ReviewJournal of biomedical science2023
Phenotypic heterogeneity in human genetic diseases: ultrasensitivity-mediated threshold effects as a unifying molecular mechanism.
Review in Journal of biomedical science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 26 citations in OpenAlex.
- Optimizing diagnosis and management of patients with ENPP1 deficiency: an expert opinion.Journal of endocrinological investigation · 2026Review
- Vitiligo Information Resource database v3.NPJ systems biology and applications · 2026Article
- Review
- Article
- Opportunities for RNA sequencing in physiology: from big data to understanding homeostasis and heterogeneity.Function (Oxford, England) · 2026Review
- Intrafamilial phenotypic variability in hypophosphatasia: evidence from two families and the literature.Frontiers in endocrinology · 2026Review
- Danon Disease: Understanding the Role of LAMP2 Variants in Cardiomyopathy and Multisystemic Involvement.Arquivos brasileiros de cardiologia · 2026Review
- SIDISH integrates single-cell and bulk transcriptomics to identify high-risk cells and guide precision therapeutics through in silico perturbation.Nature communications · 2025Article
- Estimating the Genetic Risk of First-Degree Relatives for Chronic Diseases Using the Short Tandem Repeat Score as Model of Polygenic Inheritance.Biochemical genetics · 2025Article
- Exploring skeletal disorders in cattle and sheep: a WGS-based framework for diagnosis and classification.Genetics, selection, evolution : GSE · 2025Article
- GJA8-associated developmental eye disorders: a new multicentre study highlights mutational hotspots and genotype-phenotype correlations.European journal of human genetics : EJHG · 2025Article
- Rare Case of Adult-Onset Gitelman Syndrome in a Patient With Multiple Comorbidities: A Case Report.Clinical case reports · 2025Article
- Genomic characterization ofFrontiers in microbiology · 2025Article
- Expanding the clinical spectrum of PPP3CA variants - alternative isoforms matter.Orphanet journal of rare diseases · 2024Article
- MetaPhenotype: A Transferable Meta-Learning Model for Single-Cell Mass Spectrometry-Based Cell Phenotype Prediction Using Limited Number of Cells.Analytical chemistry · 2024Article
- Haploinsufficiency and Alzheimer's Disease: The Possible Pathogenic and Protective Genetic Factors.International journal of molecular sciences · 2024Review
- LRPPRC and SLIRP synergize to maintain sufficient and orderly mammalian mitochondrial translation.Nucleic acids research · 2024Article
- Effects on keratinocytes of the traditional combination of herb extract (Royal Oji Complex) implicated the improvement of young children's skin moisture and barrier.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2024Article
- Loss of embryonic vestibular ganglion neurons in a chick model of congenital vestibular disorders.Frontiers in neurologyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phenotypic heterogeneity is very common in genetic systems and in human diseases and has important consequences for disease diagnosis and treatment. In addition to the many genetic and non-genetic (e.g., epigenetic, environmental) factors reported to account for part of the heterogeneity, we stress the importance of stochastic fluctuation and regulatory network topology in contributing to phenotypic heterogeneity. We argue that a threshold effect is a unifying principle to explain the phenomenon; that ultrasensitivity is the molecular mechanism for this threshold effect; and discuss the three conditions for phenotypic heterogeneity to occur. We suggest that threshold effects occur not only at the cellular level, but also at the organ level. We stress the importance of context-dependence and its relationship to pleiotropy and edgetic mutations. Based on this model, we provide practical strategies to study human genetic diseases. By understanding the network mechanism for ultrasensitivity and identifying the critical factor, we may manipulate the weak spot to gently nudge the system from an ultrasensitive state to a stable non-disease state. Our analysis provides a new insight into the prevention and treatment of genetic diseases.
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.