TNFSF11

The protein functions as a cytokine that binds to osteoprotegerin and RANK receptor, serving as a key factor for osteoclast differentiation and activation, and also regulates T-cell dependent immune responses and dendritic cell survival. Mutations cause autosomal recessive osteopetrosis type 2, characterized by defective bone resorption due to absent or dysfunctional osteoclasts, leading to dense but brittle bones and potential complications including bone marrow failure and cranial nerve compression. This gene shows low constraint against loss-of-function variants (pLI 0.005), consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.