XIAP |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- XIAP (HGNC:592) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- X-linked inhibitor of apoptosis
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- API3, BIRC4
- Alias symbols
- hILP, ILP-1
- %HI
- 3.36(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.92(Read more about gnomAD pLI score)
- LOEUF
- 0.37(Read more about gnomAD LOEUF score)
- Cytoband
- Xq25
- Genomic Coordinates
-
GRCh37/hg19: chrX:122993558-123047822 NCBI Ensembl UCSC GRCh38/hg38: chrX:123859708-123913972 NCBI Ensembl UCSC - MANE Select Transcript
- NM_001167.4 ENST00000371199.8 (Read more about MANE Select)
- 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 (PubMed:11447297, PubMed:12121969, PubMed:9230442, PubMed:11257230, PubMed:11257231, PubMed:12620238, PubMed:17967870, PubMed:19473982, PubMed:20154138, PubMed:22103349, PubMed:17560374). Acts as a direct caspase inhibitor (PubMed:11257230, PubMed:11257231, PubM... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- X-linked lymphoproliferative disease due to XIAP deficiency Monarch
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PUBMED:
17080092
Rigaud et al., 2006, reported three large families with several males in multiple generations diagnosed with lymphoproliferative syndrome. Most males in these families developed lymphohystiocytosis, usually but not always related to EBV infection. The clinical phenotype was described as similar to what is seen in patients with SH2D1A mutations, however genetic sequencing of the SH2D1A gene in these families was negative. Mapping studies followed by sequencing revealed that all three families were found to harbor loss of function variants in XIAP. Mothers of affected individuals were found to be asymptomatic heterozygous carriers, and healthy siblings who were tested were found not to carry the variant. Expression of XIAP was not detected in the lysates of lymphocytes in affected individuals.
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PUBMED:
20489057
Marsh et al., 2010, reported 10 male individuals from eight families and concluded that XIAP deficiency is better defined as an X-linked form of familial hymophagocytic lymphohistiocytosis (HLH), rather than X-linked lymphoproliferative disease (XLP), as nine out of 10 patients developed HLH by eight years of age, with zero cases of lymphoma. In those who were tested (9/10), XIAP protein expression was decreased or undetectable. Of the eight unique variants identified, five represented truncating or single or multi-exon deletions. Five of the 10 individuals presented in infancy, four in the first decade, and one represented an asymptomatic male sibling at four years of age.
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PUBMED:
24942515
Aguilar et al., 2014, reported 17 male individuals from 11 families with diagnoses of inflammatory bowel disease (IBD), diagnosed between the ages of three months to 41 years, who were found to have hemizygous variants in XIAP. Of the 11 unique variants that were identified, eight represented truncating variants or multi-exon deletions. All 17 individuals had decreased or absent XIAP protein expression. In addition, two female relatives were reported to be affected. X-inactivation studies showed skewing toward the allele carrying the familial variant in both cases, which was not the case in seven unaffected female carriers.
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PUBMED:
25943627
Dziadzio et al., 2015, reported one large family of Caucasian descent who carried a truncating variant in XIAP and displayed segregation over four generations (at least 8 segregations). Affected males presented with inflammatory bowel disease, though the age of onset and clinical outcomes were highly variable. Additionally, all female carriers but one were affected, with variable gastrointestinal diagnoses and chronic erythema nodosum.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.