AKT1: A Key Oncogenic Kinase in Cancer and PI3K/AKT/mTOR Signaling
Comprehensive gene card for AKT1 (AKT Serine/Threonine Kinase 1) including genomic data, expression, mutations, and clinical relevance.
Gene Information Card
| Symbol | AKT1 |
|---|---|
| Full Name | AKT serine/threonine kinase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 14q32.33 |
| NCBI Gene ID | 207 ncbi.nlm.nih.gov/gene/207 |
| Ensembl ID | ENSG00000142208 |
| UniProt ID | P31749 |
| OMIM ID | 164730 |
| HGNC ID | 391 |
| Aliases | PKB, RAC, RAC-alpha, PKBalpha, RAC-PK-alpha |
Description
AKT1 (AKT serine/threonine kinase 1) encodes a member of the AKT subfamily of serine/threonine kinases, which are key regulators of cell survival, proliferation, metabolism, and angiogenesis. AKT1 is activated by phosphatidylinositol 3-kinase (PI3K) and is frequently hyperactivated in human cancers due to mutations, amplification, or loss of PTEN. The most common activating mutation is E17K in the pleckstrin homology domain, which promotes membrane localization and constitutive signaling.
Disease Associations
| Disease Name | Disease Description |
|---|---|
| Breast cancer | Activating mutations (E17K) and amplification lead to constitutive PI3K/AKT signaling, promoting cell survival and proliferation. |
| Ovarian cancer | AKT1 amplification and E17K mutation drive tumor growth and resistance to apoptosis. |
| Colorectal cancer | AKT1 activation via PI3K pathway mutations contributes to tumor progression and metastasis. |
| Proteus syndrome | Somatic activating mutations in AKT1 (e.g., E17K) cause segmental overgrowth and predisposition to tumors. |
| Cowden syndrome 6 | Germline AKT1 mutations (e.g., E17K) are associated with increased risk of breast, thyroid, and other cancers. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 24.3 | High |
| Heart | 18.7 | Medium |
| Liver | 12.1 | Medium |
| Lung | 15.4 | Medium |
| Kidney | 20.5 | Medium |
| Breast | 22.8 | High |
| Ovary | 19.6 | Medium |
| Colon | 16.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 28.5 | High expression; AKT1 activation supports estrogen-independent growth. |
| A549 (lung cancer) | 22.1 | Moderate expression; contributes to PI3K/AKT signaling. |
| HeLa (cervical cancer) | 25.3 | High expression; involved in cell cycle progression. |
| HCT116 (colorectal cancer) | 19.8 | Moderate expression; associated with resistance to apoptosis. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Mutation site | Type | Frequency | Functional Description |
|---|---|---|---|
| E17K | Missense (G>A) | ~5-8% in breast cancer; rare in other cancers | Gain-of-function; constitutive membrane localization and kinase activation. |
| Q79K | Missense | <1% | Gain-of-function; increased kinase activity. |
| L52R | Missense | <1% | Gain-of-function; enhanced PI3K binding. |
| D323Y | Missense | <1% | Loss-of-function; reduced kinase activity (rare). |
Mutation functional classification
Loss of Function (LOF)
Rare missense mutations (e.g., D323Y) that impair kinase activity or stability; not commonly observed in cancer.
Gain of Function (GOF)
Common hotspot E17K and other PH-domain mutations (Q79K, L52R) that increase membrane recruitment and constitutive activation, driving oncogenic signaling.
Dominant Negative (DN)
Not well-documented for AKT1; most reported mutations are gain-of-function.
View complete mutation data：ClinVar: https://www.clinvar.com/gene/207 COSMIC: https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=AKT1
Gene Ontology (GO)
| • GO:0004672 – protein kinase activity | • GO:0005524 – ATP binding |
| • GO:0046777 – protein autophosphorylation | • GO:0048015 – phosphatidylinositol-mediated signaling |
| • GO:0006915 – apoptotic process | • GO:0008283 – cell proliferation |
| • GO:0006468 – protein phosphorylation | • GO:0035556 – intracellular signal transduction |
Pathways
• PI3K/AKT signaling pathway (KEGG: hsa04151)
• mTOR signaling pathway (KEGG: hsa04150)
• FoxO signaling pathway (KEGG: hsa04068)
• Apoptosis (KEGG: hsa04210)
• EGFR tyrosine kinase inhibitor resistance (KEGG: hsa01521)
Protein Summary
AKT1 is a 480-amino acid serine/threonine kinase composed of an N-terminal pleckstrin homology (PH) domain, a central kinase domain, and a C-terminal regulatory tail. Upon PI3K activation, AKT1 translocates to the plasma membrane via PH-domain binding to PIP3, where it is phosphorylated at Thr308 and Ser473 by PDK1 and mTORC2, respectively. Active AKT1 phosphorylates numerous substrates (e.g., FOXO, GSK3B, BAD, MDM2) to promote cell survival, growth, and metabolism. Dysregulation of AKT1 is a hallmark of many cancers, making it a key therapeutic target.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AKT1 Knockout HEK293 Cell Line | EDJ-KQ446 | Human | 207 | Details Get a Quote |
| AKT1S1 Knockout HEK293 Cell Line | EDJ-KQ613 | Human | 84335 | Details Get a Quote |
| AKT1 Knockout HCT 116 Cell Line | EDJ-KQ18004 | Human | 207 | Details Get a Quote |
| AKT1 Knockout A-549 Cell Line | EDC90037 | Human | 207 | Details Get a Quote |
| AKT1 Knockout HeLa Cell Line | EDJ-KQ18341 | Human | 207 | Details Get a Quote |
| AKT1S1 Knockout A-549 Cell Line | EDJ-KQ20424 | Human | 84335 | Details Get a Quote |
| AKT1S1 Knockout HCT 116 Cell Line | EDJ-KQ20425 | Human | 84335 | Details Get a Quote |
| AKT1S1 Knockout HeLa Cell Line | EDJ-KQ20426 | Human | 84335 | Details Get a Quote |
| AKT1 (p.E17K) Point Mutation in HCT 116 Cell Line | EDC03101 | Human | 201 | Details Get a Quote |
| AKT1 (c.567+35G>T )Point Mutation in HAP1 Cell Line | EDC03396 | Human | 207 | Details Get a Quote |
| AKT1 and AKT2 Knockout A-549 Cell Line | EDC90155 | Human | 207 and 208 | Details Get a Quote |
| AKT1 and AKT3 Knockout A-549 Cell Line | EDC90264 | Human | 207 and 10000 | Details Get a Quote |
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