XAF1

Chr 17

XIAP associated factor 1

Also known as: BIRC4BP, HSXIAPAF1, XIAPAF1

NCBI Gene: 54739ENSG00000132530UniProt: Q6GPH4

This gene encodes a protein which binds to and counteracts the inhibitory effect of a member of the IAP (inhibitor of apoptosis) protein family. IAP proteins bind to and inhibit caspases which are activated during apoptosis. The proportion of IAPs and proteins which interfere with their activity, such as the encoded protein, affect the progress of the apoptosis signaling pathway. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

83
ClinVar variants
21
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— XAF1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 53 VUS of 83 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.70LOEUF
pLI 0.000
Z-score -0.49
OE 1.14 (0.77–1.70)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.11Z-score
OE missense 0.98 (0.86–1.11)
161 obs / 164.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.14 (0.77–1.70)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.86–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.08
0≤1.21.6
LoF obs/exp: 16 / 14.0Missense obs/exp: 161 / 164.8Syn Z: -0.49

ClinVar Variant Classifications

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic1
VUS53
Likely Benign8
Benign1
20
Pathogenic
1
Likely Pathogenic
53
VUS
8
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
1
0
1
VUS
0
45
8
0
53
Likely Benign
0
8
0
0
8
Benign
0
1
0
0
1
Total05429083

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

XAF1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrated analysis of single-cell RNA-seq and chipset data unravels PANoptosis-related genes in sepsis.
Dai W et al.·Front Immunol
2024
A commonly inherited human PCSK9 germline variant drives breast cancer metastasis via LRP1 receptor.
Mei W et al.·Cell
2025
Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients.
Zhu L et al.·Immunity
2020Cohort
XAF1 promotes colorectal cancer metastasis via VCP-RNF114-JUP axis.
Xia J et al.·J Cell Biol
2024
Immunological landscape of human lymphoid explants during measles virus infection.
Acklin JA et al.·JCI Insight
2024
YY1 negatively regulates the XAF1 gene expression in prostate cancer.
Camacho-Moctezuma B et al.·Biochem Biophys Res Commun
2019
Granuloma genes in sarcoidosis: what is new?
Fischer A et al.·Curr Opin Pulm Med
2015Review
Epigenetic silencing of XAF1 in high-grade gliomas is associated with IDH1 status and improved clinical outcome.
Reich TR et al.·Oncotarget
2017
XAF1 expression levels in a non-small cell lung cancer cohort and its potential association with carcinogenesis.
Schluckebier L et al.·Oncol Rep
2017Cohort
Rheumatoid arthritis and gout: a rare combination or overlooked coexistence?
Li S et al.·Arthritis Res Ther
2026
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Gamabufotalin impedes NSCLC progression by inhibiting the mitochondrial factor CHCHD2 and modulating XAF1 expression.
Cai Y et al.·Biochem Pharmacol
2026
Single-Nucleus Transcriptomics Uncovers Xaf1-Driven PANoptosis as a Therapeutic Target in Aminoglycoside-Induced Hearing Loss.
Wang X et al.·Cell Prolif
2026🔓 Open Access
Germline TP53 p.R337H and XAF1 p.E134* Variants: Prevalence in Paraguay and Comparison with Rates in Brazilian State of Paraná and Previous Findings at the Paraguayan-Brazilian Border.
Falcon-de Legal E et al.·Curr Oncol
2025🔓 Open Access
TRIM47 promotes head and neck squamous cell carcinoma malignant progression by degrading XAF1 through ubiquitination.
Yu C et al.·iScience
2025🔓 Open Access
XAF1 is secreted from stressed tumor cells to activate T cell-mediated tumor surveillance via Lck-ERK signaling.
Ahn J et al.·Neoplasia
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Pancreas Cancer

Prospective Cohort Study of Pancreatic Cancer Patients Treated With Proton Beam Therapy

ENROLLING BY INVITATION
NCT04466189National Cancer Center, KoreaStarted 2018-09-21

External Resources

Links to major genomics databases and tools