We analyzed single nucleotide polymorphisms (SNPs) inPKNOX1(rs2839629) and in the intergenic region betweenPKNOX1andCBS(rs915854) by Sanger sequencing in 88 patients with multiple myeloma treated with bortezomib. All patients (n = 13) harboring a homozygous mutation inPKNOX1(rs2839629) also had a homozygous mutated rs915854 genotype. Homozygous mutated genotypes of rs2839629 and rs915854 were significantly enriched in patients with painful peripheral neuropathy (PNP) (P< 0.0001), and homozygous mutated rs2839629 genotype was significantly enriched in patients with pain compared to patients with no pain (P= 0.04). In summary, both SNPs rs2839629 and/or rs915854 may be potential biomarkers predicting an increased risk to develop painful PNP under bortezomib.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40364-023-00490-9.