BACKGROUND: Genetic variants in coagulation factor IX (FIX) are associated with haemophilia B, a rare bleeding disease. F9 variants are widespread across the gene and were summarised in our FIX variant database introduced in 2013. OBJECTIVE: We rationalise the molecular basis for 598 new F9 variants and 1645 new clinical cases, making a total of 1692 F9 variants and 5358 related patient cases. METHODS: New F9 variants were identified from publications and on-line resources, and compiled into a MySQL database for comparison with the human FIXa protein structure. RESULTS: The new total of 1692 F9 variants correspond to 406 (88%) of the 461 FIX residues and now include 70 additional residues. These comprise 945 unique point variants, 281 deletions, 352 polymorphisms, 63 insertions, and 51 others. Most FIX variants were point variants, although their proportion (56%) has reduced compared to 2013 (73%), while the proportion of polymorphisms has increased from 5% to 21%.The 764 unique mild severity variants in the mature protein with known phenotypes include 74 (9.7%) quantitative type I variants and 116 (15.2%) predominantly qualitative type II variants. The remaining 574 variants types are unspecified. Inhibitors are associated with 152 haemophilia B cases out of 5358 patients (2.8%), an increase of 93 from the previous database. CONCLUSION: The even distribution of the F9 variants revealed few mutational hotspots, and most variants were associated with small perturbations in the FIX protein structure. The updated database will assist clinicians and researchers in assessing treatments for haemophilia B patients.