Gene "COL1A1"
Found 4 records
Gene information
Gene symbol:
COL1A1
See related:
Ensembl: ENSG00000108821, Gene ID: 1277
Additive variants :
Undetected
Genetic interaction partners
No data
Modifier statisitcs
Record:
4
Disorder:
2
Vriant:
4
Reference:
2
Effect type:
Expressivity(4)
Modifier effect:
Altered severity(3)
,Risk factor(1)
Details:
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Variant 1:Gene:Genomic location:dbSNP ID:Target disease:Procollagen Type I C-Terminal Peptide(NCIT_C116020)Effect type:ExpressivityModifier effect:Altered severityEvidence:Gene activity studyEffect:The polymorphism is associated with the disease severity.Reference:Title:Type I procollagen C-propeptide defects: study of genotype-phenotype correlation and predictive role of crystal structure.Species studied:HumanAbstract:The type I procollagen carboxyterminal(C-)propeptides are crucial in directing correct assembly of the procollagen heterotrimers. Defects in these domains have anecdotally been reported in patients with Osteogenesis Imperfecta (OI) and few genotype-phenotype correlations have been described. To gain insight in the functional consequences of C-propeptide defects, we performed a systematic review of clinical, molecular, and biochemical findings in all patients in whom we identified a type I procollagen C-propeptide defect, and compared this with literature data. We report 30 unique type I procollagen C-propeptide variants, 24 of which are novel. The outcome of COL1A1 nonsense and frameshift variants depends on the location of the premature termination codon. Those located prior to 50-55 nucleotides upstream of the most 3' exon-exon junction lead to nonsense-mediated mRNA decay (NMD) and cause mild OI. Those located beyond this boundary escape NMD, generally lead to production of stable, overmodified procollagen chains, which may partly be retained intracellularly, and are usually associated with severe-to-lethal OI. Proα1(I)-C-propeptide defects that permit chain association result in more severe phenotypes than those inhibiting chain association. We demonstrate that the crystal structure of the proα1(III)-C-propeptide is a reliable tool to predict phenotypic severity for most COL1A1-C-propeptide missense variants, whereas for COL1A2-C-propeptide variants, the phenotypic outcome is milder than predicted.
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Variant 2:Gene:Genomic location:dbSNP ID:Target disease:Procollagen Type I C-Terminal Peptide(NCIT_C116020)Effect type:ExpressivityModifier effect:Altered severityEvidence:Gene activity studyEffect:The polymorphism is associated with the disease severity.Reference:Title:Type I procollagen C-propeptide defects: study of genotype-phenotype correlation and predictive role of crystal structure.Species studied:HumanAbstract:The type I procollagen carboxyterminal(C-)propeptides are crucial in directing correct assembly of the procollagen heterotrimers. Defects in these domains have anecdotally been reported in patients with Osteogenesis Imperfecta (OI) and few genotype-phenotype correlations have been described. To gain insight in the functional consequences of C-propeptide defects, we performed a systematic review of clinical, molecular, and biochemical findings in all patients in whom we identified a type I procollagen C-propeptide defect, and compared this with literature data. We report 30 unique type I procollagen C-propeptide variants, 24 of which are novel. The outcome of COL1A1 nonsense and frameshift variants depends on the location of the premature termination codon. Those located prior to 50-55 nucleotides upstream of the most 3' exon-exon junction lead to nonsense-mediated mRNA decay (NMD) and cause mild OI. Those located beyond this boundary escape NMD, generally lead to production of stable, overmodified procollagen chains, which may partly be retained intracellularly, and are usually associated with severe-to-lethal OI. Proα1(I)-C-propeptide defects that permit chain association result in more severe phenotypes than those inhibiting chain association. We demonstrate that the crystal structure of the proα1(III)-C-propeptide is a reliable tool to predict phenotypic severity for most COL1A1-C-propeptide missense variants, whereas for COL1A2-C-propeptide variants, the phenotypic outcome is milder than predicted.
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Variant 3:Gene:Genomic location:dbSNP ID:Target disease:Hypertrophic Cardiomyopathy(DOID_11984)Effect type:ExpressivityModifier effect:Risk factorEvidence:For noncarriers of polymorphic col1a1 allele [HR=2.76, 95% CI: (1.26-6.05), P=0.011] and a trend in homozygous carriers of adrb1 arg389 variant [HR=1.98, 95% CI:(1.99-4.02); P=0.057]Effect:COL1A1 polymorphism (2046G>T) is an independent predictor of prognosis in HCM patients supporting the importance of nonsarcomeric genes on clinical prognosis in HCM.Reference:Title:Clinical implications of nonsarcomeric gene polymorphisms in hypertrophic cardiomyopathy.Species studied:HumanAbstract:Hypertrophic cardiomyopathy (HCM) is characterized by cardiomyocyte hypertrophy and fibrosis. Although is an autosomal dominant trait, a group of nonsarcomeric genes have been postulated as modifiers of the phenotypic heterogeneity.
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Variant 4:Gene:Genomic location:dbSNP ID:Target disease:Procollagen Type I C-Terminal Peptide(NCIT_C116020)Effect type:ExpressivityModifier effect:Altered severityEvidence:Gene activity studyEffect:The polymorphism is associated with the disease severity.Reference:Title:Type I procollagen C-propeptide defects: study of genotype-phenotype correlation and predictive role of crystal structure.Species studied:HumanAbstract:The type I procollagen carboxyterminal(C-)propeptides are crucial in directing correct assembly of the procollagen heterotrimers. Defects in these domains have anecdotally been reported in patients with Osteogenesis Imperfecta (OI) and few genotype-phenotype correlations have been described. To gain insight in the functional consequences of C-propeptide defects, we performed a systematic review of clinical, molecular, and biochemical findings in all patients in whom we identified a type I procollagen C-propeptide defect, and compared this with literature data. We report 30 unique type I procollagen C-propeptide variants, 24 of which are novel. The outcome of COL1A1 nonsense and frameshift variants depends on the location of the premature termination codon. Those located prior to 50-55 nucleotides upstream of the most 3' exon-exon junction lead to nonsense-mediated mRNA decay (NMD) and cause mild OI. Those located beyond this boundary escape NMD, generally lead to production of stable, overmodified procollagen chains, which may partly be retained intracellularly, and are usually associated with severe-to-lethal OI. Proα1(I)-C-propeptide defects that permit chain association result in more severe phenotypes than those inhibiting chain association. We demonstrate that the crystal structure of the proα1(III)-C-propeptide is a reliable tool to predict phenotypic severity for most COL1A1-C-propeptide missense variants, whereas for COL1A2-C-propeptide variants, the phenotypic outcome is milder than predicted.