AKT3: A Key Regulator of Cell Growth and Metabolism
Comprehensive gene overview of AKT3, including genomic context, expression, mutations, and disease associations.
Gene Information Card
| Symbol | AKT3 |
|---|---|
| Full Name | AKT serine/threonine kinase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q44 |
| NCBI Gene ID | 10000 ncbi.nlm.nih.gov/gene/10000 |
| Ensembl ID | ENSG00000117020 |
| UniProt ID | Q9Y243 |
| OMIM ID | 611223 |
| HGNC ID | 393 |
| Aliases | PKB gamma, PRKBG, RAC-gamma |
Description
AKT3 (AKT serine/threonine kinase 3) encodes a member of the AKT subfamily of serine/threonine protein kinases. AKT kinases are key regulators of cell survival, proliferation, growth, and metabolism. AKT3 is activated by phosphoinositide 3-kinase (PI3K) and is involved in downstream signaling through phosphorylation of various substrates. It plays a critical role in brain development and is implicated in cancer and overgrowth syndromes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Proteus syndrome | Activating mutations in AKT3 lead to constitutive PI3K/AKT signaling, causing tissue overgrowth. | OMIM #176920; PMID: 21793738 |
| Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH) | Germline activating mutations in AKT3 result in increased brain size and cortical malformations. | OMIM #615937; PMID: 22939651 |
| Breast cancer | AKT3 amplification or overexpression contributes to tumor progression and therapy resistance. | COSMIC; PMID: 22985903 |
| Melanoma | AKT3 activation promotes cell survival and resistance to apoptosis. | COSMIC; PMID: 16959973 |
| Breast cancer | AKT3 amplification leads to increased kinase activity and downstream signaling promoting cell survival and proliferation. | PMID: 22980975; COSMIC |
| Melanoma | Activating mutations (e.g., E17K) in AKT3 enhance PI3K/AKT signaling, contributing to tumor progression. | PMID: 18451266; ClinVar |
| Prostate cancer | AKT3 overexpression correlates with poor prognosis and resistance to therapy. | PMID: 23382250; NCBI Gene |
| Colorectal cancer | AKT3 copy number gains and overexpression activate mTOR pathway. | PMID: 25605242; COSMIC |
| Ovarian cancer | AKT3 amplification is associated with aggressive disease. | PMID: 21502544; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Testis | 8.2 | Medium |
| Adipose tissue | 6.1 | Medium |
| Heart | 4.3 | Low |
| Liver | 2.1 | Low |
| Brain | 12.3 | High |
| Testis | 8.7 | Medium |
| Thyroid | 6.5 | Medium |
| Adipose tissue | 5.2 | Medium |
| Liver | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.3 | High expression in embryonic kidney cells |
| SH-SY5Y | 11.8 | Neuroblastoma cell line |
| MCF7 | 7.4 | Breast cancer cell line |
| A549 | 5.6 | Lung carcinoma cell line |
| MCF7 (breast cancer) | 15.4 | High expression |
| A549 (lung cancer) | 9.8 | Medium expression |
| HEK293 (embryonic kidney) | 7.3 | Medium expression |
| HepG2 (liver cancer) | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.49G>A (p.Glu17Lys) | Missense | Rare | Gain-of-function; associated with Proteus syndrome |
| c.113C>T (p.Pro38Leu) | Missense | Rare | Gain-of-function; associated with MPPH syndrome |
| c.1A>G (p.Met1Val) | Missense | Rare | Loss-of-function; reduced kinase activity |
| Amplification | Copy number gain | Frequent in breast cancer | Increased AKT3 expression and signaling |
| E17K | Missense | <1% | Gain-of-function; increases membrane localization and kinase activity |
| Q79K | Missense | <1% | Gain-of-function; enhances AKT signaling |
| R465H | Missense | <1% | Unknown functional effect |
| Amplification | Copy number gain | ~5-10% in breast cancer | Increased gene dosage and protein expression |
Mutation functional classification
Loss of Function (LOF)
Rare missense mutations (e.g., p.Met1Val) reduce kinase activity and downstream signaling.
Gain of Function (GOF)
Activating mutations (e.g., p.Glu17Lys, p.Pro38Leu) enhance AKT3 phosphorylation and promote cell growth.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for AKT3.
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in cancer; knockout models show reduced cell growth.
Gain of Function (GOF)
E17K and Q79K are activating mutations that increase AKT3 kinase activity and promote oncogenic signaling.
Dominant Negative (DN)
Not described for AKT3.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 - protein kinase activity | • GO:0005524 - ATP binding |
| • GO:0006468 - protein phosphorylation | • GO:0046777 - protein autophosphorylation |
| • GO:0008286 - insulin receptor signaling pathway | • GO:0048015 - phosphatidylinositol 3-kinase signaling |
| • GO:0006915 - apoptotic process | • GO:0008284 - positive regulation of cell proliferation |
Pathways
• PI3K/AKT signaling pathway (KEGG hsa04151)
• mTOR signaling pathway (KEGG hsa04150)
• FoxO signaling pathway (KEGG hsa04068)
• Apoptosis (KEGG hsa04210)
Protein Summary
AKT3 (also known as PKB gamma) is a 479-amino acid serine/threonine kinase with a pleckstrin homology (PH) domain, a central kinase domain, and a C-terminal regulatory tail. It is activated by phosphorylation at Thr305 and Ser472 in response to PI3K signaling. AKT3 regulates cell survival, metabolism, and growth by phosphorylating substrates such as FOXO, GSK3B, and TSC2. It is highly expressed in brain and testis, and its dysregulation is linked to overgrowth syndromes and cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AKT3 Knockout HEK293 Cell Line | EDJ-KQ449 | Human | 10000 | Details Get a Quote |
| AKT3 Knockout A-549 Cell Line | EDJ-KQ18752 | Human | 10000 | Details Get a Quote |
| AKT3 Knockout HeLa Cell Line | EDJ-KQ55295 | Human | 10000 | Details Get a Quote |
| AKT3 Knockout HCT 116 Cell Line | EDJ-KQ72236 | Human | 10000 | Details Get a Quote |
| AKT1 and AKT3 Knockout A-549 Cell Line | EDC90264 | Human | 207 and 10000 | Details Get a Quote |
| AKT2 and AKT3 Knockout A-549 Cell Line | EDC90416 | Human | 208 and 10000 | Details Get a Quote |
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