PHLPP1
PH Domain and Leucine Rich Repeat Protein Phosphatase 1
Gene Information Card
| Symbol | PHLPP1 |
|---|---|
| Full Name | PH domain and leucine rich repeat protein phosphatase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 18q21.33 |
| NCBI Gene ID | 23239 ncbi.nlm.nih.gov/gene/23239 |
| Ensembl ID | ENSG00000081913 |
| UniProt ID | O60346 |
| OMIM ID | 609396 |
| HGNC ID | 20610 |
| Aliases | SCOP, PHLPP, PHLPP1alpha, PHLPP1beta |
Description
PHLPP1 encodes a member of the serine/threonine phosphatase family that specifically dephosphorylates and inactivates Akt (PKB) and other AGC kinases. It acts as a tumor suppressor by promoting apoptosis and inhibiting cell proliferation. Alternative splicing generates isoforms with distinct regulatory properties.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate cancer | Loss of PHLPP1 expression leads to increased Akt phosphorylation and tumor progression | PMID: 15899842 |
| Colorectal cancer | Reduced PHLPP1 levels correlate with poor prognosis and metastasis | PMID: 20010870 |
| Glioblastoma | PHLPP1 downregulation promotes Akt signaling and tumor growth | PMID: 17699752 |
| Type 2 diabetes | PHLPP1 regulates insulin signaling via Akt dephosphorylation | PMID: 20628056 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Medium |
| Liver | 4.1 | Low |
| Kidney | 6.7 | Medium |
| Testis | 15.2 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Embryonic kidney |
| HeLa | 7.8 | Cervical cancer |
| MCF7 | 5.4 | Breast cancer |
| PC3 | 3.2 | Prostate cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T | Missense | <0.1% | p.R412W; potential loss of function |
| c.567_568del | Frameshift | <0.1% | p.E189fs; truncation |
| c.2345A>G | Missense | <0.1% | p.N782S; unknown significance |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the phosphatase domain lead to loss of Akt dephosphorylation activity.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
Missense mutations in the PH domain may interfere with membrane localization and substrate access.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004722 (GO:0004722) | • GO:0006470 (GO:0006470) |
| • GO:0016311 (GO:0016311) | • GO:0035556 (GO:0035556) |
| • GO:0043066 (GO:0043066) | • GO:0046777 (GO:0046777) |
Pathways
• PI3K/Akt signaling pathway (KEGG: hsa04151)
• Insulin signaling pathway (KEGG: hsa04910)
• mTOR signaling pathway (KEGG: hsa04150)
Protein Summary
PHLPP1 is a 1205-amino acid protein containing an N-terminal PH domain, leucine-rich repeats, a PP2C-like phosphatase domain, and a C-terminal PDZ-binding motif. It dephosphorylates Akt at Ser473, leading to inactivation of Akt and suppression of downstream survival signals. PHLPP1 also targets other AGC kinases including PKC and S6K1.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PHLPP1 Knockout HEK293 Cell Line | EDJ-KQ261 | Human | 23239 | Details Get a Quote |
| PHLPP1 Knockout A-549 Cell Line | EDJ-KQ19626 | Human | 23239 | Details Get a Quote |
| PHLPP1 Knockout HCT 116 Cell Line | EDJ-KQ19628 | Human | 23239 | Details Get a Quote |
| PHLPP1 Knockout HeLa Cell Line | EDJ-KQ19629 | Human | 23239 | Details Get a Quote |
