Gene "RPGRIP1L"
Found 3 records
Gene information
Gene symbol:
RPGRIP1L
See related:
Ensembl: ENSG00000103494, Gene ID: 23322
Additive variants :
Undetected
Genetic interaction partners
No data
Modifier statisitcs
Record:
3
Disorder:
3
Vriant:
2
Reference:
3
Effect type:
Expressivity(2)
,Penetrance(1)
Modifier effect:
Altered severity(2)
,Altered incidence(1)
Details:
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Variant 1:Gene:Genomic location:chr16:53720436dbSNP ID:Target disease:Retinal Degeneration(DOID_8466)Effect type:PenetranceModifier effect:Altered incidenceEvidence:Gene activity studyEffect:The absence of 229T might have a protective effect from RP.Reference:Title:A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies.Species studied:HumanAbstract:Despite rapid advances in the identification of genes involved in disease, the predictive power of the genotype remains limited, in part owing to poorly understood effects of second-site modifiers. Here we demonstrate that a polymorphic coding variant of RPGRIP1L (retinitis pigmentosa GTPase regulator-interacting protein-1 like), a ciliary gene mutated in Meckel-Gruber (MKS) and Joubert (JBTS) syndromes, is associated with the development of retinal degeneration in individuals with ciliopathies caused by mutations in other genes. As part of our resequencing efforts of the ciliary proteome, we identified several putative loss-of-function RPGRIP1L mutations, including one common variant, A229T. Multiple genetic lines of evidence showed this allele to be associated with photoreceptor loss in ciliopathies. Moreover, we show that RPGRIP1L interacts biochemically with RPGR, loss of which causes retinal degeneration, and that the Thr229-encoded protein significantly compromises this interaction. Our data represent an example of modification of a discrete phenotype of syndromic disease and highlight the importance of a multifaceted approach for the discovery of modifier alleles of intermediate frequency and effect.
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Variant 2:Gene:Genomic location:chr16:53682949dbSNP ID:Alias:RPGRIP1L:rs2302677Target disease:Retinitis Pigmentosa(DOID_10584)Effect type:ExpressivityModifier effect:Altered severityEvidence:P=0.0493Effect:association with disease severityReference:Title:Allelic heterogeneity and genetic modifier loci contribute to clinical variation in males with X-linked retinitis pigmentosa due to RPGR mutations.Species studied:HumanAbstract:Mutations in RPGR account for over 70% of X-linked retinitis pigmentosa (XlRP), characterized by retinal degeneration and eventual blindness. The clinical consequences of RPGR mutations are highly varied, even among individuals with the same mutation: males demonstrate a wide range of clinical severity, and female carriers may or may not be affected. This study describes the phenotypic diversity in a cohort of 98 affected males from 56 families with RPGR mutations, and demonstrates the contribution of genetic factors (i.e., allelic heterogeneity and genetic modifiers) to this diversity. Patients were categorized as grade 1 (mild), 2 (moderate) or 3 (severe) according to specific clinical criteria. Patient DNAs were genotyped for coding SNPs in 4 candidate modifier genes with products known to interact with RPGR protein: RPGRIP1, RPGRIP1L, CEP290, and IQCB1. Family-based association testing was performed using PLINK. A wide range of clinical severity was observed both between and within families. Patients with mutations in exons 1-14 were more severely affected than those with ORF15 mutations, and patients with predicted null alleles were more severely affected than those predicted to make RPGR protein. Two SNPs showed association with severe disease: the minor allele (N) of I393N in IQCB1 (p=0.044) and the common allele (R) of R744Q in RPGRIP1L (p=0.049). These data demonstrate that allelic heterogeneity contributes to phenotypic diversity in XlRP and suggest that this may depend on the presence or absence of RPGR protein. In addition, common variants in 2 proteins known to interact with RPGR are associated with severe disease in this cohort.
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Variant 3:Gene:Genomic location:chr16:53682949dbSNP ID:Alias:RPGRIP1L:rs2302677Target disease:X-linked intellectual disability-retinitis pigmentosa syndrome(Orphanet_85332)Effect type:ExpressivityModifier effect:Altered severityEvidence:Pedigree analysisEffect:The polymorphism is associated with the disease severity.Reference:Title:Polymorphic variation of RPGRIP1L and IQCB1 as modifiers of X-linked retinitis pigmentosa caused by mutations in RPGR.Species studied:HumanAbstract:No data