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CYB5R2 cytochrome b5 reductase 2 [ Homo sapiens (human) ]

Gene ID: 51700, updated on 3-Apr-2024

Summary

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Official Symbol
CYB5R2provided by HGNC
Official Full Name
cytochrome b5 reductase 2provided by HGNC
Primary source
HGNC:HGNC:24376
See related
Ensembl:ENSG00000166394 MIM:608342; AllianceGenome:HGNC:24376
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
B5R.2
Summary
The protein encoded by this gene belongs to the flavoprotein pyridine nucleotide cytochrome reductase family of proteins. Cytochrome b-type NAD(P)H oxidoreductases are implicated in many processes including cholesterol biosynthesis, fatty acid desaturation and elongation, and respiratory burst in neutrophils and macrophages. Cytochrome b5 reductases have soluble and membrane-bound forms that are the product of alternative splicing. In animal cells, the membrane-bound form binds to the endoplasmic reticulum, where it is a member of a fatty acid desaturation complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]
Expression
Biased expression in testis (RPKM 34.1), skin (RPKM 7.5) and 8 other tissues See more
Orthologs
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Genomic context

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See CYB5R2 in Genome Data Viewer
Location:
11p15.4
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (7665095..7674267, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (7723469..7735468, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (7686326..7695498, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene olfactomedin like 1 Neighboring gene leucine-rich repeat extensin-like protein 5 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4365 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3110 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4366 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4367 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4368 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4369 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4370 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4371 Neighboring gene MPRA-validated peak1190 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4372 Neighboring gene PPFIA binding protein 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4373 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr11:7584372-7584873 Neighboring gene uncharacterized LOC105376535 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:7595102-7595926 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:7595927-7596750 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:7599169-7599403 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4374 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr11:7651972-7653171 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4375 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr11:7672104-7673303 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4376 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4377 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3111 Neighboring gene uncharacterized LOC105376533 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr11:7712245-7713444 Neighboring gene ovochymase 2 Neighboring gene uncharacterized LOC124902626

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Intratumoral Heterogeneity for Inactivating Frameshift Mutation of CYB5R2 Gene in Colorectal Cancers. Jo YS, et al. Pathol Oncol Res, 2020 Jan. PMID 29532410
  2. Genetic, epigenetic, and molecular landscapes of multifocal and multicentric glioblastoma. Liu Q, et al. Acta Neuropathol, 2015 Oct. PMID 26323991, Free PMC Article
  3. Cytochrome b5 reductase 2 is a novel candidate tumor suppressor gene frequently inactivated by promoter hypermethylation in human nasopharyngeal carcinoma. Xiao X, et al. Tumour Biol, 2014 Apr. PMID 24338690, Free PMC Article
  4. Identification of cytochrome-b5 reductase as the enzyme responsible for NADH-dependent lucigenin chemiluminescence in human spermatozoa. Baker MA, et al. Biol Reprod, 2005 Aug. PMID 15858218
  5. NADH-Cytochrome B5 reductase 2 suppresses retinal vascular dysfunction through regulation of vascular endothelial growth factor A in diabetic retinopathy. Chen J, et al. Exp Eye Res, 2022 Sep. PMID 35820466

See all (23) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. NADH-Cytochrome B5 reductase 2 suppresses retinal vascular dysfunction through regulation of vascular endothelial growth factor A in diabetic retinopathy.
    Title: NADH-Cytochrome B5 reductase 2 suppresses retinal vascular dysfunction through regulation of vascular endothelial growth factor A in diabetic retinopathy.
  2. Long non-coding RNA MEG3 inhibits neovascularization in diabetic retinopathy by regulating microRNA miR-6720-5p and cytochrome B5 reductase 2.
    Title: Long non-coding RNA MEG3 inhibits neovascularization in diabetic retinopathy by regulating microRNA miR-6720-5p and cytochrome B5 reductase 2.
  3. Intratumoral Heterogeneity for Inactivating Frameshift Mutation of CYB5R2 Gene in Colorectal Cancers.
    Title: Intratumoral Heterogeneity for Inactivating Frameshift Mutation of CYB5R2 Gene in Colorectal Cancers.
  4. Study showed that multifocal or multicentric glioblastomas have some underlying genetic and epigenetic characteristics that are associated with poor prognosis and that CYB5R2 is a new epigenetic marker for glioblastoma prognosis
    Title: Genetic, epigenetic, and molecular landscapes of multifocal and multicentric glioblastoma.
  5. findings suggest that CYB5R2 may be a functional tumor suppressor gene, frequently inactivated by hypermethylation of its promoter in nasopharyngeal carcinoma
    Title: Cytochrome b5 reductase 2 is a novel candidate tumor suppressor gene frequently inactivated by promoter hypermethylation in human nasopharyngeal carcinoma.
  6. Observational study of gene-disease association. (HuGE Navigator)
    Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
  7. CYB5R2 is a key enzyme involved in the mediation of NADH-induced redox activity in human spermatozoa.
    Title: Identification of cytochrome-b5 reductase as the enzyme responsible for NADH-dependent lucigenin chemiluminescence in human spermatozoa.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ12494

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables FAD binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables cytochrome-b5 reductase activity, acting on NAD(P)H IDA
Inferred from Direct Assay
more info
 PubMed 
enables cytochrome-b5 reductase activity, acting on NAD(P)H TAS
Traceable Author Statement
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in bicarbonate transport TAS
Traceable Author Statement
more info
  
involved_in sterol biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
  
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus HDA PubMed 

General protein information

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Preferred Names
NADH-cytochrome b5 reductase 2
Names
cytochrome b5 reductase b5R.2
NP_001289755.1
NP_001289756.1
NP_057313.2
XP_006718314.1
XP_011518486.2
XP_011518487.2
XP_024304348.1
XP_047283080.1
XP_047283081.1
XP_054225097.1
XP_054225098.1
XP_054225099.1
XP_054225100.1
XP_054225101.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001302826.2 → NP_001289755.1  NADH-cytochrome b5 reductase 2 isoform 1

    See identical proteins and their annotated locations for NP_001289755.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). Both variants 1 and 2 encode the same protein.
    Source sequence(s)
    AC104237, AK290102, BF061336, BM693762, DB460012
    Consensus CDS
    CCDS7780.1
    UniProtKB/Swiss-Prot
    Q6BCY4, Q9BVA3, Q9UF68, Q9UHJ0
    UniProtKB/TrEMBL
    A8K237
    Related
    ENSP00000437041.1, ENST00000533558.5
    Conserved Domains (1) summary
    cl26810
    Location:8 → 276
    PLN02252; nitrate reductase [NADPH]

  2. NM_001302827.1 → NP_001289756.1  NADH-cytochrome b5 reductase 2 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in its 5' UTR and uses an alternate splice site in the 3' coding region, which results in a frameshift compared to variant 1. It encodes isoform 2, which has a shorter and distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AC104237, BF061336, BG495762, BQ431043, HY211860
    Conserved Domains (1) summary
    cd06183
    Location:20 → 188
    cyt_b5_reduct_like; Cytochrome b5 reductase catalyzes the reduction of 2 molecules of cytochrome b5 using NADH as an electron donor. Like ferredoxin reductases, these proteins have an N-terminal FAD binding subdomain and a C-terminal NADH binding subdomain, separated by a ...

  3. NM_016229.5 → NP_057313.2  NADH-cytochrome b5 reductase 2 isoform 1

    See identical proteins and their annotated locations for NP_057313.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein (isoform 1).
    Source sequence(s)
    AC104237, AY665398, CB149369
    Consensus CDS
    CCDS7780.1
    UniProtKB/Swiss-Prot
    Q6BCY4, Q9BVA3, Q9UF68, Q9UHJ0
    UniProtKB/TrEMBL
    A8K237
    Related
    ENSP00000299498.6, ENST00000299498.11
    Conserved Domains (1) summary
    cl26810
    Location:8 → 276
    PLN02252; nitrate reductase [NADPH]

RNA

  1. NR_126508.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate first exon and contains an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC104237, AK290102, BC001346, BF061336
    Related
    ENST00000524790.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    7665095..7674267 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047427125.1 → XP_047283081.1  NADH-cytochrome b5 reductase 2 isoform X3

    Related
    ENSP00000434969.1, ENST00000531096.5

  2. XM_011520184.3 → XP_011518486.2  NADH-cytochrome b5 reductase 2 isoform X1

    UniProtKB/Swiss-Prot
    Q6BCY4, Q9BVA3, Q9UF68, Q9UHJ0

  3. XM_006718251.4 → XP_006718314.1  NADH-cytochrome b5 reductase 2 isoform X1

    See identical proteins and their annotated locations for XP_006718314.1

    UniProtKB/Swiss-Prot
    Q6BCY4, Q9BVA3, Q9UF68, Q9UHJ0
    UniProtKB/TrEMBL
    A8K237
    Conserved Domains (1) summary
    cl26810
    Location:8 → 276
    PLN02252; nitrate reductase [NADPH]

  4. XM_024448580.2 → XP_024304348.1  NADH-cytochrome b5 reductase 2 isoform X1

    UniProtKB/Swiss-Prot
    Q6BCY4, Q9BVA3, Q9UF68, Q9UHJ0
    UniProtKB/TrEMBL
    A8K237
    Conserved Domains (1) summary
    cl26810
    Location:8 → 276
    PLN02252; nitrate reductase [NADPH]

  5. XM_047427124.1 → XP_047283080.1  NADH-cytochrome b5 reductase 2 isoform X1

    UniProtKB/Swiss-Prot
    Q6BCY4, Q9BVA3, Q9UF68, Q9UHJ0

  6. XM_011520185.4 → XP_011518487.2  NADH-cytochrome b5 reductase 2 isoform X2

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    7723469..7735468 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054369122.1 → XP_054225097.1  NADH-cytochrome b5 reductase 2 isoform X4

  2. XM_054369126.1 → XP_054225101.1  NADH-cytochrome b5 reductase 2 isoform X7

  3. XM_054369125.1 → XP_054225100.1  NADH-cytochrome b5 reductase 2 isoform X1

  4. XM_054369123.1 → XP_054225098.1  NADH-cytochrome b5 reductase 2 isoform X5

  5. XM_054369124.1 → XP_054225099.1  NADH-cytochrome b5 reductase 2 isoform X6

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001001336.1: Suppressed sequence

    Description
    NM_001001336.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q6BCY4.1 GenPept UniProtKB/Swiss-Prot:Q6BCY4

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