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. This database can be accessed at http://www.housekeeping.unicamp.br.
Housekeeping gene regulation Housekeeping genes account for majority of the active genes in the genome, and their expression is obviously vital to survival. The housekeeping gene expression levels are fine-tuned to meet the metabolic requirements in various tissues. Biochemical studies on transcription initiation of the housekeeping gene promoters have been difficult, partly due to the less-characterized promoter motifs and transcription initiation process. Human housekeeping gene promoters are generally depleted of TATA-box, have high GC content and high incidence of CpG Islands. 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. The database was constructed by mining more than 12000 human and mouse RNA-seq datasets.
Gene expression
Transcription factors
Repressors PUF60 Homo sapiens fuse-binding protein-interacting repressor (SIAHBP1), transcript
RNA splicing
Translation factors
tRNA synthesis
RNA binding protein ELAVL1
Ribosomal proteins
Mitochondrial ribosomal proteins
RNA polymerase
Protein processing
Heat shock proteins
Histone
Cell cycle There is significant overlap in function with regards to some of these proteins. In particular, the Rho-related genes are important in nuclear trafficking (i.e.: mitosis) as well as with mobility along the cytoskeleton in general. These genes of particular interest in cancer research.
Apoptosis DAD1 Defender against cell death DAP3 Involved in mediating interferon-gamma-induced cell death. DAXX Death Associated Protein 6
Oncogenes ARAF MAZ (gene) MYC also considered a transcription factor
DNA repair/replication MCM3AP possibly a primase XRCC5 NM_021141 Ku80 XRCC6 NM_001469 Homo sapiens thyroid autoantigen: Single-stranded DNA-dependent ATP-dependent helicase. Has a role in chromosome translocation.
Metabolism
Carbohydrate metabolism
Citric Acid Cycle SDHA NM_004168 Succinate Dehydrogenase subunit A SDHAF2 NM_017841 SDHB NM_002973 Iron-sulfur protein (IP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q) SDHC NM_003000 Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). SDHD NM_003001
Lipid metabolism HADHA Trifunctional protein subunit alpha
Amino acid metabolism COMT Catechol-O-methyl transferase)
NADH dehydrogenase
Cytochrome C oxidase (Note that COX1, COX2, and COX3 are mitochondrially encoded)
ATPase
Lysosome
Proteasome
Ribonuclease RNH Ribonuclease inhibitor
Thioreductase
Structural
Cytoskeletal
Organelle synthesis A specialized form of cell signaling
Mitochondrion MTX2
Surface
Cell adhesion
Channels and transporters
Receptors ACVR1 NM_001105 similar to ACVRL1 TGF Beta receptor family Rendu-Osler-Weber syndrome ACVR1B NM_004302 CD23 FCER2 low affinity IgE receptor (lectin)
HLA/immunoglobulin/cell recognition BAT1 aka DDX39B which is involved in RNA splicing BSG Basigin Immunoglobulin Superfamily, extracellular metalloproteinase MIF macrophage migration inhibitory factor TAPBP
Kinases/signalling
Growth factors AIF1 HDGF Hepatoma derived growth factor (translocates to nucleus) HGS LTBP4 VEGFB ZFP36L1
Tissue necrosis factor CD40 formerly TNFRSF5
Casein kinase CSNK1E CSNK2B
Miscellaneous
Open_reading_frame C11Orf13 C14orf2 GATD3
Sperm/Testis Although this page is devoted to genes that should be ubiquitously expressed, this section is for genes whose current name reflects their relative upregulation in testes
See also Inducible gene Genevestigator Spatiotemporal gene expression Essential proteins in protein complexes Gene Genome Minimal genome List of gene families
References
External links Hounkpe B (2020). "Updated list of human and mouse housekeeping genes and transcripts. HRT Atlas database". Nucleic Acids Research. 49 (D1). University of Campinas: D947–D955. doi:10.1093/nar/gkaa609. PMC 7778946. PMID 32663312. From Hounkpe BW, Chenou F; de Lima F; De Paula E Nucleic Acids Research Eisenberg E. "List of housekeeping human genes". Tel Aviv University. From Eisenberg E, Levanon EY; Trends in Genetics 19, 362–365 (2003) Eisenberg E. "List of human housekeeping genes". Tel Aviv University. From Eisenberg E, Levanon EY; Trends in Genetics, 29 (2013)