Practice question

Cystic fibrosis is autosomal recessive disorder due to CFTR ABCC7 mutations at chromosome 7q31.2 with more than 2000 variants catalogued in CFTR2 database. F508del deletion of phenylalanine 508 in NBD1 causes misfolding, endoplasmic reticulum retention, proteasomal degradation and minimal surface expression, representing class II trafficking defect. G551D missense in NBD1 signature motif impairs ATP-dependent gating though protein reaches membrane, class III gating defect. R117H in transmembrane domain reduces conductance, class IV. G542X nonsense truncates protein, class I no synthesis. Compound heterozygosity combinations determine phenotype severity including elevated sweat chloride, pancreatic insufficiency, bronchiectasis and male infertility due to congenital bilateral absence vas deferens. Recognition that diverse mechanisms cause same clinical disease underpins precision medicine: correctors elexacaftor and tezacaftor improve folding of F508del, potentiator ivacaftor enhances open probability of gating mutants, combined triple therapy benefits most patients carrying at least one F508del allele. Such detailed mechanistic insight is frequently examined in competitive tests including NEET, CUET, CSIR-NET and GATE where transporter classification, energetics and disease linkage are integrated into problem-solving questions.