ZNF664 encodes a zinc finger protein likely involved in transcriptional regulation, functioning as a DNA-binding transcription factor with specific activity at RNA polymerase II cis-regulatory regions [GO annotations]. The protein localizes to the nucleus and binds DNA to regulate RNA polymerase II-dependent transcription. Genetically, ZNF664 variants associate with multiple metabolic and cardiovascular traits. The locus shows independent associations with adiponectin levels 1 and replicated associations with high-density lipoprotein cholesterol (HDL-C) in candidate gene studies 2. ZNF664 emerged as a pleiotropic gene influencing metabolic syndrome and inflammatory markers 3, with specific variants associated with body mass index in women 4. Beyond metabolic disease, ZNF664 variants have been implicated in vascular and skeletal phenotypes. An intergenic SNP between NCOR2 and ZNF664 showed significant association with isolated clubfoot, a common congenital birth defect 5. Additionally, ZNF664 was identified in genome-wide studies of varicose veins 6 and chr12 venous insufficiency, where variants in mRNA-miRNA binding regions may affect gene expression 7. Notably, ZNF664 coding and regulatory regions were systematically sequenced in studies of HDL-C phenotypic extremes 8, confirming its role in lipid metabolism variation.