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50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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AKT1
AKT serine/threonine kinase 1
Chromosome 14 · 14q32.33
NCBI Gene: 207Ensembl: ENSG00000142208.20HGNC: HGNC:391UniProt: B0LPE5
3,746PubMed Papers
24Diseases
15Drugs
4Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneKinaseOncogeneTransporter
RESEARCH IMPACT
Highly StudiedLandmark Gene
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of G1/S transition of mitotic cell cycleprotein phosphorylationactivation-induced cell death of T cellsintracellular signal transductionProteus syndromeCowden syndrome 6cancerbreast cancer
✦AI Summary

AKT1 is a serine/threonine kinase that regulates metabolism, cell proliferation, survival, and growth through phosphorylation of >100 downstream substrates 1234. In glucose homeostasis, AKT1 mediates insulin-stimulated GLUT4 translocation to the cell surface and inhibits GSK3 to promote glycogen storage 5. AKT1 activates mTORC1 signaling by phosphorylating TSC2, CASTOR1, and DEPDC5, driving protein synthesis and cell growth 6789. The kinase promotes cell survival by phosphorylating MAP3K5 to suppress apoptosis 10 and regulates transcription factors including FOXO proteins and CREB1 to induce pro-survival gene expression 1112. In cancer contexts, AKT1 activation drives metabolic reprogramming toward aerobic glycolysis 1314 and can be activated through gain-of-function mutations like AKT1E17K in breast cancer 15. AKT1 phosphorylation is dynamically regulated by microRNAs and phosphatases, affecting sensitivity to growth factor stimulation and therapeutic inhibitors 1617. In pancreatic β cells, AKT1 specifically regulates β cell proliferation and mass 18. Dysregulation of AKT1 is implicated in multiple cancers including breast, colorectal, and lung cancers, where dual inhibition targeting AKT1 and downstream effectors can overcome drug resistance 19.

Sources cited
1
In glucose homeostasis, AKT1 mediates insulin-stimulated GLUT4 translocation to the cell surface and inhibits GSK3 to promote glycogen storage .
PMID: 11994271
2
The kinase promotes cell survival by phosphorylating MAP3K5 to suppress apoptosis and regulates transcription factors including FOXO proteins and CREB1 to induce pro-survival gene expression , 9829964].
PMID: 11154276
3
In cancer contexts, AKT1 activation drives metabolic reprogramming toward aerobic glycolysis , 25322691] and can be activated through gain-of-function mutations like AKT1E17K in breast cancer .
PMID: 40135844
4
In pancreatic β cells, AKT1 specifically regulates β cell proliferation and mass .
PMID: 26318486
5
Dysregulation of AKT1 is implicated in multiple cancers including breast, colorectal, and lung cancers, where dual inhibition targeting AKT1 and downstream effectors can overcome drug resistance .
PMID: 36203195
Disease Associationsⓘ24
Proteus syndromeOpen Targets
0.76Strong
Cowden syndrome 6Open Targets
0.68Moderate
cancerOpen Targets
0.67Moderate
breast cancerOpen Targets
0.65Moderate
breast adenocarcinomaOpen Targets
0.64Moderate
breast carcinomaOpen Targets
0.62Moderate
colorectal adenocarcinomaOpen Targets
0.62Moderate
ovarian carcinomaOpen Targets
0.58Moderate
neoplasmOpen Targets
0.49Moderate
clear cell renal carcinomaOpen Targets
0.48Moderate
neurodegenerative diseaseOpen Targets
0.47Moderate
meningiomaOpen Targets
0.47Moderate
breast neoplasmOpen Targets
0.46Moderate
endometrial cancerOpen Targets
0.45Moderate
colon carcinomaOpen Targets
0.41Moderate
ovarian cancerOpen Targets
0.40Weak
prostate cancerOpen Targets
0.39Weak
prostate carcinomaOpen Targets
0.38Weak
Lung Sclerosing HemangiomaOpen Targets
0.38Weak
breast ductal adenocarcinomaOpen Targets
0.37Weak
Breast cancerUniProt
Colorectal cancerUniProt
Cowden syndrome 6UniProt
Proteus syndromeUniProt
Pathogenic Variants4
NM_001382430.1(AKT1):c.49G>A (p.Glu17Lys)Pathogenic
Breast adenocarcinoma|Carcinoma of colon|Ovarian neoplasm|Proteus syndrome|Cowden syndrome 6|not provided|Neoplasm|Meningioma|Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype|Medulloblastoma SHH activated and TP53 wild-type
★★☆☆2025→ Residue 17
NM_001382430.1(AKT1):c.49_50delinsAG (p.Glu17Arg)Pathogenic
Proteus syndrome
★☆☆☆2019→ Residue 17
NM_001382430.1(AKT1):c.73C>T (p.Arg25Cys)Pathogenic
Cowden syndrome 6
☆☆☆☆2013→ Residue 25
NM_001382430.1(AKT1):c.1303A>C (p.Thr435Pro)Pathogenic
Cowden syndrome 6
☆☆☆☆2013→ Residue 435
View on ClinVar ↗
Drug Targets15
AFURESERTIBPhase III
Serine/threonine-protein kinase AKT inhibitor
breast cancer
BAY-1125976Phase I
Serine/threonine-protein kinase AKT inhibitor
CAPIVASERTIBApproved
Serine/threonine-protein kinase AKT inhibitor
breast cancer
GSK-690693Phase I
Protein kinase C (PKC) inhibitor
IPATASERTIBPhase III
Serine/threonine-protein kinase AKT inhibitor
breast cancer
LY-2780301Phase I
Ribosomal protein S6 kinase (P70S6K) inhibitor
MIRANSERTIBPhase II
Serine/threonine-protein kinase AKT inhibitor
Proteus syndrome
MK-2206Phase II
Serine/threonine-protein kinase AKT inhibitor
rectal adenocarcinoma
PIFUSERTIBPhase II
Serine/threonine-protein kinase AKT negative allosteric modulator
neoplasm
RUPITASERTIBPhase I
Ribosomal protein S6 kinase (P70S6K) inhibitor
SR-13668Phase I
Serine/threonine-protein kinase AKT inhibitor
TAS0612Phase I
Serine/threonine-protein kinase AKT inhibitor
neoplasm
TRICIRIBINE PHOSPHATEPhase I/II
Serine/threonine-protein kinase AKT inhibitor
ovarian cancer
UPROSERTIBPhase II
Serine/threonine-protein kinase AKT inhibitor
colorectal cancer
XL-418Phase I
Serine/threonine-protein kinase AKT inhibitor
Related Genes
GRK2Protein interaction100%BADProtein interaction100%MDM2Protein interaction100%PKN2Protein interaction100%TBC1D4Protein interaction100%PHLPP2Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Lung
83%
Liver
83%
Brain
58%
Ovary
48%
Bone Marrow
45%
Gene Interaction Network
Click a node to explore
AKT1GRK2BADMDM2PKN2TBC1D4PHLPP2
PROTEIN STRUCTURE
Preparing viewer…
PDB1UNQ · 0.98 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.47Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.33 [0.23–0.47]
RankingsWhere AKT1 stands among ~20K protein-coding genes
  • #10of 20,598
    Most Researched3,746 · top 1%
  • #707of 1,025
    FDA-Approved Drug Targets1
  • #3,657of 5,498
    Most Pathogenic Variants4
  • #2,734of 17,882
    Most Constrained (LOEUF)0.47 · top quartile
Genes detectedAKT1
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Costunolide is a dual inhibitor of MEK1 and AKT1/2 that overcomes osimertinib resistance in lung cancer.
PMID: 36203195
Mol Cancer · 2022
1.00
2
The identification of metabolites from gut microbiota in autism spectrum disorder via network pharmacology.
PMID: 40877409
Sci Rep · 2025
0.90
3
AKT1 phosphorylation of cytoplasmic ME2 induces a metabolic switch to glycolysis for tumorigenesis.
PMID: 38263319
Nat Commun · 2024
0.90
4
AKT1-Mediated NOTCH1 phosphorylation promotes gastric cancer progression via targeted regulation of IRS-1 transcription.
PMID: 39724412
J Cancer Res Clin Oncol · 2024
0.82
5
AKT1
PMID: 40135844
Adv Sci (Weinh) · 2025
0.80