ArticleGenetics in medicine : official journal of the American College of Medical Genetics2025
Unique signatures of highly constrained genes across publicly available genomic databases.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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Who cites it
2 citing papers in PubMed.
- Genetic architectures of brain-related traits are shaped by strong selective constraints.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Genetic architectures of brain-related traits are shaped by strong selective constraints.bioRxiv : the preprint server for biology · 2026Article
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7 authors.
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Abstract
purposePublicly available genomic databases are critical in understanding human genetic variation. They also provide unique insights into patterns of genetic constraints and their relationship with human disease.
methodsWe utilized one of the largest publicly available databases, Genome Aggregate Database, to determine genes that are highly constrained for only loss-of-function, only missense, and both loss-of-function/missense variants. We identified their unique signatures and explored their causal relationship with human diseases. Those genes were also evaluated for chromosomal location, tissue-level expression, Gene Ontology analysis, and gene family categorization using multiple publicly available databases.
resultsWe identified unique patterns of inheritance, protein size, and enrichment in distinct molecular pathways for those constrained genes associated with human disease. In addition, we identified genes that are currently not known to cause human disease, which may be excellent gene discovery candidates.
conclusionWe elucidate biological pathways of highly constrained genes that expand our understanding of critical cellular proteins. The findings can also advance research in rare diseases.
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