ArticleHuman molecular genetics2014
Inheritance of rare functional GCKR variants and their contribution to triglyceride levels in families.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Glucokinase activity suppresses hepatic cholesterol synthesis and triglyceride accumulation: A new model for the effects of the GKRP P466L common human variant.Molecular metabolism · 2026Article
- Glucokinase activity suppresses hepatic cholesterol synthesis and triglyceride accumulation: A new model for the effects of the GKRP P466L common human variant.bioRxiv : the preprint server for biology · 2026Article
- Significant Association Between Glucokinase Regulatory Protein Variants and Genetic and Metabolic Diseases.Current issues in molecular biology · 2025Review
- A case of familial partial lipodystrophy type 2 masquerading as Cushing syndrome: Explaining an atypical phenotype by whole-exome sequencing.Archives of endocrinology and metabolism · 2025Article
- Hypometric genetics: Improved power in genetic discovery by incorporating quality control flags.American journal of human genetics · 2024Article
- Pleiotropic Effects of Common and RareGenes · 2022Article
- Genetics of Hypertriglyceridemia.Frontiers in endocrinology · 2020Review
- Very Severe Hypertriglyceridemia in a Large US County Health Care System: Associated Conditions and Management.Journal of the Endocrine Society · 2019Article
- Pathogenic Anti-Müllerian Hormone Variants in Polycystic Ovary Syndrome.The Journal of clinical endocrinology and metabolism · 2017Article
- Genetics of Triglycerides and the Risk of Atherosclerosis.Current atherosclerosis reports · 2017Review
- Human genetics as a model for target validation: finding new therapies for diabetes.Diabetologia · 2017Review
- Genetic effects on hypertriglyceridemic waist phenotype:International journal of clinical and experimental pathology · 2017Article
- Type 1 Hyperlipoproteinemia Due to Compound Heterozygous Rare Variants in GCKR.The Journal of clinical endocrinology and metabolism · 2016Article
- Genetics of Lipid and Lipoprotein Disorders and Traits.Current genetic medicine reports · 2016Review
- Glucokinase regulatory protein: complexity at the crossroads of triglyceride and glucose metabolism.Current opinion in lipidology · 2015Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
Abstract
Significant resources have been invested in sequencing studies to investigate the role of rare variants in complex disease etiology. However, the diagnostic interpretation of individual rare variants remains a major challenge, and may require accurate variant functional classification and the collection of large numbers of variant carriers. Utilizing sequence data from 458 individuals with hypertriglyceridemia and 333 controls with normal plasma triglyceride levels, we investigated these issues using GCKR, encoding glucokinase regulatory protein. Eighteen rare non-synonymous GCKR variants identified in these 791 individuals were comprehensively characterized by a range of biochemical and cell biological assays, including a novel high-throughput-screening-based approach capable of measuring all variant proteins simultaneously. Functionally deleterious variants were collectively associated with hypertriglyceridemia, but a range of in silico prediction algorithms showed little consistency between algorithms and poor agreement with functional data. We extended our study by obtaining sequence data on family members; however, functional variants did not co-segregate with triglyceride levels. Therefore, despite evidence for their collective functional and clinical relevance, our results emphasize the low predictive value of rare GCKR variants in individuals and the complex heritability of lipid traits.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.