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    EGLN2 egl-9 family hypoxia inducible factor 2 [ Homo sapiens (human) ]

    Gene ID: 112398, updated on 10-Dec-2024

    Summary

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    Official Symbol
    EGLN2provided by HGNC
    Official Full Name
    egl-9 family hypoxia inducible factor 2provided by HGNC
    Primary source
    HGNC:HGNC:14660
    See related
    Ensembl:ENSG00000269858 MIM:606424; AllianceGenome:HGNC:14660
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    EIT6; PHD1; EIT-6; HPH-1; HPH-3; HIFPH1; HIF-PH1
    Summary
    The hypoxia inducible factor (HIF) is a transcriptional complex that is involved in oxygen homeostasis. At normal oxygen levels, the alpha subunit of HIF is targeted for degration by prolyl hydroxylation. This gene encodes an enzyme responsible for this post-translational modification. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream RAB4B (RAB4B, member RAS oncogene family) gene. [provided by RefSeq, Feb 2011]
    Expression
    Broad expression in testis (RPKM 61.2), spleen (RPKM 33.0) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See EGLN2 in Genome Data Viewer
    Location:
    19q13.2
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (40799191..40808434)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (43619870..43629113)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (41305096..41314339)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10647 Neighboring gene MIA-RAB4B readthrough (NMD candidate) Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10648 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14667 Neighboring gene RAB4B-EGLN2 readthrough (NMD candidate) Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:41285223-41285754 Neighboring gene MIA SH3 domain containing Neighboring gene RAB4B, member RAS oncogene family Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10649 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10650 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:41306857-41307531 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:41307710-41308450 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14668 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:41314255-41314754 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:41317625-41318515 Neighboring gene cytochrome P450 family 2 subfamily T member 1, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14669 Neighboring gene cytochrome P450 family 2 subfamily F member 2, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:41332287-41332788

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. An insertion/deletion polymorphism within the proximal promoter of EGLN2 is associated with susceptibility for gastric cancer in the Chinese population. Wang J, et al. Genet Test Mol Biomarkers, 2014 Apr. PMID 24517638, Free PMC Article
    2. Soluble nickel inhibits HIF-prolyl-hydroxylases creating persistent hypoxic signaling in A549 cells. Davidson TL, et al. Mol Carcinog, 2006 Jul. PMID 16649251
    3. Somatic pairing of chromosome 19 in renal oncocytoma is associated with deregulated EGLN2-mediated [corrected] oxygen-sensing response. Koeman JM, et al. PLoS Genet, 2008 Sep 5. PMID 18773095, Free PMC Article
    4. Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro. Pan Y, et al. Mol Cell Biol, 2007 Feb. PMID 17101781, Free PMC Article
    5. Association of EGLN2 rs10680577 Polymorphism with the Risk and Clinicopathological Features of Patients with Prostate Cancer. Rahimi N, et al. Asian Pac J Cancer Prev, 2020 May 1. PMID 32458625, Free PMC Article

    See all (113) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. VHL suppresses autophagy and tumor growth through PHD1-dependent Beclin1 hydroxylation.
      Title: VHL suppresses autophagy and tumor growth through PHD1-dependent Beclin1 hydroxylation.
    2. Loss of prolyl hydroxylase 1 and 2 in SM22alpha-expressing cells prevents Hypoxia-Induced pulmonary hypertension.
      Title: Loss of prolyl hydroxylase 1 and 2 in SM22α-expressing cells prevents Hypoxia-Induced pulmonary hypertension.
    3. Association of EGLN2 rs10680577 Polymorphism with the Risk and Clinicopathological Features of Patients with Prostate Cancer.
      Title: Association of EGLN2 rs10680577 Polymorphism with the Risk and Clinicopathological Features of Patients with Prostate Cancer.
    4. Meta-analysis showed that EGLN2 rs10680577 polymorphism was significantly associated with cancer risk.
      Title: Association between an indel polymorphism within the distal promoter of EGLN2 and cancer risk: An updated meta-analysis.
    5. Study consistently found that hypermethylation at cg25923056-EGLN2 downregulated the corresponding gene EGLN2 expression in lung adenocarcinomas (LUAD) tumor tissues. Meanwhile, EGLN2 expression was negatively correlated with HIF1A expression in tumor tissues and significantly interacted with HIF1A expression on overall survival.
      Title: EGLN2 DNA methylation and expression interact with HIF1A to affect survival of early-stage NSCLC.
    6. Adenylosuccinate lyase (ADSL) is an EglN2 hydroxylase substrate in triple negative breast cancer.
      Title: Prolyl hydroxylase substrate adenylosuccinate lyase is an oncogenic driver in triple negative breast cancer.
    7. The authors did not detect prolyl-hydroxylase activity on any reported non-HIF protein or peptide, using conditions supporting robust HIF-alpha hydroxylation.
      Title: Lack of activity of recombinant HIF prolyl hydroxylases (PHDs) on reported non-HIF substrates.
    8. TCF7L2 positively regulated aerobic glycolysis by suppressing Egl-9 family hypoxia inducible factor 2 (EGLN2), leading to upregulation of hypoxia inducible factor 1 alpha subunit (HIF-1alpha).
      Title: TCF7L2 positively regulates aerobic glycolysis via the EGLN2/HIF-1α axis and indicates prognosis in pancreatic cancer.
    9. High PHD1 expression is associated with liver fibrosis.
      Title: Loss of Prolyl-Hydroxylase 1 Protects against Biliary Fibrosis via Attenuated Activation of Hepatic Stellate Cells.
    10. 4-bp Insertion/deletion Polymorphism within the Promoter of EGLN2 is associated with breast cancer.
      Title: Detection of a 4-bp Insertion/deletion Polymorphism within the Promoter of EGLN2 Using Mismatch PCR-RFLP and Its Association with Susceptibility to Breast Cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (59)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13.
    EBI GWAS Catalog
    Genome-wide meta-analyses identify multiple loci associated with smoking behavior.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Readthrough RAB4B-EGLN2

    Readthrough gene: RAB4B-EGLN2, Included gene: RAB4B

    Homology

    Clone Names

    • FLJ95603, DKFZp434E026

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 2-oxoglutarate-dependent dioxygenase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables L-ascorbic acid binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ferrous iron binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ferrous iron binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ferrous iron binding NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables hypoxia-inducible factor-proline dioxygenase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables oxygen sensor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables peptidyl-proline 4-dioxygenase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables peptidyl-proline 4-dioxygenase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cell redox homeostasis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to hypoxia IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in estrogen receptor signaling pathway NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in peptidyl-proline hydroxylation to 4-hydroxy-L-proline IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of protein catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of cell growth NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of neuron apoptotic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of neuron apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in response to hypoxia IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    prolyl hydroxylase EGLN2
    Names
    HIF-prolyl hydroxylase 1
    egl nine homolog 2
    estrogen-induced tag 6
    hypoxia-inducible factor prolyl hydroxylase 1
    prolyl hydroxylase domain-containing protein 1
    NP_444274.1
    NP_542770.2

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_053046.4 → NP_444274.1  prolyl hydroxylase EGLN2

      See identical proteins and their annotated locations for NP_444274.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) differs in the 5' UTR compared to variant 3. Both variants 1 and 3 utilize alternative start codons that result in expression of two isoforms known as PHD1p43 and PHD1p40.
      Source sequence(s)
      AA994838, BC036051, DB049419
      Consensus CDS
      CCDS12567.1
      UniProtKB/Swiss-Prot
      A8K5S0, Q8WWY4, Q96KS0, Q9BV14
      Related
      ENSP00000385253.1, ENST00000406058.6
      Conserved Domains (1) summary
      smart00702
      Location:199 → 375
      P4Hc; Prolyl 4-hydroxylase alpha subunit homologues

    2. NM_080732.4 → NP_542770.2  prolyl hydroxylase EGLN2

      See identical proteins and their annotated locations for NP_542770.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) represents the longer transcript. Both variants 1 and 3 utilize alternative start codons that result in expression of two isoforms known as PHD1p43 and PHD1p40.
      Source sequence(s)
      AA994838, BC001723, DA300182
      Consensus CDS
      CCDS12567.1
      UniProtKB/Swiss-Prot
      A8K5S0, Q8WWY4, Q96KS0, Q9BV14
      Related
      ENSP00000307080.3, ENST00000303961.9
      Conserved Domains (1) summary
      smart00702
      Location:199 → 375
      P4Hc; Prolyl 4-hydroxylase alpha subunit homologues

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      40799191..40808434
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      43619870..43629113
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_017555.1: Suppressed sequence

      Description
      NM_017555.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96KS0.1 GenPept UniProtKB/Swiss-Prot:Q96KS0

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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