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ALOX12 (Arachidonate 12-Lipoxygenase) Homo sapiens

Written2007-03Sreeparna Banerjee, Asli Erdog
Department of Biology (SB), Department of Biotechnology (AE), Middle East Technical University, Ankara 06531 Turkey

(Note : for Links provided by Atlas : click)

Identity

Alias_namesarachidonate 12-lipoxygenase
Alias_symbol (synonym)12S-LOX
HGNC (Hugo) ALOX12
LocusID (NCBI) 239
Atlas_Id 620
Location 17p13.1  [Link to chromosome band 17p13]
Location_base_pair Starts at 6899384 and ends at 6914055 bp from pter ( according to hg19-Feb_2009)  [Mapping ALOX12.png]
Local_order According to NCBI Map Viewer, genes flanking ALOX15 in centromere to telomere direction on 17p13 are: GABARAP 17p13.1 GABA(A) receptor-associated protein, ASGR2 asialoglycoprotein receptor 2, ALOX12 17p13.1 arachidonate 12-lipoxygenase (Homo sapiens), ALOX12P2 17p13 arachidonate 12-lipoxygenase pseudogene 2, TEKT1 tektin 1, FBXO39 F-box protein 39.
Fusion genes
(updated 2016)
ALOX12 (17p13.1) / RNASEK (17p13.1)ALOX12 (17p13.1) / RNASEK-C17orf49 (17p13.1)SLC35G6 (17p13.1) / ALOX12 (17p13.1)
Note Arachidonate 12-Lipoxygenase (12-LOX) is one of several LOX isoforms that has iron as a cofactor and oxygenates polyunsaturated fatty acids. This particular isoform was also the first documented LOX in the animal kingdom.

DNA/RNA

Note With the exception of ALOX5, all human LOX genes, including ALOX12, are clustered on the short arm of chromosome 17 within a few megabases of each other. ALOX15, which has 86% sequence homology to ALOX12, is in closest proximity (17p13.2). Since chromosome 17 is known for gene duplications, the multiple LOX genes on the same chromosome may be as a result of such duplications.
 
  Diagram of the ALOX12 gene. Exons are represented by grey boxes (in scale) untranscribed sequences in black, with exon numbers on the bottom.
Description According to Entrez-Gene, ALOX12 gene maps to NC_000017.9 and spans a region of 16.1 kilo bases. According to Spidey (mRNA to genomic sequence alignment tool), ALOX15 has 14 exons, the sizes being 168, 202, 82, 123, 104, 161, 144, 210, 87, 170, 122, 101, 171 and 490 bp.
Transcription ALOX12 mRNA NM_000697 has 2335bp. Characterization of the 5' flanking region of the human ALOX12 in epidermoid carcinoma A431 cells indicated the presence of two Sp1 recognition motifs residing at -158 to -150 bp and -123 to -114 bp which are essential for gene expression.
The proposed mechanism of action is as follows: epidermal growth factor induces MAPK activation in cells, followed by the activation of JUN/AP1. The biosynthesis of c-Jun is thereby increased. Sp1 recruits HDAC1 together with c-Jun to the gene promoter. When Sp1 is deacetylated it interacts with acetylate histone 3, following which p300 is recruited to the gene promoter leading to the enhancement of the expression of 12(S)-lipoxygenase .
Pseudogene According to Entrez Gene the arachidonate 12-lipoxygenase pseudogene (ALOX12P2) (HGNC: 13742) is located on 17p13.1. This is the 'epidermal type' 12-LOX (e-12LO) that was cloned using a murine e-LO12 probe. Humans express this functional pseudogene in the skin and hair follicles.

Protein

Note 12S-lipoxygenases has three isoforms, named after their site of initial identification: platelet, leukocyte and epidermis. The leukocyte-type enzyme is expressed widely, while the platelet and epidermal enzymes are present in only a relatively limited number of cell types. Owing to the similarities in their genetic location, sequence and biological activities, leukocyte 12-LOX and 15-LOX-1 are often referred to as 12/15 lipoxygenase.
Description 12-LOX protein consists of 662 amino acids, with a molecular weight of 75536 Da and contains non heme iron as a cofactor. According to the NCBI conserved domain search, the presence of a polycystin/lipoxygenase/alpha-toxin (PLAT) domain in the 12-LOX protein allows it access and enables it to catalyze enzymatic lipid peroxidation in complex biological structures via direct dioxygenation of phospholipids and cholesterol esters of biomembranes and plasma lipoproteins. The same conserved domain in 15-LOX-1 also enables it to oxidize complex lipids. Although cytosolic, both types of enzymes need this domain to access their sequestered membrane or micelle bound substrates.
Expression The platelet type 12-LOX is expressed in the platelets and skin in humans. Based on structural and enzymatic properties, 15-LOX-1 is said to be a homolog of leukocyte type 12-LOX and are both expressed in mast cells, eosinophils, activated monocytes or dendritic cells, and bronchial epithelial cells.
Localisation All 12-LOX isoforms have been localized to the cytoplasm. In addition, the platelet-type 12S-lipoxygenase was found in both cytosol and microsomal fractions of epidermal cells of human skin.
Function 12-LOX is a member of the inflammatory leukotriene biosynthesis pathway where, in presence of molecular oxygen, it converts arachidonic acid to 12-hydroxyeicosatetraenoic acid (12-HETE). The leukocyte type 12-LOX can, in addition, effectively oxygenate linoleic acid and phospholipids. This isoform can also generate significant amounts of the 15-LOX product in addition to 12-HETE.
Homology C. familiaris: LOC479476 similar to arachidonate 12-lipoxygenase, P. troglodytes: ALOX12, R. norvegicus: Alox12 (predicted), M. musculus: Alox12 arachidonate 12-lipoxygenase (12/15LOX), D. rerio: wufb72a11.

Implicated in

Note
Entity Inflammation and cancer
Note End product of arachidonic acid metabolism by the platelet-type 12-LOX 12(S)-Hydroxy eicosatetraenoic acid (12(S)-HETE) is shown to induce invasion, motility, and angiogenesis and protect tumour cells from apoptosis. Great many biological activities of 12(S)-HETE appear to be partly mediated by the activation of NFkappaB. NF-kappaB is a family of five DNA binding proteins that regulate the expression of a variety of genes involved in host immune responses and inflammation. A direct relationship between platelet-type 12-LOX overexpression and NF-kappaB activation is reported in prostate cancer cells.
  
Entity Polymorphisms associated with diseases
Note Aberrant arachidonic acid metabolism by 12-lipoxygenase (12-LOX) is implicated in carcinogenesis. Genetic polymorphisms 12-LOX is therefore thought to influence its function and/or expression and may modify the risk for colorectal adenoma. One of the single nucleotide polymorphisms (SNPs) reported in the 12-LOX gene located in exon 6 resulting in an Arg to Gln substitution at amino acid 261 of 12-LOX is in a highly conserved region of the lipoxygenase domain. Data from a community-based, case-control study of incident, sporadic colorectal adenoma that included 162 cases and 211 controls have shown an inverse association between the Arg261Gln polymorphism in 12-LOX and colorectal adenoma (OR, 0.63; 95% CI, 0.40-1.00). A significant interaction also is observed between the 12-LOX polymorphism (Arg261Gln) and the use of nonsteroidal anti-inflammatory drugs. Another study argues that Gln261Arg in ALOX12 does not appear to be associated with colon cancer risk.
Studies have shown higher urinary excretion of the arachidonic acid-derived metabolite 12-(S)hydroxyeicosatetraenoic acid (12(S)-HETE) in essential hypertension. For analysis of the association of polymorphisms in ALOX12 with hypertension and urinary levels of 12(S)-HETE, a study with 200 patients with essential hypertension and 166 matched controls is performed and as a result, the distribution of genotypes of the R261Q (Arg to Gln) polymorphism is found to be significantly different between patients and controls. These results indicate that a nonsynonymous polymorphism in ALOX12 is associated to essential hypertension and to urinary levels of 12(S)-HETE.
Peak BMD is a major determinant of osteoporosis which is a complex disease with both genetic and environmental risk factors. In a population - and family - based association study of ALOX15 and ALOX12, SNPs distributed across the two genes are genotyped. Moderate evidence of association is found between spine BMD and six SNPs in the ALOX12 gene in both men and women. These data conclude that polymorphisms in the ALOX12 gene may contribute to normal variation in spine BMD.
  
Entity Alzheimer's disease
Note Alzheimer's disease (AD) is a chronic neurodegenerative disorder that impairs cognition and behavior. Although the initiating molecular events are not known, increasing evidence suggests that 12/15-LOX is a major source of oxidative stress which could play a functional role in pathogenesis. Quantitative Western blot analysis confirmed by immunohistochemical studies demonstrate that in affected frontal and temporal regions of AD brains, the amount of 12/15-LOX is higher compared to controls. Also metabolic products of 12/15-LOX are markedly elevated in AD brains compared to controls.
  
Entity Bladder cancer
Note 12-LOX expression is shown to be induced in bladder cancer tissues by an immunohistochemistry analysis. Also lipoxygenase inhibitors cause marked inhibition of bladder cancer cells in a concentration and time dependent manner. Cells treated with lipoxygenase inhibitors show chromatin condensation, cellular shrinkage, small membrane bound bodies (apoptotic bodies) and cytoplasmic condensation.
  
Entity Testicular cancer
Note 12-LOX is only slightly expressed in normal testis tissues, however, 12-LOX expression is found to be significant in testicular cancer tissues by immunohistochemistry studies. Specific LOX inhibitors have also been shown to inhibit the growth of testicular cancer in cell lines.
  
Entity Prostate cancer
Note Research focusing on mechanisms of action of 12-lipoxygenase in prostate cancer cells revealed that overexpression of 12-lipoxygenase in PC-3 cells results in a 3-fold increase in VEGF protein level when compared with vector control cells and there is an increase in PI3-kinase activity in 12-LOX-transfected PC-3 cells.
The expression of 12-LOX is detected to be low in benign prostatic hyperplasia and normal prostate tissues, whereas marked expression of 12-lipoxygenase is detected in prostatic intraepithelial neoplasia and prostate cancer tissues. The LOX inhibitors cause marked cellular death through apoptosis in prostate cancer cells in a concentration and time-dependent manner.
Another effect of 12-LOX in prostate cancer cells is that increase in 12-LOX expression enhances the metastatic potential of human prostate cancer cells. 12-LOX transfected PC-3 cells show a significant change in cell adhesiveness, spreading, motility, and invasiveness.
  
Entity Breast cancer
Note Total cellular RNA extraction from 64 frozen tissue samples of breast carcinoma and their corresponding normal adjacent tissues is performed for expression analysis of cyclooxygenase-2 and 12-lipooxygenase using RT-PCR. 62.5% of carcinoma samples showed over-expression of 12-lipooxygenase as compared to normal breast tissues. Results also reveal that and 12-lipooxygenase mRNA expressions are associated with TNM staging in human breast cancer.
A second study indicates that levels of 12- lipoxygenases together with 5-lipoxygenase are also particularly high in tumours from patients who died of breast cancer. Therefore raised level of 12-lipoxygenase might have prognostic value in patients with breast cancer.
  

Bibliography

Transcription factor Sp1 functions as an anchor protein in gene transcription of human 12(S)-lipoxygenase.
Chang WC, Chen BK
Biochemical and biophysical research communications. 2005 ; 338 (1) : 117-121.
PMID 16122700
 
Common polymorphisms in 5-lipoxygenase and 12-lipoxygenase genes and the risk of incident, sporadic colorectal adenoma.
Gong Z, Hebert JR, Bostick RM, Deng Z, Hurley TG, Dixon DA, Nitcheva D, Xie D
Cancer. 2007 ; 109 (5) : 849-857.
PMID 17236225
 
Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) polymorphisms and colon cancer risk.
Goodman JE, Bowman ED, Chanock SJ, Alberg AJ, Harris CC
Carcinogenesis. 2004 ; 25 (12) : 2467-2472.
PMID 15308583
 
Sp1 deacetylation induced by phorbol ester recruits p300 to activate 12(S)-lipoxygenase gene transcription.
Hung JJ, Wang YT, Chang WC
Molecular and cellular biology. 2006 ; 26 (5) : 1770-1785.
PMID 16478997
 
Human ALOX12, but not ALOX15, is associated with BMD in white men and women.
Ichikawa S, Koller DL, Johnson ML, Lai D, Xuei X, Edenberg HJ, Klein RF, Orwoll ES, Hui SL, Foroud TM, Peacock M, Econs MJ
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2006 ; 21 (4) : 556-564.
PMID 16598376
 
Levels of expression of lipoxygenases and cyclooxygenase-2 in human breast cancer.
Jiang WG, Douglas-Jones A, Mansel RE
Prostaglandins, leukotrienes, and essential fatty acids. 2003 ; 69 (4) : 275-281.
PMID 12907138
 
Platelet-type 12-lipoxygenase activates NF-kappaB in prostate cancer cells.
Kandouz M, Nie D, Pidgeon GP, Krishnamoorthy S, Maddipati KR, Honn KV
Prostaglandins & other lipid mediators. 2003 ; 71 (3-4) : 189-204.
PMID 14518561
 
Transcriptional activation of human 12-lipoxygenase gene promoter is mediated through Sp1 consensus sites in A431 cells.
Liu YW, Arakawa T, Yamamoto S, Chang WC
The Biochemical journal. 1997 ; 324 ( Pt 1) : 133-140.
PMID 9164849
 
Expression of lipoxygenase in human prostate cancer and growth reduction by its inhibitors.
Matsuyama M, Yoshimura R, Mitsuhashi M, Hase T, Tsuchida K, Takemoto Y, Kawahito Y, Sano H, Nakatani T
International journal of oncology. 2004 ; 24 (4) : 821-827.
PMID 15010818
 
Characterization of epidermal 12(S) and 12(R) lipoxygenases.
McDonnell M, Li H, Funk CD
Advances in experimental medicine and biology. 2002 ; 507 : 147-153.
PMID 12664578
 
Expression of cyclooxygenase-2 and 12-lipoxygenase in human breast cancer and their relationship with HER-2/neu and hormonal receptors: impact on prognosis and therapy.
Mohammad AM, Abdel HA, Abdel W, Ahmed AM, Wael T, Eiman G
Indian journal of cancer. 2006 ; 43 (4) : 163-168.
PMID 17192687
 
Mechanisms regulating tumor angiogenesis by 12-lipoxygenase in prostate cancer cells.
Nie D, Krishnamoorthy S, Jin R, Tang K, Chen Y, Qiao Y, Zacharek A, Guo Y, Milanini J, Pages G, Honn KV
The Journal of biological chemistry. 2006 ; 281 (27) : 18601-18609.
PMID 16638750
 
Increased metastatic potential in human prostate carcinoma cells by overexpression of arachidonate 12-lipoxygenase.
Nie D, Nemeth J, Qiao Y, Zacharek A, Li L, Hanna K, Tang K, Hillman GG, Cher ML, Grignon DJ, Honn KV
Clinical & experimental metastasis. 2003 ; 20 (7) : 657-663.
PMID 14669797
 
12/15-lipoxygenase is increased in Alzheimer's disease: possible involvement in brain oxidative stress.
Praticò D, Zhukareva V, Yao Y, Uryu K, Funk CD, Lawson JA, Trojanowski JQ, Lee VM
The American journal of pathology. 2004 ; 164 (5) : 1655-1662.
PMID 15111312
 
A coding polymorphism in the 12-lipoxygenase gene is associated to essential hypertension and urinary 12(S)-HETE.
Quintana LF, Guzm´n B, Collado S, Clària J, Poch E
Kidney international. 2006 ; 69 (3) : 526-530.
PMID 16514435
 
Cloning of a human epidermal-type 12-lipoxygenase-related gene and chromosomal localization to 17p13.
Sun D, Elsea SH, Patel PI, Funk CD
Cytogenetics and cell genetics. 1998 ; 81 (1) : 79-82.
PMID 9691181
 
Investigation of the oxygenation of phospholipids by the porcine leukocyte and human platelet arachidonate 12-lipoxygenases.
Takahashi Y, Glasgow WC, Suzuki H, Taketani Y, Yamamoto S, Anton M, Kühn H, Brash AR
European journal of biochemistry / FEBS. 1993 ; 218 (1) : 165-171.
PMID 8243462
 
Associations of functional polymorphisms in cyclooxygenase-2 and platelet 12-lipoxygenase with risk of occurrence and advanced disease status of colorectal cancer.
Tan W, Wu J, Zhang X, Guo Y, Liu J, Sun T, Zhang B, Zhao D, Yang M, Yu D, Lin D
Carcinogenesis. 2007 ; 28 (6) : 1197-1201.
PMID 17151091
 
Arachidonate 12-lipoxygenase.
Yoshimoto T, Yamamoto S
Journal of lipid mediators and cell signalling. 1995 ; 12 (2-3) : 195-212.
PMID 8777566
 
Relationship between lipoxygenase and human testicular cancer.
Yoshimura R, Matsuyama M, Mitsuhashi M, Takemoto Y, Tsuchida K, Kawahito Y, Sano H, Nakatani T
International journal of molecular medicine. 2004 ; 13 (3) : 389-393.
PMID 14767568
 

Citation

This paper should be referenced as such :
Erdog, A ; Banerjee, S
ALOX12 (arachidonate 12-lipoxygenase) Homo sapiens
Atlas Genet Cytogenet Oncol Haematol. 2007;11(3):222-225.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/ALOX12ID620ch17p13.html


External links

Nomenclature
HGNC (Hugo)ALOX12   429
Cards
AtlasALOX12ID620ch17p13
Entrez_Gene (NCBI)ALOX12  239  arachidonate 12-lipoxygenase
Aliases12-LOX; 12S-LOX; LOG12
GeneCards (Weizmann)ALOX12
Ensembl hg19 (Hinxton)ENSG00000108839 [Gene_View]  chr17:6899384-6914055 [Contig_View]  ALOX12 [Vega]
Ensembl hg38 (Hinxton)ENSG00000108839 [Gene_View]  chr17:6899384-6914055 [Contig_View]  ALOX12 [Vega]
ICGC DataPortalENSG00000108839
TCGA cBioPortalALOX12
AceView (NCBI)ALOX12
Genatlas (Paris)ALOX12
WikiGenes239
SOURCE (Princeton)ALOX12
Genetics Home Reference (NIH)ALOX12
Genomic and cartography
GoldenPath hg19 (UCSC)ALOX12  -     chr17:6899384-6914055 +  17p13.1   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)ALOX12  -     17p13.1   [Description]    (hg38-Dec_2013)
EnsemblALOX12 - 17p13.1 [CytoView hg19]  ALOX12 - 17p13.1 [CytoView hg38]
Mapping of homologs : NCBIALOX12 [Mapview hg19]  ALOX12 [Mapview hg38]
OMIM152391   
Gene and transcription
Genbank (Entrez)AF143883 BC069557 M35418 M58704 M62982
RefSeq transcript (Entrez)NM_000697
RefSeq genomic (Entrez)NC_000017 NC_018928 NT_010718 NW_004929405
Consensus coding sequences : CCDS (NCBI)ALOX12
Cluster EST : UnigeneHs.654431 [ NCBI ]
CGAP (NCI)Hs.654431
Alternative Splicing GalleryENSG00000108839
Gene ExpressionALOX12 [ NCBI-GEO ]   ALOX12 [ EBI - ARRAY_EXPRESS ]   ALOX12 [ SEEK ]   ALOX12 [ MEM ]
Gene Expression Viewer (FireBrowse)ALOX12 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)239
GTEX Portal (Tissue expression)ALOX12
Protein : pattern, domain, 3D structure
UniProt/SwissProtP18054   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP18054  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP18054
Splice isoforms : SwissVarP18054
Catalytic activity : Enzyme1.13.11.31 [ Enzyme-Expasy ]   1.13.11.311.13.11.31 [ IntEnz-EBI ]   1.13.11.31 [ BRENDA ]   1.13.11.31 [ KEGG ]   
PhosPhoSitePlusP18054
Domaine pattern : Prosite (Expaxy)LIPOXYGENASE_1 (PS00711)    LIPOXYGENASE_2 (PS00081)    LIPOXYGENASE_3 (PS51393)    PLAT (PS50095)   
Domains : Interpro (EBI)LipOase    LipOase_C    LipOase_CS    LipOase_Fe_BS    LipOase_mml    PLAT/LH2_dom   
Domain families : Pfam (Sanger)Lipoxygenase (PF00305)    PLAT (PF01477)   
Domain families : Pfam (NCBI)pfam00305    pfam01477   
Domain families : Smart (EMBL)LH2 (SM00308)  
Conserved Domain (NCBI)ALOX12
DMDM Disease mutations239
Blocks (Seattle)ALOX12
PDB (SRS)2ABU    3D3L   
PDB (PDBSum)2ABU    3D3L   
PDB (IMB)2ABU    3D3L   
PDB (RSDB)2ABU    3D3L   
Structural Biology KnowledgeBase2ABU    3D3L   
SCOP (Structural Classification of Proteins)2ABU    3D3L   
CATH (Classification of proteins structures)2ABU    3D3L   
SuperfamilyP18054
Human Protein AtlasENSG00000108839
Peptide AtlasP18054
HPRD01066
IPIIPI00218915   IPI00879611   
Protein Interaction databases
DIP (DOE-UCLA)P18054
IntAct (EBI)P18054
FunCoupENSG00000108839
BioGRIDALOX12
STRING (EMBL)ALOX12
ZODIACALOX12
Ontologies - Pathways
QuickGOP18054
Ontology : AmiGOarachidonate 12-lipoxygenase activity  arachidonate 12-lipoxygenase activity  iron ion binding  protein binding  cytoplasm  cytosol  cytosol  movement of cell or subcellular component  aging  positive regulation of cell proliferation  positive regulation of cell proliferation  positive regulation of endothelial cell migration  positive regulation of gene expression  negative regulation of muscle cell apoptotic process  membrane  linoleate 13S-lipoxygenase activity  oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen  arachidonic acid metabolic process  arachidonic acid metabolic process  lipoxygenase pathway  lipoxygenase pathway  fatty acid oxidation  positive regulation of cell growth  positive regulation of cell migration  sarcolemma  superoxide anion generation  negative regulation of apoptotic process  negative regulation of apoptotic process  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  linoleic acid metabolic process  linoleic acid metabolic process  positive regulation of endothelial cell differentiation  positive regulation of angiogenesis  positive regulation of cell adhesion  positive regulation of vasodilation  hepoxilin-epoxide hydrolase activity  positive regulation of smooth muscle cell proliferation  hepoxilin A3 synthase activity  hepoxilin metabolic process  hepoxilin biosynthetic process  positive regulation of mitochondrial depolarization  establishment of skin barrier  extracellular exosome  cellular response to lipid  reactive oxygen species metabolic process  negative regulation of platelet aggregation  leukotriene A4 metabolic process  leukotriene A4 metabolic process  lipoxin metabolic process  lipoxin A4 biosynthetic process  lipoxin B4 biosynthetic process  
Ontology : EGO-EBIarachidonate 12-lipoxygenase activity  arachidonate 12-lipoxygenase activity  iron ion binding  protein binding  cytoplasm  cytosol  cytosol  movement of cell or subcellular component  aging  positive regulation of cell proliferation  positive regulation of cell proliferation  positive regulation of endothelial cell migration  positive regulation of gene expression  negative regulation of muscle cell apoptotic process  membrane  linoleate 13S-lipoxygenase activity  oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen  arachidonic acid metabolic process  arachidonic acid metabolic process  lipoxygenase pathway  lipoxygenase pathway  fatty acid oxidation  positive regulation of cell growth  positive regulation of cell migration  sarcolemma  superoxide anion generation  negative regulation of apoptotic process  negative regulation of apoptotic process  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  linoleic acid metabolic process  linoleic acid metabolic process  positive regulation of endothelial cell differentiation  positive regulation of angiogenesis  positive regulation of cell adhesion  positive regulation of vasodilation  hepoxilin-epoxide hydrolase activity  positive regulation of smooth muscle cell proliferation  hepoxilin A3 synthase activity  hepoxilin metabolic process  hepoxilin biosynthetic process  positive regulation of mitochondrial depolarization  establishment of skin barrier  extracellular exosome  cellular response to lipid  reactive oxygen species metabolic process  negative regulation of platelet aggregation  leukotriene A4 metabolic process  leukotriene A4 metabolic process  lipoxin metabolic process  lipoxin A4 biosynthetic process  lipoxin B4 biosynthetic process  
Pathways : KEGGArachidonic acid metabolism    Serotonergic synapse   
REACTOMEP18054 [protein]
REACTOME PathwaysR-HSA-2142700 Synthesis of Lipoxins (LX) [pathway]
REACTOME PathwaysR-HSA-2142712 Synthesis of 12-eicosatetraenoic acid derivatives [pathway]
REACTOME PathwaysR-HSA-2142696 Synthesis of Hepoxilins (HX) and Trioxilins (TrX) [pathway]
NDEx NetworkALOX12
Atlas of Cancer Signalling NetworkALOX12
Wikipedia pathwaysALOX12
Orthology - Evolution
OrthoDB239
GeneTree (enSembl)ENSG00000108839
Phylogenetic Trees/Animal Genes : TreeFamALOX12
HOVERGENP18054
HOGENOMP18054
Homologs : HomoloGeneALOX12
Homology/Alignments : Family Browser (UCSC)ALOX12
Gene fusions - Rearrangements
Fusion : MitelmanSLC35G6/ALOX12 [17p13.1/17p13.1]  [t(17;17)(p13;p13)]  
Fusion: TCGASLC35G6 17p13.1 ALOX12 17p13.1 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerALOX12 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ALOX12
dbVarALOX12
ClinVarALOX12
1000_GenomesALOX12 
Exome Variant ServerALOX12
ExAC (Exome Aggregation Consortium)ALOX12 (select the gene name)
Genetic variants : HAPMAP239
Genomic Variants (DGV)ALOX12 [DGVbeta]
DECIPHER (Syndromes)17:6899384-6914055  ENSG00000108839
CONAN: Copy Number AnalysisALOX12 
Mutations
ICGC Data PortalALOX12 
TCGA Data PortalALOX12 
Broad Tumor PortalALOX12
OASIS PortalALOX12 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICALOX12  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDALOX12
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch ALOX12
DgiDB (Drug Gene Interaction Database)ALOX12
DoCM (Curated mutations)ALOX12 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ALOX12 (select a term)
intoGenALOX12
NCG5 (London)ALOX12
Cancer3DALOX12(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM152391   
Orphanet
MedgenALOX12
Genetic Testing Registry ALOX12
NextProtP18054 [Medical]
TSGene239
GENETestsALOX12
Huge Navigator ALOX12 [HugePedia]
snp3D : Map Gene to Disease239
BioCentury BCIQALOX12
ClinGenALOX12
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD239
Chemical/Pharm GKB GenePA45
Clinical trialALOX12
Miscellaneous
canSAR (ICR)ALOX12 (select the gene name)
Probes
Litterature
PubMed130 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineALOX12
EVEXALOX12
GoPubMedALOX12
iHOPALOX12
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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