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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

CYB5R3 Gene

protein-coding   GIFtS: 64
GCID: GC22M043014

cytochrome b5 reductase 3

(Previous name: diaphorase (NADH) (cytochrome b-5 reductase) )
(Previous symbol: DIA1)
 Explore 27 diseases affiliated with
CYB5R3 via
MalaCards
our new
 Human Malady Compendium 
Biological research products
for CYB5R3    

Aliases
for CYB5R3 gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section
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-13     

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


Summaries
for CYB5R3 gene

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section
Entrez Gene summary for CYB5R3:
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)

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


Genomic Views
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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000022.10  NC_018933.1  NT_011520.12  
Regulatory elements:
   SABiosciences 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 SABiosciences Chromatin IP Primers for CYB5R3

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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

Proteins
for CYB5R3 gene

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section
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)
Subcellular location: Isoform 1: Endoplasmic reticulum membrane; Lipid-anchor; Cytoplasmic side. Mitochondrion outer
membrane; Lipid-anchor; Cytoplasmic side
Subcellular location: Isoform 2: Cytoplasm. Note=Produces the soluble form found in erythrocytes
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

Post-translational modifications:

  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_P00387

    • 4/16 DME Specific Peptides for CYB5R3 (P00387) (see all 16)
     YTPISSD  GQHIYLS  SHDTRRF  LWYTLDR 

    CYB5R3 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

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

    ENSEMBL proteins: 
     ENSP00000338461   ENSP00000384834   ENSP00000415224   ENSP00000384457   ENSP00000385679  
     ENSP00000403439   ENSP00000354468   ENSP00000379597  
    Reactome Protein details: P00387
    Human Recombinant Protein Products: 
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    ProSpec Recombinant Protein for CYB5R3
    Uscn Proteins for CYB5R3

    Gene Ontology (GO): 5/8 cellular component terms (GO ID links to tree view) (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm TAS9207238
    GO:0005741mitochondrial outer membrane TAS--
    GO:0005743mitochondrial inner membrane IEA--
    GO:0005783endoplasmic reticulum IDA--
    GO:0005789endoplasmic reticulum membrane IEA--


    CYB5R3 for ontologies           About GeneDecksing



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    Uscn ELISAs and CLIAs for CYB5R3

    Protein Domains /
    Families
    for CYB5R3 gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    CYB5R3 for domains           About GeneDecksing

    5/6 InterPro domains/families (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 families:
    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


    Function
    for CYB5R3 gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section
    Function Summary:

         UniProtKB/Swiss-Prot: 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

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    hsa-miR-544 hsa-miR-767-3p hsa-miR-561
    SwitchGear 3'UTR luciferase reporter plasmid: CYB5R3 3' UTR sequence
    Inhib. RNA
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    Gene Editing
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    Clone
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    Gene Ontology (GO): 5/7 molecular function terms (GO ID links to tree view) (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



    Pathways & Interactions
    for CYB5R3 gene

    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways - 5/7 super-pathways (see all 7) About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1NAD metabolism
    		NAD metabolism1.00
    		NAD metabolism1.00
    2Vitamin B5 (pantothenate) metabolism
    		Metabolism of vitamins and cofactors0.21
    		Metabolism of water-soluble vitamins and cofactors0.21
    3Vitamin C (ascorbate) metabolism
    		Vitamin C (ascorbate) metabolism1.00
    4Methylene Blue Pathway, Pharmacodynamics
    		Methylene Blue Pathway, Pharmacodynamics1.00
    5Amino sugar and nucleotide sugar metabolism
    		Amino sugar and nucleotide sugar metabolism1.00

    Pathway sources
    See GeneCards unified pathways
    Show all pathways

    1 EMD Millipore Pathway for CYB5R3
        NAD metabolism


    1 GeneGo (Thomson Reuters) Pathway for CYB5R3
        NAD metabolism

    1 BioSystems Pathway for CYB5R3 
        cytochrome P450

    4        Reactome Pathways for CYB5R3
        Metabolism
    Metabolism of vitamins and cofactors
    Metabolism of water-soluble vitamins and cofactors
    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

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for CYB5R3

    STRING Interaction Network Preview (showing 5 interactants - click image to see 16)

    5/19 Interacting proteins for CYB5R3 (P003873 ENSP000003384614) via UniProtKB, MINT, STRING, and/or I2D (see all 19)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CYB5AP001673, ENSP000003416254I2D: score=2 STRING: ENSP00000341625
    CYCSP999993, ENSP000003077864I2D: score=2 STRING: ENSP00000307786
    HBG2P698923, ENSP000003380824I2D: score=1 STRING: ENSP00000338082
    UBCP0CG483, ENSP000003448184I2D: score=1 STRING: ENSP00000344818
    PRKAB1Q9Y4783, ENSP000002293284I2D: score=1 STRING: ENSP00000229328
    About this table

    Gene Ontology (GO): 5/6 biological process terms (GO ID links to tree view) (see all 6):    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



    Drugs & Compounds
    for CYB5R3 gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    CYB5R3 for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for CYB5R3

    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

    10/43 Novoseek 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
    Drug/compound PharmGKB Annotation
    dapsoneDL  
    methylene blueDL  
    primaquineDL  
    About this table

    Search CenterWatch for drugs/clinical trials and news about CYB5R3 / NB5R3 

    Transcripts
    for CYB5R3 gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
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    About This Section
    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
    10 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000352397 ENST00000407623 ENST00000414587 ENST00000407332 ENST00000470741
    ENST00000402438 ENST00000438270 ENST00000466276 ENST00000361740(uc011aps.2)
    ENST00000396303(uc021wqn.1 uc003bcy.3 uc003bcx.3 uc003bcz.3)


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    Inhib. RNA
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    Additional cDNA 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 

    24/53 DOTS entries (see all 53):

    DT.95069144  DT.100045068  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 

    24/712 AceView cDNA sequences (see all 712):

    CN482499 BI768166 CR621834 BX449375 AA306117 CA421136 CR618034 BM927260 
    BF724852 CB106199 CB132968 AA636055 CD367102 CR616501 CR623803 CB154557 
    BI834357 CR601590 CR594068 AU141069 CR613363 CR600483 CR591561 CA389060 

    GeneLoc Exon Structure

    5/7 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

    Expression
    for CYB5R3 gene

    (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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    CYB5R3 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: --

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)
    About this image

    CYB5R3 expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    2 LifeMap In Vivo Development Anatomical Compartments/Cells 
    Tissue Anatomical Compartment CellCategory (developmental path)
    Skeletal MuscleHyoid Arch MusclesMononuclear MyocytesSkeletal Muscle
    Skeletal MuscleMandibular Arch MusclesMononuclear MyocytesSkeletal Muscle
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization

    See CYB5R3 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for CYB5R3

    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

        SABiosciences Expression via Pathway-Focused PCR Arrays including CYB5R3: 
              Lipoprotein Signaling & Cholesterol Metabolism in human mouse rat
              Drug Metabolism in human mouse rat

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    In Situ
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    Orthologs
    for CYB5R3 gene

    (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)
    About This Section
    This gene was present in the common ancestor of eukaryotes.

    Orthologs for CYB5R3 gene from 8/30 species (see all 30)    About this table
    Organism Taxonomic
    classification    		 Gene Description Human
    Similarity    		 Orthology
    Type    		 Details
    chicken
    (Gallus gallus)    		 Aves CYB5R31 cytochrome b5 reductase 3 70.52(n)
    72.79(a)    		   418220  XM_416445.3  XP_416445.1 
    lizard
    (Anolis carolinensis)    		 Reptilia CYB5R36
    		 --
    		 73(a)
    		 1 ↔ 1
    		 5(91548581-91563309)
    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
    		 54(a)
    53(a)
    		 many ↔ many
    many ↔ many
    		 V(6438919-6440075)
    V(6436591-6437867)
    thale cress
    (Arabidopsis thaliana)    		 eudicotyledons NIA11 nitrate reductase [NADH] 54.46(n)
    51.18(a)    		   844112  NM_106425.2  NP_177899.1 
    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
    for CYB5R3 gene

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for CYB5R3 gene
    CYB5R22  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



    Genomic Variants
    for CYB5R3 gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    UniProtKB/Swiss-Prot: NB5R3_HUMAN, P00387
    Polymorphism: 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


    10/784 NCBI SNPs in CYB5R3 are shown (see all 784)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 22 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs18004571,2
    		C,F,O,H,non-pathogenic27673453(-) GGACAC/GCCATC 10 T S mis1 ese320Minor allele frequency- G:0.10NS NA EA WA EU 7469
    rs1219650091,2
    		C,pathogenic27670819(-) GCTTCA/GTGGAC 10 M V mis10--------
    rs617326091,2
    		C,Fpathogenic27674044(+) AGGTCA/C/G/T 
                GATGG     		20 R G * syn1 mis1 stg12NS NA 4626
    rs1219650181,2
    		Cpathogenic27677911(-) GCTGGA/GCAGAG 10 D G mis11Minor allele frequency- G:0.00NA 4552
    rs734231551,2
    		C,--25974304(+) GGCCCG/TCCTTC 5 -- ds50011Minor allele frequency- T:0.50WA 2
    rs124837671,2
    		C,H,--25974412(+) AGCCTA/GGCCCC 5 -- ds50014Minor allele frequency- G:0.08NA WA EA 360
    rs713291511,2
    		C,F--25974418(+) GCCCCG/ACCTCC 5 -- ds50012Minor allele frequency- A:0.50NA 4
    rs783619121,2
    		F,--25974510(+) TCCAAC/TGGCAG 5 -- ut311Minor allele frequency- T:0.09WA 118
    rs81904771,2
    		C,F,--25974748(-) CGAGGC/TTGCTG 5 -- ut319Minor allele frequency- T:0.06NS NA WA CSA 316
    rs57588101,2
    		F,--25974774(+) ACTGGG/AGTTGC 5 -- ut311Minor allele frequency- A:0.07EA 120

    HapMap Linkage Disequilibrium report for CYB5R3 (43013846 - 43045574 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
    Database of Genomic Variants (DGV): 4 variations for CYB5R3
         4 CNVs: 3242 4129 103183 50870
    Human Gene Mutation Database (HGMD): CYB5R3

    SABiosciences Cancer Mutation PCR Assays
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    DNA2.0 Custom Variant and Variant Library Synthesis for CYB5R3

    Disorders / Diseases
    for CYB5R3 gene

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    CYB5R3 for disorders           About GeneDecksing

    OMIM gene information: 613213   
    OMIM disorders: 250800  
    UniProtKB/Swiss-Prot: NB5R3_HUMAN, P00387
  • Defects in CYB5R3 are the cause of 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

    20/27 diseases for CYB5R3 (see all 27):    About MalaCards
    methemoglobinemia    methemoglobinemia, type ii    methemoglobinemia, type i    ceroid lipofuscinosis
    neuronal ceroid-lipofuscinosis    non-small cell lung carcinoma    cholesterol    monkeypox
    acute lymphoblastic leukemia    lymphoblastic leukemia    smallpox    intrahepatic cholangiocarcinoma
    stomatitis    lung carcinoma    cholangiocarcinoma    diarrhea
    vaccinia    leukemia    lung cancer    glioblastoma

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

    10 Novoseek 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)

    Human Genome Epidemiology (HuGE) Navigator: CYB5R3 (1 document)

    Export disorders for CYB5R3 gene to outside databases

    Publications
    for CYB5R3 gene

    (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)
    About This Section

    PubMed articles for CYB5R3 gene, integrated from 9 sources (see all 207):
    (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. (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. (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. (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. (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. (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. (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. (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. (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. (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. (1997)

    External Searches for CYB5R3 gene

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  
      Query String
    		PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    Genome Databases showing CYB5R3 gene

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

    Other Databases showing CYB5R3 gene

    (According to HUGE)
    About This Section
    		   --

    Specialized Databases showing CYB5R3 gene

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

    Intellectual Property
    for CYB5R3 gene

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

    GeneCards and IP:
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