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    ALOXE3 arachidonate epidermal lipoxygenase 3 [ Homo sapiens (human) ]

    Gene ID: 59344, updated on 2-Nov-2024

    Summary

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    Official Symbol
    ALOXE3provided by HGNC
    Official Full Name
    arachidonate epidermal lipoxygenase 3provided by HGNC
    Primary source
    HGNC:HGNC:13743
    See related
    Ensembl:ENSG00000179148 MIM:607206; AllianceGenome:HGNC:13743
    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
    LI5; ARCI3; E-LOX; eLOX3; eLOX-3
    Summary
    This gene is a member of the lipoxygenase family, which are catabolized by arachidonic acid-derived compounds. The encoded enzyme is a hydroperoxide isomerase that synthesizes a unique type of epoxy alcohol (8R-hydroxy-11R,12R-epoxyeicosa-5Z,9E,14Z-trienoic acid) from 12R-hydroperoxyeicosatetraenoic acid (12R-HPETE). This epoxy alcohol can activate the the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha), which is implicated in epidermal differentiation. Loss of function of the enzyme encoded by this gene results in ichthyosis, implicating the function of this gene in the differentiation of human skin. This gene is part of a cluster of lipoxygenase genes on 17p13.1. Mutations in this gene result in nonbullous congenital ichthyosiform erythroderma (NCIE). Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]
    Expression
    Restricted expression toward skin (RPKM 14.1) See more
    Orthologs
    mouse all
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    Genomic context

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    See ALOXE3 in Genome Data Viewer
    Location:
    17p13.1
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (8095900..8118916, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (8001351..8024291, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (7999218..8022234, complement)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene arachidonate 12-lipoxygenase, 12R type Neighboring gene uncharacterized LOC107985075 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8149 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11660 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:7990062-7990810 Neighboring gene microRNA 4314 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8150 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8151 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr17:8020998-8022197 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11663 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8152 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8153 Neighboring gene tRNA-Lys (anticodon TTT) 3-5 Neighboring gene tRNA-Gln (anticodon CTG) 1-5

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. The ALOXE3 gene variants from patients with Dravet syndrome decrease gene expression and enzyme activity. Gao MM, et al. Brain Res Bull, 2021 May. PMID 33581311
    2. Identification, by homozygosity mapping, of a novel locus for autosomal recessive congenital ichthyosis on chromosome 17p, and evidence for further genetic heterogeneity. Krebsová A, et al. Am J Hum Genet, 2001 Jul. PMID 11398099, Free PMC Article
    3. Lamellar ichthyosis caused by a previously unreported homozygous ALOXE3 mutation in East Asia. Sugiura K, et al. Acta Derm Venereol, 2015 Sep. PMID 25423909
    4. Characterization of Epidermal Lipoxygenase Expression in Normal Human Skin and Tissue-Engineered Skin Substitutes. Simard-Bisson C, et al. J Histochem Cytochem, 2018 Nov. PMID 29985723, Free PMC Article
    5. Identification and association of recurrent ALOXE3 mutation with non-bullous congenital ichthyosiform erythroderma in two ethnically distinct Pakistani families. Rahman SB, et al. Congenit Anom (Kyoto), 2019 May. PMID 29935003, Free PMC Article

    See all (42) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The ALOXE3 gene variants from patients with Dravet syndrome decrease gene expression and enzyme activity.
      Title: The ALOXE3 gene variants from patients with Dravet syndrome decrease gene expression and enzyme activity.
    2. Phenotypic suppression of acral peeling skin syndrome in a patient with autosomal recessive congenital ichthyosis.
      Title: Phenotypic suppression of acral peeling skin syndrome in a patient with autosomal recessive congenital ichthyosis.
    3. Meta-Analysis of Mutations in ALOX12B or ALOXE3 Identified in a Large Cohort of 224 Patients.
      Title: Meta-Analysis of Mutations in ALOX12B or ALOXE3 Identified in a Large Cohort of 224 Patients.
    4. Variants in NIPAL4 and ALOXE3 cause autosomal recessive congenital ichthyosis in Pakistani families.
      Title: Variants in NIPAL4 and ALOXE3 cause autosomal recessive congenital ichthyosis in Pakistani families.
    5. Identification and association of recurrent ALOXE3 mutation with non-bullous congenital ichthyosiform erythroderma in two ethnically distinct Pakistani families has been reported.
      Title: Identification and association of recurrent ALOXE3 mutation with non-bullous congenital ichthyosiform erythroderma in two ethnically distinct Pakistani families.
    6. Study found that DNA methylation at cg25365794 in ALOXE3 gene is associated with urinary 8-isoprostane levels and with specific cancer outcomes. Whoever, the association between urinary 8-isoprostane levels and DNA methylation at the ALOXE3 gene may not be causal.
      Title: The associations of DNA methylation alterations in oxidative stress-related genes with cancer incidence and mortality outcomes: a population-based cohort study.
    7. Case Report: ALOXE3 mutation causing congenital ichthyosis and recurrent eczema.
      Title: Congenital Ichthyosis and Recurrent Eczema Associated with a Novel ALOXE3 Mutation.
    8. In summary, we have identified three novel sequence variants, one in TGM1 and two in ALOXE3, in three consanguineous families segregating lamellar ichthyosis and congenital ichthyosiform erythroderma types of autosomal recessive congenital ichthyosis.
      Title: Novel mutations in the genes TGM1 and ALOXE3 underlying autosomal recessive congenital ichthyosis.
    9. Case Report: homozygous ALOXE3 mutation causing autosomal recessive congenital ichthyosis.
      Title: Lamellar ichthyosis caused by a previously unreported homozygous ALOXE3 mutation in East Asia.
    10. Loss-of-function mutations in the LOX genes ALOX12B and ALOXE3 have been found to represent the second most common cause of autosomal recessive congenital ichthyosis. [review]
      Title: The role of lipoxygenases in epidermis.
    Submit: New GeneRIF Correction See all GeneRIFs (23)

    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

    Associated conditions

    Description Tests
    Autosomal recessive congenital ichthyosis 2
    MedGen: C3888093 OMIM: 242100 GeneReviews: Autosomal Recessive Congenital Ichthyosis
    		not available
    Autosomal recessive congenital ichthyosis 3
    MedGen: C3539888 OMIM: 606545 GeneReviews: Not available
    		not available

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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

    Homology

    Clone Names

    • MGC119694, MGC119695, MGC119696

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables hepoxilin A3 synthase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables hepoxilin A3 synthase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables hepoxilin A3 synthase activity TAS
    Traceable Author Statement
    more info
    		  
    enables hydroperoxy icosatetraenoate dehydratase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables hydroperoxy icosatetraenoate isomerase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables intramolecular hydroxytransferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables iron ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    NOT enables oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen 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 arachidonate metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in arachidonate metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in ceramide biosynthetic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in establishment of skin barrier ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in fat cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in hepoxilin biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in hepoxilin biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in linoleic acid metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in linoleic acid metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in lipid oxidation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in lipoxygenase pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in lipoxygenase pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in lipoxygenase pathway TAS
    Traceable Author Statement
    more info
    		  
    involved_in peroxisome proliferator activated receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in sensory perception of pain ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in sphingolipid metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    hydroperoxide isomerase ALOXE3
    Names
    Epidermal lipoxygenase-3
    Lamellar ichthyosis 5
    arachidonate lipoxygenase 3
    e-LOX-3
    epidermal LOX-3
    epidermal lipoxygenase
    epidermis-type lipoxygenase 3
    hydroperoxy dehydratase ALOXE3
    hydroperoxy icosatetraenoate dehydratase
    hydroperoxy icosatetraenoate isomerase
    NP_001159432.1
    NP_001356375.1
    NP_067641.2
    XP_016880410.1
    XP_016880411.1
    XP_016880412.1
    XP_016880413.1
    XP_016880414.1
    XP_047292466.1
    XP_047292467.1
    XP_054172822.1
    XP_054172823.1
    XP_054172824.1
    XP_054172825.1
    XP_054172826.1
    XP_054172827.1
    XP_054172828.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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.

    Genomic

    1. NG_015807.1 RefSeqGene

      Range
      5403..28017
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001165960.1 → NP_001159432.1  hydroperoxide isomerase ALOXE3 isoform 1

      See identical proteins and their annotated locations for NP_001159432.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AF182218, AK296416, DC376381
      UniProtKB/TrEMBL
      J3KPH2
      Conserved Domains (2) summary
      cd01753
      Location:134 → 248
      PLAT_LOX; PLAT domain of 12/15-lipoxygenase. As a unique subfamily of the mammalian lipoxygenases, they catalyze enzymatic lipid peroxidation in complex biological structures via direct dioxygenation of phospholipids and cholesterol esters of biomembranes and ...
      pfam00305
      Location:400 → 834
      Lipoxygenase; Lipoxygenase

    2. NM_001369446.1 → NP_001356375.1  hydroperoxide isomerase ALOXE3 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC129492
      UniProtKB/TrEMBL
      B3KVD2
      Conserved Domains (2) summary
      cd01753
      Location:2 → 116
      PLAT_LOX; PLAT domain of 12/15-lipoxygenase. As a unique subfamily of the mammalian lipoxygenases, they catalyze enzymatic lipid peroxidation in complex biological structures via direct dioxygenation of phospholipids and cholesterol esters of biomembranes and ...
      pfam00305
      Location:267 → 701
      Lipoxygenase

    3. NM_021628.3 → NP_067641.2  hydroperoxide isomerase ALOXE3 isoform 2

      See identical proteins and their annotated locations for NP_067641.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) represents use of an alternate promoter and 5' UTR and uses a downstream start codon, compared to variant 1. The resulting isoform (2) has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AF182218, AK313677, DA183156
      Consensus CDS
      CCDS11130.1
      UniProtKB/Swiss-Prot
      B2R981, B7Z3W0, Q3ZB74, Q9BYJ1, Q9H4F2, Q9HC22
      UniProtKB/TrEMBL
      B3KVD2
      Related
      ENSP00000400581.2, ENST00000448843.7
      Conserved Domains (2) summary
      cd01753
      Location:2 → 116
      PLAT_LOX; PLAT domain of 12/15-lipoxygenase. As a unique subfamily of the mammalian lipoxygenases, they catalyze enzymatic lipid peroxidation in complex biological structures via direct dioxygenation of phospholipids and cholesterol esters of biomembranes and ...
      cl27717
      Location:268 → 702
      Lipoxygenase; Lipoxygenase

    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_000017.11 Reference GRCh38.p14 Primary Assembly

      Range
      8095900..8118916 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047436510.1 → XP_047292466.1  hydroperoxide isomerase ALOXE3 isoform X3

    2. XM_017024921.3 → XP_016880410.1  hydroperoxide isomerase ALOXE3 isoform X1

      UniProtKB/TrEMBL
      B3KVD2

    3. XM_017024922.3 → XP_016880411.1  hydroperoxide isomerase ALOXE3 isoform X2

    4. XM_047436511.1 → XP_047292467.1  hydroperoxide isomerase ALOXE3 isoform X5

    5. XM_017024924.3 → XP_016880413.1  hydroperoxide isomerase ALOXE3 isoform X5

    6. XM_017024923.3 → XP_016880412.1  hydroperoxide isomerase ALOXE3 isoform X4

      UniProtKB/TrEMBL
      A0AAQ5BHH1
      Related
      ENSP00000519433.1, ENST00000714144.1

    7. XM_017024925.3 → XP_016880414.1  hydroperoxide isomerase ALOXE3 isoform X5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      8001351..8024291 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054316849.1 → XP_054172824.1  hydroperoxide isomerase ALOXE3 isoform X3

    2. XM_054316847.1 → XP_054172822.1  hydroperoxide isomerase ALOXE3 isoform X1

    3. XM_054316848.1 → XP_054172823.1  hydroperoxide isomerase ALOXE3 isoform X2

    4. XM_054316852.1 → XP_054172827.1  hydroperoxide isomerase ALOXE3 isoform X5

    5. XM_054316851.1 → XP_054172826.1  hydroperoxide isomerase ALOXE3 isoform X5

    6. XM_054316850.1 → XP_054172825.1  hydroperoxide isomerase ALOXE3 isoform X4

      UniProtKB/TrEMBL
      A0AAQ5BHH1

    7. XM_054316853.1 → XP_054172828.1  hydroperoxide isomerase ALOXE3 isoform X5

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9BYJ1.1 GenPept UniProtKB/Swiss-Prot:Q9BYJ1

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