PhenoModifier-Variant Detail

Variant "XIAP:c.*80G>C"

Search result: 1 record

Variant information

Gene:

XIAP

Variant:

XIAP:c.*80G>C

Genomic location:

chrX:123041111(hg19)

HGVS:

SO Term	RefSeq
protein_coding	NM_001167.3:c.*80G>C
protein_coding	NM_001204401.1:c.*80G>C
pseudogene	NR_037916.1:n.824G>C

dbSNP ID:

rs12838858

GWAS trait:

no data

Modifier statisitcs

Record:

1

Disorder:

1

Reference:

1

Effect type:

Expressivity(1)

Modifier effect:

Altered onset time(1)

Detail：

Target disease:

Wilson Disease (DOID_893)

Effect type:

Expressivity

Modifier effect:

Altered onset time

Evidence:

Assessment of genotype–phenotype associations

Effect:

BIRC9/XIAP as a putative modifier gene of Wilson Disease

Reference:

PMID20517649

Title:

Genetic analysis of BIRC4/XIAP as a putative modifier gene of Wilson disease.

Species studied:

Human

Abstract:

Wilson disease (WD) is an autosomal-recessive copper overload disorder caused by mutations in the copper-transporting adenosine triphosphatase (ATPase) ATP7B. It presents with a highly variable clinical phenotype ranging from asymptomatic to fulminant hepatic failure or progressive neurological involvement. No clear genotype-phenotype correlation has been established. Thus, variants in modifier genes could have an impact on WD manifestation and severity. Recently, the antiapoptotic protein baculoviral IAP repeat-containing protein 4 BIRC4/XIAP has been suggested as a regulator of copper-induced cell death. With the aim of investigating a putative role of BIRC4/XIAP as modifier gene in individuals with copper overload, we analyzed a WD patient cohort (n = 98) for sequence variants at the BIRC4/XIAP locus. When compared with clinical data, the previously described coding single nucleotide polymorphisms (SNPs) at the BRIC4/XIAP locus (rs28382721, rs28382722, rs28382723, rs5956583, rs28382740, rs12838858, rs28382741) did not correlate with age of onset or clinical presentation in our collective. However, three previously unreported variants in the BIRC4/XIAP gene were identified (c.1-26 T > G; c.1408A > T; p.T470S; c.1019A > G; p.N340S). The two patients with variants leading to amino acid exchanges in the BIRC4/XIAP protein showed a remarkably early disease onset at the age of 5 years. Furthermore, one of these patients was only heterozygous for disease-causing mutations in the ATP7B gene. In summary, these data emphasize the need to further elucidate a role of BIRC4/XIAP variants as putative pathogenetic factors in copper overload disorders.