Housekeeping gene


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 and housekeeping genes and reference genes/transcripts, named , 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 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

RNA splicing

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
  • AARS NM_001605 alanyl-tRNA synthetase
  • AARS2 NM_020745 alanyl-tRNA synthetase 2, mitochondrial
  • AARSD1 NM_001261434 alanyl-tRNA synthetase domain containing 1
  • CARS NM_001751 cysteinyl-tRNA synthetase
  • CARS2 NM_024537 cysteinyl-tRNA synthetase 2, mitochondrial
  • DARS NM_001349 aspartyl-tRNA synthetase
  • DARS2 NM_018122 aspartyl-tRNA synthetase 2, mitochondrial
  • EARS2 NM_001083614 glutamyl-tRNA synthetase 2, mitochondrial
  • FARS2 NM_006567 phenylalanyl-tRNA synthetase 2, mitochondrial
  • FARSA NM_004461 phenylalanyl-tRNA synthetase, alpha subunit
  • FARSB NM_005687 phenylalanyl-tRNA synthetase, beta subunit
  • GARS NM_002047 glycyl-tRNA synthetase
  • HARS NM_002109 histidyl-tRNA synthetase
  • HARS2 NM_012208 histidyl-tRNA synthetase 2, mitochondrial
  • IARS NM_002161 isoleucyl-tRNA synthetase
  • IARS2 NM_018060 isoleucyl-tRNA synthetase 2, mitochondrial
  • KARS NM_005548 Homo sapiens lysyl-tRNA synthetase, mRNA
  • LARS2 NM_015340 isoleucyl-tRNA synthetase 2, mitochondrial
  • MARS NM_004990 methionyl-tRNA synthetase
  • MARS2 NM_138395 methionyl-tRNA synthetase 2, mitochondrial
  • NARS NM_004539 asparaginyl-tRNA synthetase
  • NARS2 NM_024678 asparaginyl-tRNA synthetase 2, mitochondrial
  • QARS NM_005051 glutaminyl-tRNA synthetase
  • RARS NM_002884 arginyl-tRNA synthetase
  • RARS2 NM_020320 arginyl-tRNA synthetase 2, mitochondrial
  • SARS NM_006513 Homo sapiens seryl-tRNA synthetase, mRNA
  • TARS NM_152295 threonyl-tRNA synthetase
  • VARS2 NM_020442 valyl-tRNA synthetase 2, mitochondrial
  • WARS2 NM_015836 tryptophanyl tRNA synthetase 2, mitochondrial
  • YARS NM_003680 Homo sapiens tyrosyl-tRNA synthetase, mRNA
  • YARS2 NM_001040436 Homo sapiens tyrosyl-tRNA synthetase, mRNA mitochondrial
    RNA binding protein
  • ELAVL1

Ribosomal proteins

Mitochondrial ribosomal proteins

RNA polymerase

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

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 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

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

  • PRKAG1 Senses energy level and inactivates HMGCoA reductase and Acetyl CoA Carboxylase
  • PRKAA1 NM_006251 Catalytic subunit of AMP-activated protein kinase, an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism
  • PRKAB1 NM_006253 Non-catalytic subunit of AMP-activated protein kinase, an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism
  • PRKACA NM_002730 Phosphorylates a large number of substrates in the cytoplasm and the nucleus.
  • PRKAG1 NM_002733 Homo sapiens protein kinase, AMP-activated, gamma 1 non-catalytic subunit, mRNA
  • PRKAR1A NM_002734 Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells
  • PRKRIP1 NM_024653 Binds double-stranded RNA. Inhibits EIF2AK2 kinase activity.

Carbohydrate metabolism

Citric Acid Cycle

  • SDHA NM_004168 Succinate Dehydrogenase subunit A
  • SDHAF2 NM_017841
  • SDHB NM_002973 Iron-sulfur protein subunit of succinate dehydrogenase that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone
  • SDHC NM_003000 Membrane-anchoring subunit of succinate dehydrogenase that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone.
  • SDHD NM_003001

Lipid metabolism

  • HADHA Trifunctional protein subunit alpha

Amino acid metabolism

  • COMT Catechol-O-methyl transferase)

NADH dehydrogenase

Cytochrome C oxidase

  • COX4I1 001861
  • COX5B NM_001862
  • COX6B1 NM_001863
  • COX6C NM_004374
  • COX7A2 NM_001865 Homo sapiens cytochrome c oxidase subunit VIIa polypeptide 2 ,
  • COX7A2L NM_004718
  • COX7C NM_001867
  • COX8
  • COX8A NM_004074 Homo sapiens cytochrome c oxidase subunit VIII, nuclear gene encoding
  • COX11 NM_004375
  • COX14 NM_032901
  • COX15 NM_004376
  • COX16 NM_016468
  • COX19 NM_001031617
  • COX20 NM_198076
  • CYC1 Homo sapiens cytochrome c-1
  • UQCC NM_018244 Required for the assembly of the ubiquinol-cytochrome c reductase complex
  • UQCR10 NM_013387
  • UQCR11 NM_006830 Homo sapiens ubiquinol-cytochrome c reductase subunit, mRNA
  • UQCRB NM_006294
  • UQCRC1 NM_003365 Homo sapiens ubiquinol-cytochrome c reductase core protein I, mRNA
  • UQCRC2 NM_003366
  • UQCRHL NM_001089591
  • UQCRQ NM_014402 Homo sapiens low molecular mass ubiquinone-binding protein , mRNA

ATPase

  • ATP2C1 NM_014382
  • ATP5A1 NM_004046 Homo sapiens ATP synthase, H+ transporting, mitochondrial F1 complex, alpha
  • ATP5B NM_001686
  • ATP5C1 NM_005174
  • ATP5D NM_001687 Homo sapiens ATP synthase, H+ transporting, mitochondrial F1 complex, delta
  • ATP5F1 NM_001688
  • ATP5G2 NM_005176
  • ATP5G3 NM_001689 Homo sapiens ATP synthase, H+ transporting, mitochondrial F0 complex, subunit c
  • ATP5H NM_006356 Homo sapiens ATP synthase, H+ transporting, mitochondrial F0 complex, subunit d
  • ATP5J NM_001685
  • ATP5J2 NM_004889 Homo sapiens ATP synthase, H+ transporting, mitochondrial F0 complex, subunit f,
  • ATP5J2-PTCD1 NM_001198879
  • ATP5L NM_006476
  • ATP5O NM_001697 Homo sapiens ATP synthase, H+ transporting, mitochondrial F1 complex, O subunit
  • ATP5S NM_015684
  • ATP5SL NM_018035
  • ATP6AP1 NM_001183 Homo sapiens ATPase, H+ transporting, lysosomal interacting protein 1,
  • ATP6V0A2 NM_012463
  • ATP6V0B NM_004047 Homo sapiens ATPase, H+ transporting, lysosomal 21kDa, V0 subunit c,
  • ATP6V0C NM_001694 Homo sapiens ATPase, H+ transporting, lysosomal 16kDa, V0 subunit c,
  • ATP6V0D1 NM_004691
  • ATP6V0E1 NM_003945
  • ATP6V1C1 NM_001695
  • ATP6V1D NM_015994
  • ATP6V1E1 NM_001696 Homo sapiens ATPase, H+ transporting, lysosomal 31kDa, V1 subunit E isoform 1
  • ATP6V1F NM_004231 Homo sapiens ATPase, H+ transporting, lysosomal 14kDa, V1 subunit F,
  • ATP6V1G1 NM_004888 Homo sapiens ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G isoform 1
  • ATP6V1H NM_015941
  • ATPAF2 NM_145691
  • ATPIF1 NM_016311

Lysosome

Proteasome

Ribonuclease

  • RNH Ribonuclease inhibitor

Thioreductase

Structural

Cytoskeletal

Organelle synthesis

A specialized form of cell signaling

Mitochondrion

Surface

Cell adhesion

Channels and transporters

Receptors

HLA/immunoglobulin/cell recognition

Kinases/signalling

Growth factors

Tissue necrosis factor

  • CD40 formerly TNFRSF5

Casein kinase

Miscellaneous

Open_reading_frame

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