Previously, we found that the Noggin family proteins could bind to activin, a member of the TGF-β superfamily, and repress the corresponding signaling cascade. In this work, we characterized a mutant of the Xenopus laevis Noggin2 protein bearing a W203R substitution. This point mutation was shown to enhance the affinity of Noggin to activin, while weakening its affinity to bone morphogenetic proteins. Also, we demonstrated that the W203R mutant inhibited the activin-dependent signaling cascade more effectively. It is interesting that the homologous mutation of human Noggin was associated with certain hereditary skeletal anomalies. These effects of the point amino acid substitution in Noggin2 demonstrated the potential of this approach for generation of Noggin variants with the enhanced affinity to some members of the TGF-β superfamily.