XIAP
X-linked inhibitor of apoptosis, the group of Ring finger proteins|Baculoviral IAP repeat containing
Basic information
Region (hg38): X:123859711-123913972
Previous symbols: [ "API3", "BIRC4" ]
Links
Phenotypes
GenCC
Source:
- X-linked lymphoproliferative disease due to XIAP deficiency (Supportive), mode of inheritance: XL
- X-linked lymphoproliferative disease due to XIAP deficiency (Strong), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Lymphoproliferative syndrome, X-linked, 2 | XL | Allergy/Immunology/Infectious; Hematologic; Oncologic | Surveillance for EBV infections is indicated; Prompt recognition and treatment of hemophagocytic lymphohistiocytosis (with immunologic agents or rituximab in the case of EBV infection); Treatment for individuals with hypogammaglobulinemia (with IVIG) may be beneficial; Awareness of the increased risk of lymphoma may allow prompt recognition and treatment; HSCT has been described, and is indicated in many individuals | Allergy/Immunology/Infectious; Hematologic; Oncologic | 17080092; 20301580; 21119115; 21543760; 21971331; 32374962 |
| Digenic disease (with CD40LG) have been reported |
ClinVar
This is a list of variants' phenotypes submitted to
- X-linked lymphoproliferative disease due to XIAP deficiency (271 variants)
- not provided (28 variants)
- Lymphoproliferative disorder (15 variants)
- Autoinflammatory syndrome (8 variants)
- Inborn genetic diseases (7 variants)
- not specified (4 variants)
- XIAP-related condition (3 variants)
- Recurrent infections;Sepsis (1 variants)
- X-linked lymphoproliferative disease due to XIAP deficiency;X-linked lymphoproliferative disease due to SH2D1A deficiency (1 variants)
- See cases (1 variants)
- Lymphoproliferative syndrome 2 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the XIAP gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 28 | 38 | ||||
| missense | 78 | 10 | 10 | 98 | ||
| nonsense | 11 | 13 | ||||
| start loss | 0 | |||||
| frameshift | 16 | 19 | ||||
| inframe indel | 2 | |||||
| splice donor/acceptor (+/-2bp) | 4 | |||||
| splice region ? | 2 | 6 | 4 | 12 | ||
| non coding ? | 41 | 10 | 64 | 115 | ||
| Total | 28 | 5 | 126 | 48 | 82 |
Variants in XIAP
This is a list of pathogenic ClinVar variants found in the XIAP region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| XIAP | protein_coding | protein_coding | ENST00000371199 | 6 | 54256 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.918 | 0.0816 | 125724 | 1 | 2 | 125727 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.49 | 123 | 179 | 0.686 | 0.0000127 | 3291 |
| Missense in Polyphen | 17 | 53.414 | 0.31827 | 1000 | ||
| Synonymous | 0.912 | 51 | 60.0 | 0.850 | 0.00000417 | 908 |
| Loss of Function | 3.35 | 2 | 16.8 | 0.119 | 0.00000136 | 289 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000254 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000535 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, CASP3, CASP7, CASP8, CASP9, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS and BIRC5/survivin. Ubiquitinion of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation. Plays a role in copper homeostasis by ubiquitinationg COMMD1 and promoting its proteasomal degradation. Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation. Acts as an important regulator of innate immune signaling via regulation of Nodlike receptors (NLRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES. Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta- catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program. {ECO:0000269|PubMed:11447297, ECO:0000269|PubMed:12121969, ECO:0000269|PubMed:14645242, ECO:0000269|PubMed:14685266, ECO:0000269|PubMed:17560374, ECO:0000269|PubMed:17967870, ECO:0000269|PubMed:19473982, ECO:0000269|PubMed:20154138, ECO:0000269|PubMed:21145488, ECO:0000269|PubMed:22103349, ECO:0000269|PubMed:22304967, ECO:0000269|PubMed:9230442}.;
- Disease
- DISEASE: Lymphoproliferative syndrome, X-linked, 2 (XLP2) [MIM:300635]: A rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma. {ECO:0000269|PubMed:17080092}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Focal adhesion - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Apoptosis - multiple species - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Necroptosis - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Apoptosis - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Busulfan Pathway, Pharmacodynamics;Nucleotide-binding Oligomerization Domain (NOD) pathway;Apoptosis Modulation and Signaling;Apoptosis;Focal Adhesion;Copper homeostasis;Apoptotic Signaling Pathway;NO-cGMP-PKG mediated Neuroprotection;Signaling by WNT;Signal Transduction;caspase cascade in apoptosis;Regulation of PTEN localization;Regulation of PTEN stability and activity;SMAC-mediated dissociation of IAP:caspase complexes ;SMAC-mediated apoptotic response;Apoptotic factor-mediated response;Intrinsic Pathway for Apoptosis;Apoptosis;Regulated Necrosis;Programmed Cell Death;BMP2 signaling TAK1;RIPK1-mediated regulated necrosis;Deactivation of the beta-catenin transactivating complex;TNFR1-induced NFkappaB signaling pathway;BMP receptor signaling;TNF signaling;SMAC binds to IAPs ;PTEN Regulation;PIP3 activates AKT signaling;Death Receptor Signalling;Regulation of TNFR1 signaling;TGF-beta signaling TAK1;TNFalpha;Intracellular signaling by second messengers;Caspase Cascade in Apoptosis;TCF dependent signaling in response to WNT;p75(NTR)-mediated signaling;TGF-beta receptor signaling
(Consensus)
Intolerance Scores
- loftool
- 0.245
- rvis_EVS
- 0.02
- rvis_percentile_EVS
- 55.22
Haploinsufficiency Scores
- pHI
- 0.169
- hipred
- Y
- hipred_score
- 0.704
- ghis
- 0.599
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.834
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Xiap
- Phenotype
- endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype;
Gene ontology
- Biological process
- apoptotic process;cellular response to DNA damage stimulus;Wnt signaling pathway;protein ubiquitination;regulation of BMP signaling pathway;positive regulation of protein ubiquitination;regulation of cell population proliferation;negative regulation of apoptotic process;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;regulation of innate immune response;regulation of inflammatory response;copper ion homeostasis;regulation of nucleotide-binding oligomerization domain containing signaling pathway;positive regulation of canonical Wnt signaling pathway;positive regulation of protein linear polyubiquitination;inhibition of cysteine-type endopeptidase activity involved in apoptotic process
- Cellular component
- nucleus;nucleoplasm;cytoplasm;cytosol
- Molecular function
- ubiquitin-protein transferase activity;protein binding;identical protein binding;cysteine-type endopeptidase inhibitor activity involved in apoptotic process;metal ion binding;ubiquitin protein ligase activity