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CYB5R3 Gene

protein-coding   GIFtS: 66
GCID: GC22M043014

Cytochrome B5 Reductase 3

(Previous name: diaphorase (NADH) (cytochrome b-5 reductase))
(Previous symbol: DIA1)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Cytochrome B5 Reductase 31 2     NADH-Cytochrome B5 Reductase 32
DIA11 2 3 5     NADH-Cytochrome B5 Reductase 3 Membrane-Bound Form2
B5R2 3 5     NADH-Cytochrome B5 Reductase 3 Soluble Form2
EC 1.6.2.23 8     Diaphorase-13
Diaphorase (NADH) (Cytochrome B-5 Reductase)1     Cytochrome B5 Reductase3
diaphorase-12     

External Ids:    HGNC: 28731   Entrez Gene: 17272   Ensembl: ENSG000001002437   OMIM: 6132135   UniProtKB: P003873   

Export aliases for CYB5R3 gene to outside databases

Previous GC identifers: GC22M041340 GC22M025974


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for CYB5R3 Gene:
This gene encodes cytochrome b5 reductase, which includes a membrane-bound form in somatic cells (anchored in the
endoplasmic reticulum, mitochondrial and other membranes) and a soluble form in erythrocytes. The membrane-bound
form exists mainly on the cytoplasmic side of the endoplasmic reticulum and functions in desaturation and
elongation of fatty acids, in cholesterol biosynthesis, and in drug metabolism. The erythrocyte form is located
in a soluble fraction of circulating erythrocytes and is involved in methemoglobin reduction. The membrane-bound
form has both membrane-binding and catalytic domains, while the soluble form has only the catalytic domain.
Alternate splicing results in multiple transcript variants. Mutations in this gene cause methemoglobinemias.
(provided by RefSeq, Jan 2010)

GeneCards Summary for CYB5R3 Gene:
CYB5R3 (cytochrome b5 reductase 3) is a protein-coding gene. Diseases associated with CYB5R3 include methemoglobinemia, type i, and congenital methemoglobinemia. GO annotations related to this gene include ADP binding and flavin adenine dinucleotide binding. An important paralog of this gene is ENSG00000256407.

UniProtKB/Swiss-Prot: NB5R3_HUMAN, P00387
Function: Desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and, in
erythrocyte, methemoglobin reduction

Gene Wiki entry for CYB5R3 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000022.11  NC_018933.2  NT_011520.13  
Regulatory elements:
   Regulatory transcription factor binding sites in the CYB5R3 gene promoter:
         GR   SRF   Sp1   SRF (504 AA)   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): CYB5R3 promoter sequence
   Search Chromatin IP Primers for CYB5R3

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CYB5R3


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 22q13.2   Ensembl cytogenetic band:  22q13.2   HGNC cytogenetic band: 22q13.2

CYB5R3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CYB5R3 gene location

GeneLoc information about chromosome 22         GeneLoc Exon Structure

GeneLoc location for GC22M043014:  view genomic region     (about GC identifiers)

Start:
43,013,846 bp from pter      End:
43,045,574 bp from pter
Size:
31,729 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: NB5R3_HUMAN, P00387 (See protein sequence)
Recommended Name: NADH-cytochrome b5 reductase 3  
Size: 301 amino acids; 34235 Da
Cofactor: FAD
Subunit: Component of a complex composed of cytochrome b5, NADH-cytochrome b5 reductase (CYB5R3) and MOSC2 (By
similarity)
2 PDB 3D structures from and Proteopedia for CYB5R3:
1M91 (3D)        1UMK (3D)    
Secondary accessions: B1AHF2 B7Z7L3 O75675 Q8TDL8 Q8WTS8 Q9UEN4 Q9UEN5 Q9UL55 Q9UL56
Alternative promoter usage, Alternative splicing: 3 isoforms:  P00387-1   P00387-2   P00387-3   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for CYB5R3: NX_P00387

Explore proteomics data for CYB5R3 at MOPED

Post-translational modifications: 

  • Ubiquitination2 at Lys42, Lys120, Lys126, Lys173, Lys214, Lys234
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for CYB5R3 (P00387) (see all 16)
     YTPISSD  GQHIYLS  SHDTRRF  LWYTLDR 


    See CYB5R3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (5 alternative transcripts): 
    NP_000389.1  NP_001123291.1  NP_001165131.1  NP_001165132.1  NP_015565.1  

    ENSEMBL proteins: 
     ENSP00000338461   ENSP00000384834   ENSP00000384457   ENSP00000385679   ENSP00000403439  
     ENSP00000354468   ENSP00000379597  
    Reactome Protein details: P00387

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 6):
     IPR017927 Fd_Rdtase_FAD-bd
     IPR008333 OxRdtase_FAD-bd_dom
     IPR001433 OxRdtase_FAD/NAD-bd
     IPR001709 Flavoprot_Pyr_Nucl_cyt_Rdtase
     IPR001834 NADH-Cyt_B5_reductase

    Graphical View of Domain Structure for InterPro Entry P00387

    ProtoNet protein and cluster: P00387

    4 Blocks protein domains:
    IPB001433 Oxidoreductase FAD/NAD(P)-binding
    IPB001709 Flavoprotein pyridine nucleotide cytochrome reductase signature
    IPB001834 Cytochrome B5 reductase signature
    IPB008333 Oxidoreductase FAD-binding region


    UniProtKB/Swiss-Prot: NB5R3_HUMAN, P00387
    Similarity: Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family
    Similarity: Contains 1 FAD-binding FR-type domain


    CYB5R3 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: NB5R3_HUMAN, P00387
    Function: Desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and, in
    erythrocyte, methemoglobin reduction
    Catalytic activity: NADH + 2 ferricytochrome b5 = NAD(+) + H(+) + 2 ferrocytochrome b5

         Enzyme Number (IUBMB): EC 1.6.2.21 2

         Gene Ontology (GO): Selected molecular function terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004128cytochrome-b5 reductase activity, acting on NAD(P)H TAS--
    GO:0016208AMP binding IEA--
    GO:0016491oxidoreductase activity ----
    GO:0043531ADP binding IEA--
    GO:0050660flavin adenine dinucleotide binding IEA--
         
    CYB5R3 for ontologies           About GeneDecksing


    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for CYB5R3
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    miRNA
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    miRTarBase miRNAs that target CYB5R3:
    hsa-mir-98-5p (MIRT027454), hsa-mir-378a-3p (MIRT043904), hsa-mir-92a-3p (MIRT049610), hsa-mir-484 (MIRT042354), hsa-mir-744-5p (MIRT037551)

    Block miRNA regulation of human, mouse, rat CYB5R3 using miScript Target Protectors
    3 qRT-PCR Assays for microRNAs that regulate CYB5R3:
    hsa-miR-544 hsa-miR-767-3p hsa-miR-561
    SwitchGear 3'UTR luciferase reporter plasmidCYB5R3 3' UTR sequence
    Inhib. RNA
    Products:
        
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    Predesigned siRNA for gene silencing in human, mouse, rat CYB5R3

    Gene Editing
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    Clone
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    GenScript: all cDNA clones in your preferred vector (see all 5): CYB5R3 (NM_001129819)
    Browse Sino Biological Human cDNA Clones
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CYB5R3


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    NB5R3_HUMAN, P00387: Isoform 1: Endoplasmic reticulum membrane; Lipid-anchor; Cytoplasmic side. Mitochondrion
    outer membrane; Lipid-anchor; Cytoplasmic side
    NB5R3_HUMAN, P00387: Isoform 2: Cytoplasm. Note=Produces the soluble form found in erythrocytes
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    endoplasmic reticulum5
    mitochondrion5
    cytosol4
    extracellular2
    cytoskeleton1
    golgi apparatus1
    peroxisome1
    plasma membrane1

    Gene Ontology (GO): Selected cellular component terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm TAS9207238
    GO:0005739mitochondrion IDA--
    GO:0005741mitochondrial outer membrane TAS--
    GO:0005743mitochondrial inner membrane IEA--
    GO:0005783endoplasmic reticulum IDA--

    CYB5R3 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for CYB5R3 About   (see all 7)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Defective BTD causes biotidinase deficiency
    Defective BTD causes biotidinase deficiency1.00
    Metabolism of vitamins and cofactors1.00
    Defective AMN causes hereditary megaloblastic anemia 11.00
    Defective MMACHC causes methylmalonic aciduria and homocystinuria type cblC1.00
    Defective MMAA causes methylmalonic aciduria type cblA1.00
    Defective MUT causes methylmalonic aciduria mut type1.00
    Defective CD320 causes methylmalonic aciduria1.00
    Defects in cobalamin (B12) metabolism1.00
    2Cytochrome P450 - arranged by substrate type
    cytochrome P4500.74
    3Nicotinate and nicotinamide metabolism
    NAD metabolism0.43
    4Metabolism
    Metabolism0.38
    5Methylene Blue Pathway, Pharmacodynamics
    Methylene Blue Pathway, Pharmacodynamics

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 Downloadable PowerPoint Slide of GeneGlobe Pathway Central Maps for CYB5R3
        Antioxidant Action of Vitamin-C

    1 GeneGo (Thomson Reuters) Pathway for CYB5R3
        NAD metabolism

    1 BioSystems Pathway for CYB5R3
        cytochrome P450

    1 Reactome Pathway for CYB5R3
        Vitamin C (ascorbate) metabolism

    1 PharmGKB Pathway for CYB5R3
        Methylene Blue Pathway, Pharmacodynamics

    1 Kegg Pathway  (Kegg details for CYB5R3):
        Amino sugar and nucleotide sugar metabolism


    CYB5R3 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including CYB5R3: 
              Lipoprotein Signaling & Cholesterol Metabolism in human mouse rat
              Drug Metabolism in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for CYB5R3

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for CYB5R3 (P003873 ENSP000003384614) via UniProtKB, MINT, STRING, and/or I2D (see all 34)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ACSL1P331213, ENSP000002814554I2D: score=1 STRING: ENSP00000281455
    CYB5AP001673, ENSP000003416254I2D: score=2 STRING: ENSP00000341625
    CYCSP999993, ENSP000003077864I2D: score=2 STRING: ENSP00000307786
    HBG2P698923, ENSP000003380824I2D: score=1 STRING: ENSP00000338082
    UBCP0CG483, ENSP000003448184I2D: score=1 STRING: ENSP00000344818
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006695cholesterol biosynthetic process IEA--
    GO:0006766vitamin metabolic process TAS--
    GO:0006767water-soluble vitamin metabolic process TAS--
    GO:0008015blood circulation TAS1400360
    GO:0019852L-ascorbic acid metabolic process TAS--

    CYB5R3 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for CYB5R3 (NB5R3)

    5 HMDB Compounds for CYB5R3    About this table
    CompoundSynonyms CAS #PubMed Ids
    FAD1H-Purin-6-amine flavin dinucleotide (see all 21)146-14-5--
    Ferricytochrome553-12-8 (FREE ACID) (see all 21)1818-68-4--
    Ferrocytochrome553-12-8 (FREE ACID) (see all 21)1818-68-4--
    NAD3-Carbamoyl-1-D-ribofuranosylpyridinium hydroxide 5'-ester with adenosine 5'-pyrophosphate (see all 28)53-84-9--
    NADH1,4-Dihydronicotinamide adenine dinucleotide (see all 17)58-68-4--

    3 DrugBank Compounds for CYB5R3    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    NADHbeta-DPNH (see all 18)606-68-8target--17341833 17401193 16814740 17082011 17040106
    Flavin-Adenine Dinucleotide-- 146-14-5target--17139284 17016423 10592235
    Nicotinamide-Adenine-Dinucleotide-- 53-84-9target--10592235

    Selected Novoseek inferred chemical compound relationships for CYB5R3 gene (see all 43)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    benzamidoxime 88.2 4 9351903 (1), 15862605 (1), 15302896 (1), 16973608 (1)
    nadh 84.3 131 8883403 (6), 15302896 (6), 8402680 (5), 2162152 (4) (see all 56)
    sulfamethoxazole hydroxylamine 83 9 19997042 (3), 15302896 (2), 15862605 (1)
    dicoumarol 65.1 3 12171070 (2), 8402680 (1)
    p-hydroxymercuribenzoate 64.7 4 12171070 (1), 14552588 (1), 8883403 (1)
    flavin-adenine dinucleotide 64.2 1 11159544 (1)
    phmb 56.4 2 8883403 (1)
    ferricyanide 53.9 1 2189408 (1)
    nadph 53.3 12 10611283 (2), 8005794 (2), 11263680 (1), 2161167 (1) (see all 9)
    nad+ 47.6 6 8874222 (1), 10807796 (1), 11159544 (1), 12756024 (1)

    3 PharmGKB related drug/compound annotations for CYB5R3 gene    About this table
    Drug/compound PharmGKB Annotation
    dapsone
    methylene blue
    primaquine



    CYB5R3 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for CYB5R3 gene (5 alternative transcripts): 
    NM_000398.6  NM_001129819.2  NM_001171660.1  NM_001171661.1  NM_007326.4  

    Unigene Cluster for CYB5R3:

    Cytochrome b5 reductase 3
    Hs.561064  [show with all ESTs]
    Unigene Representative Sequence: NM_001129819
    9 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000352397 ENST00000407623 ENST00000407332 ENST00000470741 ENST00000402438
    ENST00000438270 ENST00000466276 ENST00000361740(uc011aps.2) ENST00000396303(uc021wqn.1 uc003bcy.3 uc003bcx.3 uc003bcz.3)

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    hsa-miR-544 hsa-miR-767-3p hsa-miR-561
    SwitchGear 3'UTR luciferase reporter plasmidCYB5R3 3' UTR sequence
    Inhib. RNA
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    GenScript: all cDNA clones in your preferred vector (see all 5): CYB5R3 (NM_001129819)
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CYB5R3
    Primer
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    OriGene qSTAR qPCR primer pairs in human, mouse for CYB5R3
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat CYB5R3
      QuantiTect SYBR Green Assays in human, mouse, rat CYB5R3
      QuantiFast Probe-based Assays in human, mouse, rat CYB5R3

    Additional mRNA sequence: 

    AF361370.1 AJ010116.1 AJ010117.1 AJ010118.1 AJ310899.1 AJ310900.1 AK302204.1 AY421733.1 
    AY421734.1 BC004821.1 BT009821.1 CR456435.1 M16461.1 M16462.1 Y09501.1 

    Selected DOTS entries (see all 53):

    DT.100045068  DT.95069144  DT.95069119  DT.100892769  DT.100045067  DT.100830765  DT.100892785  DT.100892800 
    DT.100892754  DT.100892777  DT.95069139  DT.100892796  DT.120630305  DT.100892762  DT.100645199  DT.100892757 
    DT.95069141  DT.100645065  DT.100705538  DT.100892752  DT.100892770  DT.100892794  DT.120630295  DT.120630457 

    Selected AceView cDNA sequences (see all 712):

    CR614892 BM994088 CR590472 BM563185 CR596646 BU902529 AJ310899 BX462940 
    BM826404 AU280031 BM669254 CB105598 BQ432105 AA279986 BM800594 CD676286 
    BI918699 BM998563 BU159515 BI906705 BU931781 BU554185 CR597031 CB106006 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for CYB5R3 (see all 7)    About this scheme

    ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7a · 7b ^ 8a · 8b ^ 9 ^ 10a · 10b ^ 11a · 11b · 11c · 11d
    SP1:                    -     -                 -                 -                       -                                 
    SP2:                    -     -                 -           -     -                       -                                 
    SP3:                    -     -                 -           -     -     -     -     -     -                                 
    SP4:                                            -                 -                                                         
    SP5:                          -                 -                                                                           


    ECgene alternative splicing isoforms for CYB5R3

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    CYB5R3 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    CYB5R3 Expression
    About this image


    CYB5R3 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 18) fully expand
     
     Brain (Nervous System)    fully expand to see all 4 entries
             Cerebral Cortex
     
     Ovary (Reproductive System)    fully expand to see all 2 entries
             Ovarian Mesenchymal Stroma Cells Ovary Interstitium
             Oviduct
     
     Testis (Reproductive System)
             Leydig Cells Testis Interstitium
     
     Liver (Hepatobiliary System)
             Hepatocytes Liver Lobule
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
    CYB5R3 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    CYB5R3 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.561064

    UniProtKB/Swiss-Prot: NB5R3_HUMAN, P00387
    Tissue specificity: Isoform 2 is expressed at late stages of erythroid maturation

        Pathway & Disease-focused RT2 Profiler PCR Arrays including CYB5R3: 
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of eukaryotes.

    Orthologs for CYB5R3 gene from Selected species (see all 18)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Cyb5r35 cytochrome b5 reductase 3   --   15 (39.40 cM) 83153494 
    chicken
    (Gallus gallus)
    Aves CYB5R36
    cytochrome b5 reductase 3
    72(a)
    1 ↔ 1
    1(68448251-68462610)
    lizard
    (Anolis carolinensis)
    Reptilia CYB5R36
    cytochrome b5 reductase 3
    73(a)
    1 ↔ 1
    5(91545172-91578903)
    African clawed frog
    (Xenopus laevis)
    Amphibia BC045265.12   -- 76.74(n)    BC045265.1 
    zebrafish
    (Danio rerio)
    Actinopterygii BC045880.12   -- 74.71(n)   393158  BC045880.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG59466
    --
    53(a)
    1 → many
    3L(11810083-11815375)
    worm
    (Caenorhabditis elegans)
    Secernentea T05H4.46
    hpo-196
    Protein HPO-19 (hpo-19) mRNA, complete cds
    54(a)
    52(a)
    many ↔ many
    many ↔ many
    V(6438936-6440092) WBGene00020267
    V(6436608-6437884) WBGene00020268
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes CBR16
    PGA36
    (see all 3)
    Microsomal cytochrome b reductase, not essential f...
    Putative cytochrome b5 reductase, localized to the...
    (see all 3)
    33(a)
    29(a)
    (see all 3)
    many ↔ many
    many ↔ many
    (see all 3)
    IX(274072-274926) YIL043C
    XIII(20761-21699) YML125C
    rice
    (Oryza sativa)
    Liliopsida Os.47172 Oryza sativa (japonica cultivar-group) cDNA clone002-127-A08, full insert sequence less 72.37(n)    AK101662.1 


    ENSEMBL Gene Tree for CYB5R3 (if available)
    TreeFam Gene Tree for CYB5R3 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for CYB5R3 gene
    ENSG000002564072  CYB5R22  CYB5RL2  CYB5R42  CYB5R12  
    4 SIMAP similar genes for CYB5R3 using alignment to 2 protein entries:     NB5R3_HUMAN (see all proteins):
    CYB5R1    CYB5R2    CYB5R4    CYB5RL

    CYB5R3 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Polymorphic Variants from UniProtKB/Swiss-Prot
    NB5R3_HUMAN, P00387: Ser-117 seems to only be found in persons of African origin. The allele frequency is 0.23 in African
    Americans. It was not found in Caucasians, Asians, Indo-Aryans, or Arabs. There seems to be no effect on the
    enzyme activity


    Selected SNPs for CYB5R3 (see all 985)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 22 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs2012325181,2,,4
    Methemoglobinemia CYB5R3-related (METHB-CYB5R3)4 --26940443(+) CTCCCA/GCGATC 10 A V mis10--------
    rs1219650091,2,,4
    CMethemoglobinemia CYB5R3-related (METHB-CYB5R3)4 pathogenic126943726(-) GCTTCA/GTGGAC 10 M V mis10--------
    VAR_0107504
    Methemoglobinemia CYB5R3-related (METHB-CYB5R3)4--see VAR_0107502 L P mis40--------
    VAR_0107544
    Methemoglobinemia CYB5R3-related (METHB-CYB5R3)4--see VAR_0107542 C Y mis40--------
    VAR_0046194
    Methemoglobinemia CYB5R3-related (METHB-CYB5R3)4--see VAR_0046192 R Q mis40--------
    VAR_0046224
    Methemoglobinemia CYB5R3-related (METHB-CYB5R3)4--see VAR_0046222 L P mis40--------
    VAR_0373164
    Methemoglobinemia CYB5R3-related (METHB-CYB5R3)4--see VAR_0373162 G D mis40--------
    VAR_0107534
    Methemoglobinemia CYB5R3-related (METHB-CYB5R3)4--see VAR_0107532 C R mis40--------
    VAR_0046214
    Methemoglobinemia CYB5R3-related (METHB-CYB5R3)4--see VAR_0046212 S P mis40--------
    rs18004571,2,,4
    C,F,O,Hnon-pathogenic126941092(-) GGACAC/GCCATC 10 T S mis1 ese320Minor allele frequency- G:0.10NS NA EA WA EU 7469

    HapMap Linkage Disequilibrium report for CYB5R3 (43013846 - 43045574 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 10 variations for CYB5R3:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2438931CNV Deletion19546169
    nsv524028CNV Loss19592680
    dgv260n21CNV Loss19592680
    nsv915180CNV Loss21882294
    dgv4983n71CNV Loss21882294
    nsv915185CNV Gain21882294
    nsv428391CNV Gain18775914
    essv20414CNV CNV17122850
    essv4940CNV CNV17122850
    dgv1407e1CNV Complex17122850

    Human Gene Mutation Database (HGMD): CYB5R3
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing CYB5R3
    DNA2.0 Custom Variant and Variant Library Synthesis for CYB5R3

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 613213   
    OMIM disorders: 250800  
    UniProtKB/Swiss-Prot: NB5R3_HUMAN, P00387
  • Methemoglobinemia CYB5R3-related (METHB-CYB5R3) [MIM:250800]: A form of methemoglobinemia, a hematologic
    disease characterized by the presence of excessive amounts of methemoglobin in blood cells, resulting in
    decreased oxygen carrying capacity of the blood, cyanosis and hypoxia. There are two types of methemoglobinemia
    CYB5R3-related. In type 1, the defect affects the soluble form of the enzyme, is restricted to red blood cells,
    and causes well-tolerated methemoglobinemia. In type 2, the defect affects both the soluble and microsomal forms
    of the enzyme and is thus generalized, affecting red cells, leukocytes and all body tissues. Type 2
    methemoglobinemia is associated with mental deficiency and other neurologic symptoms. Note=The disease is caused
    by mutations affecting the gene represented in this entry

  • Selected diseases for CYB5R3 (see all 27):    
    About MalaCards
    methemoglobinemia, type i    congenital methemoglobinemia    methemoglobinemia, type ii    methemoglobinemia
    nadh cytochrome b5 reductase deficiency    monkeypox    vaccinia    neuronal ceroid lipofuscinosis
    smallpox    stomatitis    diarrhea    intrahepatic cholangiocarcinoma
    cholangiocarcinoma    mental retardation    lymphoblastic leukemia    pneumonia
    hypoxia    thyroiditis    neuronitis    tonsillitis

    4 diseases from the University of Copenhagen DISEASES database for CYB5R3:
    Methemoglobinemia     Smallpox     Monkeypox     Vaccinia

    CYB5R3 for disorders           About GeneDecksing

    10 Novoseek inferred disease relationships for CYB5R3 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    methemoglobinemia hereditary 97.9 42 1400360 (3), 11243135 (3), 2107882 (3), 10979206 (3) (see all 18)
    methemoglobinemia 92.6 61 10807796 (3), 10874300 (3), 10534899 (3), 7860238 (3) (see all 34)
    methemoglobinemia acquired 70.3 2 15921385 (1), 10870338 (1)
    enzyme deficiency 67.1 6 1400360 (1), 2323714 (1), 1707593 (1), 2107882 (1) (see all 5)
    rare disease 15.5 3 18202104 (1), 7668255 (1)
    mental retardation 15.2 4 8352247 (1), 8427971 (1), 8143727 (1)
    genetic disorder 8.92 2 2323714 (1)
    tumors 4.2 4 18794327 (2), 8005794 (1), 7987842 (1)
    cancer 0 9 17040106 (1), 8883403 (1), 19082487 (1)
    congenital malformation 0 2 7668255 (1)

    Genetic Association Database (GAD): CYB5R3
    Human Genome Epidemiology (HuGE) Navigator: CYB5R3 (1 document)

    Export disorders for CYB5R3 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for CYB5R3 gene, integrated from 10 sources (see all 212):
    (articles sorted by number of sources associating them with CYB5R3)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The organization and the complete nucleotide sequence of the human NADH-cytochrome b5 reductase gene. (PubMed id 2479590)1, 2, 3 Tomatsu S.... Sakaki Y. (Gene 1989)
    2. An erythroid-specific transcript generates the soluble form of NADH- cytochrome b5 reductase in humans. (PubMed id 9639531)1, 2, 9 Bulbarelli A....Borgese N. (Blood 1998)
    3. A novel mutation in the NADH-cytochrome b5 reductase gene of a Chinese patient with recessive congenital methemoglobinemia. (PubMed id 10807796)1, 2, 9 Wang Y.... Zhu Z.-Y. (Blood 2000)
    4. Molecular basis of hereditary methaemoglobinaemia, types I and II: two novel mutations in the NADH-cytochrome b5 reductase gene. (PubMed id 9886302)1, 2, 9 Higasa K.... Fukumaki Y. (Br. J. Haematol. 1998)
    5. A high-frequency polymorphism of NADH-cytochrome b5 reductase in African-Americans. (PubMed id 9048929)1, 2, 9 Jenkins M.M. and Prchal J.T. (Hum. Genet. 1997)
    6. Identification of a novel point mutation (Leu72-to-Pro) in the NADH- cytochrome b5 reductase gene of a patient with hereditary methaemoglobinaemia type I. (PubMed id 9695975)1, 2, 9 Wu Y.-S.... Zhu Z.-Y. (Br. J. Haematol. 1998)
    7. Role of cysteine residues in human NADH-cytochrome b5 reductase studied by site-directed mutagenesis. Cys-273 and Cys-283 are located close to the NADH-binding site but are not catalytically essential. (PubMed id 2019583)1, 2, 9 Shirabe K.... Takeshita M. (J. Biol. Chem. 1991)
    8. Enzymatic instability of NADH-cytochrome b5 reductase as a cause of hereditary methemoglobinemia type I (red cell type). (PubMed id 1400360)1, 2, 9 Shirabe K....Takeshita M. (J. Biol. Chem. 1992)
    9. Exonic point mutations in NADH-cytochrome B5 reductase genes of homozygotes for hereditary methemoglobinemia, types I and III: putative mechanisms of tissue-dependent enzyme deficiency. (PubMed id 1707593)1, 2, 9 Katsube T.... Fukumaki Y. (Am. J. Hum. Genet. 1991)
    10. Arginine-glutamine replacement at residue 57 of NADH-cytochrome b5 reductase in Chinese hereditary methemoglobinemia. (PubMed id 15622768)1, 2, 9 Huang C.-H.... Wu Y.-S. (Zhonghua Xue Ye Xue Za Zhi 1997)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 1727 HGNC: 2873 AceView: DIA1 Ensembl:ENSG00000100243 euGenes: HUgn1727
    ECgene: CYB5R3 Kegg: 1727 H-InvDB: CYB5R3

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for CYB5R3 Pharmacogenomics, SNPs, Pathways
    NIEHS-SNPshttp://egp.gs.washington.edu/data/dia1/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for CYB5R3 gene:
    Search GeneIP for patents involving CYB5R3

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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