XAF1: XIAP Associated Factor 1
A pro-apoptotic tumor suppressor gene involved in cancer and immune regulation
Gene Information Card
| Symbol | XAF1 |
|---|---|
| Full Name | XIAP Associated Factor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 17p13.2 |
| NCBI Gene ID | 54739 ncbi.nlm.nih.gov/gene/54739 |
| Ensembl ID | ENSG00000108821 |
| UniProt ID | Q6GPH4 |
| OMIM ID | 606717 |
| HGNC ID | 30932 |
| Aliases | BIRC4BP, XIAPAF1, HSXIAPAF1 |
Description
XAF1 (XIAP Associated Factor 1) is a pro-apoptotic tumor suppressor gene located on chromosome 17p13.2. It encodes a protein that binds to and inhibits XIAP (X-linked inhibitor of apoptosis protein), thereby promoting caspase activation and apoptosis. XAF1 is frequently silenced by promoter methylation in various cancers, contributing to tumor progression and resistance to therapy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gastric Cancer | XAF1 promoter hypermethylation leads to loss of expression, reducing apoptosis and promoting tumor growth | PMID: 16936731 |
| Colorectal Cancer | XAF1 downregulation via methylation correlates with poor prognosis and resistance to chemotherapy | PMID: 17909012 |
| Melanoma | XAF1 loss enhances XIAP activity, increasing cell survival and metastasis | PMID: 19351830 |
| Breast Cancer | Reduced XAF1 expression associated with aggressive tumor phenotypes and shorter survival | PMID: 21573172 |
| Hepatocellular Carcinoma | XAF1 silencing by methylation contributes to hepatocarcinogenesis | PMID: 20574955 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Spleen | 8.2 | Low |
| Lymph node | 6.9 | Low |
| Bone marrow | 5.4 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.3 | Embryonic kidney cells |
| HeLa | 7.8 | Cervical carcinoma cells |
| MCF7 | 4.5 | Breast cancer cells |
| HCT116 | 3.2 | Colorectal carcinoma cells |
| A549 | 2.9 | Lung carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G | Missense | <0.01% | p.Met1Val; potential loss of start codon |
| c.214C>T | Nonsense | <0.01% | p.Gln72*; premature truncation |
| c.347G>A | Missense | <0.01% | p.Arg116Gln; altered protein function |
| c.500_501insA | Frameshift | <0.01% | p.Asn167Lysfs*5; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations (nonsense, frameshift, missense) result in loss of pro-apoptotic function, contributing to tumorigenesis.
Gain of Function (GOF)
No gain-of-function mutations have been documented in XAF1.
Dominant Negative (DN)
No dominant-negative mutations have been reported for XAF1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Apoptosis (KEGG hsa04210)
• Intrinsic Pathway for Apoptosis (Reactome R-HSA-109606)
• XIAP-mediated regulation of caspases (Reactome R-HSA-111463)
Protein Summary
The XAF1 protein (UniProt Q6GPH4) is a 301-amino acid polypeptide that localizes to both the cytoplasm and nucleus. It contains a zinc finger domain and interacts directly with XIAP, neutralizing its anti-apoptotic activity. XAF1 is widely expressed in normal tissues but frequently downregulated in cancers due to epigenetic silencing. Its restoration induces apoptosis and sensitizes cancer cells to chemotherapy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| XAF1 Knockout HEK293 Cell Line | EDJ-KQ11986 | Human | 54739 | Details Get a Quote |
| XAF1 Knockout HeLa Cell Line | EDJ-KQ56464 | Human | 54739 | Details Get a Quote |
| XAF1 Knockout A-549 Cell Line | EDJ-KQ64957 | Human | 54739 | Details Get a Quote |
| XAF1 Knockout HCT 116 Cell Line | EDJ-KQ73401 | Human | 54739 | Details Get a Quote |
