AKT1

AKT serine/threonine kinase 1

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. [provided by RefSeq, Jul 2020]

Known Variants669 total

rsidPosition (GRCh37)AllelesClassClinVar
rs249880114:105,235,558T/Cregulatory region variant—
rs20050840514:105,236,672G/A—benign
rs189230732214:105,236,681G/C—likely benign
rs55518715714:105,236,684C/T—likely benign
rs20129125914:105,236,685G/A—uncertain significance
rs120561692914:105,236,689C/T—uncertain significance
rs20021356114:105,236,690G/A—likely benign
rs189230882714:105,236,693G/A—likely benign
rs74860308714:105,236,696C/T—conflicting classifications of pathogenicity
rs254209930614:105,236,699G/A—likely benign
rs254209933414:105,236,701A/G—uncertain significance
rs122153951514:105,236,702G/C—likely benign
rs18426365514:105,236,705G/A—likely benign
rs118487295914:105,236,717G/A—likely benign
rs254209946414:105,236,722G/A—uncertain significance
rs254209949114:105,236,724C/T—uncertain significance
rs141899452914:105,236,725T/C—uncertain significance
rs254209951214:105,236,726G/C—likely benign
rs11354752314:105,236,727C/T—conflicting classifications of pathogenicity
rs77037010014:105,236,728G/A—uncertain significance
rs74580378814:105,236,731C/T—uncertain significance
rs14411207514:105,236,732G/A—benign
rs254209960714:105,236,733C/A—uncertain significance
rs254209961614:105,236,734T/C—uncertain significance
rs76284964314:105,236,735G/A—likely benign
rs76383140214:105,236,738C/T—likely benign
rs13939428514:105,236,741A/G—likely benign
rs254209967514:105,236,742C/A—uncertain significance
rs254209970314:105,236,744C/T—likely benign
rs58777801814:105,236,748A/G—uncertain significance
rs136078267214:105,236,749T/C—uncertain significance
rs254209978914:105,236,755C/T—uncertain significance
rs11377794514:105,236,760G/A—conflicting classifications of pathogenicity
rs121875934014:105,236,766G/A—likely benign
rs75553041314:105,236,767T/C—likely benign
rs254209993814:105,236,768A/G—likely benign
rs6176124814:105,237,070G/A—benign
rs92645122214:105,237,073G/A—likely benign
rs75970231514:105,237,084T/C—uncertain significance
rs254210283414:105,237,085G/C—uncertain significance
rs254210286714:105,237,088C/G—uncertain significance
rs159523903314:105,237,092T/C—likely benign
rs189234031314:105,237,094G/A—uncertain significance
rs159523904014:105,237,095T/G—likely benign
rs254210296114:105,237,100T/A—uncertain significance
rs75883378914:105,237,101G/A—likely benign
rs106050482014:105,237,104G/T—likely benign
rs75197695814:105,237,107C/A—uncertain significance
rs254210312014:105,237,113G/A—likely benign
rs37689321214:105,237,116C/T—likely benign
rs254210319514:105,237,122C/T—likely benign
rs189234204714:105,237,123T/C—uncertain significance
rs115994212014:105,237,125C/A—uncertain significance
rs254210327714:105,237,127C/T—uncertain significance
rs189234267914:105,237,134A/G—likely benign
rs78086094114:105,237,140G/A—likely benign
rs39751464514:105,237,142T/Gmissense variantpathogenic
rs254210346414:105,237,146A/G—likely benign
rs254210348814:105,237,147G/T—uncertain significance
rs75010445214:105,237,152C/T—likely benign
rs75559778914:105,237,153G/A—uncertain significance
rs77944750114:105,237,155C/T—likely benign
rs74918639414:105,237,156G/A—uncertain significance
rs254210357214:105,237,161C/T—likely benign
rs135203599414:105,237,164G/A—likely benign
rs159523912014:105,237,167C/T—likely benign
rs189234438714:105,237,168T/G—uncertain significance
rs254210368514:105,237,174G/T—uncertain significance
rs254210373414:105,237,178G/A—uncertain significance
rs156681516414:105,237,184G/A—uncertain significance
rs254210389514:105,237,192G/A—likely benign
rs127831032114:105,237,194T/G—likely benign
rs37628414514:105,237,202C/T—likely benign
rs144398520114:105,237,203G/A—likely benign
rs77124835814:105,237,204G/A—likely benign
rs11809842514:105,237,380G/A—likely benign
rs714073514:105,237,401G/A—benign
rs249473114:105,237,680G/A——
rs18073174914:105,238,477G/A—benign
rs6176124514:105,238,512G/A—likely benign
rs249880014:105,238,604C/T—benign
rs15086153714:105,238,609G/A—likely benign
rs1784683214:105,238,636G/C—benign
rs819270014:105,238,670C/T—benign
rs189243876014:105,238,683A/G—likely benign
rs76298112214:105,238,684T/C—likely benign
rs76875073314:105,238,686C/T—likely benign
rs77478664714:105,238,687G/A—likely benign
rs76538364114:105,238,690G/A—benign
rs75082396114:105,238,695G/A—likely benign
rs76036581014:105,238,697C/T—uncertain significance
rs76599960314:105,238,698G/A—uncertain significance
rs11211762514:105,238,701C/G—uncertain significance
rs254211509214:105,238,708C/T—likely benign
rs76486328214:105,238,710C/T—uncertain significance
rs13929765914:105,238,711G/A—likely benign
rs146800177614:105,238,713A/C—uncertain significance
rs159524105714:105,238,714C/T—likely benign
rs130819088314:105,238,716C/T—uncertain significance
rs75847641614:105,238,717G/C—uncertain significance

Showing 100 of 669 variants. Use the SNP search for the full list.

Gene information from NCBI Gene. Variant classifications from ClinVar.