The objective of this study is to create a database of common “rare” Mendelian disorders and their associated genes and encoded proteins to aid future drug discovery efforts. “Simple” Mendelian diseases are rare genetic disorders with phenotypes linked to pathogenic variants in single genes. Although these disorders are considered promising drug targets due to their simple etiology, their rare nature has historically discouraged drug discovery efforts in the pharmaceutical industry. However, a number or these diseases are not that rare. We initially compiled a list of common “rare” disorders documented in ORPHANET, which we define as those disorders that have a prevalence or incidence of higher than 5.0 (1 in 20,000 people) and that are known to be caused by single mutations in any one or more genes. After narrowing down the list of diseases, we catalogued the associated proteins targets, gene targets, and relevant nonsense/missense mutations from the Human Gene Mutation Database (HGMD). Clinical genetics reviews were also used to confirm the identities of genes implicated in the specific disorder. To confirm the Mendelian basis for each disorder, disease etiology was corroborated based on data compiled from genome and rare disease databases (ORPHANET, Online Mendelian Inheritance in Man (OMIM), Genetic and Rare Diseases Information Center (GARD), PubMed, and GeneReview and relevant literature reviews. 74 common “rare” Mendelian disorders have been documented with associated gene/protein targets and the number of single nucleotide variants (SNVs) documented in the most commonly-causitive gene. The current database provides list of simple Mendelian disorders that have a high enough incidence in the population to motivate drug discovery efforts even by those who, for various possible reasons. wish to conduct drug discovery to target “rare” disorders that afflict a relatively high number of people.

Database of causitive genes/proteins for common “rare” monogenic mendelian disorders

ACS Fall 2021

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