the binding of membrane-bound ligands such as receptor tyrosine kinases, G-protein coupled receptors, and integrin-linked kinase. These AKT proteins therefore regulate a wide variety of cellular functions including cell proliferation, survival, metabolism, and angiogenesis in both normal and malignant cells. AKT proteins are recruited to the cell membrane by phosphatidylinositol 3,4,5-trisphosphate (PIP3) after phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) by PI3K. Subsequent phosphorylation of both threonine residue 308 and serine residue 473 is required for full activation of the AKT1 protein encoded by this gene. Phosphorylation of additional residues also occurs, for example, in response to insulin growth factor-1 and epidermal growth factor. Protein phosphatases act as negative regulators of AKT proteins by dephosphorylating AKT or PIP3. The PI3K/AKT signalling pathway is crucial for tumor cell survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating AKT1 which then phosphorylates and inactivates components of the apoptotic machinery. AKT proteins also participate in the mammalian target of rapamycin (mTOR) signalling pathway which controls the assembly of the eukaryotic translation initiation factor 4F (eIF4E) complex and this pathway, in addition to responding to extracellular signals from growth factors and cytokines, is disregulated in many cancers. Mutations in this gene are associated with multiple types of cancer and excessive tissue growth including Proteus syndrome and Cowden syndrome 6, and breast, colorectal, and ovarian cancers. Multiple alternatively spliced transcript variants have been found for this gene.

Gene is located in Chromosome: 14

Location in Chromosome : 14q32.33

Description of this Gene: AKT serine/threonine kinase 1

Type of Gene: protein-coding

rs61759760 in AKT1 gene and Body Height PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs397514644 in AKT1 gene and COWDEN SYNDROME 6 PMID 23246288 2013 Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes.

rs2498796 in AKT1 gene and Endometrial Carcinoma PMID 27135401 2016 Five endometrial cancer risk loci identified through genome-wide association analysis.

rs2494748 in AKT1 gene and High density lipoprotein measurement PMID 30275531 2018 Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.

rs121434592 in AKT1 gene and Proteus Syndrome PMID 18954143 2008 Molecular mechanism of an oncogenic mutation that alters membrane targeting: Glu17Lys modifies the PIP lipid specificity of the AKT1 PH domain.

PMID 21793738 2011 Of 29 patients with the Proteus syndrome, 26 had a somatic activating mutation (c.49G→A, p.Glu17Lys) in the oncogene AKT1, encoding the AKT1 kinase, an enzyme known to mediate processes such as cell proliferation and apoptosis.

rs2494748 in AKT1 gene and White Blood Cell Count procedure PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs1057519804 in AKT1 gene and melanoma PMID 24265152 2014 A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition.