ArticlePLoS genetics2017
Rapid functional analysis of computationally complex rare human IRF6 gene variants using a novel zebrafish model.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 32 citations in OpenAlex.
- PubMind: literature-based genetic variant extraction and functional annotation using large language models.Nature communications · 2026Article
- A small-molecule screen identifies that elafibranor links mechanical cues and Irf6-dependent epithelial differentiation.Disease models & mechanisms · 2026Article
- Compound inheritance of EHHADH and MASP1 mutations contributes to nonsyndromic cleft lip: familial analysis and zebrafish models.Biology open · 2025Article
- Rare variants in PRKCI cause Van der Woude syndrome and other features of peridermopathy.American journal of human genetics · 2025Article
- Neural crest and periderm-specific requirements of Irf6 during neural tube and craniofacial development.Developmental biology · 2025Review
- Genetic variant classification by predicted protein structure: A case study on IRF6.Computational and structural biotechnology journal · 2024Article
- Functional analysis of ESRP1/2 gene variants and CTNND1 isoforms in orofacial cleft pathogenesis.Communications biology · 2024Article
- Functional analysis ofbioRxiv : the preprint server for biology · 2024Article
- Neural crest and periderm-specific requirements ofbioRxiv : the preprint server for biology · 2024Article
- A Variant in theJournal of dental research · 2023Article
- Zebrafish Is a Powerful Tool for Precision Medicine Approaches to Neurological Disorders.Frontiers in molecular neuroscience · 2022Review
- AnDevelopment (Cambridge, England) · 2020Article
- Non-random distribution of deleterious mutations in the DNA and protein-binding domains of IRF6 are associated with Van Der Woude syndrome.Molecular genetics & genomic medicine · 2020Review
- Analysis of zebrafish periderm enhancers facilitates identification of a regulatory variant near humaneLife · 2020Article
- Functional Characterization of a Novel IRF6 Frameshift Mutation From a Van Der Woude Syndrome Family.Frontiers in genetics · 2020Article
- Drug-selective Anesthetic Insensitivity of Zebrafish Lacking γ-Aminobutyric Acid Type A Receptor β3 Subunits.Anesthesiology · 2019Article
- The TFAP2A-IRF6-GRHL3 genetic pathway is conserved in neurulation.Human molecular genetics · 2019Article
- Loss-of-function of sox3 causes follicle development retardation and reduces fecundity in zebrafish.Protein & cell · 2019Article
- Exon sequencing reveals that missense mutation ofInternational journal of clinical and experimental pathology · 2019Article
- Genetic Requirement ofPlastic and reconstructive surgery. Global open · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Large-scale sequencing efforts have captured a rapidly growing catalogue of genetic variations. However, the accurate establishment of gene variant pathogenicity remains a central challenge in translating personal genomics information to clinical decisions. Interferon Regulatory Factor 6 (IRF6) gene variants are significant genetic contributors to orofacial clefts. Although approximately three hundred IRF6 gene variants have been documented, their effects on protein functions remain difficult to interpret. Here, we demonstrate the protein functions of human IRF6 missense gene variants could be rapidly assessed in detail by their abilities to rescue the irf6 -/- phenotype in zebrafish through variant mRNA microinjections at the one-cell stage. The results revealed many missense variants previously predicted by traditional statistical and computational tools to be loss-of-function and pathogenic retained partial or full protein function and rescued the zebrafish irf6 -/- periderm rupture phenotype. Through mRNA dosage titration and analysis of the Exome Aggregation Consortium (ExAC) database, IRF6 missense variants were grouped by their abilities to rescue at various dosages into three functional categories: wild type function, reduced function, and complete loss-of-function. This sensitive and specific biological assay was able to address the nuanced functional significances of IRF6 missense gene variants and overcome many limitations faced by current statistical and computational tools in assigning variant protein function and pathogenicity. Furthermore, it unlocked the possibility for characterizing yet undiscovered human IRF6 missense gene variants from orofacial cleft patients, and illustrated a generalizable functional genomics paradigm in personalized medicine.
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.