ArticleHuman mutation2017
Landscape of Pleiotropic Proteins Causing Human Disease: Structural and System Biology Insights.
Article in Human mutation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 38 citations in OpenAlex.
- Signatures of selection in pleiotropic genes involved in insect neuronal and immune systems.G3 (Bethesda, Md.) · 2026Article
- Phenotype-Specific Recalibration of MAVE Data Enables Repurposing ofmedRxiv : the preprint server for health sciences · 2026Article
- Signatures of selection in pleiotropic genes involved in insect neuronal and immune systems.bioRxiv : the preprint server for biology · 2026Article
- Pleiotropy increases with gene age in six model multicellular eukaryotes.Evolution letters · 2025Article
- Comprehensive analysis of Metacrinus rotundus full length transcriptome.Scientific reports · 2025Article
- Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lens.Human genomics · 2024Review
- Putting proteins in context.Cell systems · 2024Article
- Most Pleiotropic Effects of Gene Knockouts Are Evolutionarily Transient in Yeasts.Molecular biology and evolution · 2024Article
- FLT4 causes developmental disorders of the cardiovascular and lymphovascular systems via pleiotropic molecular mechanisms.Cardiovascular research · 2024Article
- Contextual AI models for single-cell protein biology.Nature methods · 2024Article
- Contextual AI models for single-cell protein biology.bioRxiv : the preprint server for biology · 2024Article
- In Silico Pleiotropy Analysis in KEGG Signaling Networks Using a Boolean Network Model.Biomolecules · 2022Article
- Incomplete Penetrance and Variable Expressivity: From Clinical Studies to Population Cohorts.Frontiers in genetics · 2022Review
- Article
- TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila.American journal of human genetics · 2021Article
- Missense3D-DB web catalogue: an atom-based analysis and repository of 4M human protein-coding genetic variants.Human genetics · 2021Article
- Challenges in Clinicogenetic Correlations: One Gene - Many Phenotypes.Movement disorders clinical practice · 2021Review
- Review
- A polygenic biomarker to identify patients with severe hypercholesterolemia of polygenic origin.Molecular genetics & genomic medicine · 2020Article
- A-to-I RNA editing contributes to the persistence of predicted damaging mutations in populations.Genome research · 2019Article
Corrections and comments
- Commented on by
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Pleiotropy is the phenomenon by which the same gene can result in multiple phenotypes. Pleiotropic proteins are emerging as important contributors to rare and common disorders. Nevertheless, little is known on the mechanisms underlying pleiotropy and the characteristic of pleiotropic proteins. We analyzed disease-causing proteins reported in UniProt and observed that 12% are pleiotropic (variants in the same protein cause more than one disease). Pleiotropic proteins were enriched in deleterious and rare variants, but not in common variants. Pleiotropic proteins were more likely to be involved in the pathogenesis of neoplasms, neurological, and circulatory diseases and congenital malformations, whereas non-pleiotropic proteins in endocrine and metabolic disorders. Pleiotropic proteins were more essential and had a higher number of interacting partners compared with non-pleiotropic proteins. Significantly more pleiotropic than non-pleiotropic proteins contained at least one intrinsically long disordered region (P < 0.001). Deleterious variants occurring in structurally disordered regions were more commonly found in pleiotropic, rather than non-pleiotropic proteins. In conclusion, pleiotropic proteins are an important contributor to human disease. They represent a biologically different class of proteins compared with non-pleiotropic proteins and a better understanding of their characteristics and genetic variants can greatly aid in the interpretation of genetic studies and drug design.
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.