We attempt to explain the latter finding using molecular modelling of the RRM2B missense mutations identified in this study, which suggests the variants can be broadly divided into two groups: mutations that severely impair ribonucleotide reductase activity and cause autosomal-dominant disease through a dominant-negative effect; and mutations associated with autosomal-recessive disease, which are predicted to result in moderately decreased catalytic activity or decreased levels of functional protein through reduced protein folding efficiency. Here, RRM2B is linked to autosomal recessive disease.