PHLDA3
Pleckstrin Homology Like Domain Family A Member 3: A Tumor Suppressor and Regulator of AKT Signaling
Gene Information Card
| Symbol | PHLDA3 |
|---|---|
| Full Name | Pleckstrin Homology Like Domain Family A Member 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q32.1 |
| NCBI Gene ID | 23644 ncbi.nlm.nih.gov/gene/23644 |
| Ensembl ID | ENSG00000143178 |
| UniProt ID | Q9Y5H6 |
| OMIM ID | 607054 |
| HGNC ID | 8934 |
| Aliases | TIH1, PH domain-containing protein A3, 1-2-3 |
Description
PHLDA3 (Pleckstrin Homology Like Domain Family A Member 3) encodes a protein containing a pleckstrin homology (PH) domain. It functions as a tumor suppressor by binding phosphatidylinositol lipids and inhibiting AKT signaling. The gene is located on chromosome 1q32.1 and is frequently downregulated or mutated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pancreatic neuroendocrine tumors | Loss of heterozygosity and promoter methylation lead to reduced PHLDA3 expression, activating AKT signaling. | PMID: 24614137 |
| Lung cancer | Frequent copy number loss and reduced expression contribute to tumor progression. | PMID: 26929214 |
| Breast cancer | Epigenetic silencing via hypermethylation correlates with poor prognosis. | PMID: 25605274 |
| Colorectal cancer | Downregulation promotes cell proliferation and invasion through AKT pathway. | PMID: 27864367 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 12.5 | Medium |
| Lung | 8.3 | Medium |
| Breast | 6.1 | Low |
| Colon | 5.4 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | Embryonic kidney, moderate expression |
| A549 | 7.8 | Lung carcinoma, reduced vs normal |
| MCF7 | 4.3 | Breast cancer, low expression |
| HCT116 | 3.9 | Colorectal carcinoma, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Likely loss of start codon, loss of function |
| c.100C>T (p.Arg34Trp) | Missense | <0.1% | Disrupts PH domain, reduced lipid binding |
| c.200_201del (p.Glu67fs) | Frameshift | <0.1% | Premature truncation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations (missense, frameshift, nonsense) lead to loss of PH domain function and inability to inhibit AKT.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • phosphatidylinositol binding | • protein kinase B signaling |
| • negative regulation of cell proliferation | • apoptotic process |
| • nucleus | • cytoplasm |
Pathways
• PI3K-Akt signaling pathway
• Tumor suppressor pathways
Protein Summary
PHLDA3 is a 127-amino acid protein containing a single PH domain that specifically binds phosphatidylinositol (3,4,5)-trisphosphate (PIP3). By sequestering PIP3, it inhibits AKT membrane recruitment and activation, thereby suppressing cell survival and proliferation. Loss of PHLDA3 expression is common in multiple cancer types and is associated with poor prognosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PHLDA3 Knockout HEK293 Cell Line | EDJ-KQ2832 | Human | 23612 | Details Get a Quote |
| PHLDA3 Knockout HCT 116 Cell Line | EDJ-KQ22446 | Human | 23612 | Details Get a Quote |
| PHLDA3 Knockout A-549 Cell Line | EDJ-KQ23813 | Human | 23612 | Details Get a Quote |
| PHLDA3 Knockout HeLa Cell Line | EDJ-KQ23815 | Human | 23612 | Details Get a Quote |
