ArticleCell2013
A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway.
Article in Cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 9 of them syntheses that pooled it.
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
125 citing papers in PubMed, 9 syntheses or guidelines pooled it, 225 citations in OpenAlex.
- Genetic Architecture of Idiopathic Inflammatory Myopathies From Meta-Analyses.Arthritis & rheumatology (Hoboken, N.J.) · 2025Pooled it
- Genetic determinants of skin ageing: a systematic review and meta-analysis of genome-wide association studies and candidate genes.Journal of physiological anthropology · 2025Pooled it
- Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer.Nature genetics · 2022Pooled it
- Genome-wide association study of actinic keratosis identifies new susceptibility loci implicated in pigmentation and immune regulation pathways.Communications biology · 2022Pooled it
- Common genetic polymorphisms contribute to the association between chronic lymphocytic leukaemia and non-melanoma skin cancer.International journal of epidemiology · 2021Pooled it
- Genome-wide meta-analysis identifies eight new susceptibility loci for cutaneous squamous cell carcinoma.Nature communications · 2020Pooled it
- Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness.Nature communications · 2017Pooled it
- Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.Nature genetics · 2016Pooled it
- Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma.Nature genetics · 2015Pooled it
- Multi-omic analysis of deep learning-derived phenotypes links ophthalmic imaging to cardiovascular and neurological traits.Nature cardiovascular research · 2026Article
- Sequential transcriptional waves and NF-κB-driven chromatin remodeling direct drug-induced dedifferentiation in cancer.Nature communications · 2026Article
- Multi-trait analysis of pigmentation traits in relation to skin and ocular cancers: Relevance for evolutionary medicine.Evolution, medicine, and public health · 2026Article
- Harnessing population genetics and animal models to uncover the genetics of skin scarring.Journal of plastic, reconstructive & aesthetic surgery : JPRAS · 2026Review
- Interferon regulatory factor 4 as a context-dependent regulator of inflammation: transcriptional and epigenetic control, skin diseases, and translational challenges.Frontiers in immunology · 2026Review
- Genetic Background Predicts Uveal Melanoma Patients' Outcomes.Ophthalmology science · 2026Article
- The genetic architecture of human skin pigmentation: evolution and adaptation across global populations.Frontiers in genetics · 2026Review
- Exploring the roles of conserved context-dependent cis-regulatory elements (cdCREs) in multicellularity, human health and disease.The FEBS journal · 2025Review
- The molecular puzzle of autoinflammatory skin diseases-a review of chosen conditions.Journal of applied genetics · 2025Review
- Ophthalmic imaging as a measure of cardiovascular and neurological health: a multi-omic analysis of deep-learning derived phenotypes.medRxiv : the preprint server for health sciences · 2025Article
- Assessment of the Influence of UVR in Cutaneous Melanoma.Photodermatology, photoimmunology & photomedicine · 2025Review
65 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
33 authors at 13 institutions in 5 countries.
Funding
Abstract
Sequence polymorphisms linked to human diseases and phenotypes in genome-wide association studies often affect noncoding regions. A SNP within an intron of the gene encoding Interferon Regulatory Factor 4 (IRF4), a transcription factor with no known role in melanocyte biology, is strongly associated with sensitivity of skin to sun exposure, freckles, blue eyes, and brown hair color. Here, we demonstrate that this SNP lies within an enhancer of IRF4 transcription in melanocytes. The allele associated with this pigmentation phenotype impairs binding of the TFAP2A transcription factor that, together with the melanocyte master regulator MITF, regulates activity of the enhancer. Assays in zebrafish and mice reveal that IRF4 cooperates with MITF to activate expression of Tyrosinase (TYR), an essential enzyme in melanin synthesis. Our findings provide a clear example of a noncoding polymorphism that affects a phenotype by modulating a developmental gene regulatory network.
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.