PMAIP1 (NOXA) Gene
Pro-apoptotic BCL2 family member, key mediator of p53-dependent apoptosis
Gene Information Card
| Symbol | PMAIP1 |
|---|---|
| Full Name | Phorbol-12-myristate-13-acetate-induced protein 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 18q21.32 |
| NCBI Gene ID | 5366 ncbi.nlm.nih.gov/gene/5366 |
| Ensembl ID | ENSG00000141682 |
| UniProt ID | Q13794 |
| OMIM ID | 604959 |
| HGNC ID | 9108 |
| Aliases | NOXA, APR, PMAIP1 |
Description
PMAIP1 (phorbol-12-myristate-13-acetate-induced protein 1), commonly known as NOXA, is a pro-apoptotic BH3-only member of the BCL2 protein family. It is a direct transcriptional target of p53 and plays a critical role in DNA damage-induced apoptosis by neutralizing anti-apoptotic BCL2 family members, particularly MCL1, leading to mitochondrial outer membrane permeabilization and caspase activation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal Cancer | PMAIP1 upregulation via p53 promotes apoptosis; loss of function contributes to chemoresistance | PMID: 15626734 |
| Chronic Lymphocytic Leukemia | NOXA mediates apoptosis in response to BCR signaling inhibitors; low expression correlates with poor prognosis | PMID: 23327920 |
| Melanoma | NOXA induction by BH3 mimetics sensitizes cells to apoptosis; resistance linked to MCL1 overexpression | PMID: 24043772 |
| Hepatocellular Carcinoma | PMAIP1 silencing via promoter methylation reduces apoptosis and promotes tumor growth | PMID: 19351800 |
| Acute Myeloid Leukemia | NOXA expression predicts response to cytarabine; loss confers resistance | PMID: 21536891 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.3 | Medium |
| Spleen | 10.1 | Medium |
| Bone marrow | 8.7 | Medium |
| Small intestine | 6.5 | Low |
| Colon | 5.2 | Low |
| Liver | 3.8 | Low |
| Lung | 2.1 | Not detected |
| Brain | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.4 | High expression |
| HeLa | 12.8 | High expression |
| MCF7 | 9.2 | Medium expression |
| HCT116 | 8.1 | Medium expression |
| A549 | 6.3 | Low expression |
| K562 | 4.7 | 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% (COSMIC) | Loss of start codon, likely loss of function |
| c.43C>T (p.Arg15*) | Nonsense | <0.1% (COSMIC) | Premature truncation, loss of BH3 domain |
| c.82_83insA (p.Thr28Asnfs*12) | Frameshift | <0.1% (COSMIC) | Frameshift, loss of function |
| c.130G>A (p.Glu44Lys) | Missense | <0.1% (COSMIC) | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg15*, p.Thr28Asnfs*12) abolish BH3 domain, impairing pro-apoptotic activity.
Gain of Function (GOF)
Not reported for PMAIP1.
Dominant Negative (DN)
Not reported for PMAIP1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• p53-dependent apoptosis (Reactome: R-HSA-111471)
• Intrinsic Pathway for Apoptosis (KEGG: hsa04210)
• BCL2 family interactions (Reactome: R-HSA-111453)
• Apoptotic cleavage of cellular proteins (Reactome: R-HSA-111468)
Protein Summary
PMAIP1 (NOXA) is a 54-amino acid BH3-only protein that localizes to mitochondria. It binds specifically to the anti-apoptotic protein MCL1 via its BH3 domain, displacing pro-apoptotic effectors BAK and BAX, leading to mitochondrial outer membrane permeabilization (MOMP) and caspase activation. NOXA is transcriptionally induced by p53 in response to DNA damage and by other stress signals. Its short half-life is regulated by ubiquitin-proteasome degradation. NOXA is a key determinant of sensitivity to BH3 mimetics and chemotherapeutic agents.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PMAIP1 Knockout HEK293 Cell Line | EDJ-KQ50519 | Human | 5366 | Details Get a Quote |
| PMAIP1 Knockout HeLa Cell Line | EDJ-KQ54161 | Human | 5366 | Details Get a Quote |
| PMAIP1 Knockout A-549 Cell Line | EDJ-KQ62657 | Human | 5366 | Details Get a Quote |
| PMAIP1 Knockout HCT 116 Cell Line | EDJ-KQ71124 | Human | 5366 | Details Get a Quote |
