EPO (erythropoietin)

Gene

• Entrez ID: 2056
• Gene name: Erythropoietin
• Gene symbol: EPO
• Synonyms (NCBI Gene): DBAL, ECYT5, EP, MVCD2
• Chromosome: 7
• Chromosome location: 7q22.1
• Summary: 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 product

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1617640	C>A,G,T	Risk-factor	Upstream transcript variant
rs1358275550	G>A	Pathogenic	Coding sequence variant, missense variant
rs1554393458	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1554393463	G>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT022112	hsa-miR-125b-5p	Other	20194440
MIRT022112	hsa-miR-125b-5p	Luciferase reporter assay	24165569
MIRT022112	hsa-miR-125b-5p	Luciferase reporter assay	24165569
MIRT022112	hsa-miR-125b-5p	Luciferase reporter assay	24165569
MIRT022112	hsa-miR-125b-5p	Luciferase reporter assay	24165569
MIRT022112	hsa-miR-125b-5p	Luciferase reporter assay	24165569
MIRT022112	hsa-miR-125b-5p	Luciferase reporter assay	24165569
MIRT022112	hsa-miR-125b-5p	Luciferase reporter assay	24165569
MIRT022112	hsa-miR-125b-5p	Luciferase reporter assay	24165569
MIRT755730	hsa-miR-144-5p	Luciferase reporter assay, Western blotting, Microarray, qRT-PCR, Immunohistochemistry (IHC), Flow cytometry	36763178
MIRT967163	hsa-miR-125a-5p	CLIP-seq
MIRT967164	hsa-miR-125b	CLIP-seq
MIRT967165	hsa-miR-1323	CLIP-seq
MIRT967166	hsa-miR-3185	CLIP-seq
MIRT967167	hsa-miR-338-3p	CLIP-seq
MIRT967168	hsa-miR-4319	CLIP-seq
MIRT967169	hsa-miR-4421	CLIP-seq
MIRT967170	hsa-miR-4535	CLIP-seq
MIRT967171	hsa-miR-4682	CLIP-seq
MIRT967172	hsa-miR-4709-3p	CLIP-seq
MIRT967173	hsa-miR-4731-3p	CLIP-seq
MIRT967174	hsa-miR-4732-3p	CLIP-seq
MIRT967175	hsa-miR-4776-5p	CLIP-seq
MIRT967176	hsa-miR-4793-5p	CLIP-seq
MIRT967177	hsa-miR-4801	CLIP-seq
MIRT967178	hsa-miR-548o	CLIP-seq
MIRT967179	hsa-miR-670	CLIP-seq
MIRT967180	hsa-miR-760	CLIP-seq
MIRT967181	hsa-miR-890	CLIP-seq
MIRT1986500	hsa-miR-3176	CLIP-seq
MIRT1986501	hsa-miR-326	CLIP-seq
MIRT1986502	hsa-miR-330-5p	CLIP-seq
MIRT1986503	hsa-miR-3655	CLIP-seq
MIRT1986504	hsa-miR-378	CLIP-seq
MIRT1986505	hsa-miR-378b	CLIP-seq
MIRT1986506	hsa-miR-378c	CLIP-seq
MIRT1986507	hsa-miR-378d	CLIP-seq
MIRT1986508	hsa-miR-378e	CLIP-seq
MIRT1986509	hsa-miR-378f	CLIP-seq
MIRT1986510	hsa-miR-378h	CLIP-seq
MIRT1986511	hsa-miR-378i	CLIP-seq
MIRT1986512	hsa-miR-3922-3p	CLIP-seq
MIRT1986513	hsa-miR-422a	CLIP-seq
MIRT1986514	hsa-miR-4326	CLIP-seq
MIRT1986515	hsa-miR-4520a-3p	CLIP-seq
MIRT1986516	hsa-miR-4638-3p	CLIP-seq
MIRT1986517	hsa-miR-578	CLIP-seq
MIRT2221039	hsa-miR-1285	CLIP-seq
MIRT2221040	hsa-miR-2115	CLIP-seq
MIRT2221041	hsa-miR-296-5p	CLIP-seq
MIRT2221042	hsa-miR-3074-5p	CLIP-seq
MIRT2221043	hsa-miR-3187-5p	CLIP-seq
MIRT2221044	hsa-miR-3194-3p	CLIP-seq
MIRT2221045	hsa-miR-3194-5p	CLIP-seq
MIRT1986501	hsa-miR-326	CLIP-seq
MIRT1986502	hsa-miR-330-5p	CLIP-seq
MIRT2221046	hsa-miR-370	CLIP-seq
MIRT2221047	hsa-miR-378g	CLIP-seq
MIRT2221048	hsa-miR-3943	CLIP-seq
MIRT2221049	hsa-miR-4486	CLIP-seq
MIRT2221050	hsa-miR-516a-3p	CLIP-seq
MIRT2221051	hsa-miR-612	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
ARNT	Activation	8663540
EP300	Activation	20368990
GATA1	Activation	16471262
GATA1	Repression	8677751
GATA2	Repression	8677751
GATA3	Repression	8677751
HIF1A	Activation	8089148;8663540
HIF1A	Unknown	16281953
NCOA1	Activation	20368990
NCOA3	Activation	20368990
SMAD3	Unknown	14741200
SMAD4	Unknown	14741200
SP1	Activation	14741200

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IMP	16497104
GO:0001666	Process	Response to hypoxia	IEA
GO:0001666	Process	Response to hypoxia	IEA
GO:0005125	Function	Cytokine activity	IBA
GO:0005125	Function	Cytokine activity	IDA	9774108, 28283061
GO:0005128	Function	Erythropoietin receptor binding	IBA
GO:0005128	Function	Erythropoietin receptor binding	IEA
GO:0005128	Function	Erythropoietin receptor binding	IMP	28283061
GO:0005179	Function	Hormone activity	IBA
GO:0005179	Function	Hormone activity	IDA	9722506
GO:0005179	Function	Hormone activity	IEA
GO:0005515	Function	Protein binding	IPI	9774108, 26481148, 29997244, 33961781
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IDA	32989016
GO:0005615	Component	Extracellular space	IDA	14569084
GO:0005615	Component	Extracellular space	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IEA
GO:0006915	Process	Apoptotic process	IEA
GO:0006950	Process	Response to stress	IEA
GO:0006953	Process	Acute-phase response	IEA
GO:0007165	Process	Signal transduction	NAS	3838366
GO:0007566	Process	Embryo implantation	IEA
GO:0007584	Process	Response to nutrient	IEA
GO:0008015	Process	Blood circulation	NAS	3838366
GO:0008284	Process	Positive regulation of cell population proliferation	IDA	9722506
GO:0008284	Process	Positive regulation of cell population proliferation	IEA
GO:0009651	Process	Response to salt stress	IEA
GO:0009986	Component	Cell surface	IDA	14569084
GO:0010523	Process	Negative regulation of calcium ion transport into cytosol	IDA	14569084
GO:0010976	Process	Positive regulation of neuron projection development	IEA
GO:0030218	Process	Erythrocyte differentiation	IBA
GO:0030218	Process	Erythrocyte differentiation	IDA	15084469
GO:0030218	Process	Erythrocyte differentiation	IEA
GO:0030218	Process	Erythrocyte differentiation	IMP	28283061
GO:0030295	Function	Protein kinase activator activity	IBA
GO:0030295	Function	Protein kinase activator activity	IEA
GO:0032496	Process	Response to lipopolysaccharide	IEA
GO:0033028	Process	Myeloid cell apoptotic process	IEA
GO:0033033	Process	Negative regulation of myeloid cell apoptotic process	IEA
GO:0033189	Process	Response to vitamin A	IEA
GO:0033574	Process	Response to testosterone	IEA
GO:0038162	Process	Erythropoietin-mediated signaling pathway	IBA
GO:0038162	Process	Erythropoietin-mediated signaling pathway	IDA	2163696, 9657743
GO:0038162	Process	Erythropoietin-mediated signaling pathway	IDA	9722506, 9774108
GO:0038162	Process	Erythropoietin-mediated signaling pathway	IMP	28283061
GO:0042104	Process	Positive regulation of activated T cell proliferation	IEA
GO:0042541	Process	Hemoglobin biosynthetic process	IEA
GO:0043066	Process	Negative regulation of apoptotic process	IEA
GO:0043161	Process	Proteasome-mediated ubiquitin-dependent protein catabolic process	IDA	11781573, 34518685
GO:0043249	Process	Erythrocyte maturation	IEA
GO:0043627	Process	Response to estrogen	IEA
GO:0044297	Component	Cell body	IEA
GO:0045666	Process	Positive regulation of neuron differentiation	IEA
GO:0045893	Process	Positive regulation of DNA-templated transcription	IDA	9722506
GO:0046579	Process	Positive regulation of Ras protein signal transduction	IDA	9722506
GO:0048678	Process	Response to axon injury	IEA
GO:0051602	Process	Response to electrical stimulus	IEA
GO:0055093	Process	Response to hyperoxia	IEA
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IEA
GO:0070555	Process	Response to interleukin-1	IEA
GO:0071474	Process	Cellular hyperosmotic response	IDA	14569084
GO:0071548	Process	Response to dexamethasone	IEA
GO:0097696	Process	Cell surface receptor signaling pathway via STAT	IBA
GO:0097696	Process	Cell surface receptor signaling pathway via STAT	IDA	9722506
GO:1902219	Process	Negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress	IDA	14569084
GO:1902251	Process	Negative regulation of erythrocyte apoptotic process	IDA	14569084

Other IDs

• MIM: 133170
• HGNC: 3415
• e!Ensembl: ENSG00000130427

Protein

• UniProt ID: P01588
• Protein name: Erythropoietin (Epoetin)
• Protein function: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass (PubMed:28283061). Binds to EPOR leading to EPOR dimerization and JAK2 activation th
• PDB: 1BUY, 1CN4, 1EER
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00758	EPO_TPO	31 → 192	Erythropoietin/thrombopoietin	Domain

• Tissue specificity: TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals. {ECO:0000269|PubMed:3865178}.
• Sequence:

  MGVHECPAWLWLLLSLLSLPLGLPVLGAPPRLICDSRVLERYLLEAKEAENITTGCAEHC
  SLNENITVPDTKVNFYAWKRMEVGQQAVEVWQGLALLSEAVLRGQALLVNSSQPWEPLQL
  HVDKAVSGLRSLTTLLRALGAQKEAISPPDAASAAPLRTITADTFRKLFRVYSNFLRGKL
  KLYTGEACRTGDR

• Sequence length: 193

Pathways

KEGG:

Cytokine-cytokine receptor interaction
HIF-1 signaling pathway
Hormone signaling
Efferocytosis
PI3K-Akt signaling pathway
JAK-STAT signaling pathway
Hematopoietic cell lineage
Pathways in cancer

Reactome:

Regulation of gene expression by Hypoxia-inducible Factor
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)
Erythropoietin activates RAS

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Diamond-Blackfan anemia-like	Pathogenic	rs1358275550	RCV000590853	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Erythrocytosis, familial, 5	Pathogenic	rs1554393463, rs1554393458	RCV000590858 RCV000590862	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMERS DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANEMIA	—	CTD, Disgenet, GWAS catalog CTD, Disgenet, GWAS catalog CTD, Disgenet, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANEMIA, HEMOLYTIC	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT SECONDARY POLYCYTHEMIA	—	CTD, Disgenet, Orphanet CTD, Disgenet, Orphanet CTD, Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BETA THALASSEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BETA-THALASSEMIA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BRAIN INJURIES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CALCINOSIS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARDIOMYOPATHIES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CENTRAL NERVOUS SYSTEM DISEASES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC ISCHEMIC HEART DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COGNITION DISORDERS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGESTIVE HEART FAILURE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERIOSCLEROSIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERY DISEASE	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY HEART DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CROHN'S DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEGENERATIVE DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DELIRIUM, DEMENTIA, AMNESTIC, COGNITIVE DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETIC ANGIOPATHIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETIC NEUROPATHIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETIC PERIPHERAL ANGIOPATHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETIC RETINOPATHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DISORDERS OF PORPHYRIN METABOLISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPO-related disorder	Uncertain significance; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GASTRIC ULCER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLAUCOMA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART DISEASES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART FAILURE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART SEPTAL DEFECTS, VENTRICULAR	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOLYTIC-UREMIC SYNDROME	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSION	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSIVE DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INFLAMMATORY BOWEL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KIDNEY DISEASES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KIDNEY FAILURE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KIDNEY FAILURE, ACUTE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KIDNEY FAILURE, CHRONIC	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MELANOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microvascular complications of diabetes, susceptibility to, 2	risk factor	ClinVar CTD, ClinVar CTD, ClinVar	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MYELODYSPLASTIC SYNDROMES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL INFARCTION	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL ISCHEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEPHROTIC SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEGENERATIVE DISEASES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEGENERATIVE DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PANCYTOPENIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARANEOPLASTIC SYNDROMES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARKINSON DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POLYCYTHEMIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POLYNEUROPATHIES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POLYNEUROPATHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PRIMARY CARDIOMYOPATHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SARCOMA, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
STATUS EPILEPTICUS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THROMBOCYTOPENIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THROMBOSIS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THYROID NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TRANSIENT ISCHEMIC ATTACK	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ULCERATIVE COLITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
UREMIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VASCULAR DISEASES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VENOUS THROMBOSIS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VENTRICULAR FIBRILLATION	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VENTRICULAR SEPTAL DEFECTS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations