This gene encodes a secreted, glycosylated cytokine composed of four alpha helical bundles. The encoded protein is mainly synthesized in the kidney, secreted into the blood plasma, and binds to the erythropoietin receptor to promote red blood cell production, or erythropoiesis, in the bone marrow. Expression of this gene is upregulated under hypoxic conditions, in turn leading ... See more...

Aliases for EPO Gene

Aliases for EPO Gene

  • Erythropoietin 2 3 4 5
  • Epoetin 3 4
  • ECYT5 3
  • MVCD2 3
  • DBAL 3
  • EP 3

External Ids for EPO Gene

Previous GeneCards Identifiers for EPO Gene

  • GC07P098853
  • GC07P099916
  • GC07P099929
  • GC07P099963
  • GC07P100156
  • GC07P100318
  • GC07P094949

Summaries for EPO Gene

Entrez Gene Summary for EPO Gene

  • This gene encodes a secreted, glycosylated cytokine composed of four alpha helical bundles. The encoded protein is mainly synthesized in the kidney, secreted into the blood plasma, and binds to the erythropoietin receptor to promote red blood cell production, or erythropoiesis, in the bone marrow. Expression of this gene is upregulated under hypoxic conditions, in turn leading to increased erythropoiesis and enhanced oxygen-carrying capacity of the blood. Expression of this gene has also been observed in brain and in the eye, and elevated expression levels have been observed in diabetic retinopathy and ocular hypertension. Recombinant forms of the encoded protein exhibit neuroprotective activity against a variety of potential brain injuries, as well as antiapoptotic functions in several tissue types, and have been used in the treatment of anemia and to enhance the efficacy of cancer therapies. [provided by RefSeq, Aug 2017]

GeneCards Summary for EPO Gene

EPO (Erythropoietin) is a Protein Coding gene. Diseases associated with EPO include Diamond-Blackfan Anemia-Like and Erythrocytosis, Familial, 5. Among its related pathways are Hematopoietic cell lineage and Development EPO-induced Jak-STAT pathway. Gene Ontology (GO) annotations related to this gene include hormone activity and erythropoietin receptor binding.

UniProtKB/Swiss-Prot Summary for EPO Gene

  • Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation thereby activating specific downstream effectors, including STAT1 and STAT3.

Gene Wiki entry for EPO Gene

Additional gene information for EPO Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for EPO Gene

Genomics for EPO Gene

GeneHancer (GH) Regulatory Elements for EPO Gene

Promoters and enhancers for EPO Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH07J100720 Promoter 1.2 EPDnew Ensembl 500.7 +0.2 233 0.6 NCOR1 CTCF TGIF2 ZBTB7A EZH2 TFDP1 GABPB1 HDAC1 MNT TAF15 EPO ZAN RF00017-6483 RF00017-6488
GH07J100719 Enhancer 0.7 ENCODE 500.7 -0.6 -635 0.2 NCOR1 CTCF KDM6A SKI SAP130 CREM FOXP1 SMAD4 BCL6 ADNP EPO RF00017-6489 RF00017-6483 RF00017-6488
GH07J100725 Enhancer 0.8 ENCODE 0.4 +6.1 6095 2.6 CTCF JUND FOS REST MYC CTBP1 RAD21 TRIM22 SMC3 FOXA2 MOSPD3 EPO ZAN RF00017-6483 RF00017-6488
GH07J100733 Promoter 0.3 EPDnew 0.4 +13.1 13108 0.1 ZAN EPO RF00017-6488
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around EPO on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for EPO

Top Transcription factor binding sites by QIAGEN in the EPO gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • CREB
  • deltaCREB
  • GATA-1
  • p300

Genomic Locations for EPO Gene

Genomic Locations for EPO Gene
chr7:100,720,468-100,723,700
(GRCh38/hg38)
Size:
3,233 bases
Orientation:
Plus strand
chr7:100,318,423-100,321,323
(GRCh37/hg19)
Size:
2,901 bases
Orientation:
Plus strand

Genomic View for EPO Gene

Genes around EPO on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
EPO Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for EPO Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EPO Gene

Proteins for EPO Gene

  • Protein details for EPO Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P01588-EPO_HUMAN
    Recommended name:
    Erythropoietin
    Protein Accession:
    P01588
    Secondary Accessions:
    • Q2M2L6
    • Q549U2
    • Q9UDZ0
    • Q9UEZ5
    • Q9UHA0

    Protein attributes for EPO Gene

    Size:
    193 amino acids
    Molecular mass:
    21307 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for EPO Gene

neXtProt entry for EPO Gene

Post-translational modifications for EPO Gene

  • Glycosylation at Asn51, Asn65, Asn110, and Ser153
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

Other Protein References for EPO Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

Assay Products

  • Abcam assays for EPO

No data available for DME Specific Peptides for EPO Gene

Domains & Families for EPO Gene

Gene Families for EPO Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Candidate cardiovascular disease genes
  • Disease related genes
  • Predicted secreted proteins

Protein Domains for EPO Gene

Blocks:
  • Erythropoietin signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for EPO Gene

GenScript: Design optimal peptide antigens:
  • EPO protein (B7ZKK5_HUMAN)
  • Erythropoietin (EPO_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P01588

UniProtKB/Swiss-Prot:

EPO_HUMAN :
  • Belongs to the EPO/TPO family.
Family:
  • Belongs to the EPO/TPO family.
genes like me logo Genes that share domains with EPO: view

Function for EPO Gene

Molecular function for EPO Gene

UniProtKB/Swiss-Prot Function:
Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation thereby activating specific downstream effectors, including STAT1 and STAT3.
GENATLAS Biochemistry:
erythropoietin,46kDa,expressed in liver and kidney,stimulating cellular differentiation of bone marrow cells at an early stage,activating a voltage independent calcium channel dependent on tyrosine phosphorylation

LifeMap Function Summary for EPO Gene

EPO as growth factor is involved in stem cell differentiation protocols towards the derivation of the following cells:

Phenotypes From GWAS Catalog for EPO Gene

Gene Ontology (GO) - Molecular Function for EPO Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005125 cytokine activity IDA 28283061
GO:0005128 erythropoietin receptor binding IMP 28283061
GO:0005179 hormone activity IEA --
GO:0005515 protein binding IPI 9774108
GO:0030295 protein kinase activator activity IBA 21873635
genes like me logo Genes that share ontologies with EPO: view
genes like me logo Genes that share phenotypes with EPO: view

Human Phenotype Ontology for EPO Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for EPO Gene

MGI Knock Outs for EPO:
  • Epo Epo<tm1Jae>

Animal Model Products

CRISPR Products

miRNA for EPO Gene

miRTarBase miRNAs that target EPO

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for EPO

Clone Products

  • Addgene plasmids for EPO

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for EPO Gene

Localization for EPO Gene

Subcellular locations from UniProtKB/Swiss-Prot for EPO Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for EPO gene
Compartment Confidence
extracellular 5
cytosol 4
plasma membrane 3
mitochondrion 3
nucleus 3
cytoskeleton 2
endoplasmic reticulum 2
endosome 2
lysosome 2
peroxisome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for EPO Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IDA,IEA 14569084
GO:0009986 cell surface IDA 14569084
GO:0044297 cell body IEA --
genes like me logo Genes that share ontologies with EPO: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for EPO Gene

Pathways & Interactions for EPO Gene

genes like me logo Genes that share pathways with EPO: view

Pathways by source for EPO Gene

3 GeneGo (Thomson Reuters) pathways for EPO Gene
  • Development EPO-induced Jak-STAT pathway
  • Development EPO-induced MAPK pathway
  • G-protein signaling_K-RAS regulation pathway
3 Qiagen pathways for EPO Gene
  • Erythropoietin Pathway
  • HIF1Alpha Pathway
  • JAK-STAT Pathway

SIGNOR curated interactions for EPO Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for EPO Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IMP 16497104
GO:0001666 response to hypoxia IBA,IEA 21873635
GO:0006357 regulation of transcription by RNA polymerase II IEA --
GO:0006915 apoptotic process IEA --
GO:0006953 acute-phase response IEA --
genes like me logo Genes that share ontologies with EPO: view

Drugs & Compounds for EPO Gene

(113) Drugs for EPO Gene - From: ClinicalTrials and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Iron Approved, Experimental Pharma 1496
Benzocaine Approved, Investigational Pharma 2900
Darbepoetin alfa Approved, Investigational Pharma 211
Lenograstim Approved, Investigational Pharma 1351
Panobinostat Approved, Investigational Pharma Histone deacetylase (HDAC)inhibitors 142

(50) Additional Compounds for EPO Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with EPO: view

Transcripts for EPO Gene

mRNA/cDNA for EPO Gene

1 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for EPO

Clone Products

  • Addgene plasmids for EPO

Alternative Splicing Database (ASD) splice patterns (SP) for EPO Gene

No ASD Table

Relevant External Links for EPO Gene

GeneLoc Exon Structure for
EPO

Expression for EPO Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for EPO Gene

mRNA differential expression in normal tissues according to GTEx for EPO Gene

This gene is overexpressed in Liver (x36.9) and Pancreas (x5.4).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for EPO

SOURCE GeneReport for Unigene cluster for EPO Gene:

Hs.2303

mRNA Expression by UniProt/SwissProt for EPO Gene:

P01588-EPO_HUMAN
Tissue specificity: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals.

Evidence on tissue expression from TISSUES for EPO Gene

  • Nervous system(4.6)
  • Urine(4.4)
  • Blood(3.5)
  • Bone marrow(3.3)
  • Kidney(3.1)
  • Liver(2.8)
  • Heart(2.6)
  • Muscle(2.3)
  • Spleen(2.2)
genes like me logo Genes that share expression patterns with EPO: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for EPO Gene

Orthologs for EPO Gene

This gene was present in the common ancestor of chordates.

Orthologs for EPO Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia EPO 31 30
  • 99.48 (n)
OneToOne
dog
(Canis familiaris)
Mammalia EPO 31 30
  • 86.75 (n)
OneToOne
cow
(Bos Taurus)
Mammalia EPO 31 30
  • 85.69 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Epo 17 31 30
  • 80.52 (n)
rat
(Rattus norvegicus)
Mammalia Epo 30
  • 79.92 (n)
oppossum
(Monodelphis domestica)
Mammalia EPO 31
  • 55 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia epo 30
  • 49.56 (n)
zebrafish
(Danio rerio)
Actinopterygii epo 31 30
  • 48.83 (n)
OneToOne
Species where no ortholog for EPO was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for EPO Gene

ENSEMBL:
Gene Tree for EPO (if available)
TreeFam:
Gene Tree for EPO (if available)
Aminode:
Evolutionary constrained regions (ECRs) for EPO: view image

Paralogs for EPO Gene

No data available for Paralogs for EPO Gene

Variants for EPO Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for EPO Gene

SNP ID Clinical significance and condition Chr 07 pos Variation AA Info Type
rs11976235 Erythrocytosis, familial, 5 (ECYT5) [MIM:617907] p.Pro114Leu
rs1358275550 Pathogenic: DIAMOND-BLACKFAN ANEMIA-LIKE. Diamond-Blackfan anemia-like (DBAL) [MIM:617911] 100,723,081(+) G/Ap.Arg177Gln MISSENSE_VARIANT
rs137953994 Erythrocytosis, familial, 5 (ECYT5) [MIM:617907] p.Gly84Arg
rs149431976 Erythrocytosis, familial, 5 (ECYT5) [MIM:617907] p.Ser147Cys
rs1554393458 Pathogenic: ERYTHROCYTOSIS, FAMILIAL, 5 100,721,562(+) TC/T FRAMESHIFT_VARIANT

Additional dbSNP identifiers (rs#s) for EPO Gene

Structural Variations from Database of Genomic Variants (DGV) for EPO Gene

Variant ID Type Subtype PubMed ID
dgv1940e212 CNV loss 25503493
esv2734888 CNV deletion 23290073
esv3572021 CNV loss 25503493
nsv1020837 CNV loss 25217958
nsv470381 CNV loss 18288195
nsv607933 CNV gain 21841781
nsv8184 CNV loss 18304495
nsv831072 CNV loss 17160897

Variation tolerance for EPO Gene

Residual Variation Intolerance Score: 76.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.18; 23.81% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for EPO Gene

Human Gene Mutation Database (HGMD)
EPO
SNPedia medical, phenotypic, and genealogical associations of SNPs for
EPO

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for EPO Gene

Disorders for EPO Gene

MalaCards: The human disease database

(152) MalaCards diseases for EPO Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
diamond-blackfan anemia-like
  • dbal
erythrocytosis, familial, 5
  • ecyt5
microvascular complications of diabetes 2
  • proliferative retinopathy, diabetic
autosomal dominant secondary polycythemia
  • autosomal dominant secondary erythrocytosis
pure red-cell aplasia
  • primary red cell aplasia
- elite association - COSMIC cancer census association via MalaCards
Search EPO in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

EPO_HUMAN
  • Microvascular complications of diabetes 2 (MVCD2) [MIM:612623]: Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
  • Erythrocytosis, familial, 5 (ECYT5) [MIM:617907]: An autosomal dominant disorder characterized by elevated serum hemoglobin and hematocrit. Some patients have increased serum erythropoietin levels. {ECO:0000269 PubMed:27651169, ECO:0000269 PubMed:29514032}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Diamond-Blackfan anemia-like (DBAL) [MIM:617911]: An autosomal recessive hematologic disease characterized by severe red cell hypoplastic anemia, selective absence of red cell precursors and progenitors seen on bone marrow biopsy, and increased serum erythropoietin. {ECO:0000269 PubMed:28283061}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for EPO

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with EPO: view

No data available for Genatlas for EPO Gene

Publications for EPO Gene

  1. Promoter polymorphism of the erythropoietin gene in severe diabetic eye and kidney complications. (PMID: 18458324) Tong Z … Zhang K (Proceedings of the National Academy of Sciences of the United States of America 2008) 3 4 41 54
  2. Large-scale sequencing of two regions in human chromosome 7q22: analysis of 650 kb of genomic sequence around the EPO and CUTL1 loci reveals 17 genes. (PMID: 9799793) Glöckner G … Rosenthal A (Genome research 1998) 2 3 4 54
  3. Isolation and characterization of genomic and cDNA clones of human erythropoietin. (PMID: 3838366) Jacobs K … Fritsch EF (Nature 1985) 2 3 4 54
  4. A Gain-of-Function Mutation in EPO in Familial Erythrocytosis. (PMID: 29514032) Zmajkovic J … Skoda RC (The New England journal of medicine 2018) 3 4 54
  5. Functional Selectivity in Cytokine Signaling Revealed Through a Pathogenic EPO Mutation. (PMID: 28283061) Kim AR … Sankaran VG (Cell 2017) 3 4 54

Products for EPO Gene

  • Addgene plasmids for EPO

Sources for EPO Gene