In molecular biology, housekeeping genes are typically constitutive genes that are required for the maintenance of basic cellular function, and are expressed in all cells of an organism under normal and patho-physiological conditions. Although some housekeeping genes are expressed at relatively constant rates in most non-pathological situations, the expression of other housekeeping genes may vary depending on experimental conditions.

The origin of the term "housekeeping gene" remains obscure. Literature from 1976 used the term to describe specifically tRNA and rRNA. For experimental purposes, the expression of one or multiple housekeeping genes is used as a reference point for the analysis of expression levels of other genes. The key criterion for the use of a housekeeping gene in this manner is that the chosen housekeeping gene is uniformly expressed with low variance under both control and experimental conditions. Validation of housekeeping genes should be performed before their use in gene expression experiments such as RT-PCR. In 2020, a web-based database of human and mouse housekeeping genes and reference genes/transcripts, named Housekeeping and Reference Transcript Atlas (HRT Atlas), was developed to offer updated list of housekeeping genes and reliable candidate reference genes/transcripts for RT-qPCR data normalization. In Drosophila, where promoter specific CpG Islands are absent, housekeeping gene promoters contain DNA elements like DRE, E-box or DPE. Transcription start sites of housekeeping genes can span over a region of around 100 bp whereas transcription start sites of developmentally regulated genes are usually focused in a narrow region. Little is known about how the dispersed transcription initiation of housekeeping gene is established. There are transcription factors that are specifically enriched on and regulate housekeeping gene promoters. Furthermore, housekeeping promoters are regulated by housekeeping enhancers but not developmentally regulated enhancers.

Common housekeeping genes in humans

The following is a partial list of "housekeeping genes." For a more complete and updated list, see HRT Atlas database compiled by Bidossessi W. Hounkpe et al.

  • POLR3C
  • POLR3E
  • POLR3GL
  • POLR3K

Protein processing

  • PPID Peptidyl-prolyl cis-trans isomerase D
  • PPIE Peptidyl-prolyl cis-trans isomerase E
  • PPIF Peptidyl-prolyl cis-trans isomerase F
  • PPIG Peptidyl-prolyl cis-trans isomerase G
  • PPIH Cyclophilin H
  • CANX
  • ALDOA
  • GSK3B
  • TPI1
  • ANXA6