GPI-anchor biosynthesis

GPI-anchor biosynthesis compiles and curates pathogenic genetic variants associated with glycophosphatidylinositol (GPI) biosynthesis to support interpretation of GPI-anchored protein (GPI-AP)–related genetic variation.

Key Features:

• Comprehensive Variant Collection: Aggregates published pathogenic variants from the LOVD database for genes involved in GPI biosynthesis, comprising data on 276 individuals and 192 unique public variants.
• Variant Prediction and Analysis: Reports that 92% of recorded variants are predicted as damaging by bioinformatics tools.
• Variant Types and Effects: Records that 81% of mutations are substitution variants, predominantly resulting in missense and frameshift alterations, with 2% affecting untranslated regions.
• Deleterious Variant Scoring: Uses CADD score analysis showing 97% of variants rank among the top 1% of deleterious variants across the human genome.
• Gene-Specific Insights: Provides gene-level data such as PIGL having the highest frequency of reported pathogenic variants with an estimated carrier rate of approximately 1 in 937 individuals.

Scientific Applications:

• Interpreting Genetic Test Results: Provides a centralized repository of known pathogenic variants to aid interpretation of molecular genetic test results.
• Facilitating Research on GPI-APs: Enables exploration of the molecular genetics of GPI-anchor biosynthesis and its implications for developmental processes including embryogenesis and neurogenesis.
• Supporting Clinical Decision-Making: Supplies variant data that can inform understanding of conditions linked to GPI biosynthesis defects and support diagnostic and therapeutic considerations.

Methodology:

Variants were aggregated from the LOVD database and annotated with bioinformatics damaging predictions and CADD score analysis.