The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
MetaDome: Pathogenicity analysis of genetic variants through aggregation of homologous human protein domains
Open accessAbstract
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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ClinVar: public archive of interpretations of clinically relevant variants
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Genome sequencing identifies major causes of severe intellectual disability
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Self-citationGenic Intolerance to Functional Variation and the Interpretation of Personal Genomes
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TMEM151A variants associated with paroxysmal kinesigenic dyskinesia
Huang, H. L., Zhang, Q. X., Huang, F., Long, X. Y., Song, Z., Xiao, B., Li, G. L., Ma, C. Y., & Liu, D. (2023) · Human Genetics · doi:10.1007/s00439-023-02535-3 · Cited by 8
Heterozygous loss-of-function variants in DOCK4 cause neurodevelopmental delay and microcephaly
Herbst, C., Bothe, V., Wegler, M., Axer-Schaefer, S., Audebert-Bellanger, S., Gecz, J., Cogne, B., Feldman, H. B., Horn, A. H. C., Hurst, A. C. E., et al. (2024) · Human Genetics · doi:10.1007/s00439-024-02655-4 · Cited by 7
“0.0 (Karczewski et al. 2020) below 1%, impact on protein function via different in silico programs (CADD (Rentzsch et al. 2021), REVEL (Ioannidis et al. 2016), MutPred2 (Pejaver et al. 2020) and Metadome (Wiel et al. 2019)) and involvement of candidate genes in neuronal processes.”
Influential
Metadata
- Authors
- Wiel, L., Baakman, C., Gilissen, D., Veltman, J. A., Vriend, G., & Gilissen, C.
- Venue
- Human Mutation
- Publisher
- Wiley
- Published
- 2019-05-22
- Volume
- 40
- Issue
- 8
- Pages
- 1030-1038
- ISSN
- 1059-7794 (ISSN-L)
- 1098-1004
- OpenAlex
- W2949860192
- Cited by
- 257
- References
- 7
- FWCI
- 15.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
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