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Aliases for CYB5R3 Gene

Aliases for CYB5R3 Gene

  • Cytochrome B5 Reductase 3 2 3 5
  • NADH-Cytochrome B5 Reductase 3 2 3
  • Diaphorase-1 3 4
  • EC 1.6.2.2 4 61
  • DIA1 3 4
  • B5R 3 4
  • NADH-Cytochrome B5 Reductase 3 Membrane-Bound Form 3
  • Diaphorase (NADH) (Cytochrome B-5 Reductase) 2
  • NADH-Cytochrome B5 Reductase 3 Soluble Form 3
  • Mutant NADH-Cytochrome B5 Reductase 3
  • Cytochrome B5 Reductase 4

External Ids for CYB5R3 Gene

Previous HGNC Symbols for CYB5R3 Gene

  • DIA1

Previous GeneCards Identifiers for CYB5R3 Gene

  • GC22M041340
  • GC22M043014
  • GC22M025974

Summaries for CYB5R3 Gene

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 Hereditary Methemoglobinemia. Among its related pathways are Metabolism and Immune System. GO annotations related to this gene include oxidoreductase activity and NAD binding. An important paralog of this gene is CYB5R1.

UniProtKB/Swiss-Prot for CYB5R3 Gene

  • Desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and, in erythrocyte, methemoglobin reduction.

Gene Wiki entry for CYB5R3 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CYB5R3 Gene

Genomics for CYB5R3 Gene

Regulatory Elements for CYB5R3 Gene

Enhancers for CYB5R3 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
GH22F042681 1.2 FANTOM5 Ensembl ENCODE 24.3 -36.5 -36471 8.9 ATF1 PKNOX1 ARID4B DMAP1 YY1 ZNF121 ZNF263 JUNB KAT8 NFIL3 A4GALT CYB5R3 POLDIP3 SERHL2 TSPO MCAT GC22M042668
GH22F042612 0.2 ENCODE 19.2 +35.1 35084 4.3 CREB3L1 MLX ZFP64 FEZF1 DMAP1 YY1 SLC30A9 ZNF143 ZNF263 SP3 XRCC6 RPL5P34 FAM109B RRP7BP CYB5R3 SERHL2 ATP5L2 NAGA GC22P042614 PIR37149
GH22F042679 1.4 FANTOM5 Ensembl ENCODE 19.1 -31.1 -31101 1.5 SAP130 JUN INSM2 DMAP1 ZBTB40 ZFHX2 ZNF366 TRIM24 FOS ZNF600 A4GALT CYB5R3 ARFGAP3 SERHL2 NFAM1 GC22M042668
GH22F042608 1 FANTOM5 Ensembl ENCODE 19.1 +39.6 39614 3.4 ARNT SIN3A FEZF1 GATA2 FOS ZNF263 JUNB NCOA1 TBX21 MBD2 RRP7BP CYB5R3 ATP5L2 SERHL2 GC22P042614 PIR37149
GH22F042673 0.8 Ensembl ENCODE 18.4 -24.6 -24633 0.8 ZNF121 NFIA RFXANK HLF HNF4G PRDM10 RFX5 A4GALT CYB5R3 ATP5L2 GC22M042668
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around CYB5R3 on UCSC Golden Path with GeneCards custom track

Promoters for CYB5R3 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00001532994 268 1801 HDGF PKNOX1 MLX ARID4B SIN3A DMAP1 ZNF2 YY1 SLC30A9 ZNF143

Genomic Location for CYB5R3 Gene

Chromosome:
22
Start:
42,617,840 bp from pter
End:
42,649,568 bp from pter
Size:
31,729 bases
Orientation:
Minus strand

Genomic View for CYB5R3 Gene

Genes around CYB5R3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CYB5R3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CYB5R3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CYB5R3 Gene

Proteins for CYB5R3 Gene

  • Protein details for CYB5R3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P00387-NB5R3_HUMAN
    Recommended name:
    NADH-cytochrome b5 reductase 3
    Protein Accession:
    P00387
    Secondary Accessions:
    • B1AHF2
    • B7Z7L3
    • O75675
    • Q8TDL8
    • Q8WTS8
    • Q9UEN4
    • Q9UEN5
    • Q9UL55
    • Q9UL56

    Protein attributes for CYB5R3 Gene

    Size:
    301 amino acids
    Molecular mass:
    34235 Da
    Cofactor:
    Name=FAD; Xref=ChEBI:CHEBI:57692;
    Quaternary structure:
    • Component of a complex composed of cytochrome b5, NADH-cytochrome b5 reductase (CYB5R3) and MOSC2.

    Three dimensional structures from OCA and Proteopedia for CYB5R3 Gene

    Alternative splice isoforms for CYB5R3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CYB5R3 Gene

Post-translational modifications for CYB5R3 Gene

  • Ubiquitination at Lys 42, Lys 120, Lys 126, Lys 173, Lys 214, and Lys 234
  • Modification sites at PhosphoSitePlus

Domains & Families for CYB5R3 Gene

Suggested Antigen Peptide Sequences for CYB5R3 Gene

Graphical View of Domain Structure for InterPro Entry

P00387

UniProtKB/Swiss-Prot:

NB5R3_HUMAN :
  • Contains 1 FAD-binding FR-type domain.
  • Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.
Domain:
  • Contains 1 FAD-binding FR-type domain.
Family:
  • Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.
genes like me logo Genes that share domains with CYB5R3: view

No data available for Gene Families for CYB5R3 Gene

Function for CYB5R3 Gene

Molecular function for CYB5R3 Gene

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

Enzyme Numbers (IUBMB) for CYB5R3 Gene

Gene Ontology (GO) - Molecular Function for CYB5R3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004128 cytochrome-b5 reductase activity, acting on NAD(P)H TAS --
GO:0016208 AMP binding IEA --
GO:0016491 oxidoreductase activity IEA --
GO:0043531 ADP binding IEA --
GO:0050660 flavin adenine dinucleotide binding IEA --
genes like me logo Genes that share ontologies with CYB5R3: view
genes like me logo Genes that share phenotypes with CYB5R3: view

Human Phenotype Ontology for CYB5R3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

Flow Cytometry Products

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for CYB5R3 Gene

Localization for CYB5R3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CYB5R3 Gene

Isoform 1: Endoplasmic reticulum membrane; Lipid-anchor; Cytoplasmic side. Mitochondrion outer membrane; Lipid-anchor; Cytoplasmic side.
Isoform 2: Cytoplasm. Note=Produces the soluble form found in erythrocytes.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for CYB5R3 Gene COMPARTMENTS Subcellular localization image for CYB5R3 gene
Compartment Confidence
cytosol 5
endoplasmic reticulum 5
extracellular 5
mitochondrion 5
golgi apparatus 2
plasma membrane 2
peroxisome 1

Gene Ontology (GO) - Cellular Components for CYB5R3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA,TAS 9207238
GO:0005739 mitochondrion IEA,IDA 20833797
GO:0005741 mitochondrial outer membrane IEA,TAS --
GO:0005743 mitochondrial inner membrane IEA --
GO:0005783 endoplasmic reticulum IEA,IDA --
genes like me logo Genes that share ontologies with CYB5R3: view

Pathways & Interactions for CYB5R3 Gene

genes like me logo Genes that share pathways with CYB5R3: view

Pathways by source for CYB5R3 Gene

1 BioSystems pathway for CYB5R3 Gene
1 PharmGKB pathway for CYB5R3 Gene
1 KEGG pathway for CYB5R3 Gene
1 GeneGo (Thomson Reuters) pathway for CYB5R3 Gene
1 Qiagen pathway for CYB5R3 Gene

Gene Ontology (GO) - Biological Process for CYB5R3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006629 lipid metabolic process IEA --
GO:0006694 steroid biosynthetic process IEA --
GO:0006695 cholesterol biosynthetic process IEA --
GO:0008015 blood circulation TAS 1400360
GO:0008202 steroid metabolic process IEA --
genes like me logo Genes that share ontologies with CYB5R3: view

No data available for SIGNOR curated interactions for CYB5R3 Gene

Drugs & Compounds for CYB5R3 Gene

(29) Drugs for CYB5R3 Gene - From: DrugBank, PharmGKB, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
FAD Approved Pharma Target 0
Lidocaine Approved, Vet_approved Pharma Antagonist, Pore Blocker Anasthetic and class Ib antiarrhythmic agent 1226
Metoclopramide Approved, Investigational Pharma Dopamine receptor antagonist 116
Prilocaine Approved Pharma 79
Primaquine Approved Pharma 76

(24) Additional Compounds for CYB5R3 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Ferrocytochrome
  • 553-12-8 (FREE ACID)
  • Ferrocytochrome b-561
  • H2ppIX
  • HEM
  • Kammerer'S porphyrin
1818-68-4
Hydrogen Ion
  • Hydrogen cation
  • Hydron
  • Proton
genes like me logo Genes that share compounds with CYB5R3: view

Transcripts for CYB5R3 Gene

Unigene Clusters for CYB5R3 Gene

Cytochrome b5 reductase 3:
Representative Sequences:

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for CYB5R3 Gene

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: - -
SP6: -
SP7:

Relevant External Links for CYB5R3 Gene

GeneLoc Exon Structure for
CYB5R3
ECgene alternative splicing isoforms for
CYB5R3

Expression for CYB5R3 Gene

mRNA expression in normal human tissues for CYB5R3 Gene

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for CYB5R3 Gene



Protein tissue co-expression partners for CYB5R3 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of CYB5R3 Gene:

CYB5R3

SOURCE GeneReport for Unigene cluster for CYB5R3 Gene:

Hs.561064

mRNA Expression by UniProt/SwissProt for CYB5R3 Gene:

P00387-NB5R3_HUMAN
Tissue specificity: Isoform 2 is expressed at late stages of erythroid maturation.
genes like me logo Genes that share expression patterns with CYB5R3: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Protein differential expression in normal tissues for CYB5R3 Gene

Orthologs for CYB5R3 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for CYB5R3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CYB5R3 35
  • 95 (a)
OneToOne
cow
(Bos Taurus)
Mammalia CYB5R3 35
  • 91 (a)
OneToOne
dog
(Canis familiaris)
Mammalia CYB5R3 35
  • 88 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Cyb5r3 35
  • 86 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia CYB5R3 35
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CYB5R3 35
  • 71 (a)
OneToOne
chicken
(Gallus gallus)
Aves CYB5R3 35
  • 72 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CYB5R3 35
  • 73 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii cyb5r3 35
  • 72 (a)
OneToOne
-- 34
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.1357 34
fruit fly
(Drosophila melanogaster)
Insecta CG5946 35
  • 53 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea T05H4.4 35
  • 54 (a)
ManyToMany
hpo-19 35
  • 52 (a)
ManyToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes CBR1 35
  • 33 (a)
ManyToMany
PGA3 35
  • 29 (a)
ManyToMany
AIM33 35
  • 28 (a)
ManyToMany
rice
(Oryza sativa)
Liliopsida Os.4717 34
corn
(Zea mays)
Liliopsida Zm.4080 34
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.4536 34
Species where no ortholog for CYB5R3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • 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)
  • 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)
  • rat (Rattus norvegicus)
  • 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)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for CYB5R3 Gene

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

Paralogs for CYB5R3 Gene

Paralogs for CYB5R3 Gene

(4) SIMAP similar genes for CYB5R3 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with CYB5R3: view

Variants for CYB5R3 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for CYB5R3 Gene

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.

Sequence variations from dbSNP and Humsavar for CYB5R3 Gene

SNP ID Clin Chr 22 pos Sequence Context AA Info Type
rs121965006 Methemoglobinemia CYB5R3-related (METHB-CYB5R3) [MIM:250800], Pathogenic 42,628,233(-) AGATG(C/T)CTCAG reference, missense
rs121965007 Methemoglobinemia CYB5R3-related (METHB-CYB5R3) [MIM:250800], Pathogenic 42,631,431(-) CACCC(A/G)GCGCT reference, missense
rs121965008 Methemoglobinemia CYB5R3-related (METHB-CYB5R3) [MIM:250800], Pathogenic 42,628,169(-) GCTGC(C/T)GGTCT reference, missense
rs121965009 Methemoglobinemia CYB5R3-related (METHB-CYB5R3) [MIM:250800], Pathogenic 42,630,899(-) GCTTC(A/G)TGGAC reference, missense
rs121965011 Methemoglobinemia CYB5R3-related (METHB-CYB5R3) [MIM:250800], Pathogenic 42,627,327(-) CTGTG(C/T)GCCAC reference, missense

Structural Variations from Database of Genomic Variants (DGV) for CYB5R3 Gene

Variant ID Type Subtype PubMed ID
dgv260n21 CNV loss 19592680
esv2438931 CNV deletion 19546169
esv2758839 CNV gain+loss 17122850
nsv1127922 CNV deletion 24896259
nsv428391 CNV gain 18775914
nsv524028 CNV loss 19592680

Variation tolerance for CYB5R3 Gene

Residual Variation Intolerance Score: 50.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.46; 71.56% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for CYB5R3 Gene

Human Gene Mutation Database (HGMD)
CYB5R3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CYB5R3

Disorders for CYB5R3 Gene

MalaCards: The human disease database

(7) MalaCards diseases for CYB5R3 Gene - From: OMIM, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
methemoglobinemia, type i
  • methemoglobinemia, type ii
hereditary methemoglobinemia
  • congenital methemoglobinemia
methemoglobinemia
congenital methemoglobinemia
  • hemoglobin m disease
vaccinia
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

NB5R3_HUMAN
  • 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. {ECO:0000269 PubMed:10807796, ECO:0000269 PubMed:12393396, ECO:0000269 PubMed:1400360, ECO:0000269 PubMed:15622768, ECO:0000269 PubMed:1707593, ECO:0000269 PubMed:1898726, ECO:0000269 PubMed:7718898, ECO:0000269 PubMed:8119939, ECO:0000269 PubMed:9695975, ECO:0000269 PubMed:9886302}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for CYB5R3

Genetic Association Database (GAD)
CYB5R3
Human Genome Epidemiology (HuGE) Navigator
CYB5R3
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
CYB5R3
genes like me logo Genes that share disorders with CYB5R3: view

No data available for Genatlas for CYB5R3 Gene

Publications for CYB5R3 Gene

  1. Structure of human erythrocyte NADH-cytochrome b5 reductase. (PMID: 15502298) Bando S. … Nakagawa A. (Acta Crystallogr. D 2004) 3 4 22 64
  2. A novel mutation in the NADH-cytochrome b5 reductase gene of a Chinese patient with recessive congenital methemoglobinemia. (PMID: 10807796) Wang Y. … Zhu Z.-Y. (Blood 2000) 3 4 22 64
  3. Identification of a novel point mutation (Leu72-to-Pro) in the NADH- cytochrome b5 reductase gene of a patient with hereditary methaemoglobinaemia type I. (PMID: 9695975) Wu Y.-S. … Zhu Z.-Y. (Br. J. Haematol. 1998) 3 4 22 64
  4. An erythroid-specific transcript generates the soluble form of NADH- cytochrome b5 reductase in humans. (PMID: 9639531) Bulbarelli A. … Borgese N. (Blood 1998) 3 4 22 64
  5. Molecular basis of hereditary methaemoglobinaemia, types I and II: two novel mutations in the NADH-cytochrome b5 reductase gene. (PMID: 9886302) Higasa K. … Fukumaki Y. (Br. J. Haematol. 1998) 3 4 22 64

Products for CYB5R3 Gene

Sources for CYB5R3 Gene

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