ArticleMolecular and cellular biology2013
Age-related macular degeneration-associated silent polymorphisms in HtrA1 impair its ability to antagonize insulin-like growth factor 1.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Progress in the Study of the Role and Mechanism of HTRA1 in Diseases Related to Vascular Abnormalities.International journal of general medicine · 2024Review
- A systems biology approach uncovers novel disease mechanisms in age-related macular degeneration.Cell genomics · 2023Article
- Genome-wide association study and identification of systemic comorbidities in development of age-related macular degeneration in a hospital-based cohort of Han Chinese.Frontiers in genetics · 2023Article
- Review
- An update on long-acting therapies in chronic sight-threatening eye diseases of the posterior segment: AMD, DMO, RVO, uveitis and glaucoma.Eye (London, England) · 2022Review
- circHtra1/miR-3960/GRB10 Axis Promotes Neuronal Loss and Immune Deficiency in Traumatic Brain Injury.Oxidative medicine and cellular longevity · 2022Article
- Ongoing controversies and recent insights of the ARMS2-HTRA1 locus in age-related macular degeneration.Experimental eye research · 2021Review
- Chromosome 10q26-driven age-related macular degeneration is associated with reduced levels ofProceedings of the National Academy of Sciences of the United States of America · 2021Article
- The Serine Protease HTRA-1 Is a Biomarker for ROP and Mediates Retinal Neovascularization.Frontiers in molecular neuroscience · 2020Article
- ER stress-induced aggresome trafficking of HtrA1 protects against proteotoxicity.Journal of molecular cell biology · 2017Article
- Recombinant Haplotypes Narrow the ARMS2/HTRA1 Association Signal for Age-Related Macular Degeneration.Genetics · 2017Article
- Gene expression levels of the insulin-like growth factor family in patients with AMD before and after ranibizumab intravitreal injections.Clinical interventions in aging · 2017Article
- The nicotinic acetylcholine receptor alpha 4 subunit contains a functionally relevant SNP Haplotype.BMC genetics · 2015Article
- Insulin-like growth factor 1 (IGF-1) stabilizes nascent blood vessels.The Journal of biological chemistry · 2015Article
- Rare codons capacitate Kras-driven de novo tumorigenesis.The Journal of clinical investigation · 2015Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Synonymous single nucleotide polymorphisms (SNPs) within a transcript's coding region produce no change in the amino acid sequence of the protein product and are therefore intuitively assumed to have a neutral effect on protein function. We report that two common variants of high-temperature requirement A1 (HTRA1) that increase the inherited risk of neovascular age-related macular degeneration (NvAMD) harbor synonymous SNPs within exon 1 of HTRA1 that convert common codons for Ala34 and Gly36 to less frequently used codons. The frequent-to-rare codon conversion reduced the mRNA translation rate and appeared to compromise HtrA1's conformation and function. The protein product generated from the SNP-containing cDNA displayed enhanced susceptibility to proteolysis and a reduced affinity for an anti-HtrA1 antibody. The NvAMD-associated synonymous polymorphisms lie within HtrA1's putative insulin-like growth factor 1 (IGF-1) binding domain. They reduced HtrA1's abilities to associate with IGF-1 and to ameliorate IGF-1-stimulated signaling events and cellular responses. These observations highlight the relevance of synonymous codon usage to protein function and implicate homeostatic protein quality control mechanisms that may go awry in NvAMD.
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