SP4 encodes the brain-specific Sp4 zinc finger transcription factor.46 In several small samples, modest association to bipolar disorder was observed for SNPs in an Sp4 binding site in the promoter of ADRBK2 (beta adrenergic receptor kinase 2; previously GRK3, G-protein receptor kinase 3)47 as well as in SP4 itself.48 SP4 mutant mice showed decreased granule cell density in the hippocampal dentate gyrus49, deficits in sensorimotor gating and contextual learning50, and infertility in surviving male knockout mice despite histologically intact testes and mature sperm, suggesting a possible behavioral deficit51. In our data, association is observed primarily in females; it may be noteworthy that Sp4 forms gene-regulating complexes with estrogen receptors.52 Sp4 may also play a role in glutamate-induced neurotoxicity.53, 54
