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
ATF1 NM_005171 ATF2 NM_001880 ATF4 Activating transcription factor 4 NM_001675 ATF6 NM_007348 ATF7 NM_001206682 ATF7IP NM_018179 BTF3 NM_001207 Homo sapiens basic transcription factor 3 E2F4 Homo sapiens E2F transcription factor 4, p107/p130-binding (E2F4), mRNA ERH (gene) Enhancer of rudimentary homolog of drosophila (which in turn is the first enzymatic step in pyrimidine synthesis. Regulated by MITF) HMGB1 High mobility group box binds DNA ILF2 Homo sapiens interleukin enhancer binding factor 2, 45kDa (ILF2), mRNA IER2 formerly ETR101 Immediate Early Protein? JUND Homo sapiens jun D proto-oncogene (JUND), mRNA TCEB2 Elongin Matheo er rar
Repressors PUF60 Homo sapiens fuse-binding protein-interacting repressor (SIAHBP1), transcript
RNA splicing
BAT1 aka DDX39B HNRPD Homo sapiens heterogeneous nuclear ribonucleoprotein D (AU-rich element RNA HNRPK Homo sapiens heterogeneous nuclear ribonucleoprotein K (HNRPK), transcript PABPN1 poly(A) binding protein, nuclear 1 SRSF3 splicing factor, arginine/serine-rich
Translation factors
EIF1 aka SUI1 EIF1AD EIF1B EIF2A EIF2AK1 EIF2AK3 EIF2AK4 EIF2AK1 EIF2B2 EIF2B3 EIF2B4 EIF2S2 EIF3A EIF3B EIF3D formerly EIF3S4 EIF3G EIF3I EIF3H EIF3J EIF3K EIF3L EIF3M EIF3S5 EIF3S8 EIF4A1 EIF4A2 EIF4A3 EIF4E2 EIF4G1 EIF4G2 EIF4G3 EIF4H EIF5 EIF5 EIF5A EIF5AL1 EIF5B EIF6 TUFM Tu translational elongation factor mitochondrial
tRNA synthesis
AARS1 NM_001605 alanyl-tRNA synthetase AARS2 NM_020745 alanyl-tRNA synthetase 2, mitochondrial AARSD1 NM_001261434 alanyl-tRNA synthetase domain containing 1 CARS1 NM_001751 cysteinyl-tRNA synthetase CARS2 NM_024537 cysteinyl-tRNA synthetase 2, mitochondrial (putative) DARS1 NM_001349 aspartyl-tRNA synthetase DARS2 NM_018122 aspartyl-tRNA synthetase 2, mitochondrial EARS2 NM_001083614 glutamyl-tRNA synthetase 2, mitochondrial FARSA NM_004461 phenylalanyl-tRNA synthetase, alpha subunit FARSB NM_005687 phenylalanyl-tRNA synthetase, beta subunit FARS2 NM_006567 phenylalanyl-tRNA synthetase 2, mitochondrial GARS1 NM_002047 glycyl-tRNA synthetase HARS1 NM_002109 histidyl-tRNA synthetase HARS2 NM_012208 histidyl-tRNA synthetase 2, mitochondrial IARS1 NM_002161 isoleucyl-tRNA synthetase IARS2 NM_018060 isoleucyl-tRNA synthetase 2, mitochondrial KARS1 NM_005548 Homo sapiens lysyl-tRNA synthetase (KARS), mRNA LARS2 NM_015340 isoleucyl-tRNA synthetase 2, mitochondrial MARS1 NM_004990 methionyl-tRNA synthetase MARS2 NM_138395 methionyl-tRNA synthetase 2, mitochondrial NARS1 NM_004539 asparaginyl-tRNA synthetase NARS2 NM_024678 asparaginyl-tRNA synthetase 2, mitochondrial QARS1 NM_005051 glutaminyl-tRNA synthetase RARS1 NM_002884 arginyl-tRNA synthetase RARS2 NM_020320 arginyl-tRNA synthetase 2, mitochondrial SARS1 NM_006513 Homo sapiens seryl-tRNA synthetase (SARS1), mRNA TARS1 NM_152295 threonyl-tRNA synthetase VARS2 NM_020442 valyl-tRNA synthetase 2, mitochondrial WARS2 NM_015836 tryptophanyl tRNA synthetase 2, mitochondrial YARS1 NM_003680 Homo sapiens tyrosyl-tRNA synthetase (YARS), mRNA YARS2 NM_001040436 Homo sapiens tyrosyl-tRNA synthetase (YARS), mRNA mitochondrial
RNA binding protein ELAVL1
Ribosomal proteins
RPL5 RPL8 RPL9 RPL10A RPL11 RPL14 RPL25 RPL26L1 RPL27 RPL30 RPL32 RPL34 RPL35 RPL35A RPL36AL RPS5 RPS6 RPS6KA3 RPS6KB1 RPS6KB2 RPS13 RPS19BP1 RPS20 RPS23 RPS24 RPS27 transcribed with ubiquitin (see FAU (gene)) RPN1 Ribophorin anchors the ribosome to rough endoplasmic reticulum
Mitochondrial ribosomal proteins
MRPL9 MRPL1 MRPL10 MRPL11 MRPL12 MRPL13 MRPL14 MRPL15 MRPL16 MRPL17 MRPL18 MRPL19 MRPL2 MRPL20 MRPL21 MRPL22 MRPL23 MRPL24 MRPL27 MRPL28 MRPL3 MRPL30 MRPL32 MRPL33 MRPL35 MRPL36 MRPL37 MRPL38 MRPL4 MRPL40 MRPL41 MRPL42 MRPL43 MRPL44 MRPL45 MRPL46 MRPL47 MRPL48 MRPL49 MRPL50 MRPL51 MRPL52 MRPL53 MRPL54 MRPL55 MRPL9 MRPS10 MRPS11 MRPS12 MRPS14 MRPS15 MRPS16 MRPS17 MRPS18A MRPS18B MRPS18C MRPS2 MRPS21 MRPS22 MRPS23 MRPS24 MRPS25 MRPS26 MRPS27 MRPS28 MRPS30 MRPS31 MRPS33 MRPS34 MRPS35 MRPS5 MRPS6 MRPS7 MRPS9
RNA polymerase
POLR1C POLR1D POLR1E POLR2A POLR2B POLR2C POLR2D POLR2E POLR2F POLR2G POLR2H POLR2I POLR2J POLR2K POLR2L 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 Calnexin. Folding of glycoproteins within endoplasmic reticulum CAPN1 Calpain subunit CAPN7 CAPNS1 Calpain protease subunit NACA Nascent polypeptide associated complex alpha polypeptide NACA2 PFDN2 Prefoldin 2 PFDN4 Prefoldin 4 PFDN5 Prefoldin 5 PFDN6 Prefoldin 6 SNX2 Sorting nexin 2 SNX3 Sorting nexin 3 SNX4 Sorting nexin 4 SNX5 Sorting nexin 5 SNX6 Sorting nexin 6 SNX9 Sorting nexin 9 SNX12 Sorting nexin 12 SNX13 Sorting nexin 13 SNX17 Sorting nexin 17 SNX18 Sorting nexin 18 SNX19 Sorting nexin 19 SNX25 Sorting nexin 25 SSR1 Translocon-associated protein TRAPA. Protein translocation in ER SSR2 Translocon-associated protein TRAPB. Protein translocation in ER SSR3 Translocon-associated protein TRAPG. Protein translocation in ER SUMO1 Protein targeting SUMO3 Protein targeting
Heat shock proteins
HSPA4 HSPA5 HSPA8 HSPA9 HSPA14 HSBP1
Histone
HIST1H2BC H1FX H2AFV H2AFX H2AFY Histone 2 Subfamily H2AFZ essential for embryogenesis
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.
ARHGAP35 ARHGAP5 ARHGDIA ARHGEF10L Rho guanine nucleotide exchange factor 10L ARHGEF11 Rho guanine nucleotide exchange factor 11 ARHGEF40 Rho guanine nucleotide exchange factor 40 ARHGEF7 Rho guanine nucleotide exchange factor 7 RAB10 NM_016131 The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes RAB11A NM_004663 RAB11B NM_004218 RAB14 NM_016322 RAB18 NM_021252 RAB1A NM_004161 Homo sapiens RAB1A, member RAS oncogene family (RAB1A), mRNA RAB1B NM_030981 RAB21 NM_014999 RAB22A NM_020673 RAB2A NM_002858 RAB2B NM_001163380 RAB3GAP1 NM_012233 RAB3GAP2 NM_012414 RAB40C NM_021168 RAB4A NM_004578 RAB5A NM_004162 RAB5B NM_002865 RAB5C NM_004583 RAB6A NM_002868 RAB7A NM_004637 RAB9A NM_004251 RABEP1 NM_004703 RABEPK NM_005833 RABGEF1 NM_014504 RABGGTA NM_004581 RABGGTB NM_004582 CENPB Centromere protein B CTBP1 Centromere protein T CCNB1IP1 NM_021178 E3 ubiquitin-protein ligase. Modulates cyclin B levels and participates in the regulation of cell cycle progression through the G2 phase CCNDBP1 NM_012142 May negatively regulate cell cycle progression CCNG1 NM_004060 May play a role in growth regulation CCNH NM_001239 Involved in cell cycle control and in RNA transcription by RNA polymerase II. Its expression and activity are constant throughout the cell cycle CCNK NM_001099402 Regulatory subunit of cyclin-dependent kinases that mediates phosphorylation of the large subunit of RNA polymerase II CCNL1 NM_020307 Transcriptional regulator which participates in regulating the pre-mRNA splicing process CCNL2 NM_030937 Transcriptional regulator which participates in regulating the pre-mRNA splicing process. Also modulates the expression of critical apoptotic factor, leading to cell apoptosis. CCNY NM_145012 Positive regulatory subunit of the cyclin-dependent kinases CDK14/PFTK1 and CDK16. Acts as a cell-cycle regulator of Wnt signaling pathway during G2/M phase PPP1CA NM_002708 Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets PPP1CC NM_002710 PPP1R10 NM_002714 PPP1R11 NM_021959 Homo sapiens protein phosphatase 1, regulatory (inhibitor) subunit 11 (PPP1R11), PPP1R15B NM_032833 PPP1R37 NM_019121 PPP1R7 NM_002712 PPP1R8 NM_002713 PPP2CA NM_002715 PPP2CB NM_001009552 PPP2R1A NM_014225 Negative regulator of growth and cell divisionHomo sapiens protein phosphatase 2 (formerly 2A), regulatory subunit A (PR 65), PPP2R2A NM_002717 PPP2R2D NM_018461 PPP2R3C NM_017917 PPP2R4 NM_021131 PPP2R5A NM_006243 PPP2R5B NM_006244 PPP2R5C NM_002719 PPP2R5D NM_006245 PPP2R5E NM_006246 PPP4C NM_002720 PPP4R1 NM_005134 PPP4R2 NM_174907 PPP5C NM_006247 PPP6C NM_002721 PPP6R2 NM_014678 PPP6R3 NM_018312 RAD1Homo sapiens ribonuclease/angiogenin inhibitor (RNH), mRNA RAD17 NM_002869 Essential for sustained cell growth, maintenance of chromosomal stability, and ATR-dependent checkpoint activation upon DNA damage RAD23B NM_002873 RAD50 NM_005732 RAD51C NM_002874 IST1 (locates to central dividing line of dividing cells)
Apoptosis DAD1 Defender against cell death DAP3 Involved in mediating interferon-gamma-induced cell death. DAXX Death Associated Protein 6
Oncogenes