ArticleHuman mutation2019
MetaDome: Pathogenicity analysis of genetic variants through aggregation of homologous human protein domains.
Article in Human mutation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers, 2 of them syntheses that pooled it.
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Who cites it
201 citing papers in PubMed, 2 syntheses or guidelines pooled it, 236 citations in OpenAlex.
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- GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements.Nature communications · 2022Pooled it
- Monoallelic loss-of-function variants in ZNF536 are associated with a neurodevelopmental disorder with prominent behavioral features.American journal of human genetics · 2026Article
- Elucidating the Role of SET as a Key Contributor to Neurodevelopmental Disability Within the 9q34.11 Deletion Syndrome Interval.Clinical genetics · 2026Article
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- Comprehensive Assessment of the KDM2B-Associated Neurodevelopmental Disorder and the 12q24.31 Microdeletion Syndrome.Clinical genetics · 2026Article
- Diagnostic utility of clinical genome reanalysis in rare pediatric disorders using long-read sequencing.HGG advances · 2026Article
- The NeuroWES project: lessons learned from comprehensive phenotyping and genetic analysis of neurodevelopmental disorders over a decade.Human genetics · 2026Article
- Missense variants in KATNA1 alter microtubule dynamics and underlie dominant macular dystrophy.Research square · 2026Article
- Trio analysis in dystonia identifies de novo KLC1 variants in a kinesinopathy with distinct motor and neurodevelopmental features.EBioMedicine · 2026Article
- Monoallelic PSMB8 variants cause PRAAS with immunodeficiency through impaired immunoproteasome assembly.American journal of human genetics · 2026Article
- Genetic variants in Rps4x cause intellectual disability with dysmorphic features, microcephaly, and autism.NPJ genomic medicine · 2026Article
- Variants in the ciliopathy gene SCLT1 are associated with non-syndromic and syndromic retinal degeneration of variable severity.NPJ genomic medicine · 2026Article
- Differential negative dominance by KCNA2 variants associated with global developmental delay suggests KCNA2 haploinsufficiency in humans.The Journal of physiology · 2026Article
- Pathogenic variants in the cohesin loader subunit MAU2 underlie a distinct Cornelia de Lange Syndrome subtype.Nature communications · 2026Article
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- NEDAMSS syndrome-related truncating and missense mutations are associated with aberrant liquid-liquid phase separation of IRF2BPL.Nature communications · 2026Article
- A novel spliceosomopathy caused by de novo SF3B3 variants.Genome medicine · 2026Article
- Heterozygous loss of SRRM1 may be associated with neurodevelopmental phenotypes and anomalies in cell growth and neurite morphology.European journal of human genetics : EJHG · 2026Article
- Expanding the Early Childhood Manifestations ofNeurology. Genetics · 2026Article
141 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The growing availability of human genetic variation has given rise to novel methods of measuring genetic tolerance that better interpret variants of unknown significance. We recently developed a concept based on protein domain homology in the human genome to improve variant interpretation. For this purpose, we mapped population variation from the Exome Aggregation Consortium (ExAC) and pathogenic mutations from the Human Gene Mutation Database (HGMD) onto Pfam protein domains. The aggregation of these variation data across homologous domains into meta-domains allowed us to generate amino acid resolution of genetic intolerance profiles for human protein domains. Here, we developed MetaDome, a fast and easy-to-use web server that visualizes meta-domain information and gene-wide profiles of genetic tolerance. We updated the underlying data of MetaDome to contain information from 56,319 human transcripts, 71,419 protein domains, 12,164,292 genetic variants from gnomAD, and 34,076 pathogenic mutations from ClinVar. MetaDome allows researchers to easily investigate their variants of interest for the presence or absence of variation at corresponding positions within homologous domains. We illustrate the added value of MetaDome by an example that highlights how it may help in the interpretation of variants of unknown significance. The MetaDome web server is freely accessible at https://stuart.radboudumc.nl/metadome.
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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.