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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
XIAP
X-linked inhibitor of apoptosis
Chromosome X Β· Xq25
NCBI Gene: 331Ensembl: ENSG00000101966.15HGNC: HGNC:592UniProt: B2R9R2
684PubMed Papers
21Diseases
0Drugs
71Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Highly StudiedVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein K63-linked ubiquitinationpositive regulation of protein linear polyubiquitinationnucleuscytoplasmX-linked lymphoproliferative diseaseneurodegenerative diseaseinflammatory bowel diseaseSplenomegaly
✦AI Summary

XIAP is a multifunctional E3 ubiquitin ligase and direct caspase inhibitor that regulates cell survival, immunity, and cellular homeostasis. Structurally, XIAP directly binds the active site pockets of caspase-3 and caspase-7, obstructing substrate entry, while inactivating caspase-9 by maintaining its monomeric state 12. As an E3 ligase, XIAP ubiquitinates diverse substrates including RIPK1, RIPK2, and MAP3K proteins, modulating NF-ΞΊB and MAPK signaling pathways 34. XIAP critically regulates innate immunity by catalyzing Lys-63-linked polyubiquitination of RIPK2 downstream of NOD1/NOD2 pattern recognition receptors, orchestrating antibacterial responses and intestinal inflammation control 56. In cancer, XIAP upregulation promotes progression through multiple mechanisms. Recent evidence shows XIAP ubiquitinates the m6A reader YTHDC1, degrading it to enhance MMP-2 expression and bladder cancer metastasis 7. XIAP also ubiquitinates YTHDC1 and other substrates to regulate cell survival signaling, autophagy, and necroptosis 8. XIAP deficiency causes severe immunological consequences, including inflammatory bowel disease and hemophagocytic lymphohistiocytosis through dysregulated caspase-8-driven apoptosis and pyroptotic crosstalk 910. Defective autophagy and NLRP3 inflammasome hyperactivation drive IL-1Ξ²-mediated hyperinflammation in patient macrophages 10.

Sources cited
1
Recent evidence shows XIAP ubiquitinates the m6A reader YTHDC1, degrading it to enhance MMP-2 expression and bladder cancer metastasis .
PMID: 40133252
2
XIAP also ubiquitinates YTHDC1 and other substrates to regulate cell survival signaling, autophagy, and necroptosis .
PMID: 33138314
3
XIAP deficiency causes severe immunological consequences, including inflammatory bowel disease and hemophagocytic lymphohistiocytosis through dysregulated caspase-8-driven apoptosis and pyroptotic crosstalk , .
PMID: 38820590
⚠Limited data available β€” This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
X-linked lymphoproliferative diseaseOpen Targets
0.80Strong
neurodegenerative diseaseOpen Targets
0.56Moderate
inflammatory bowel diseaseOpen Targets
0.47Moderate
SplenomegalyOpen Targets
0.46Moderate
SepsisOpen Targets
0.34Weak
lymphoproliferative syndrome 2Open Targets
0.34Weak
Recurrent infectionsOpen Targets
0.34Weak
X-linked sideroblastic anemia 1Open Targets
0.34Weak
autoinflammatory syndromeOpen Targets
0.32Weak
genetic disorderOpen Targets
0.19Weak
lymphoproliferative syndromeOpen Targets
0.16Weak
neoplasmOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
renal cell carcinomaOpen Targets
0.11Weak
ovarian cancerOpen Targets
0.10Weak
esophageal squamous cell carcinomaOpen Targets
0.10Weak
cancerOpen Targets
0.10Weak
acute lymphoblastic leukemiaOpen Targets
0.10Suggestive
acute myeloid leukemiaOpen Targets
0.10Suggestive
urinary bladder carcinomaOpen Targets
0.09Suggestive
Lymphoproliferative syndrome, X-linked, 2UniProt
Pathogenic Variants71
NM_001167.4(XIAP):c.1021_1022del (p.Asn341fs)Pathogenic
X-linked lymphoproliferative disease due to XIAP deficiency|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 341
NM_001167.4(XIAP):c.664C>T (p.Arg222Ter)Pathogenic
X-linked lymphoproliferative disease due to XIAP deficiency|Nonpapillary renal cell carcinoma|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 222
NM_001167.4(XIAP):c.389_392del (p.Asp130fs)Pathogenic
X-linked lymphoproliferative disease due to XIAP deficiency|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 130
NM_001167.4(XIAP):c.894_898del (p.Lys299fs)Pathogenic
not provided|X-linked lymphoproliferative disease due to XIAP deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 299
NM_001167.4(XIAP):c.609TGG[1] (p.Gly205del)Pathogenic
X-linked lymphoproliferative disease due to XIAP deficiency|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 205
NM_001167.4(XIAP):c.1141C>T (p.Arg381Ter)Pathogenic
Recurrent infections;Sepsis|not provided|X-linked lymphoproliferative disease due to XIAP deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 381
NM_001167.4(XIAP):c.345C>G (p.Tyr115Ter)Pathogenic
not provided|X-linked lymphoproliferative disease due to XIAP deficiency
β˜…β˜…β˜†β˜†2024β†’ Residue 115
NM_001167.4(XIAP):c.108del (p.Pro37fs)Pathogenic
not provided|X-linked lymphoproliferative disease due to XIAP deficiency
β˜…β˜…β˜†β˜†2024β†’ Residue 37
NM_001167.4(XIAP):c.985del (p.Tyr329fs)Pathogenic
X-linked lymphoproliferative disease due to XIAP deficiency
β˜…β˜…β˜†β˜†2023β†’ Residue 329
NM_001167.4(XIAP):c.1009G>T (p.Glu337Ter)Pathogenic
X-linked lymphoproliferative disease due to XIAP deficiency|XIAP-related disorder
β˜…β˜…β˜†β˜†2023β†’ Residue 337
NM_001167.4(XIAP):c.1481T>A (p.Ile494Asn)Likely pathogenic
X-linked lymphoproliferative disease due to XIAP deficiency
β˜…β˜†β˜†β˜†2026β†’ Residue 494
NM_001167.4(XIAP):c.631G>T (p.Glu211Ter)Pathogenic
X-linked lymphoproliferative disease due to XIAP deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 211
NM_001167.4(XIAP):c.1114C>T (p.Gln372Ter)Pathogenic
X-linked lymphoproliferative disease due to XIAP deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 372
NM_001167.4(XIAP):c.568dup (p.Tyr190fs)Pathogenic
X-linked lymphoproliferative disease due to XIAP deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 190
NM_001167.4(XIAP):c.518G>A (p.Trp173Ter)Pathogenic
X-linked lymphoproliferative disease due to XIAP deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 173
NM_001167.4(XIAP):c.449C>G (p.Ser150Ter)Pathogenic
X-linked sideroblastic anemia 1
β˜…β˜†β˜†β˜†2025β†’ Residue 150
NM_001167.4(XIAP):c.1038_1041dup (p.Leu348fs)Pathogenic
X-linked lymphoproliferative disease due to XIAP deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 348
NM_001167.4(XIAP):c.1386del (p.Phe462fs)Pathogenic
X-linked lymphoproliferative disease due to XIAP deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 462
NM_001167.4(XIAP):c.134C>G (p.Ser45Ter)Pathogenic
X-linked lymphoproliferative disease due to XIAP deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 45
NM_001167.4(XIAP):c.1087dup (p.Thr363fs)Pathogenic
X-linked lymphoproliferative disease due to XIAP deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 363
View on ClinVar β†—
Related Genes
APAF1Protein interaction100%TRAF5Protein interaction100%IKBKBProtein interaction100%TNFProtein interaction100%RIPK1Protein interaction100%TRAF2Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Heart
61%
Liver
51%
Lung
43%
Bone Marrow
40%
Ovary
32%
Gene Interaction Network
Click a node to explore
XIAPAPAF1TRAF5IKBKBTNFRIPK1TRAF2
PROTEIN STRUCTURE
Preparing viewer…
PDB4J44 Β· 1.30 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.23Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.09 [0.04–0.23]
RankingsWhere XIAP stands among ~20K protein-coding genes
  • #318of 20,598
    Most Researched684 Β· top 5%
  • #1,021of 5,498
    Most Pathogenic Variants71 Β· top quartile
  • #660of 17,882
    Most Constrained (LOEUF)0.23 Β· top 5%
Genes detectedXIAP
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
XIAP promotes metastasis of bladder cancer cells by ubiquitylating YTHDC1.
PMID: 40133252
Cell Death Dis Β· 2025
1.00
2
XIAP's Profile in Human Cancer.
PMID: 33138314
Biomolecules Β· 2020
0.90
3
Growth-Suppressive and Apoptosis-Inducing Effects of Tetrandrine in SW872 Human Malignant Liposarcoma Cells via Activation of Caspase-9, Down-Regulation of XIAP and STAT-3, and ER Stress.
PMID: 35740967
Biomolecules Β· 2022
0.80
4
RIPK2 NODs to XIAP and IBD.
PMID: 32631784
Semin Cell Dev Biol Β· 2021
0.80
5
Moracin D suppresses cell growth and induces apoptosis via targeting the XIAP/PARP1 axis in pancreatic cancer.
PMID: 38489888
Phytomedicine Β· 2024
0.78