EPAS1 Gene (Protein Coding)

Endothelial PAS Domain Protein 1

GC02P046293
GIFtS:
49
This gene encodes a transcription factor involved in the induction of genes regulated by oxygen, which is induced as oxygen levels fall. The encoded protein contains a basic-helix-loop-helix domain protein dimerization domain as well as a domain found in proteins in signal transduction pathways which respond to oxygen levels. Mutations in this gene are associated with erythrocy... See more...

Aliases for EPAS1 Gene

Aliases for EPAS1 Gene

  • Endothelial PAS Domain Protein 1 2 3 5
  • Endothelial PAS Domain-Containing Protein 1 3 4
  • Class E Basic Helix-Loop-Helix Protein 73 3 4
  • Basic-Helix-Loop-Helix-PAS Protein MOP2 3 4
  • PAS Domain-Containing Protein 2 3 4
  • Member Of PAS Protein 2 3 4
  • HIF-1-Alpha-Like Factor 3 4
  • HIF-2-Alpha 3 4
  • HIF2-Alpha 3 4
  • BHLHe73 3 4
  • EPAS-1 3 4
  • HIF2A 3 4
  • PASD2 3 4
  • MOP2 3 4
  • HLF 3 4
  • Hypoxia-Inducible Factor 2 Alpha 3
  • Hypoxia-Inducible Factor 2-Alpha 4
  • HIF-1 Alpha-Like Factor 2
  • HIF-1alpha-Like Factor 3
  • BHLHE73 4
  • ECYT4 3

External Ids for EPAS1 Gene

Previous GeneCards Identifiers for EPAS1 Gene

  • GC02P046542
  • GC02P046693
  • GC02P046499
  • GC02P046436
  • GC02P046262

Summaries for EPAS1 Gene

Entrez Gene Summary for EPAS1 Gene

  • This gene encodes a transcription factor involved in the induction of genes regulated by oxygen, which is induced as oxygen levels fall. The encoded protein contains a basic-helix-loop-helix domain protein dimerization domain as well as a domain found in proteins in signal transduction pathways which respond to oxygen levels. Mutations in this gene are associated with erythrocytosis familial type 4. [provided by RefSeq, Nov 2009]

CIViC Summary for EPAS1 Gene

GeneCards Summary for EPAS1 Gene

EPAS1 (Endothelial PAS Domain Protein 1) is a Protein Coding gene. Diseases associated with EPAS1 include Erythrocytosis, Familial, 4 and Sporadic Pheochromocytoma. Among its related pathways are Cellular Senescence (REACTOME) and Developmental Biology. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and protein heterodimerization activity. An important paralog of this gene is HIF1A.

UniProtKB/Swiss-Prot Summary for EPAS1 Gene

  • Transcription factor involved in the induction of oxygen regulated genes. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation requires recruitment of transcriptional coactivators such as CREBBP and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD (By similarity).

Gene Wiki entry for EPAS1 Gene

Additional gene information for EPAS1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for EPAS1 Gene

Genomics for EPAS1 Gene

GeneHancer (GH) Regulatory Elements for EPAS1 Gene

Promoters and enhancers for EPAS1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around EPAS1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the EPAS1 gene promoter:
  • HEN1
  • HNF-1
  • HNF-1A
  • IRF-1
  • PPAR-gamma1
  • PPAR-gamma2
  • Sp1

Genomic Locations for EPAS1 Gene

Genomic Locations for EPAS1 Gene
chr2:46,293,667-46,386,703
(GRCh38/hg38)
Size:
93,037 bases
Orientation:
Plus strand
chr2:46,520,806-46,613,842
(GRCh37/hg19)
Size:
93,037 bases
Orientation:
Plus strand

Genomic View for EPAS1 Gene

Genes around EPAS1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
EPAS1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for EPAS1 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for EPAS1 Gene

Proteins for EPAS1 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for EPAS1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99814-EPAS1_HUMAN
    Recommended name:
    Endothelial PAS domain-containing protein 1
    Protein Accession:
    Q99814
    Secondary Accessions:
    • Q86VA2
    • Q99630

    Protein attributes for EPAS1 Gene

    Size:
    870 amino acids
    Molecular mass:
    96459 Da
    Quaternary structure:
    • Interacts with HIF3A (By similarity). Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (PubMed:16181639). Interacts with CREBBP (By similarity). Interacts with EGLN1. Interacts with VHL (PubMed:19208626).

    Three dimensional structures from OCA and Proteopedia for EPAS1 Gene

neXtProt entry for EPAS1 Gene

Protein Expression for EPAS1 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for EPAS1 Gene

  • In normoxia, is probably hydroxylated on Pro-405 and Pro-531 by EGLN1/PHD1, EGLN2/PHD2 and/or EGLN3/PHD3. The hydroxylated prolines promote interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation. Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization (By similarity).
  • In normoxia, is hydroxylated on Asn-847 by HIF1AN thus probably abrogating interaction with CREBBP and EP300 and preventing transcriptional activation.
  • Phosphorylated on multiple sites in the CTAD.
  • The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for EPAS1 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for EPAS1 Gene

Domains & Families for EPAS1 Gene

Gene Families for EPAS1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for EPAS1 Gene

Blocks:
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for EPAS1 Gene

GenScript: Design optimal peptide antigens:
  • PAS domain-containing protein 2 (EPAS1_HUMAN)
genes like me logo Genes that share domains with EPAS1: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for EPAS1 Gene

Function for EPAS1 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for EPAS1 Gene

UniProtKB/Swiss-Prot Function:
Transcription factor involved in the induction of oxygen regulated genes. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation requires recruitment of transcriptional coactivators such as CREBBP and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD (By similarity).

Phenotypes From GWAS Catalog for EPAS1 Gene

Gene Ontology (GO) - Molecular Function for EPAS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific NAS 19274049
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IEA --
GO:0003677 DNA binding IGI 9000051
GO:0003700 DNA-binding transcription factor activity IEA --
GO:0005515 protein binding IPI 11018023
genes like me logo Genes that share ontologies with EPAS1: view
genes like me logo Genes that share phenotypes with EPAS1: view

Human Phenotype Ontology for EPAS1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for EPAS1 Gene

MGI Knock Outs for EPAS1:

Animal Model Products

CRISPR Products

Transcription Factor Targets for EPAS1 Gene

Selected GeneGlobe predicted Target genes for EPAS1
Targeted motifs for EPAS1 Gene
HOMER Transcription Factor Regulatory Elements motif EPAS1
  • Consensus sequence: GCACGTACCC Submotif: canonical Cell Type: 785_O GEO ID: GSE34871

Clone Products

  • Addgene plasmids for EPAS1

No data available for Enzyme Numbers (IUBMB) for EPAS1 Gene

Localization for EPAS1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for EPAS1 Gene

Nucleus. Nucleus speckle. Note=Colocalizes with HIF3A in the nucleus and speckles. {ECO:0000250 UniProtKB:P97481}.

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 EPAS1 gene
Compartment Confidence
nucleus 5
cytosol 5
extracellular 1
mitochondrion 1
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (4)
  • Cytosol (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for EPAS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA 21873635
GO:0005654 nucleoplasm TAS --
GO:0005667 transcription factor complex IPI 9576906
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with EPAS1: view

Pathways & Interactions for EPAS1 Gene

genes like me logo Genes that share pathways with EPAS1: view

SIGNOR curated interactions for EPAS1 Gene

Activates:

Gene Ontology (GO) - Biological Process for EPAS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001525 angiogenesis IEA --
GO:0001666 response to hypoxia IEA,IDA 11782478
GO:0001892 embryonic placenta development IEA --
GO:0001974 blood vessel remodeling IEA --
GO:0002027 regulation of heart rate IEA --
genes like me logo Genes that share ontologies with EPAS1: view

Drugs & Compounds for EPAS1 Gene

Products:

  1. Drug

(4) Drugs for EPAS1 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(5) Additional Compounds for EPAS1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with EPAS1: view

Transcripts for EPAS1 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for EPAS1 Gene

(1) REFSEQ mRNAs :
(8) Additional mRNA sequences :
(613) Selected AceView cDNA sequences:
(10) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for EPAS1

Alternative Splicing Database (ASD) splice patterns (SP) for EPAS1 Gene

No ASD Table

Relevant External Links for EPAS1 Gene

GeneLoc Exon Structure for
EPAS1
ECgene alternative splicing isoforms for
EPAS1

Expression for EPAS1 Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for EPAS1 Gene

mRNA expression in normal human tissues for EPAS1 Gene
mRNA expression by GTEx for EPAS1 GenemRNA expression by BioGPS for EPAS1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for EPAS1 Gene

This gene is overexpressed in Lung (x5.2).

Protein differential expression in normal tissues from HIPED for EPAS1 Gene

This gene is overexpressed in Placenta (65.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for EPAS1 Gene



Protein tissue co-expression partners for EPAS1 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of EPAS1 Gene:

EPAS1

SOURCE GeneReport for Unigene cluster for EPAS1 Gene:

Hs.468410

mRNA Expression by UniProt/SwissProt for EPAS1 Gene:

Q99814-EPAS1_HUMAN
Tissue specificity: Expressed in most tissues, with highest levels in placenta, lung and heart. Selectively expressed in endothelial cells.

Evidence on tissue expression from TISSUES for EPAS1 Gene

  • Nervous system(4.7)
  • Lung(4.6)
  • Eye(4.5)
  • Heart(3)
  • Kidney(2.8)
  • Liver(2.7)
  • Adrenal gland(2.5)
  • Muscle(2.5)
  • Pancreas(2.4)
  • Intestine(2.3)
  • Skin(2)
  • Thyroid gland(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for EPAS1 Gene

Germ Layers:
  • mesoderm
Systems:
  • cardiovascular
Regions:
Head and neck:
  • ear
Thorax:
  • heart
General:
  • blood
  • blood vessel
  • red blood cell
genes like me logo Genes that share expression patterns with EPAS1: view

Orthologs for EPAS1 Gene

This gene was present in the common ancestor of animals.

Orthologs for EPAS1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia EPAS1 33 32
  • 99.73 (n)
 OneToOne
dog
(Canis familiaris)
 Mammalia EPAS1 33 32
  • 88.63 (n)
 OneToOne
cow
(Bos Taurus)
 Mammalia EPAS1 33 32
  • 87.42 (n)
 OneToOne
mouse
(Mus musculus)
 Mammalia Epas1 17 33 32
  • 85.58 (n)
rat
(Rattus norvegicus)
 Mammalia Epas1 32
  • 84.62 (n)
oppossum
(Monodelphis domestica)
 Mammalia EPAS1 33
  • 81 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia EPAS1 33
  • 55 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves EPAS1 33 32
  • 72.4 (n)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia EPAS1 33
  • 74 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia epas1 32
  • 67.17 (n)
zebrafish
(Danio rerio)
 Actinopterygii epas1b 33 32
  • 64.79 (n)
 OneToMany
epas1a 33
  • 56 (a)
 OneToMany
fruit fly
(Drosophila melanogaster)
 Insecta sima 33 34
  • 17 (a)
 OneToMany
worm
(Caenorhabditis elegans)
 Secernentea hif-1 33
  • 21 (a)
 OneToMany
sea squirt
(Ciona savignyi)
 Ascidiacea -- 33
  • 28 (a)
 OneToMany
Species where no ortholog for EPAS1 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)
  • 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)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • 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)

Evolution for EPAS1 Gene

ENSEMBL:
Gene Tree for EPAS1 (if available)
TreeFam:
Gene Tree for EPAS1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for EPAS1: view image

Paralogs for EPAS1 Gene

Paralogs for EPAS1 Gene

(4) SIMAP similar genes for EPAS1 Gene using alignment to 4 proteins:

  • EPAS1_HUMAN
  • C9J9N2_HUMAN
  • Q53SM6_HUMAN
  • Q53ST6_HUMAN
genes like me logo Genes that share paralogs with EPAS1: view

Variants for EPAS1 Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations from dbSNP and Humsavar for EPAS1 Gene

SNP ID Clin Chr 02 pos Variation AA Info Type
rs10495933 benign, Familial erythrocytosis 46,385,513(+) G/A 3_prime_UTR_variant
rs111426869 likely-benign, Familial erythrocytosis 46,385,701(+) /G 3_prime_UTR_variant
rs112031193 uncertain-significance, Familial erythrocytosis 46,386,033(+) C/A/G/T 3_prime_UTR_variant
rs112500820 likely-benign, Familial erythrocytosis 46,386,274(+) C/T 3_prime_UTR_variant
rs114927662 likely-benign, Familial erythrocytosis 46,386,384(+) G/A 3_prime_UTR_variant

Structural Variations from Database of Genomic Variants (DGV) for EPAS1 Gene

Variant ID Type Subtype PubMed ID
dgv149e55 CNV loss 17911159
esv2759046 CNV loss 17122850
esv3583779 CNV loss 25503493
nsv1132485 CNV duplication 24896259
nsv2714 CNV insertion 18451855
nsv581743 CNV loss 21841781

Variation tolerance for EPAS1 Gene

Residual Variation Intolerance Score: 23.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.46; 64.15% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for EPAS1 Gene

Human Gene Mutation Database (HGMD)
EPAS1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
EPAS1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for EPAS1 Gene

Disorders for EPAS1 Gene

MalaCards: The human disease database

(18) MalaCards diseases for EPAS1 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
erythrocytosis, familial, 4
  • ecyt4
sporadic pheochromocytoma
multiple paragangliomas associated with polycythemia
  • multiple paragangliomas associated with erythrocytosis
sporadic secreting paraganglioma
autosomal dominant secondary polycythemia
  • autosomal dominant secondary erythrocytosis
- elite association - COSMIC cancer census association via MalaCards
Search EPAS1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

EPAS1_HUMAN
  • Erythrocytosis, familial, 4 (ECYT4) [MIM:611783]: An autosomal dominant disorder characterized by elevated serum hemoglobin and hematocrit, and normal platelet and leukocyte counts. {ECO:0000269 PubMed:18184961, ECO:0000269 PubMed:18378852, ECO:0000269 PubMed:19208626, ECO:0000269 PubMed:22367913}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for EPAS1

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 EPAS1: view

No data available for Genatlas for EPAS1 Gene

Publications for EPAS1 Gene

  1. Novel exon 12 mutations in the HIF2A gene associated with erythrocytosis. (PMID: 18378852) Percy MJ … Lee FS (Blood 2008) 2 3 4 23 43 56
  2. Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway. (PMID: 9079689) Hogenesch JB … Bradfield CA (The Journal of biological chemistry 1997) 2 3 4 23 56
  3. Genetic contributions to the development of retinopathy of prematurity. (PMID: 18787502) Mohamed S … Dagle JM (Pediatric research 2009) 3 23 43 56
  4. The EPAS1 gene influences the aerobic-anaerobic contribution in elite endurance athletes. (PMID: 16208515) Henderson J … Yu B (Human genetics 2005) 3 23 43 56
  5. Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. (PMID: 9000051) Tian H … Russell DW (Genes & development 1997) 2 3 4 56

ExternalLinks

View latest publications for EPAS1 gene in Mastermind

Products for EPAS1 Gene

  • Addgene plasmids for EPAS1

Sources for EPAS1 Gene