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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 4 56
  • 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 Due To Deficiency Of Methemoglobin Reductase and Hereditary Methemoglobinemia. Among its related pathways are Innate Immune System and Metabolism. Gene Ontology (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

Additional gene information for CYB5R3 Gene

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

Genomics for CYB5R3 Gene

GeneHancer (GH) Regulatory Elements for CYB5R3 Gene

Promoters and enhancers for CYB5R3 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH22I042641 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 561 +3.9 3866 9.3 HDGF PKNOX1 FOXA2 SMAD1 MLX ARID4B SIN3A DMAP1 ZNF2 YY1 CYB5R3 RRP7BP RPL5P34 SERHL2 POLDIP3 RN7SKP80 A4GALT GC22P042648 ATP5MGL
GH22I042612 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 19.2 +35.1 35084 4.3 MLX ZFP64 FEZF1 DMAP1 IRF4 YY1 SLC30A9 ZNF213 E2F8 ZNF143 POLDIP3 GC22P042614 GC22P042618 GC22P042619 RNU12 ENSG00000270022 RPL5P34 XRCC6 NAGA RRP7BP
GH22I042679 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 19.1 -31.1 -31100 1.5 JUN ZBTB11 ZSCAN4 INSM2 ZBTB40 ATF2 GABPA FOSL1 JUND ZNF366 A4GALT CYB5R3 ARFGAP3 SERHL2 NFAM1 GC22M042670
GH22I042608 Enhancer 1.3 FANTOM5 Ensembl ENCODE dbSUPER 19.1 +39.6 39614 3.4 SOX5 KLF1 FOXA2 ZIC2 TEAD3 PRDM6 POLR2A GLIS1 PRDM10 MLLT1 RRP7BP CYB5R3 ATP5MGL SERHL2 GC22P042614 POLDIP3 PIR37149
GH22I042618 Enhancer 1.3 Ensembl ENCODE dbSUPER 17.9 +28.7 28685 3.9 ARNT FEZF1 ZNF2 ZNF121 GLIS2 ZNF143 FOS RUNX3 REST SSRP1 RRP7BP CYB5R3 XRCC6 RN7SKP80 RNU12 ENSG00000270022 ATP5MGL
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around CYB5R3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the CYB5R3 gene promoter:

Genomic Locations for CYB5R3 Gene

Genomic Locations for CYB5R3 Gene
31,729 bases
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:
    Recommended name:
    NADH-cytochrome b5 reductase 3
    Protein Accession:
    Secondary Accessions:
    • B1AHF2
    • B7Z7L3
    • O75675
    • Q8TDL8
    • Q8WTS8
    • Q9UEN4
    • Q9UEN5
    • Q9UL55
    • Q9UL56

    Protein attributes for CYB5R3 Gene

    301 amino acids
    Molecular mass:
    34235 Da
    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


neXtProt entry for CYB5R3 Gene

Selected DME Specific Peptides for CYB5R3 Gene


Post-translational modifications for CYB5R3 Gene

  • Ubiquitination at posLast=4242, Lys120, Lys126, posLast=173173, Lys214, and Lys234
  • Modification sites at PhosphoSitePlus

Domains & Families for CYB5R3 Gene

Gene Families for CYB5R3 Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins
  • Predicted membrane proteins

Suggested Antigen Peptide Sequences for CYB5R3 Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.
  • Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.
genes like me logo Genes that share domains with CYB5R3: view

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

Phenotypes From GWAS Catalog 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:0005515 protein binding IPI 23123858
GO:0016208 AMP binding IEA --
GO:0016491 oxidoreductase activity IBA --
GO:0043531 ADP 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

CRISPR Products

Inhibitory RNA Products

Clone 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

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 CYB5R3 gene
Compartment Confidence
extracellular 5
mitochondrion 5
endoplasmic reticulum 5
cytosol 5
lysosome 4
plasma membrane 1
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Endoplasmic reticulum (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CYB5R3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005737 cytoplasm TAS 9207238
GO:0005739 mitochondrion IEA,HDA 20833797
GO:0005741 mitochondrial outer membrane TAS --
GO:0005743 mitochondrial inner membrane IEA --
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:0006805 xenobiotic metabolic process TAS --
GO:0008015 blood circulation TAS 1400360
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

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
NADH Approved Nutra Target 0
FAD Approved Pharma Target 0
Copper Approved, Investigational Pharma Target 202
Isosorbide Dinitrate Approved, Investigational Pharma 62
Isosorbide Mononitrate Approved Pharma 0

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

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • 553-12-8 (FREE ACID)
  • Ferrocytochrome b-561
  • H2ppIX
  • HEM
  • Kammerer'S porphyrin
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:

CRISPR Products

Inhibitory RNA Products

Clone 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: -

Relevant External Links for CYB5R3 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for CYB5R3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE 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:


SOURCE GeneReport for Unigene cluster for CYB5R3 Gene:


mRNA Expression by UniProt/SwissProt for CYB5R3 Gene:

Tissue specificity: Isoform 2 is expressed at late stages of erythroid maturation.

Evidence on tissue expression from TISSUES for CYB5R3 Gene

  • Liver(4.8)
  • Nervous system(4.6)
  • Blood(4.5)
  • Skin(3.3)
  • Intestine(3.2)
  • Lung(2.5)
  • Heart(2.2)
  • Muscle(2.2)
  • Gall bladder(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CYB5R3 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
Head and neck:
  • brain
  • cranial nerve
  • eye
  • head
  • meninges
  • neck
  • skull
  • bronchus
  • lung
  • trachea
  • blood
  • blood vessel
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
genes like me logo Genes that share expression patterns with CYB5R3: view

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
(Pan troglodytes)
Mammalia CYB5R3 34
  • 95 (a)
(Bos Taurus)
Mammalia CYB5R3 34
  • 91 (a)
(Canis familiaris)
Mammalia CYB5R3 34
  • 88 (a)
(Mus musculus)
Mammalia Cyb5r3 34
  • 86 (a)
(Monodelphis domestica)
Mammalia CYB5R3 34
  • 83 (a)
(Ornithorhynchus anatinus)
Mammalia CYB5R3 34
  • 71 (a)
(Gallus gallus)
Aves CYB5R3 34
  • 72 (a)
(Anolis carolinensis)
Reptilia CYB5R3 34
  • 73 (a)
(Danio rerio)
Actinopterygii cyb5r3 34
  • 72 (a)
-- 33
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.1357 33
fruit fly
(Drosophila melanogaster)
Insecta CG5946 34
  • 53 (a)
(Caenorhabditis elegans)
Secernentea T05H4.4 34
  • 54 (a)
hpo-19 34
  • 52 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes CBR1 34
  • 33 (a)
PGA3 34
  • 29 (a)
AIM33 34
  • 28 (a)
(Oryza sativa)
Liliopsida Os.4717 33
(Zea mays)
Liliopsida Zm.4080 33
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.4536 33
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

Gene Tree for CYB5R3 (if available)
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

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 Variation AA Info Type
rs121965006 pathogenic, Methemoglobinemia type 2, Methemoglobinemia CYB5R3-related (METHB-CYB5R3) [MIM:250800] 42,628,233(-) A/G coding_sequence_variant, missense_variant
rs121965007 pathogenic, Methemoglobinemia, type I, Methemoglobinemia CYB5R3-related (METHB-CYB5R3) [MIM:250800] 42,631,431(-) C/G/T coding_sequence_variant, missense_variant
rs121965008 pathogenic, Methemoglobinemia, type I, Methemoglobinemia CYB5R3-related (METHB-CYB5R3) [MIM:250800] 42,628,169(-) A/G coding_sequence_variant, missense_variant
rs121965009 pathogenic, Methemoglobinemia, type I, Methemoglobinemia CYB5R3-related (METHB-CYB5R3) [MIM:250800] 42,630,899(-) C/T coding_sequence_variant, missense_variant
rs121965010 pathogenic, Methemoglobinemia type 2 42,623,867(-) G/A coding_sequence_variant, stop_gained

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)

Additional Variant Information for CYB5R3 Gene

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

Disorders for CYB5R3 Gene

MalaCards: The human disease database

(10) MalaCards diseases for CYB5R3 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
methemoglobinemia due to deficiency of methemoglobin reductase
  • nadh-dependent methemoglobin reductase deficiency
hereditary methemoglobinemia
  • autosomal recessive methemoglobinemia
congenital methemoglobinemia
  • hemoglobin m disease
acquired methemoglobinemia
  • drug-induced methemoglobinemia
- elite association - COSMIC cancer census association via MalaCards


  • 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:15953014, 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.

Additional Disease Information for CYB5R3

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
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 crystallographica. Section D, Biological crystallography 2004) 3 4 22 58
  2. A novel mutation in the NADH-cytochrome b5 reductase gene of a Chinese patient with recessive congenital methemoglobinemia. (PMID: 10807796) Wang Y … Zhu ZY (Blood 2000) 3 4 22 58
  3. 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 58
  4. Identification of a novel point mutation (Leu72Pro) in the NADH-cytochrome b5 reductase gene of a patient with hereditary methaemoglobinaemia type I. (PMID: 9695975) Wu YS … Zhu ZY (British journal of haematology 1998) 3 4 22 58
  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 (British journal of haematology 1998) 3 4 22 58

Products for CYB5R3 Gene

Sources for CYB5R3 Gene

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