ACE2 Netlas

ACE2 Netlas performs a multi-level functional characterization of genes interacting with angiotensin-converting enzyme 2 (ACE2) to investigate their potential role in modulating COVID-19 susceptibility.

Key Features:

• Phenome-Wide Association Analysis: Conducts a phenome-wide association study of 51 ACE2-network genes against 4,756 traits across 26 phenotype categories, identifying enrichment in immunological, respiratory, environmental, skeletal, dermatological, and metabolic domains (p < 4e-4).
• Transcriptomic Regulation: Examines tissue-specific expression patterns of ACE2-network genes, reporting enriched expression in kidney, small intestine, and colon (p < 4.7e-4).
• Drug-Gene Interaction Mining: Queries a drug-gene interaction database to identify 47 drugs interacting with the ACE2 network, including dexamethasone and spironolactone.
• Variant Functional Annotation: Characterizes functional consequences of genetic variants within ±10 kb of ACE2-network genes with a focus on miRNA binding-site targets and over-representation of miRNA-related pathways (inflammation, aging, diabetes, heart conditions).
• COVID-19 Genetic Associations: Identifies ACE2-network genes associated with COVID-19 susceptibility, specifically RORA, SLC12A6, and SLC6A19.

Scientific Applications:

• Mechanistic Investigation of COVID-19 Susceptibility: Supports analysis of molecular mechanisms by which ACE2-interacting genes may influence individual susceptibility to SARS-CoV-2 infection.
• Genetic Prioritization: Enables prioritization of ACE2-network genes and variants as potential genetic contributors to disease severity and clinical outcomes.
• Therapeutic Target Identification and Repurposing: Facilitates identification of drug–gene interactions within the ACE2 network to inform candidate therapeutic interventions and repurposing opportunities.

Methodology:

Performs a phenome-wide association study of 51 ACE2-network genes across 4,756 traits and 26 phenotype categories; analyzes tissue-specific transcriptomic regulation for enrichment in kidney, small intestine, and colon; queries a drug-gene interaction database to identify interacting drugs; annotates variants within ±10 kb of ACE2-network genes for miRNA binding-site targets and pathway over-representation; and reports genetic associations with COVID-19 for genes including RORA, SLC12A6, and SLC6A19.