Methods of identifying ActRIIB variants

A method of identifying ActRIIB variants capable of increasing red blood cell or hemoglobin levels, comprising:

• a) testing whether an ActRIIB variant specifically inhibits or reduces binding of an ActRIIB control polypeptide to an ActRIIB ligand;
• wherein the ActRIIB ligand is one or more of myostatin and/or GDF11;
• b) wherein if the ActRIIB variant inhibits or reduces binding of the ActRIIB control polypeptide to myostatin and/or GDF11, the method further comprises the step of administering the ActRIIB variant to a subject;
• c) measuring the levels of red blood cell count and/or hemoglobin levels in the subject;
• wherein if the ActRIIB variant increases red blood cell count and/or hemoglobin levels in the subject, an ActRIIB variant that is capable of increasing red blood cell or hemoglobin levels is identified;
• wherein the ActRIIB variant comprises an amino acid sequence that is at least 80% identical to the sequence of amino acids 29-109 of SEQ ID NO:
• 1, and wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO:
• 1.