AKT1 Gene

HGNC Family	Pleckstrin homology domain containing (PLEKH)
Name	v-akt murine thymoma viral oncogene homolog 1
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n AKT1 is a central serine/threonine kinase in the phosphatidylinositol 3‐kinase (PI3K) pathway that integrates diverse extracellular signals to coordinate cell survival, growth, metabolism, and proliferation. In response to growth factors such as insulin and IGF‐1, AKT1 phosphorylates substrates including TSC2 to modulate the mammalian target of rapamycin (mTOR) pathway and promote protein synthesis and cell growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In skeletal muscle, activation of the PI3K–AKT1 axis by IGF‑1 or by direct AKT1 overexpression suppresses FoxO-mediated induction of atrophy effectors such as atrogin‑1, thereby preventing muscle wasting."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In T lymphocytes, costimulatory signals via CD28 engage PI3K–AKT1 signaling to increase glycolytic flux and support metabolic reprogramming necessary for clonal expansion, whereas negative regulators such as CTLA‑4 and PD‑1 attenuate Akt activity to modulate T-cell responses; indeed, PD‑L1 engagement further promotes regulatory T-cell development via downregulation of Akt phosphorylation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " In cancer cells, oncogenic receptor tyrosine kinases such as mutant epidermal growth factor receptor (EGFR) selectively activate AKT1 to transmit potent survival signals, rendering these cells dependent on Akt-driven pathways; moreover, microenvironment-derived factors like hepatocyte growth factor (HGF) can reactivate PI3K–AKT1 signaling to promote resistance to targeted therapies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Notably, a recurrent somatic mutation in the lipid-binding pocket of AKT1 (E17K) enhances its plasma membrane localization and constitutive activation, thereby driving transforming events and tumorigenesis while reducing sensitivity to certain allosteric inhibitors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Furthermore, in innate immune cells, Akt1 functions downstream of dectin‑1 to activate mTOR and hypoxia‑inducible factor‑1α (HIF‑1α), underpinning a metabolic switch to enhanced glycolysis that is critical for the establishment of “trained” immunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these studies underscore the pivotal role of AKT1 as a signaling hub whose regulated activity is essential for normal cellular homeostasis and whose dysregulation contributes to oncogenesis and therapeutic resistance.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ken Inoki, Yong Li, Tianquan Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb839"}], "href": "https://doi.org/10.1038/ncb839"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12172553"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12172553"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Marco Sandri, Claudia Sandri, Alex Gilbert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0092-8674(04)00400-3"}], "href": "https://doi.org/10.1016/s0092-8674(04"}, {"type": "t", "text": "00400-3) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15109499"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15109499"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kenneth A Frauwirth, James L Riley, Marian H Harris, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The CD28 signaling pathway regulates glucose metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1074-7613(02)00323-0"}], "href": "https://doi.org/10.1016/s1074-7613(02"}, {"type": "t", "text": "00323-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12121659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12121659"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Richard V Parry, Jens M Chemnitz, Kenneth A Frauwirth, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.25.21.9543-9553.2005"}], "href": "https://doi.org/10.1128/MCB.25.21.9543-9553.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16227604"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16227604"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Loise M Francisco, Victor H Salinas, Keturah E Brown, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PD-L1 regulates the development, maintenance, and function of induced regulatory T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20090847"}], "href": "https://doi.org/10.1084/jem.20090847"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20008522"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20008522"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Raffaella Sordella, Daphne W Bell, Daniel A Haber, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1101637"}], "href": "https://doi.org/10.1126/science.1101637"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15284455"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15284455"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ravid Straussman, Teppei Morikawa, Kevin Shee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature11183"}], "href": "https://doi.org/10.1038/nature11183"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22763439"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22763439"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "John D Carpten, Andrew L Faber, Candice Horn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A transforming mutation in the pleckstrin homology domain of AKT1 in cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature05933"}], "href": "https://doi.org/10.1038/nature05933"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17611497"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17611497"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Shih-Chin Cheng, Jessica Quintin, Robert A Cramer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1250684"}], "href": "https://doi.org/10.1126/science.1250684"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25258083"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25258083"}]}]}]}
Synonyms	PKB-ALPHA, AKT, RAC, PRKBA, RAC-ALPHA, CWS6, PKB
Proteins	AKT1_HUMAN
NCBI Gene ID	207
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

AKT1 has 29,370 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 151 datasets.

Click the + buttons to view associations for AKT1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

AKT1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by AKT1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of AKT1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of AKT1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of AKT1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of AKT1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of AKT1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of AKT1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving AKT1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of AKT1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of AKT1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of AKT1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of AKT1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of AKT1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of AKT1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with AKT1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with AKT1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with AKT1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of AKT1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of AKT1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of AKT1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with AKT1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with AKT1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of AKT1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of AKT1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing AKT1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing AKT1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing AKT1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing AKT1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with AKT1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with AKT1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing AKT1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of AKT1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with AKT1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with AKT1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with AKT1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of AKT1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by AKT1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate AKT1 protein from the curated DEPOD Substrates of Phosphatases dataset.
	DGIdb Drug Targets 2026	interacting drugs for AKT1 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving AKT1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.