XIAP Gene (X-Linked Inhibitor of Apoptosis)
A critical regulator of apoptosis and immune signaling; mutations cause X-linked lymphoproliferative syndrome type 2 (XLP-2).
Gene Information Card
| Symbol | XIAP |
|---|---|
| Full Name | X-linked inhibitor of apoptosis |
| Gene Type | protein-coding |
| Chromosomal Location | Xq25 |
| NCBI Gene ID | 331 ncbi.nlm.nih.gov/gene/331 |
| Ensembl ID | ENSG00000101966 |
| UniProt ID | P98170 |
| OMIM ID | 300079 |
| HGNC ID | 5928 |
| Aliases | BIRC4; API3; IAP-3; ILP1; MIHA; XLP2 |
Description
The XIAP gene encodes the X-linked inhibitor of apoptosis protein, a member of the IAP family. XIAP is a potent suppressor of apoptosis by directly inhibiting caspases 3, 7, and 9. It also participates in innate immune signaling, particularly in the NOD2 and NF-κB pathways. Mutations in XIAP cause X-linked lymphoproliferative syndrome type 2 (XLP-2), characterized by hemophagocytic lymphohistiocytosis, splenomegaly, and inflammatory bowel disease. XIAP is also implicated in cancer, where overexpression can promote tumor cell survival.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked lymphoproliferative syndrome type 2 (XLP-2) | Loss-of-function mutations impair apoptosis regulation and immune signaling, leading to hyperinflammation and immune dysregulation. | OMIM 300635; ClinVar |
| Inflammatory bowel disease (IBD) | XIAP deficiency disrupts NOD2 signaling, increasing susceptibility to early-onset IBD, particularly Crohn's disease. | OMIM 300079; ClinVar |
| Hemophagocytic lymphohistiocytosis (HLH) | Mutations in XIAP cause recurrent HLH episodes due to defective apoptosis of activated lymphocytes. | OMIM 300079; ClinVar |
| Cancers (various) | XIAP overexpression inhibits apoptosis, promoting tumor cell survival and resistance to therapy. | COSMIC; literature |
| X-linked immunodeficiency with magnesium defect (XMEN) | Although primarily associated with MAGT1, XIAP mutations can present with overlapping immune defects. | OMIM 300079; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | High | High expression in immune cells (lymphocytes, monocytes) |
| Spleen | High | High expression in splenic tissue |
| Bone Marrow | Medium | Moderate expression in hematopoietic cells |
| Liver | Medium | Moderate expression in hepatocytes |
| Lung | Low | Low expression in lung tissue |
| Brain | Low | Low expression in neuronal tissue |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | High | Cervical cancer cell line; high XIAP expression |
| K562 | Medium | Chronic myeloid leukemia cell line; moderate expression |
| MCF7 | Medium | Breast cancer cell line; moderate expression |
| HepG2 | Low | Liver cancer cell line; low expression |
| Jurkat | High | T-cell leukemia cell line; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1480C>T (p.Arg494Ter) | Nonsense | Rare | Loss of function; truncates protein, abolishing anti-apoptotic activity |
| c.973A>G (p.Thr325Ala) | Missense | Rare | Loss of function; disrupts BIR2 domain, reducing caspase inhibition |
| c.1000C>T (p.Arg334Ter) | Nonsense | Rare | Loss of function; premature stop codon, leading to protein truncation |
| c.1466G>A (p.Trp489Ter) | Nonsense | Rare | Loss of function; truncates RING domain, affecting ubiquitin ligase activity |
| c.1180C>T (p.Arg394Trp) | Missense | Rare | Loss of function; affects BIR3 domain, impairing caspase-9 inhibition |
Mutation functional classification
Loss of Function (LOF)
Most XIAP mutations are loss-of-function, leading to reduced or absent protein function. This impairs apoptosis regulation and NOD2 signaling, causing immune dysregulation and inflammation.
Gain of Function (GOF)
Gain-of-function mutations are rare but may occur in cancer, leading to increased XIAP expression or stability, enhancing anti-apoptotic activity and promoting tumor survival.
Dominant Negative (DN)
Dominant-negative effects are not well-documented for XIAP; most mutations are recessive or haploinsufficient, but some missense mutations may interfere with protein-protein interactions.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type endopeptidase inhibitor activity | • zinc ion binding |
| • ubiquitin-protein transferase activity | • apoptotic process |
| • negative regulation of apoptotic process | • innate immune response |
| • NF-kappaB signaling | • NOD2 signaling pathway |
Pathways
• Apoptosis regulation
• NOD-like receptor signaling
• NF-kappaB signaling
• Innate immune response
• Ubiquitin-proteasome pathway
Protein Summary
XIAP is a 497-amino acid protein with three BIR domains (BIR1, BIR2, BIR3) and a RING finger domain. BIR2 and BIR3 inhibit caspases 3/7 and 9, respectively. The RING domain has E3 ubiquitin ligase activity, targeting caspases and itself for degradation. XIAP also interacts with TAB1 to modulate NF-κB signaling. It is widely expressed in adult tissues, with high levels in immune cells. Mutations causing loss of function lead to XLP-2 and IBD, while overexpression in cancer contributes to chemoresistance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| XIAP Knockout HEK293 Cell Line | EDJ-KQ17915 | Human | 331 | Details Get a Quote |
| XIAP Knockout A-549 Cell Line | EDJ-KQ19058 | Human | 331 | Details Get a Quote |
| XIAP Knockout HCT 116 Cell Line | EDJ-KQ19059 | Human | 331 | Details Get a Quote |
| XIAP Knockout HeLa Cell Line | EDJ-KQ19060 | Human | 331 | Details Get a Quote |
