Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

XAF1 (XIAP associated factor-1)

Written2008-01Stéphanie Plenchette, Wai Gin Fong, Robert G Korneluk
Children's Hospital of Eastern Ontario, Apoptosis Research Centre, Research Institute, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada

(Note : for Links provided by Atlas : click)


HGNC (Hugo) XAF1
HGNC Alias symbBIRC4BP
LocusID (NCBI) 54739
Atlas_Id 44095
Location 17p13.1  [Link to chromosome band 17p13]
Location_base_pair Starts at 6756046 and ends at 6775645 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping XAF1.png]
Local_order Telomeric to TP53 gene (17p13.1)
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
XAF1 (17p13.1)::PIMREG (17p13.2)XAF1 (17p13.1)::SLC8A1 (2p22.1)


  Schematic diagram of the XAF1 gene comprising 8 exons (in grey) and transcript variants. The sizes in base pairs (bp) of exons (above) and introns (below) are shown. (*) indicates the positions of the stop codons.
Description The XAF1 gene exists as a single copy in the human genome; it contains 8 exons and was predicted to span over approximately 18 kb of the genomic DNA.
Transcription Five isoforms of XAF1 cDNA have been identified and are expressed in a cell and tissue type specific-manner:
The original XAF1, also called XAF1(A) (CDS: 906nt)
The XAF1(B) isoform (CDS: 849nt); lacks exon 3
The XAF1(C) isoform (CDS: 495nt); contains exon 4b and a new stop codon
The XAF1(D) isoform (CDS: 426nt); lacks exons 4b and 5 (new stop codon in exon 6)
The XAF1(E) isoform (CDS: 369nt); lacks exons 3, 4b and 5 (new stop codon in exon 6)
With Northern blot analysis, at least four distinct transcripts sizes have been identified in Homo sapiens (3.9 kb, 4.5 kb, 6.0 kb and 7.0 kb). How these mRNA species relate to isoform variants is not known.
Pseudogene Not known


Description The full length XAF1 protein consists of 301 amino acids corresponding to a molecular weight of 33.411 kDa. The protein contains seven zinc fingers domains. The XAF1(B) isoform is predicted to lack the third N-terminal zinc finger of the previously described XAF1. The XAF1(C) is predicted to contain the first five amino-terminal zinc finger domains of the previously described XAF1 and also a unique 24 aa carboxy terminus. There is no evidence for XAF1 isoforms (C), (D) and (E) expression at the protein level.
Expression Normal tissue: ubiquitous and differential expression in normal tissues; highest in heart and ovary and lowest in brain and testis at mRNA levels. The XAF1 protein also displays differential protein expression profile within normal cell or tissue development including placenta and motoneurons.
Cancer: as opposed to normal cells, XAF1 is found either low or undetectable in tumor cell lines at both mRNA and protein levels. Expression varies also widely among different tumor cell lines. High levels of XAF1 protein were found in glioblastoma cells (SF-539) and ovarian cells (OVCAR-5). Detectable levels were found also in various gastric and colon cancer cell lines and also myeloma cells (U266).
Localisation Nuclear and cytoplasmic distribution
Function Tumor suppressor gene: loss of heterozygosity (LOH) found in 12 of 33 (36%) human primary colorectal carcinomas. The absence or reduced expression of XAF1 in cancer cell lines by genetic or epigenetic modifications have suggested a possible role in the suppression of development and/or progression of malignancy.
IAP antagonist: XAF1 exerts a proapoptotic effect by directly interacting with BIRC4/XIAP and antagonizing its anticaspase activity. XAF1 enhances XIAP E3 ligase activity towards BIRC5/Survivin through a complex and mediates Survivin down-regulation.
Interferon (IFN)-stimulated gene (ISG): XAF1 is an important mediator of IFN-induced sensitization to TNF-related apoptosis-inducing ligand (TRAIL) in cancer.
Increasing expression of XAF1 sensitizes cells to apoptosis-induced by various stimuli including etoposide, 5-FU, TRAIL, anti-Fas Ab, TNFalpha, UV, H2O2, gamma-irradiation.
Homology XAF1 shares high amino acid similarity with the zinc finger domains of FLN29 and TRAF6.


Note Include genetic and epigenetic modification
Epigenetics Aberrant promoter hypermethylation in the 5' proximal region (from +3nt to -234 nt) in a variety of gastric, colon, bladder, kidney and prostate cancer cell lines and tumors.
Germinal Not known
Somatic No somatic mutations in tumor cell lines examined. LOH described in colon tumors.

Implicated in

Entity Colorectal cancer, gastric cancer, urogenital cancer
Oncogenesis XAF1 is proposed to be a tumor suppressor gene. Correlation of reduction in XAF1 expression with stage and grade within gastric and colorectal tumors demonstrating that the loss of XAF1 contributes to tumorigenesis.


Degradation of survivin by the X-linked inhibitor of apoptosis (XIAP)-XAF1 complex.
Arora V, Cheung HH, Plenchette S, Micali OC, Liston P, Korneluk RG
The Journal of biological chemistry. 2007 ; 282 (36) : 26202-26209.
PMID 17613533
Hypermethylation of XIAP-associated factor 1, a putative tumor suppressor gene from the 17p13.2 locus, in human gastric adenocarcinomas.
Byun DS, Cho K, Ryu BK, Lee MG, Kang MJ, Kim HR, Chi SG
Cancer research. 2003 ; 63 (21) : 7068-7075.
PMID 14612497
Frequent alteration of XAF1 in human colorectal cancers: implication for tumor cell resistance to apoptotic stresses.
Chung SK, Lee MG, Ryu BK, Lee JH, Han J, Byun DS, Chae KS, Lee KY, Jang JY, Kim HJ, Chi SG
Gastroenterology. 2007 ; 132 (7) : 2459-2477.
PMID 17570219
Switch to full-length of XAF1 mRNA expression in prostate cancer cells by the DNA methylation inhibitor.
Fang X, Liu Z, Fan Y, Zheng C, Nilson S, Egevad L, Ekman P, Xu D
International journal of cancer. Journal international du cancer. 2006 ; 118 (10) : 2485-2489.
PMID 16353137
Expression and genetic analysis of XIAP-associated factor 1 (XAF1) in cancer cell lines.
Fong WG, Liston P, Rajcan-Separovic E, St Jean M, Craig C, Korneluk RG
Genomics. 2000 ; 70 (1) : 113-122.
PMID 11087668
Gene expression and promoter methylation of the XIAP-associated Factor 1 in renal cell carcinomas: correlations with pathology and outcome.
Kempkensteffen C, Hinz S, Schrader M, Christoph F, Magheli A, Krause H, Schostak M, Miller K, Weikert S
Cancer letters. 2007 ; 254 (2) : 227-235.
PMID 17449173
Identification of X-linked inhibitor of apoptosis-associated factor-1 as an interferon-stimulated gene that augments TRAIL Apo2L-induced apoptosis.
Leaman DW, Chawla-Sarkar M, Vyas K, Reheman M, Tamai K, Toji S, Borden EC
The Journal of biological chemistry. 2002 ; 277 (32) : 28504-28511.
PMID 12029096
Promoter CpG hypermethylation and downregulation of XAF1 expression in human urogenital malignancies: implication for attenuated p53 response to apoptotic stresses.
Lee MG, Huh JS, Chung SK, Lee JH, Byun DS, Ryu BK, Kang MJ, Chae KS, Lee SJ, Lee CH, Kim JI, Chang SG, Chi SG
Oncogene. 2006 ; 25 (42) : 5807-5822.
PMID 16909101
Identification of XAF1 as an antagonist of XIAP anti-Caspase activity.
Liston P, Fong WG, Kelly NL, Toji S, Miyazaki T, Conte D, Tamai K, Craig CG, McBurney MW, Korneluk RG
Nature cell biology. 2001 ; 3 (2) : 128-133.
PMID 11175744
Low expression of XIAP-associated factor 1 in human colorectal cancers.
Ma TL, Ni PH, Zhong J, Tan JH, Qiao MM, Jiang SH
Chinese journal of digestive diseases. 2005 ; 6 (1) : 10-14.
PMID 15667552
XAF1 expression is significantly reduced in human melanoma.
Ng KC, Campos EI, Martinka M, Li G
The Journal of investigative dermatology. 2004 ; 123 (6) : 1127-1134.
PMID 15610524
Motoneuron resistance to apoptotic cell death in vivo correlates with the ratio between X-linked inhibitor of apoptosis proteins (XIAPs) and its inhibitor, XIAP-associated factor 1.
Perrelet D, Perrin FE, Liston P, Korneluk RG, MacKenzie A, Ferrer-Alcon M, Kato AC
The Journal of neuroscience : the official journal of the Society for Neuroscience. 2004 ; 24 (15) : 3777-3785.
PMID 15084658
The role of XAF1 in cancer.
Plenchette S, Cheung HH, Fong WG, LaCasse EC, Korneluk RG
Current opinion in investigational drugs (London, England : 2000). 2007 ; 8 (6) : 469-476.
PMID 17621877
Potent antitumor efficacy of XAF1 delivered by conditionally replicative adenovirus vector via caspase-independent apoptosis.
Qi R, Gu J, Zhang Z, Yang K, Li B, Fan J, Wang C, He Z, Qiao L, Lin Z, Liu XY
Cancer gene therapy. 2007 ; 14 (1) : 82-90.
PMID 17008933
Adjuvant whole abdominal intensity modulated radiotherapy (IMRT) for high risk stage FIGO III patients with ovarian cancer (OVAR-IMRT-01) - Pilot trial of a phase I/II study: study protocol.
Rochet N, Jensen AD, Sterzing F, Munter MW, Eichbaum MH, Schneeweiss A, Sohn C, Debus J, Harms W
BMC cancer. 2007 ; 7 : page 227.
PMID 18093313
All-trans retinoic acid induces XAF1 expression through an interferon regulatory factor-1 element in colon cancer.
Wang J, Peng Y, Sun YW, He H, Zhu S, An X, Li M, Lin MC, Zou B, Xia HH, Jiang B, Chan AO, Yuen MF, Kung HF, Wong BC
Gastroenterology. 2006 ; 130 (3) : 747-758.
PMID 16530516
Xaf1 can cooperate with TNFalpha in the induction of apoptosis, independently of interaction with XIAP.
Xia Y, Novak R, Lewis J, Duckett CS, Phillips AC
Molecular and cellular biochemistry. 2006 ; 286 (1-2) : 67-76.
PMID 16432762
Coexistence of high levels of apoptotic signaling and inhibitor of apoptosis proteins in human tumor cells: implication for cancer specific therapy.
Yang L, Cao Z, Yan H, Wood WC
Cancer research. 2003 ; 63 (20) : 6815-6824.
PMID 14583479
Identification of a novel splice variant of X-linked inhibitor of apoptosis-associated factor 1.
Yin W, Cheepala S, Clifford JL
Biochemical and biophysical research communications. 2006 ; 339 (4) : 1148-1154.
PMID 16343440
Correlation between the single-site CpG methylation and expression silencing of the XAF1 gene in human gastric and colon cancers.
Zou B, Chim CS, Zeng H, Leung SY, Yang Y, Tu SP, Lin MC, Wang J, He H, Jiang SH, Sun YW, Yu LF, Yuen ST, Kung HF, Wong BC
Gastroenterology. 2006 ; 131 (6) : 1835-1843.
PMID 17087954


This paper should be referenced as such :
Plenchette, S ; Fong, WG ; Korneluk, RG
XAF1 (XIAP associated factor-1)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(5):397-399.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)XAF1   30932
Entrez_Gene (NCBI)XAF1    XIAP associated factor 1
GeneCards (Weizmann)XAF1
Ensembl hg19 (Hinxton)ENSG00000132530 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000132530 [Gene_View]  ENSG00000132530 [Sequence]  chr17:6756046-6775645 [Contig_View]  XAF1 [Vega]
ICGC DataPortalENSG00000132530
TCGA cBioPortalXAF1
AceView (NCBI)XAF1
Genatlas (Paris)XAF1
SOURCE (Princeton)XAF1
Genetics Home Reference (NIH)XAF1
Genomic and cartography
GoldenPath hg38 (UCSC)XAF1  -     chr17:6756046-6775645 +  17p13.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)XAF1  -     17p13.1   [Description]    (hg19-Feb_2009)
GoldenPathXAF1 - 17p13.1 [CytoView hg19]  XAF1 - 17p13.1 [CytoView hg38]
Genome Data Viewer NCBIXAF1 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AK056908 AK091799 AK290276 AK292710 AK292848
RefSeq transcript (Entrez)NM_001353134 NM_001353135 NM_001353136 NM_001353137 NM_001353138 NM_001353139 NM_001353140 NM_017523 NM_199139
Consensus coding sequences : CCDS (NCBI)XAF1
Gene ExpressionXAF1 [ NCBI-GEO ]   XAF1 [ EBI - ARRAY_EXPRESS ]   XAF1 [ SEEK ]   XAF1 [ MEM ]
Gene Expression Viewer (FireBrowse)XAF1 [ Firebrowse - Broad ]
GenevisibleExpression of XAF1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)54739
GTEX Portal (Tissue expression)XAF1
Human Protein AtlasENSG00000132530-XAF1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ6GPH4   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ6GPH4  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ6GPH4
Domaine pattern : Prosite (Expaxy)ZF_TRAF (PS50145)   
Domains : Interpro (EBI)XAF1    XAF1_C    Znf_RING/FYVE/PHD    Znf_TRAF   
Domain families : Pfam (Sanger)XAF1_C (PF18608)   
Domain families : Pfam (NCBI)pfam18608   
Conserved Domain (NCBI)XAF1
PDB Europe2LXW   
Structural Biology KnowledgeBase2LXW   
SCOP (Structural Classification of Proteins)2LXW   
CATH (Classification of proteins structures)2LXW   
AlphaFold pdb e-kbQ6GPH4   
Human Protein Atlas [tissue]ENSG00000132530-XAF1 [tissue]
Protein Interaction databases
IntAct (EBI)Q6GPH4
Ontologies - Pathways
Ontology : AmiGOprotein binding  nucleoplasm  mitochondrion  cytosol  apoptotic process  zinc ion binding  response to interferon-beta  type I interferon signaling pathway  
Ontology : EGO-EBIprotein binding  nucleoplasm  mitochondrion  cytosol  apoptotic process  zinc ion binding  response to interferon-beta  type I interferon signaling pathway  
REACTOMEQ6GPH4 [protein]
REACTOME PathwaysR-HSA-909733 [pathway]   
NDEx NetworkXAF1
Atlas of Cancer Signalling NetworkXAF1
Wikipedia pathwaysXAF1
Orthology - Evolution
GeneTree (enSembl)ENSG00000132530
Phylogenetic Trees/Animal Genes : TreeFamXAF1
Homologs : HomoloGeneXAF1
Homology/Alignments : Family Browser (UCSC)XAF1
Gene fusions - Rearrangements
Fusion : MitelmanXAF1::FAM64A [17p13.1/17p13.2]  
Fusion : QuiverXAF1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerXAF1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)XAF1
Exome Variant ServerXAF1
GNOMAD BrowserENSG00000132530
Varsome BrowserXAF1
ACMGXAF1 variants
Genomic Variants (DGV)XAF1 [DGVbeta]
DECIPHERXAF1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisXAF1 
ICGC Data PortalXAF1 
TCGA Data PortalXAF1 
Broad Tumor PortalXAF1
OASIS PortalXAF1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICXAF1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DXAF1
Mutations and Diseases : HGMDXAF1
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)XAF1
DoCM (Curated mutations)XAF1
CIViC (Clinical Interpretations of Variants in Cancer)XAF1
NCG (London)XAF1
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry XAF1
NextProtQ6GPH4 [Medical]
Target ValidationXAF1
Huge Navigator XAF1 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDXAF1
Pharm GKB GenePA162409299
Clinical trialXAF1
DataMed IndexXAF1
PubMed79 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Oct 8 21:30:55 CEST 2021

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us