PIDD1: P53-Induced Death Domain Protein 1
A key regulator of apoptosis, NF-κB signaling, and DNA damage response
Gene Information Card
| Symbol | PIDD1 |
|---|---|
| Full Name | p53-induced death domain protein 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p15.5 |
| NCBI Gene ID | 55367 ncbi.nlm.nih.gov/gene/55367 |
| Ensembl ID | ENSG00000178927 |
| UniProt ID | Q9HB75 |
| OMIM ID | 605247 |
| HGNC ID | 16491 |
| Aliases | PIDD, LRDD |
Description
PIDD1 (p53-induced death domain protein 1) is a protein-coding gene that plays a dual role in apoptosis and NF-κB signaling. It is induced by p53 and forms the PIDDosome complex with RAIDD and caspase-2 to promote caspase-2 activation and apoptosis. PIDD1 also activates NF-κB via RIP1 and NEMO in response to genotoxic stress. The gene is located on chromosome 11p15.5 and encodes multiple isoforms through alternative splicing.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | PIDD1 overexpression linked to poor prognosis; modulates apoptosis and NF-κB | PMID: 21746896 |
| Colorectal cancer | PIDD1 expression correlates with tumor stage and survival; involved in DNA damage response | PMID: 23943788 |
| Hepatocellular carcinoma | PIDD1 promotes cell proliferation via NF-κB activation | PMID: 25605249 |
| Neuroblastoma | PIDD1 silencing reduces tumor growth; caspase-2-dependent apoptosis | PMID: 23382269 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.2 | Medium |
| Bone marrow | 8.9 | Medium |
| Lung | 6.3 | Low |
| Breast | 5.1 | Low |
| Colon | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression; used in functional studies |
| HeLa | 12.8 | Moderate expression; cervical cancer line |
| MCF7 | 9.5 | Breast cancer line; p53 wild-type |
| HCT116 | 8.1 | Colorectal cancer line; DNA damage response model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | Rare | Loss of function; truncated protein |
| c.567G>A (p.Trp189*) | Nonsense | Rare | Loss of function; premature stop codon |
| c.890A>G (p.Tyr297Cys) | Missense | Rare | Unknown effect; not in COSMIC |
| c.1022_1023insA (p.Gln341fs) | Frameshift | Rare | Loss of function; frameshift and truncation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg412*, p.Trp189*, p.Gln341fs) lead to truncated or non-functional PIDD1 protein, impairing PIDDosome assembly and caspase-2 activation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in COSMIC or ClinVar for PIDD1.
Dominant Negative (DN)
No dominant-negative mutations described in literature or databases.
View complete mutation data：
Gene Ontology (GO)
Pathways
• PIDDosome pathway (caspase-2 activation)
• NF-κB signaling pathway (via RIP1 and NEMO)
• p53-dependent DNA damage response
• Apoptosis - intrinsic pathway
Protein Summary
PIDD1 is a 910-amino acid protein containing an N-terminal ZU5 domain, a central UPA domain, and a C-terminal death domain (DD). It is primarily cytoplasmic but can translocate to the nucleus. The protein forms the PIDDosome complex with RAIDD and caspase-2, leading to caspase-2 autoproteolysis and apoptosis. PIDD1 also interacts with RIP1 and NEMO to activate NF-κB. Alternative splicing produces isoforms with distinct functions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PIDD1 Knockout HEK293 Cell Line | EDJ-KQ14756 | Human | 55367 | Details Get a Quote |
| PIDD1 Knockout A-549 Cell Line | EDJ-KQ45129 | Human | 55367 | Details Get a Quote |
| PIDD1 Knockout HCT 116 Cell Line | EDJ-KQ45130 | Human | 55367 | Details Get a Quote |
| PIDD1 Knockout HeLa Cell Line | EDJ-KQ45131 | Human | 55367 | Details Get a Quote |
