MUG

Mutations Understanding GPCRs: a curated, interactive database of natural variants in GPCR subfamily A17

MUG is a comprehensive, interactive computational framework cataloguing clinically reported mutations across the GPCR subfamily A17, a group of receptors directly implicated in neurodegenerative diseases.

GPCRs mediate numerous signalling pathways; mutations in their encoding genes can critically disrupt receptor activation, ligand binding, and downstream cytoplasmic regulation. By integrating structural 3D data with sequence annotations and Ballesteros–Weinstein (BW) nomenclature, MUG enables researchers to explore mutations by receptor family, structural domain, functional classification (GOF/LOF), and age-group distribution, offering a first step toward elucidating GPCR dysfunction at the atomic level.

Available Features

• Overall Mutations: Cross-family mutation profiles, amino acid exchange plots, and an annotated sequence table with BW nomenclature for all receptors. Filterable by mutation type and receptor family.
• Substructural Analysis: Per-residue solvent accessible surface area (SASA) and relative ASA (rASA) across all receptor structures. Interactive plots per structural domain, TM helices, ECLs, and ICLs.
• Structure Representations: 3D visualisation of receptor structures with mutation loci highlighted, enabling spatial interpretation of variant distribution across the receptor architecture.
• Structure–Mutation Mapping: Receptor-specific mutation overlay on structural models, correlating variant position with known functional microdomains and conserved signalling residues.

Key Findings

• Ligand binding pocket enrichment: mutated residues are concentrated at the ligand binding site and known activating micro-domains, suggesting functional disruption as a primary pathogenic mechanism.
• Hydrophobic residue bias: mutating residues are predominantly hydrophobic, pointing to conserved physicochemical constraints underlying subfamily A17 receptor stability.
• Conserved domain vulnerability: a considerable number of mutations map to conserved residues and domains, including transmembrane helices and intracellular coupling regions.
• Age-stratified distribution: mutation burden does not increase linearly with age; instead, variants appear restricted to specific age groups, suggesting developmental or exposure windows.

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Explore GPCR subfamily A17 mutations by receptor, structural domain, or functional class. No installation required, fully interactive in the browser.

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