ArticleMolecular genetics & genomic medicine2023
Using reported pathogenic variants to identify therapeutic opportunities for genetic diseases.
Article in Molecular genetics & genomic medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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
2 citing papers in PubMed, 4 citations in OpenAlex.
- Systematic analysis of genetic and phenotypic characteristics reveals antisense oligonucleotide therapy potential for one-third of neurodevelopmental disorders.Genome medicine · 2025Article
- Using reported pathogenic variants to identify therapeutic opportunities for genetic diseases.Molecular genetics & genomic medicine · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeDrug development strategies for genetic diseases depend critically on accurate knowledge of how pathogenic variants cause disease. For some well-studied genes, the direct effects of pathogenic variants are well documented as loss-of-function, gain-of-function or hypermorphic, or a combination of the two. For many genes, however, even the direction of effect of variants remains unclear. Classification of Mendelian disease genes in terms of whether pathogenic variants are loss- or gain-of-function would directly inform drug development strategies.
methodsWe leveraged the recent dramatic increase in reported pathogenic variants to provide a novel approach to inferring the direction of effect of pathogenic variants. Specifically, we quantify the ratio of reported pathogenic variants that are missense compared to loss-of-function.
resultsWe first show that for many genes that cause dominant Mendelian disease, the ratio of reported pathogenic missense variants is diagnostic of whether the gene causes disease through loss- or gain-of-function, or a combination. Second, we identify a set of genes that appear to cause disease largely or entirely through gain-of-function or hypermorphic pathogenic variants.
conclusionsWe suggest a set of 16 genes suitable for drug developmental efforts utilizing direct inhibition.
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.