PDCD4: Programmed Cell Death 4 – Tumor Suppressor and Translational Regulator
Comprehensive genomic and functional overview of PDCD4, a key regulator of apoptosis, translation, and tumor suppression.
Gene Information Card
| Symbol | PDCD4 |
|---|---|
| Full Name | Programmed Cell Death 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q25.2 |
| NCBI Gene ID | 27250 ncbi.nlm.nih.gov/gene/27250 |
| Ensembl ID | ENSG00000150527 |
| UniProt ID | Q53EL6 |
| OMIM ID | 608610 |
| HGNC ID | 8763 |
| Aliases | H731, MGC33046, TIS, MA-3, 197/15a |
Description
PDCD4 (Programmed Cell Death 4) is a tumor suppressor gene encoding a protein that inhibits translation initiation by binding to eukaryotic initiation factor 4A (eIF4A) and preventing cap-dependent translation. It also promotes apoptosis and negatively regulates cell proliferation. PDCD4 is frequently downregulated in various cancers, and its loss correlates with poor prognosis. The gene is located on chromosome 10q25.2 and is conserved across species.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Downregulation of PDCD4 leads to increased eIF4A activity and enhanced translation of oncogenic mRNAs, promoting tumor growth and metastasis. | ClinVar, COSMIC, PMID: 19029980 |
| Breast cancer | Loss of PDCD4 expression is associated with aggressive tumor phenotypes and poor survival; PDCD4 inhibits invasion and metastasis via suppression of uPAR and c-Myc. | ClinVar, COSMIC, PMID: 20010872 |
| Lung cancer | Reduced PDCD4 expression correlates with advanced stage and lymph node metastasis; PDCD4 suppresses proliferation and induces apoptosis in lung cancer cells. | ClinVar, COSMIC, PMID: 21573172 |
| Hepatocellular carcinoma | PDCD4 is frequently downregulated; its restoration inhibits cell growth and invasion through modulation of the PI3K/Akt pathway. | ClinVar, COSMIC, PMID: 20514494 |
| Gastric cancer | Low PDCD4 expression is linked to poor differentiation and metastasis; PDCD4 acts as a negative regulator of cell cycle progression. | ClinVar, COSMIC, PMID: 21829205 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 8.2 | Low |
| Brain | 6.5 | Low |
| Breast | 12.3 | Medium |
| Colon | 15.7 | Medium |
| Kidney | 10.1 | Medium |
| Liver | 9.8 | Medium |
| Lung | 14.2 | Medium |
| Pancreas | 7.4 | Low |
| Prostate | 11.5 | Medium |
| Skin | 13.0 | Medium |
| Stomach | 16.1 | Medium |
| Thyroid | 8.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.5 | Cervical cancer cell line; moderate expression |
| MCF7 | 22.3 | Breast cancer cell line; higher expression |
| A549 | 14.1 | Lung cancer cell line; moderate expression |
| HCT116 | 20.7 | Colorectal cancer cell line; higher expression |
| HepG2 | 12.8 | Hepatocellular carcinoma cell line; moderate expression |
| K562 | 9.4 | Leukemia cell line; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | Missense | <0.1% | Likely benign; no functional data |
| c.247C>T | Nonsense | <0.1% | Premature stop; loss of function |
| c.673_674del | Frameshift | <0.1% | Loss of function; truncated protein |
| c.1024G>A | Missense | <0.1% | Unknown significance; predicted damaging |
| c.1315C>T | Nonsense | <0.1% | Loss of function; associated with cancer |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., c.247C>T, c.673_674del) result in truncated or absent PDCD4 protein, impairing its ability to inhibit eIF4A and promote apoptosis, thereby contributing to tumorigenesis.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PDCD4.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for PDCD4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• PI3K/Akt signaling pathway
• mTOR signaling pathway
• p53 signaling pathway
• Apoptosis
• Translation regulation by eIF4A
Protein Summary
The PDCD4 protein (UniProt Q53EL6) is a 469-amino acid tumor suppressor that contains two MA-3 domains and a nuclear localization signal. It functions primarily as a translation inhibitor by binding to eIF4A, thereby blocking cap-dependent translation initiation. PDCD4 also interacts with other proteins such as p53 and Akt to modulate apoptosis and cell cycle progression. Its expression is frequently lost in cancers due to promoter methylation, miRNA regulation (e.g., miR-21), or mutation. The protein is predominantly cytoplasmic but can shuttle to the nucleus under certain conditions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDCD4 Knockout HEK293 Cell Line | EDJ-KQ3907 | Human | 27250 | Details Get a Quote |
| PDCD4 Knockout A-549 Cell Line | EDJ-KQ26125 | Human | 27250 | Details Get a Quote |
| PDCD4 Knockout HeLa Cell Line | EDJ-KQ26127 | Human | 27250 | Details Get a Quote |
| PDCD4 Knockout HCT 116 Cell Line | EDJ-KQ24782 | Human | 27250 | Details Get a Quote |
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