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Aliases for NOX4 Gene

Aliases for NOX4 Gene

  • NADPH Oxidase 4 2 3 5
  • Kidney Superoxide-Producing NADPH Oxidase 3 4
  • Renal NAD(P)H-Oxidase 3 4
  • Kidney Oxidase-1 3 4
  • KOX-1 3 4
  • RENOX 3 4
  • EC 1.6.3.- 4
  • EC 1.6.3 58
  • KOX 3

External Ids for NOX4 Gene

Previous GeneCards Identifiers for NOX4 Gene

  • GC11M091382
  • GC11M090606
  • GC11M089244
  • GC11M088747
  • GC11M088699
  • GC11M089057
  • GC11M085294

Summaries for NOX4 Gene

Entrez Gene Summary for NOX4 Gene

  • This gene encodes a member of the NOX-family of enzymes that functions as the catalytic subunit the NADPH oxidase complex. The encoded protein is localized to non-phagocytic cells where it acts as an oxygen sensor and catalyzes the reduction of molecular oxygen to various reactive oxygen species (ROS). The ROS generated by this protein have been implicated in numerous biological functions including signal transduction, cell differentiation and tumor cell growth. A pseudogene has been identified on the other arm of chromosome 11. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2009]

GeneCards Summary for NOX4 Gene

NOX4 (NADPH Oxidase 4) is a Protein Coding gene. Diseases associated with NOX4 include Pulmonary Hypertension and Pulmonary Fibrosis, Idiopathic. Among its related pathways are AGE-RAGE signaling pathway in diabetic complications and Blood-Brain Barrier and Immune Cell Transmigration: VCAM-1/CD106 Signaling Pathways. GO annotations related to this gene include nucleotide binding and heme binding. An important paralog of this gene is CYBB.

UniProtKB/Swiss-Prot for NOX4 Gene

  • Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade. May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not functional. Isoform 5 and isoform 6 display reduced activity.

  • Isoform 4: Involved in redox signaling in vascular cells. Constitutively and NADPH-dependently generates reactive oxygen species (ROS). Modulates the nuclear activation of ERK1/2 and the ELK1 transcription factor, and is capable of inducing nuclear DNA damage. Displays an increased activity relative to isoform 1.

Gene Wiki entry for NOX4 Gene

Additional gene information for NOX4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NOX4 Gene

Genomics for NOX4 Gene

Regulatory Elements for NOX4 Gene

Enhancers for NOX4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH11H089606 0.9 Ensembl ENCODE 10.1 -18.0 -18035 2 ELF3 TFE3 FOXA2 LCORL ATF1 JUN CREB1 FOXA1 NOX4 FOLH1B ENSG00000255429
GH11H089650 0.4 dbSUPER 4.1 -66.7 -66713 11 HNF4A RAD21 FOLH1B NOX4 UBTFL10
GH11H089486 0.5 FANTOM5 3 +103.3 103288 0 ZNF555 ZNF518A NOX4 GC11P089484 ENSG00000255295
GH11H089634 0.2 dbSUPER 4.1 -47.9 -47880 5 FOLH1B TUBAP2 NOX4 ENSG00000255429
GH11H089613 0.7 ENCODE dbSUPER 0.3 -24.5 -24453 1 CTCF RAD21 FOLH1B ENSG00000255429 NOX4
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around NOX4 on UCSC Golden Path with GeneCards custom track

Genomic Location for NOX4 Gene

Chromosome:
11
Start:
89,324,353 bp from pter
End:
89,589,611 bp from pter
Size:
265,259 bases
Orientation:
Minus strand

Genomic View for NOX4 Gene

Genes around NOX4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NOX4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NOX4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NOX4 Gene

Proteins for NOX4 Gene

  • Protein details for NOX4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NPH5-NOX4_HUMAN
    Recommended name:
    NADPH oxidase 4
    Protein Accession:
    Q9NPH5
    Secondary Accessions:
    • A8K715
    • B7Z520
    • E7EMD7
    • Q5K3R4
    • Q5K3R5
    • Q5K3R6
    • Q5K3R8
    • Q7Z7G3
    • Q86V92

    Protein attributes for NOX4 Gene

    Size:
    578 amino acids
    Molecular mass:
    66932 Da
    Quaternary structure:
    • Interacts with protein disulfide isomerase (By similarity). Interacts with, relocalizes and stabilizes CYBA/p22phox. Interacts with TLR4.

    Alternative splice isoforms for NOX4 Gene

neXtProt entry for NOX4 Gene

Selected DME Specific Peptides for NOX4 Gene

Q9NPH5:
  • DTHPPGCISLN
  • TICIFSGVHVAAHLVNALNFSVNYSE
  • GIGVTPF

Post-translational modifications for NOX4 Gene

  • Isoform 3 and isoform 4 are N-glycosylated. Isoform 4 glycosylation is required for its proper function.
  • Glycosylation at posLast=133133 and posLast=230230
  • Modification sites at PhosphoSitePlus

Antibody Products

Domains & Families for NOX4 Gene

Gene Families for NOX4 Gene

Human Protein Atlas (HPA):
  • Predicted membrane proteins
  • Transporters

Suggested Antigen Peptide Sequences for NOX4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with NOX4: view

No data available for UniProtKB/Swiss-Prot for NOX4 Gene

Function for NOX4 Gene

Molecular function for NOX4 Gene

UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by plumbagin (By similarity). Activated by phorbol 12-myristate 13-acetate (PMA). Activated by insulin. Inhibited by diphenylene iodonium.
UniProtKB/Swiss-Prot Function:
Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade. May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not functional. Isoform 5 and isoform 6 display reduced activity.
UniProtKB/Swiss-Prot Function:
Isoform 4: Involved in redox signaling in vascular cells. Constitutively and NADPH-dependently generates reactive oxygen species (ROS). Modulates the nuclear activation of ERK1/2 and the ELK1 transcription factor, and is capable of inducing nuclear DNA damage. Displays an increased activity relative to isoform 1.
UniProtKB/Swiss-Prot Induction:
By 7-ketocholesterol (at protein level).

Enzyme Numbers (IUBMB) for NOX4 Gene

Phenotypes From GWAS Catalog for NOX4 Gene

Gene Ontology (GO) - Molecular Function for NOX4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding TAS 10869423
GO:0005515 protein binding IPI 15356101
GO:0009055 electron carrier activity TAS 10869423
GO:0016174 NAD(P)H oxidase activity TAS 10869423
GO:0016175 superoxide-generating NADPH oxidase activity TAS --
genes like me logo Genes that share ontologies with NOX4: view
genes like me logo Genes that share phenotypes with NOX4: view

Animal Models for NOX4 Gene

MGI Knock Outs for NOX4:

Animal Model Products

  • Taconic Biosciences Mouse Models for NOX4

CRISPR Products

miRNA for NOX4 Gene

miRTarBase miRNAs that target NOX4

Inhibitory RNA Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NOX4 Gene

Localization for NOX4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NOX4 Gene

Endoplasmic reticulum membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein. Cell junction, focal adhesion. Note=May localize to plasma membrane and focal adhesions. According to PubMed:15927447, may also localize to the nucleus.
Isoform 4: Nucleus. Nucleus, nucleolus.

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 NOX4 gene
Compartment Confidence
plasma membrane 5
nucleus 5
endoplasmic reticulum 5
mitochondrion 4
cytoskeleton 3
extracellular 2
cytosol 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for NOX4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001725 stress fiber IEA --
GO:0005634 nucleus IDA --
GO:0005730 nucleolus IEA --
GO:0005739 mitochondrion IEA --
GO:0005783 endoplasmic reticulum IEA --
genes like me logo Genes that share ontologies with NOX4: view

Pathways & Interactions for NOX4 Gene

genes like me logo Genes that share pathways with NOX4: view

Gene Ontology (GO) - Biological Process for NOX4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000902 cell morphogenesis ISS 10869423
GO:0001666 response to hypoxia IEA --
GO:0006801 superoxide metabolic process IDA 18760347
GO:0006954 inflammatory response TAS 10869423
GO:0007568 aging IEA --
genes like me logo Genes that share ontologies with NOX4: view

No data available for SIGNOR curated interactions for NOX4 Gene

Drugs & Compounds for NOX4 Gene

(9) Drugs for NOX4 Gene - From: ApexBio, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
FAD Approved Pharma 0
Apocynin Investigational Pharma NADPH-oxidase inhibitor 0
GKT137831 Pharma dual NADPH oxidase Nox1/Nox4 inhibitor 0
heme Pharma Agonist 0

(7) Additional Compounds for NOX4 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
nadph
  • 2'-(Dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-b-D-ribofuranosylnicotinamide
  • 2'-(Dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-beta-delta-ribofuranosylnicotinamide
  • Adenosine 5'-(trihydrogen diphosphate) 2'-(dihydrogen phosphate) P'-5'-ester with 1,4-dihydro-1-beta-D-ribofuranosyl-3-pyridinecarboxamide
  • Adenosine 5'-(trihydrogen diphosphate) 2'-(dihydrogen phosphate) P'-5'-ester with 1,4-dihydro-1-beta-delta-ribofuranosyl-3-pyridinecarboxamide
  • b-NADPH
53-57-6

(2) ApexBio Compounds for NOX4 Gene

Compound Action Cas Number
Apocynin 498-02-2
GKT137831 dual NADPH oxidase Nox1/Nox4 inhibitor 1218942-37-0
genes like me logo Genes that share compounds with NOX4: view

Drug Products

Transcripts for NOX4 Gene

Unigene Clusters for NOX4 Gene

NADPH oxidase 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Alternative Splicing Database (ASD) splice patterns (SP) for NOX4 Gene

No ASD Table

Relevant External Links for NOX4 Gene

GeneLoc Exon Structure for
NOX4
ECgene alternative splicing isoforms for
NOX4

Expression for NOX4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for NOX4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NOX4 Gene

This gene is overexpressed in Kidney - Cortex (x10.8), Artery - Aorta (x10.8), Artery - Tibial (x5.7), and Artery - Coronary (x4.1).

NURSA nuclear receptor signaling pathways regulating expression of NOX4 Gene:

NOX4

SOURCE GeneReport for Unigene cluster for NOX4 Gene:

Hs.371036

mRNA Expression by UniProt/SwissProt for NOX4 Gene:

Q9NPH5-NOX4_HUMAN
Tissue specificity: Expressed by distal tubular cells in kidney cortex and in endothelial cells (at protein level). Widely expressed. Strongly expressed in kidney and to a lower extent in heart, adipocytes, hepatoma, endothelial cells, skeletal muscle, brain, several brain tumor cell lines and airway epithelial cells.

Evidence on tissue expression from TISSUES for NOX4 Gene

  • Kidney(4.7)
  • Lung(4.4)
  • Heart(3)
  • Muscle(2.8)
  • Blood(2.1)
genes like me logo Genes that share expression patterns with NOX4: view

Primer Products

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for NOX4 Gene

Orthologs for NOX4 Gene

This gene was present in the common ancestor of animals.

Orthologs for NOX4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NOX4 33 34
  • 99.54 (n)
cow
(Bos Taurus)
Mammalia NOX4 33 34
  • 91.7 (n)
dog
(Canis familiaris)
Mammalia NOX4 33 34
  • 89.09 (n)
oppossum
(Monodelphis domestica)
Mammalia NOX4 34
  • 89 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NOX4 34
  • 87 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Nox4 33 16 34
  • 86.97 (n)
rat
(Rattus norvegicus)
Mammalia Nox4 33
  • 86.97 (n)
chicken
(Gallus gallus)
Aves NOX4 33 34
  • 77.14 (n)
lizard
(Anolis carolinensis)
Reptilia NOX4 34
  • 76 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nox4 33
  • 67.71 (n)
zebrafish
(Danio rerio)
Actinopterygii CABZ01079296.1 34
  • 68 (a)
OneToMany
NOX4 (1 of 2) 34
  • 67 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003772 33
  • 44.59 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 31 (a)
OneToOne
Species where no ortholog for NOX4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • fruit fly (Drosophila melanogaster)
  • 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)
  • worm (Caenorhabditis elegans)

Evolution for NOX4 Gene

ENSEMBL:
Gene Tree for NOX4 (if available)
TreeFam:
Gene Tree for NOX4 (if available)

Paralogs for NOX4 Gene

Paralogs for NOX4 Gene

(3) SIMAP similar genes for NOX4 Gene using alignment to 6 proteins:

Pseudogenes.org Pseudogenes for NOX4 Gene

genes like me logo Genes that share paralogs with NOX4: view

Variants for NOX4 Gene

Sequence variations from dbSNP and Humsavar for NOX4 Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type
rs1000021612 -- 89,540,548(+) TTTGG(C/G)AGACC intron-variant
rs1000025044 -- 89,331,595(+) TCAAC(A/G)CCATA intron-variant
rs1000027210 -- 89,462,550(+) AACAA(C/T)TATAT intron-variant
rs1000033787 -- 89,366,235(+) GTAGA(-/AAAT)ACTGG intron-variant
rs1000045461 -- 89,348,395(+) GGGTA(-/ACAGAGTAAG)ACTCC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for NOX4 Gene

Variant ID Type Subtype PubMed ID
dgv165n27 CNV loss 19166990
dgv2062n54 CNV gain 21841781
esv1095170 CNV deletion 17803354
esv32702 CNV gain+loss 17666407
esv3303599 CNV mobile element insertion 20981092
esv3344726 CNV insertion 20981092
esv3353141 CNV insertion 20981092
esv3360460 CNV insertion 20981092
esv3579993 CNV gain 25503493
esv3627166 CNV loss 21293372
esv3627170 CNV loss 21293372
esv3892057 CNV gain 25118596
esv3892058 CNV loss 25118596
nsv1037020 CNV loss 25217958
nsv1037955 CNV loss 25217958
nsv1043643 CNV gain 25217958
nsv1052092 CNV gain 25217958
nsv1070978 CNV deletion 25765185
nsv1116679 CNV tandem duplication 24896259
nsv1122653 CNV deletion 24896259
nsv1127220 CNV deletion 24896259
nsv468781 CNV gain 19166990
nsv468785 CNV gain 19166990
nsv469976 CNV gain 18288195
nsv555768 CNV loss 21841781
nsv555769 CNV loss 21841781
nsv555770 CNV gain 21841781
nsv972053 CNV duplication 23825009
nsv972054 CNV duplication 23825009
nsv972055 CNV duplication 23825009
nsv975963 CNV duplication 23825009

Variation tolerance for NOX4 Gene

Residual Variation Intolerance Score: 19.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 15.00; 96.84% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for NOX4 Gene

Human Gene Mutation Database (HGMD)
NOX4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NOX4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NOX4 Gene

Disorders for NOX4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for NOX4 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
pulmonary hypertension
  • primary pulmonary hypertension
pulmonary fibrosis, idiopathic
  • idiopathic pulmonary fibrosis
- elite association - COSMIC cancer census association via MalaCards
Search NOX4 in MalaCards View complete list of genes associated with diseases

Relevant External Links for NOX4

Genetic Association Database (GAD)
NOX4
Human Genome Epidemiology (HuGE) Navigator
NOX4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
NOX4
genes like me logo Genes that share disorders with NOX4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NOX4 Gene

Publications for NOX4 Gene

  1. NAD(P)H oxidase 4 mediates transforming growth factor-beta1-induced differentiation of cardiac fibroblasts into myofibroblasts. (PMID: 16179589) Cucoranu I … Sorescu D (Circulation research 2005) 3 4 22 60
  2. Nox4 is critical for hypoxia-inducible factor 2-alpha transcriptional activity in von Hippel-Lindau-deficient renal cell carcinoma. (PMID: 16230378) Maranchie JK … Zhan Y (Cancer research 2005) 3 4 22 60
  3. Identification of novel Nox4 splice variants with impact on ROS levels in A549 cells. (PMID: 15721269) Goyal P … Hänze J (Biochemical and biophysical research communications 2005) 3 4 22 60
  4. The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H2O2 and plays an integral role in insulin signal transduction. (PMID: 14966267) Mahadev K … Goldstein BJ (Molecular and cellular biology 2004) 3 4 22 60
  5. NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells. (PMID: 15572675) Pedruzzi E … Ogier-Denis E (Molecular and cellular biology 2004) 3 4 22 60

Products for NOX4 Gene

  • Addgene plasmids for NOX4

Sources for NOX4 Gene

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