EPO
erythropoietin, the group of Receptor ligands
Basic information
Region (hg38): 7:100720468-100723700
Links
Phenotypes
GenCC
Source:
- erythrocytosis, familial, 5 (Strong), mode of inheritance: AD
- autosomal dominant secondary polycythemia (Supportive), mode of inheritance: AD
- Diamond-Blackfan anemia-like (Limited), mode of inheritance: Unknown
- erythrocytosis, familial, 5 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Erythrocytosis, familial, 5; Diamond-Blackfan anemia-like | AD/AR | Hematologic | For Erythrocytosis, phlebotomy can be used to maintain the hematocrit value in the desired range; Individuals with Diamond-Blackfan anemia-like may benefit from medical management (recombinant EPO has been described), and HSCT has been reported | Hematologic | 27651169; 28283061; 29514032 |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPO 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 | 10 | |||||
| missense | 12 | 16 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| splice region | 0 | |||||
| non coding | 9 | |||||
| Total | 0 | 0 | 14 | 14 | 8 |
Variants in EPO
This is a list of pathogenic ClinVar variants found in the EPO region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 7-100720778-C-A | not specified | Uncertain significance (Feb 06, 2024) | ||
| 7-100720818-CCACCGCGCCCGCTCTGCTCCGA-C | EPO-related disorder | Likely benign (Jul 01, 2019) | ||
| 7-100720845-G-A | EPO-related disorder | Uncertain significance (Sep 18, 2024) | ||
| 7-100720989-G-A | EPO-related disorder | Likely benign (Jun 06, 2019) | ||
| 7-100721003-C-T | EPO-related disorder | Benign (Sep 25, 2018) | ||
| 7-100721557-G-C | Uncertain significance (Mar 31, 2022) | |||
| 7-100721560-T-C | not specified | Uncertain significance (Jul 09, 2021) | ||
| 7-100721562-TC-T | Erythrocytosis, familial, 5 | Pathogenic (Mar 16, 2018) | ||
| 7-100721563-C-T | EPO-related disorder | Uncertain significance (Jul 19, 2023) | ||
| 7-100721575-TG-T | Erythrocytosis, familial, 5 | Pathogenic (Mar 16, 2018) | ||
| 7-100721598-G-A | EPO-related disorder | Benign (Dec 31, 2019) | ||
| 7-100721626-G-A | not specified | Uncertain significance (Apr 21, 2022) | ||
| 7-100721652-C-T | Benign (Jul 01, 2024) | |||
| 7-100721691-C-G | Likely benign (Dec 05, 2018) | |||
| 7-100721973-T-C | Likely benign (Dec 31, 2019) | |||
| 7-100721977-C-T | not specified | Uncertain significance (Nov 07, 2022) | ||
| 7-100722010-G-A | EPO-related disorder | Likely benign (Dec 01, 2023) | ||
| 7-100722028-T-C | not specified | Uncertain significance (Mar 13, 2023) | ||
| 7-100722039-G-A | EPO-related disorder | Benign (Dec 31, 2019) | ||
| 7-100722057-CT-C | Benign (May 27, 2021) | |||
| 7-100722521-TCACTCAC-T | Benign (May 29, 2021) | |||
| 7-100722528-C-T | Benign (May 15, 2021) | |||
| 7-100722598-G-A | Benign (May 11, 2021) | |||
| 7-100722667-G-A | Likely benign (Dec 31, 2019) | |||
| 7-100722678-C-T | Likely benign (Dec 31, 2019) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| EPO | protein_coding | protein_coding | ENST00000252723 | 5 | 2901 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0112 | 0.953 | 125737 | 0 | 9 | 125746 | 0.0000358 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.559 | 97 | 114 | 0.853 | 0.00000685 | 1201 |
| Missense in Polyphen | 28 | 38.334 | 0.73042 | 439 | ||
| Synonymous | -0.830 | 57 | 49.6 | 1.15 | 0.00000275 | 432 |
| Loss of Function | 1.82 | 5 | 11.7 | 0.426 | 7.59e-7 | 104 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000297 | 0.0000297 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000448 | 0.0000439 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000653 | 0.0000653 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- 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. {ECO:0000269|PubMed:28283061}.;
- Disease
- DISEASE: Erythrocytosis, familial, 5 (ECYT5) [MIM:617907]: An autosomal dominant disorder characterized by increased serum red blood cell mass, and 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.; DISEASE: 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.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);HIF-1 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;Regulation of Hypoxia-inducible Factor (HIF) by oxygen;Differentiation Pathway;Hematopoietic Stem Cell Differentiation;Photodynamic therapy-induced HIF-1 survival signaling;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;EPO Receptor Signaling;hypoxia-inducible factor in the cardivascular system;erythropoietin mediated neuroprotection through nf-kb;JAK STAT MolecularVariation 1;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;HIF-2-alpha transcription factor network;GPCR signaling-G alpha s Epac and ERK;epo signaling pathway;GPCR signaling-G alpha s PKA and ERK;JAK STAT pathway and regulation;EPO signaling;EPO signaling pathway;GPCR signaling-G alpha i;HIF-1-alpha transcription factor network;Signaling events mediated by Stem cell factor receptor (c-Kit)
(Consensus)
Recessive Scores
- pRec
- 0.802
Intolerance Scores
- loftool
- 0.354
- rvis_EVS
- 0.64
- rvis_percentile_EVS
- 83.78
Haploinsufficiency Scores
- pHI
- 0.397
- hipred
- Y
- hipred_score
- 0.591
- ghis
- 0.431
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.975
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Epo
- Phenotype
- muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; normal phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); 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); 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); hematopoietic system phenotype; limbs/digits/tail phenotype; skeleton phenotype; immune system phenotype; liver/biliary system phenotype; respiratory system phenotype; embryo phenotype;
Zebrafish Information Network
- Gene name
- epoa
- Affected structure
- nucleate erythrocyte
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;response to hypoxia;apoptotic process;acute-phase response;signal transduction;embryo implantation;aging;blood circulation;cell population proliferation;positive regulation of cell population proliferation;response to salt stress;regulation of signaling receptor activity;negative regulation of calcium ion transport into cytosol;positive regulation of neuron projection development;positive regulation of phosphatidylinositol 3-kinase signaling;peptidyl-serine phosphorylation;erythrocyte differentiation;activation of protein kinase activity;response to lipopolysaccharide;response to vitamin A;response to testosterone;erythropoietin-mediated signaling pathway;positive regulation of activated T cell proliferation;positive regulation of tyrosine phosphorylation of STAT protein;hemoglobin biosynthetic process;erythrocyte maturation;response to estrogen;positive regulation of transcription, DNA-templated;positive regulation of Ras protein signal transduction;response to axon injury;response to electrical stimulus;response to hyperoxia;regulation of transcription from RNA polymerase II promoter in response to hypoxia;positive regulation of ERK1 and ERK2 cascade;response to interleukin-1;cellular hyperosmotic response;response to dexamethasone;negative regulation of neuron death;negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress;negative regulation of erythrocyte apoptotic process;negative regulation of cation channel activity
- Cellular component
- extracellular region;extracellular space;cell surface;cell body
- Molecular function
- cytokine activity;erythropoietin receptor binding;hormone activity;protein binding;protein kinase activator activity