EPOR

erythropoietin receptor, the group of Fibronectin type III domain containing

Basic information

Region (hg38): 19:11377206-11384342

Links

ENSG00000187266 ∙ NCBI:2057 ∙ OMIM:133171 ∙ HGNC:3416 ∙ Uniprot:P19235 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary familial polycythemia due to EPO receptor mutation (Strong), mode of inheritance: AD
• primary familial polycythemia due to EPO receptor mutation (Supportive), mode of inheritance: AD
• primary familial polycythemia due to EPO receptor mutation (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Erythrocytosis, familial, 1	AD	Hematologic	Phlebotomy can be used to maintain the hematocrit value in the desired range	Hematologic	4052634; 1954391; 093406; 9292543; 9649565; 20700488; 21437635

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPOR gene.

• Primary familial polycythemia due to EPO receptor mutation (54 variants)
• not provided (29 variants)
• Inborn genetic diseases (18 variants)
• not specified (2 variants)
• Familial erythrocytosis (1 variants)
• Acute megakaryoblastic leukemia without down syndrome (1 variants)
• Intellectual disability-hypotonic facies syndrome, X-linked, 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPOR gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	8	6	20
missense			24	9	6	39
nonsense		2	1			3
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1	2	4
non coding			8		11	19
Total	0	3	39	17	23

Highest pathogenic variant AF is 0.0000394

Variants in EPOR

This is a list of pathogenic ClinVar variants found in the EPOR region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-11377208-T-C		Primary familial polycythemia due to EPO receptor mutation	Uncertain significance (Jan 13, 2018)
19-11377300-G-T		Primary familial polycythemia due to EPO receptor mutation	Benign (Jan 12, 2018)
19-11377314-C-T		Primary familial polycythemia due to EPO receptor mutation	Benign (Jan 12, 2018)
19-11377365-G-A		Primary familial polycythemia due to EPO receptor mutation	Uncertain significance (Jan 12, 2018)
19-11377407-T-C		Primary familial polycythemia due to EPO receptor mutation	Benign (Jan 13, 2018)
19-11377480-C-T		Primary familial polycythemia due to EPO receptor mutation	Benign (Jan 12, 2018)
19-11377559-G-A		Primary familial polycythemia due to EPO receptor mutation	Benign (Jan 13, 2018)
19-11377796-C-CAA		Familial erythrocytosis	Uncertain significance (Jun 14, 2016)
19-11377949-C-T		Primary familial polycythemia due to EPO receptor mutation	Benign (Jan 13, 2018)
19-11377952-A-G		Primary familial polycythemia due to EPO receptor mutation	Benign (Jan 13, 2018)
19-11378044-A-G		Primary familial polycythemia due to EPO receptor mutation	Uncertain significance (Jan 12, 2018)
19-11378049-G-A		Primary familial polycythemia due to EPO receptor mutation • Intellectual disability-hypotonic facies syndrome, X-linked, 1	Benign/Likely benign (Dec 18, 2023)
19-11378051-T-C		Primary familial polycythemia due to EPO receptor mutation • not specified	Benign/Likely benign (Jan 08, 2024)
19-11378055-A-G		Primary familial polycythemia due to EPO receptor mutation	Likely benign (Jan 13, 2018)
19-11378057-T-C		Inborn genetic diseases	Uncertain significance (Sep 26, 2022)
19-11378067-C-T		Primary familial polycythemia due to EPO receptor mutation • Inborn genetic diseases	Likely benign (Oct 05, 2021)
19-11378083-G-A		Primary familial polycythemia due to EPO receptor mutation	Likely benign (Jan 13, 2018)
19-11378084-G-A		Primary familial polycythemia due to EPO receptor mutation	Benign (Jan 13, 2018)
19-11378087-C-G		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
19-11378113-A-G		Primary familial polycythemia due to EPO receptor mutation	Benign (May 03, 2022)
19-11378149-G-C		Primary familial polycythemia due to EPO receptor mutation	Uncertain significance (-)
19-11378170-A-G			Benign (Dec 07, 2023)
19-11378177-A-C		Inborn genetic diseases	Uncertain significance (Feb 23, 2023)
19-11378194-C-T		Primary familial polycythemia due to EPO receptor mutation	Affects (Feb 01, 1998)
19-11378195-C-T		Primary familial polycythemia due to EPO receptor mutation • Acute megakaryoblastic leukemia without down syndrome	Likely pathogenic (Sep 01, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPOR	protein_coding	protein_coding	ENST00000222139	8	6783

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0101	0.988	125710	0	36	125746	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.14	238	293	0.813	0.0000143	3209
Missense in Polyphen		55	87.472	0.62877		1050
Synonymous	-0.262	136	132	1.03	0.00000663	1097
Loss of Function	2.72	7	20.2	0.347	8.72e-7	219

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000493	0.000477
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000470	0.0000462
European (Non-Finnish)	0.000142	0.000141
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.000175	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for erythropoietin. Mediates erythropoietin- induced erythroblast proliferation and differentiation. Upon EPO stimulation, EPOR dimerizes triggering the JAK2/STAT5 signaling cascade. In some cell types, can also activate STAT1 and STAT3. May also activate the LYN tyrosine kinase.
• Disease: DISEASE: Erythrocytosis, familial, 1 (ECYT1) [MIM:133100]: An autosomal dominant disorder characterized by increased serum red blood cell mass, elevated hemoglobin and hematocrit, hypersensitivity of erythroid progenitors to erythropoietin, erythropoietin low serum levels, and no increase in platelets nor leukocytes. It has a relatively benign course and does not progress to leukemia. {ECO:0000269|PubMed:8506290, ECO:0000269|PubMed:8608241}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);JAK-STAT-Core;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;EPO Receptor Signaling;erythropoietin mediated neuroprotection through nf-kb;JAK STAT MolecularVariation 1;KitReceptor;epo signaling pathway;JAK STAT MolecularVariation 2;JAK STAT pathway and regulation;EPO signaling;EPO signaling pathway;Signaling events mediated by Stem cell factor receptor (c-Kit) (Consensus)

Intolerance Scores

• loftool: 0.238
• rvis_EVS: 0.78
• rvis_percentile_EVS: 87.14

Haploinsufficiency Scores

• pHI: 0.593
• hipred: Y
• hipred_score: 0.552
• ghis: 0.504

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.949

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Epor
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; embryo phenotype; liver/biliary system phenotype; respiratory system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype

Zebrafish Information Network

• Gene name: epor
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: signal transduction;brain development;heart development;positive regulation of phosphatidylinositol 3-kinase signaling;erythropoietin-mediated signaling pathway;positive regulation of Ras protein signal transduction;decidualization
• Cellular component: extracellular region;plasma membrane;integral component of plasma membrane
• Molecular function: erythropoietin receptor activity;protein binding;identical protein binding