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CYB5R4 Gene(Protein Coding)

Cytochrome B5 Reductase 4

GCID:
GC06P083859
GIFtS:
56
Genes Participants
UDN Logo

Aliases for CYB5R4 Gene

Aliases for CYB5R4 Gene

  • Cytochrome B5 Reductase 4 2 3 5
  • N-Terminal Cytochrome B5 And Cytochrome B5 Oxidoreductase Domain-Containing Protein 3 4
  • NADPH Cytochrome B5 Oxidoreductase 2 3
  • Flavohemoprotein B5/B5R 3 4
  • EC 1.6.2.2 4 61
  • Cb5/Cb5R 3 4
  • NCB5OR 3 4
  • Cytochrome B-Type NAD(P)H Oxidoreductase 3
  • Flavohemoprotein B5+B5R 3
  • DJ676J13.1 3
  • B5+B5R 4

External Ids for CYB5R4 Gene

Previous HGNC Symbols for CYB5R4 Gene

  • NCB5OR

Previous GeneCards Identifiers for CYB5R4 Gene

  • GC06P084627
  • GC06P084569
  • GC06P081798

Summaries for CYB5R4 Gene

Entrez Gene Summary for CYB5R4 Gene

  • NCB5OR is a flavohemoprotein that contains functional domains found in both cytochrome b5 (CYB5A; MIM 613218) and CYB5 reductase (CYB5R3; MIM 613213) (Zhu et al., 1999 [PubMed 10611283]).[supplied by OMIM, Jan 2010]

GeneCards Summary for CYB5R4 Gene

CYB5R4 (Cytochrome B5 Reductase 4) is a Protein Coding gene. Diseases associated with CYB5R4 include Methemoglobinemia and Maturity-Onset Diabetes Of The Young. Among its related pathways are Erythrocytes take up carbon dioxide and release oxygen and PAK Pathway. GO annotations related to this gene include oxidoreductase activity and flavin adenine dinucleotide binding. An important paralog of this gene is CYB5R3.

UniProtKB/Swiss-Prot for CYB5R4 Gene

  • NADH-cytochrome b5 reductase involved in endoplasmic reticulum stress response pathway. Plays a critical role in protecting pancreatic beta-cells against oxidant stress, possibly by protecting the cell from excess buildup of reactive oxygen species (ROS). Reduces a variety of substrates in vitro, such as cytochrome c, feericyanide and methemoglobin.

Gene Wiki entry for CYB5R4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CYB5R4 Gene

Genomics for CYB5R4 Gene

Products:

  1. Regulatory Element

Regulatory Elements for CYB5R4 Gene

Enhancers for CYB5R4 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
GH06G083866 1.7 FANTOM5 Ensembl ENCODE 6.2 +8.3 8280 2.3 PKNOX1 FEZF1 ZNF2 ZNF302 CBX5 ZNF416 ZNF143 FOS ZNF548 KLF13 CEP162 RIPPLY2 CYB5R4 PIR41363 GC06P083900
GH06G083884 0.8 ENCODE 11.7 +25.0 25004 0.1 ELF3 CBX3 ARNT FEZF1 ZNF2 RAD21 CHAMP1 GATA2 MIXL1 THAP11 CEP162 CYB5R4 RIPPLY2 PIR41363 GC06P083900
GH06G083463 1.2 FANTOM5 Ensembl ENCODE 4.9 -395.1 -395058 2.3 SCRT1 PKNOX1 CEBPB FEZF1 ZEB2 ZNF843 OSR2 ARID1B PRDM6 BCL11A PRSS35 CEP162 ME1 CYB5R4
GH06G083859 1.2 ENCODE 0.7 +0.5 488 2.3 MLX CREB3L1 AGO1 ZFP64 DMAP1 YBX1 SLC30A9 ZNF143 ZNF263 SP3 RIPPLY2 CEP162 CYB5R4 PIR41363
GH06G083590 0.3 FANTOM5 1.9 -268.9 -268939 0.3 SNAP91 PRSS35 CYB5R4 RIPPLY2
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around CYB5R4 on UCSC Golden Path with GeneCards custom track

Promoters for CYB5R4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000199524 357 2001 MLX CREB3L1 AGO1 ZFP64 DMAP1 YBX1 SLC30A9 ZNF143 ZNF263 SP3

Transcription factor binding sites by QIAGEN in the CYB5R4 gene promoter:

Genomic Location for CYB5R4 Gene

Chromosome:
6
Start:
83,859,643 bp from pter
End:
83,967,424 bp from pter
Size:
107,782 bases
Orientation:
Plus strand

Genomic View for CYB5R4 Gene

Genes around CYB5R4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CYB5R4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CYB5R4 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for CYB5R4 Gene

Proteins for CYB5R4 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for CYB5R4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q7L1T6-NB5R4_HUMAN
    Recommended name:
    Cytochrome b5 reductase 4
    Protein Accession:
    Q7L1T6
    Secondary Accessions:
    • B1AEM2
    • Q5TGI9
    • Q9NUE4
    • Q9UHI9

    Protein attributes for CYB5R4 Gene

    Size:
    521 amino acids
    Molecular mass:
    59474 Da
    Cofactor:
    Name=FAD; Xref=ChEBI:CHEBI:57692;
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=AAF04812.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAI19905.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAI22326.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for CYB5R4 Gene

neXtProt entry for CYB5R4 Gene

Protein Expression for CYB5R4 Gene

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

Selected DME Specific Peptides for CYB5R4 Gene

Q7L1T6:
  • LAAGTGFTPM
  • DCWICIRG
  • DWIRLTKSG
  • RLTKSGKD
  • PYMEYHPGGE
  • SKEDVTHDT
  • VHRWVNYESMLKECLVGRMA

Post-translational modifications for CYB5R4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for CYB5R4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for CYB5R4

Domains & Families for CYB5R4 Gene

Protein Domains for CYB5R4 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for CYB5R4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q7L1T6

UniProtKB/Swiss-Prot:

NB5R4_HUMAN :
  • Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.
Family:
  • Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.
genes like me logo Genes that share domains with CYB5R4: view

No data available for Gene Families for CYB5R4 Gene

Function for CYB5R4 Gene

Products:

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

Molecular function for CYB5R4 Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=25 mM for O(2); Redox potential: E(0) is -108 mV.;
UniProtKB/Swiss-Prot CatalyticActivity:
NADH + 2 ferricytochrome b5 = NAD(+) + H(+) + 2 ferrocytochrome b5.
UniProtKB/Swiss-Prot Function:
NADH-cytochrome b5 reductase involved in endoplasmic reticulum stress response pathway. Plays a critical role in protecting pancreatic beta-cells against oxidant stress, possibly by protecting the cell from excess buildup of reactive oxygen species (ROS). Reduces a variety of substrates in vitro, such as cytochrome c, feericyanide and methemoglobin.

Enzyme Numbers (IUBMB) for CYB5R4 Gene

Gene Ontology (GO) - Molecular Function for CYB5R4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004128 cytochrome-b5 reductase activity, acting on NAD(P)H TAS,IEA --
GO:0016174 NOT NAD(P)H oxidase activity IDA 15131110
GO:0016491 oxidoreductase activity IEA --
GO:0016653 oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor IDA 15131110
GO:0020037 heme binding IEA --
genes like me logo Genes that share ontologies with CYB5R4: view
genes like me logo Genes that share phenotypes with CYB5R4: view

Animal Models for CYB5R4 Gene

MGI Knock Outs for CYB5R4:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CYB5R4 Gene

Localization for CYB5R4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CYB5R4 Gene

Endoplasmic reticulum. Note=Soluble protein.

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 CYB5R4 gene
Compartment Confidence
endoplasmic reticulum 5
mitochondrion 3
cytosol 2
nucleus 1

Gene Ontology (GO) - Cellular Components for CYB5R4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IEA,IDA 15131110
GO:0005789 endoplasmic reticulum membrane TAS --
GO:0048471 perinuclear region of cytoplasm IDA 10611283
genes like me logo Genes that share ontologies with CYB5R4: view

Pathways & Interactions for CYB5R4 Gene

genes like me logo Genes that share pathways with CYB5R4: view

Pathways by source for CYB5R4 Gene

1 BioSystems pathway for CYB5R4 Gene
1 KEGG pathway for CYB5R4 Gene
1 Qiagen pathway for CYB5R4 Gene

Gene Ontology (GO) - Biological Process for CYB5R4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003032 detection of oxygen NAS 10611283
GO:0006091 generation of precursor metabolites and energy IDA 10611283
GO:0006801 superoxide metabolic process IDA 10611283
GO:0015701 bicarbonate transport TAS --
GO:0030073 insulin secretion IEA,ISS --
genes like me logo Genes that share ontologies with CYB5R4: view

No data available for SIGNOR curated interactions for CYB5R4 Gene

Drugs & Compounds for CYB5R4 Gene

Products:

  1. Drug

(11) Drugs for CYB5R4 Gene - From: PharmGKB and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Isosorbide Dinitrate Approved Pharma 59
Isosorbide Mononitrate Approved Pharma 0
Lidocaine Approved, Vet_approved Pharma Antagonist, Pore Blocker Anasthetic and class Ib antiarrhythmic agent 1317
Metoclopramide Approved, Investigational Pharma Dopamine receptor antagonist 120
Prilocaine Approved Pharma 84

(1) Additional Compounds for CYB5R4 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Hydrogen Ion
  • Hydrogen cation
  • Hydron
  • Proton
genes like me logo Genes that share compounds with CYB5R4: view

Transcripts for CYB5R4 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone
  5. Flow Cytometry

mRNA/cDNA for CYB5R4 Gene

(1) REFSEQ mRNAs :
(5) Additional mRNA sequences :
(91) Selected AceView cDNA sequences:
(3) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for CYB5R4 Gene

Cytochrome b5 reductase 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for CYB5R4 Gene

No ASD Table

Relevant External Links for CYB5R4 Gene

GeneLoc Exon Structure for
CYB5R4
ECgene alternative splicing isoforms for
CYB5R4

Expression for CYB5R4 Gene

Products:

  1. Primer

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for CYB5R4 Gene

mRNA expression in normal human tissues for CYB5R4 Gene
mRNA expression by BioGPS for CYB5R4 GenemRNA expression by GTEx for CYB5R4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CYB5R4 Gene

This gene is overexpressed in Whole Blood (x11.4).

Protein differential expression in normal tissues from HIPED for CYB5R4 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (20.8), Platelet (10.4), Tlymphocyte (9.5), Lymph node (9.3), and Monocytes (7.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for CYB5R4 Gene



Protein tissue co-expression partners for CYB5R4 Gene

NURSA nuclear receptor signaling pathways regulating expression of CYB5R4 Gene:

CYB5R4

SOURCE GeneReport for Unigene cluster for CYB5R4 Gene:

Hs.5741

mRNA Expression by UniProt/SwissProt for CYB5R4 Gene:

Q7L1T6-NB5R4_HUMAN
Tissue specificity: Widely expressed.

Evidence on tissue expression from TISSUES for CYB5R4 Gene

  • Liver(2.1)
  • Pancreas(2)
genes like me logo Genes that share expression patterns with CYB5R4: view

Primer Products

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for CYB5R4 Gene

Orthologs for CYB5R4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for CYB5R4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia CYB5R4 34 35
  • 99.94 (n)
dog
(Canis familiaris)
 Mammalia CYB5R4 34 35
  • 91.97 (n)
cow
(Bos Taurus)
 Mammalia CYB5R4 34 35
  • 90.96 (n)
rat
(Rattus norvegicus)
 Mammalia Cyb5r4 34
  • 85.71 (n)
mouse
(Mus musculus)
 Mammalia Cyb5r4 34 16 35
  • 84.42 (n)
oppossum
(Monodelphis domestica)
 Mammalia CYB5R4 35
  • 77 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia CYB5R4 35
  • 74 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves CYB5R4 34 35
  • 70.46 (n)
lizard
(Anolis carolinensis)
 Reptilia CYB5R4 35
  • 65 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia cyb5r4 34
  • 65.22 (n)
zebrafish
(Danio rerio)
 Actinopterygii cyb5r4 34 35
  • 56.9 (n)
fruit fly
(Drosophila melanogaster)
 Insecta CG11257 34 35
  • 44.98 (n)
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP011314 34
  • 44.07 (n)
worm
(Caenorhabditis elegans)
 Secernentea CELE_Y52B11A.3 34
  • 46.21 (n)
Y52B11A.3 35
  • 30 (a)
 OneToOne
baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes CBR1 35
  • 27 (a)
 ManyToMany
AIM33 35
  • 21 (a)
 ManyToMany
PGA3 35
  • 21 (a)
 ManyToMany
IRC21 37
sea squirt
(Ciona savignyi)
 Ascidiacea -- 35
  • 35 (a)
 OneToOne
Species where no ortholog for CYB5R4 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)
  • 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 CYB5R4 Gene

ENSEMBL:
Gene Tree for CYB5R4 (if available)
TreeFam:
Gene Tree for CYB5R4 (if available)

Paralogs for CYB5R4 Gene

Paralogs for CYB5R4 Gene

(3) SIMAP similar genes for CYB5R4 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with CYB5R4: view

Variants for CYB5R4 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for CYB5R4 Gene

NB5R4_HUMAN-Q7L1T6
Variants Arg-187 and Arg-223 do not influence the pathogenesis of non-autoimmune diabetes.

Sequence variations from dbSNP and Humsavar for CYB5R4 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type
VAR_036240 A breast cancer sample
VAR_036241 A breast cancer sample
rs1000025040 -- 83,921,551(+) GTTCT(A/G)CCATA intron-variant
rs1000050890 -- 83,935,056(+) CAACT(A/G)CTAGA intron-variant
rs1000050902 -- 83,902,874(+) GTTGA(C/T)TTTGT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for CYB5R4 Gene

Variant ID Type Subtype PubMed ID
esv2669183 CNV deletion 23128226
esv3609786 CNV loss 21293372
nsv1025798 CNV gain 25217958
nsv1068710 OTHER inversion 25765185
nsv1153488 OTHER inversion 26484159
nsv830718 CNV gain+loss 17160897
nsv830719 CNV gain 17160897

Variation tolerance for CYB5R4 Gene

Residual Variation Intolerance Score: 46% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.98; 49.66% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for CYB5R4 Gene

Human Gene Mutation Database (HGMD)
CYB5R4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CYB5R4

Disorders for CYB5R4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for CYB5R4 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
methemoglobinemia
maturity-onset diabetes of the young
  • mason-type diabetes
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for CYB5R4

Genetic Association Database (GAD)
CYB5R4
Human Genome Epidemiology (HuGE) Navigator
CYB5R4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
CYB5R4
genes like me logo Genes that share disorders with CYB5R4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CYB5R4 Gene

Publications for CYB5R4 Gene

  1. Identification of a cytochrome b-type NAD(P)H oxidoreductase ubiquitously expressed in human cells. (PMID: 10611283) Zhu H. … Bunn H.F. (Proc. Natl. Acad. Sci. U.S.A. 1999) 2 3 4 22 64
  2. NCB5OR is a novel soluble NAD(P)H reductase localized in the endoplasmic reticulum. (PMID: 15131110) Zhu H. … Bunn H.F. (J. Biol. Chem. 2004) 3 4 22 64
  3. Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset diabetes of the young, and gestational diabetes mellitus. (PMID: 15504981) Andersen G. … Pedersen O. (Diabetes 2004) 3 4 46 64
  4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey S.D. … Anand S. (Diabetes Care 2010) 3 46 64
  5. Study of the individual cytochrome b5 and cytochrome b5 reductase domains of Ncb5or reveals a unique heme pocket and a possible role of the CS domain. (PMID: 20630863) Deng B. … Zhu H. (J. Biol. Chem. 2010) 3 4 64

Products for CYB5R4 Gene

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