Two single nucleotide polymorphisms in the human nescient helix-loop-helix 2 (NHLH2) gene reduce mRNA stability and DNA binding

► NHLH2 is a bHLH transcription factor that controls body weight and fertility. ► A 3′UTR and a coding region SNP both reduce functional NHLH2 protein levels. ► The 3′UTR SNP affects RNA secondary structure and mRNA stability. ► The basic domain SNP modifies the protein helical structure. ► Rare SNPs in NHLH2 may contribute to body weight or fertility phenotypes in humans.