Cystic fibrosis transmembrane conductance regulator (CFTR) gene R553X mutation (CFTR R553X)

The CFTR gene R553X mutant locus refers to a specific nonsense mutation within the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, characterized by a cytosine-to-thymine transition at nucleotide 1657 (c.1657C>T) (PubMed: 7506096). This genetic alteration introduces a premature stop codon (p.Arg553Ter), which typically results in the production of a truncated, non-functional protein or triggers the degradation of the mRNA transcript via nonsense-mediated decay (NMD) (NIH: MedlinePlus). The CFTR protein is an essential cAMP-regulated chloride and bicarbonate channel that maintains fluid and electrolyte balance across epithelial surfaces in organs such as the lungs and pancreas (UniProt: P13569). In individuals with this mutation, the absence of functional CFTR leads to the accumulation of thick, dehydrated mucus, causing chronic respiratory infections and progressive organ damage characteristic of Cystic Fibrosis (Cystic Fibrosis Foundation). Therapeutic strategies targeting this specific locus include translational read-through agents like ELX-02 and ataluren, which aim to bypass the premature stop codon during translation to produce full-length protein (ClinicalTrials.gov: NCT04135339). Additionally, the locus is a primary target for advanced gene editing technologies, such as CRISPR/Cas9 and base editing, which seek to permanently correct the mutation at the DNA level (PubMed: 32025015).

Other names

p.Arg553Terc.1657C>TArg553XR553X nonsense mutationCystic fibrosis transmembrane conductance regulator nonsense mutation R553X

Translational read-through of premature stop codons (PTCs) to restore full-length protein synthesis or precise genomic correction via gene editing technologies.