PLEKHA1 Gene: Pleckstrin Homology Domain Containing A1
A gene encoding a protein involved in phosphoinositide signaling and membrane dynamics, with implications in age-related macular degeneration and cancer.
Gene Information Card
| Symbol | PLEKHA1 |
|---|---|
| Full Name | Pleckstrin Homology Domain Containing A1 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q26.13 |
| NCBI Gene ID | 59338 ncbi.nlm.nih.gov/gene/59338 |
| Ensembl ID | ENSG00000107679 |
| UniProt ID | Q9HB21 |
| OMIM ID | 607772 |
| HGNC ID | 19235 |
| Aliases | TAPP1, TAPP-1, PH domain-containing family A member 1 |
Description
PLEKHA1 (Pleckstrin Homology Domain Containing A1) encodes a protein that contains a pleckstrin homology (PH) domain and a C-terminal PDZ-binding motif. The protein, also known as TAPP1, specifically binds phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and is involved in phosphoinositide signaling, cytoskeletal organization, and membrane trafficking. PLEKHA1 is widely expressed and has been implicated in age-related macular degeneration (AMD) and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Age-related Macular Degeneration (AMD) | Genetic variants in PLEKHA1 (e.g., rs10490924) are associated with increased risk of AMD, possibly through altered phosphoinositide signaling in retinal pigment epithelium. | GWAS studies (NCBI, OMIM #607772) |
| Breast Cancer | PLEKHA1 overexpression may promote cell migration and invasion via PI3K/Akt pathway modulation. | Expression profiling (COSMIC, NCBI) |
| Prostate Cancer | Altered PLEKHA1 expression linked to tumor progression and androgen receptor signaling. | TCGA data (COSMIC) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Lung | 8.5 | Medium |
| Liver | 6.1 | Low |
| Kidney | 12.3 | Medium |
| Testis | 15.7 | High |
| Retina | 14.0 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 11.5 | Embryonic kidney cells |
| HeLa | 9.8 | Cervical cancer cells |
| MCF7 | 13.2 | Breast cancer cells |
| A549 | 7.4 | Lung cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs10490924 (A69S) | Missense | ~0.30 (global) | Associated with increased AMD risk; may alter PH domain binding affinity. |
| c.112G>A (p.Gly38Arg) | Missense | <0.01 | Rare variant; functional impact unknown. |
| c.457C>T (p.Arg153Trp) | Missense | <0.01 | Reported in COSMIC; potential loss of function. |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in the PH domain (e.g., p.Arg153Trp) may reduce PtdIns(3,4)P2 binding, impairing membrane recruitment.
Gain of Function (GOF)
Not well characterized; overexpression in cancer may confer gain-of-function effects via enhanced PI3K signaling.
Dominant Negative (DN)
No dominant-negative mutations reported for PLEKHA1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• PI3K/Akt signaling pathway
• Phosphoinositide metabolism
• Fc gamma R-mediated phagocytosis
Protein Summary
The PLEKHA1 protein (TAPP1) is a 329-amino acid adaptor protein that contains a central pleckstrin homology (PH) domain with high specificity for phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2). It localizes to the plasma membrane upon PI3K activation and interacts with proteins such as PDK1 and Akt, modulating cell survival, proliferation, and cytoskeletal dynamics. TAPP1 also contains a C-terminal PDZ-binding motif that mediates interactions with scaffolding proteins. Its expression is highest in testis, retina, and brain, and dysregulation is linked to AMD and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PLEKHA1 Knockout HEK293 Cell Line | EDJ-KQ14026 | Human | 59338 | Details Get a Quote |
| PLEKHA1 Knockout A-549 Cell Line | EDJ-KQ45189 | Human | 59338 | Details Get a Quote |
| PLEKHA1 Knockout HCT 116 Cell Line | EDJ-KQ45190 | Human | 59338 | Details Get a Quote |
| PLEKHA1 Knockout HeLa Cell Line | EDJ-KQ45191 | Human | 59338 | Details Get a Quote |
