AKT3 Gene

HGNC Family	Pleckstrin homology domain containing (PLEKH)
Name	v-akt murine thymoma viral oncogene homolog 3
Description	The protein encoded by this gene is a member of the AKT, also called PKB, serine/threonine protein kinase family. AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake. This kinase has been shown to be stimulated by platelet-derived growth factor (PDGF), insulin, and insulin-like growth factor 1 (IGF1). Alternatively splice transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n AKT3 is emerging as a key isoform that governs cell growth and differentiation with a particular emphasis on brain development. In studies using mouse models where Akt1 and Akt2 were genetically ablated, the low‐level Akt activity provided by Akt3 alone proved insufficient to sustain normal cellular proliferation, growth, and differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In contrast to the proportional organ size reductions observed upon loss of Akt1, deletion of Akt3 specifically leads to a striking reduction in brain size—approximately 20%—attributable to both smaller and fewer cells, an effect associated with attenuated mTOR signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Consistent with its central role in neural growth regulation, activating mutations in AKT3 have been identified in overgrowth syndromes such as megalencephaly-capillary malformation and megalencephaly-polymicrogyria-polydactyly-hydrocephalus, as well as in hemimegalencephaly, thereby underscoring aberrant PI3K-AKT3-mTOR pathway activation as a driver of these neurodevelopmental disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, biochemical studies have revealed that AKT3 activity is subject to precise regulation; for instance, the phosphatase PHLPP2 selectively targets downstream effectors via Akt3 to modulate cell cycle regulators such as p27, thereby influencing cellular proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, distinct isoform-specific roles have been delineated in the context of hypoxia signaling, with Akt3 contributing to the expression of HIF1α, thus differentiating its function from that of other Akt family members."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xiao-Ding Peng, Pei-Zhang Xu, Mei-Ling Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1089403"}], "href": "https://doi.org/10.1101/gad.1089403"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12782654"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12782654"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Rachael M Easton, Han Cho, Kristin Roovers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role for Akt3/protein kinase Bgamma in attainment of normal brain size."}]}, {"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.25.5.1869-1878.2005"}], "href": "https://doi.org/10.1128/MCB.25.5.1869-1878.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15713641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15713641"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jean-Baptiste Rivière, Ghayda M Mirzaa, Brian J O'Roak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2331"}], "href": "https://doi.org/10.1038/ng.2331"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22729224"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22729224"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jeong Ho Lee, My Huynh, Jennifer L Silhavy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2329"}], "href": "https://doi.org/10.1038/ng.2329"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22729223"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22729223"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "John Brognard, Emma Sierecki, Tianyan Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2007.02.017"}], "href": "https://doi.org/10.1016/j.molcel.2007.02.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17386267"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17386267"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Alfredo Toschi, Evan Lee, Noga Gadir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential dependence of hypoxia-inducible factors 1 alpha and 2 alpha on mTORC1 and mTORC2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C800170200"}], "href": "https://doi.org/10.1074/jbc.C800170200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18945681"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18945681"}]}]}]}
Synonyms	PKBG, STK-2, MPPH2, PKB-GAMMA, RAC-GAMMA, RAC-PK-GAMMA, PRKBG
Proteins	AKT3_HUMAN
NCBI Gene ID	10000
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

AKT3 has 8,756 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 129 datasets.

Click the + buttons to view associations for AKT3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

AKT3 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 AKT3 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 AKT3 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 AKT3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of AKT3 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 AKT3 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 AKT3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of AKT3 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 AKT3 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 AKT3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of AKT3 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 AKT3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with AKT3 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with AKT3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with AKT3 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 AKT3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of AKT3 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 AKT3 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 AKT3 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of AKT3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing AKT3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing AKT3 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 AKT3 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 AKT3 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 AKT3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of AKT3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with AKT3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with AKT3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with AKT3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with AKT3 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by AKT3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate AKT3 protein from the curated DEPOD Substrates of Phosphatases dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with AKT3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with AKT3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with AKT3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with AKT3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with AKT3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with AKT3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at AKT3 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of AKT3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of AKT3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.