CYB5R3 cytochrome b5 reductase 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CYB5R3provided by HGNC
Official Full Name: cytochrome b5 reductase 3provided by HGNC
Primary source: HGNC:HGNC:2873
See related: Ensembl:ENSG00000100243 MIM:613213; AllianceGenome:HGNC:2873
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; DIA1
Summary: 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]
Expression: Ubiquitous expression in fat (RPKM 110.9), testis (RPKM 52.5) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q13.2

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (42617840..42649392, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (43098710..43130267, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (43013846..43045398, complement)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CYB5R3 T117S Genetic Mutation Is Associated With Major Adverse Cardiovascular and Cerebrovascular Events in Black Adults.
Title: CYB5R3 T117S Genetic Mutation Is Associated With Major Adverse Cardiovascular and Cerebrovascular Events in Black Adults.
Three novel mutations in CYB5R3 gene causing NADH-cytochrome b5 reductase enzyme deficiency leads to recessive congenital methaemoglobinemia.
Title: Three novel mutations in CYB5R3 gene causing NADH-cytochrome b5 reductase enzyme deficiency leads to recessive congenital methaemoglobinemia.
Mutation update: Variants of the CYB5R3 gene in recessive congenital methemoglobinemia.
Title: Mutation update: Variants of the CYB5R3 gene in recessive congenital methemoglobinemia.
The CYB5R3(c) (.350C>G) and G6PD A alleles modify severity of anemia in malaria and sickle cell disease.
Title: The CYB5R3(c) (.350C>G) and G6PD A alleles modify severity of anemia in malaria and sickle cell disease.
study indicated that novel homozygous mutation p.Arg192Cys in CYB5R3 gene present in eight cases and the possibility of high prevalence of heterozygous in Indian population causing Type I recessive congenital methemoglobinemia.
Title: Novel mutation (R192C) in CYB5R3 gene causing NADH-cytochrome b5 reductase deficiency in eight Indian patients associated with autosomal recessive congenital methemoglobinemia type-I.
Data suggest that cytochrome b5 (CYB5) and cytochrome b5 reductase 3 (CYB5R3) can reduce human cytoglobin (CYGB) and zebrafish cytoglobins at rates up to 250-fold higher than those reported for the known physiological substrates, hemoglobin and myoglobin; the three proteins (CYB5+CYB5R3+CYGB) appear to constitute a metabolon involved in generation of nitric oxide.
Title: Efficient Reduction of Vertebrate Cytoglobins by the Cytochrome b(5)/Cytochrome b(5) Reductase/NADH System.
CYB5R3 promotes colonization and metastasis formation and is a prognostic marker of disease-free and overall survival in estrogen receptor-negative breast cancer.
Title: NADH-Cytochrome b5 Reductase 3 Promotes Colonization and Metastasis Formation and Is a Prognostic Marker of Disease-Free and Overall Survival in Estrogen Receptor-Negative Breast Cancer.
Variants in CYB5A and CYB5R3 should be considered in the evaluation of breast cancer risk in African American women.
Title: Polymorphisms in the carcinogen detoxification genes CYB5A and CYB5R3 and breast cancer risk in African American women.
Genetic variation in CYB5R3 is associated with methemoglobin levels in preterm infants receiving nitric oxide therapy.
Title: Genetic variation in CYB5R3 is associated with methemoglobin levels in preterm infants receiving nitric oxide therapy.
The results unveil a potential mechanism of action by which CYB5R3 deficiency contributes to the pathophysiological underpinnings of neurological disorders in RHM patients.
Title: Membrane-bound CYB5R3 is a common effector of nutritional and oxidative stress response through FOXO3a and Nrf2.

Submit: New GeneRIF Correction See all GeneRIFs (31)

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

Associated conditions

Description	Tests
Deficiency of cytochrome-b5 reductase MedGen: C0268193 OMIM: 250800 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp160, precursor	env	HIV-1 gp160 interacts with CYB5R	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC156606P1 (e-PCR)
- UniSTS:271408

PMC156606P2 (e-PCR)
- UniSTS:271409

PMC156606P3 (e-PCR)
- UniSTS:271410

D8S2278 (e-PCR)
- UniSTS:473906

PMC156606P4 (e-PCR)
- UniSTS:271411

D8S2279 (e-PCR)
- UniSTS:473907

SHGC-7735 (e-PCR)
- UniSTS:54353

5STS03 (e-PCR)
- UniSTS:503890

L18426 (e-PCR)
- UniSTS:34648

STS-D29393 (e-PCR)
- UniSTS:33369

STS-M16462 (e-PCR)
- UniSTS:33370

RH80030 (e-PCR)
- UniSTS:87680

D22S1545 (e-PCR)
- UniSTS:13199

D11S3114 (e-PCR)
- UniSTS:152207

D16S521 (e-PCR), detects polymorphism
- UniSTS:44473

RH27822 (e-PCR)
- UniSTS:83670

RH70318 (e-PCR)
- UniSTS:67559

AL008666 (e-PCR)
- UniSTS:71918

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ADP binding	IEA Inferred from Electronic Annotation more info
enables AMP binding	IEA Inferred from Electronic Annotation more info
enables FAD binding	IBA Inferred from Biological aspect of Ancestor more info
enables FAD binding	IDA Inferred from Direct Assay more info	PubMed
enables NAD binding	IEA Inferred from Electronic Annotation 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	IMP Inferred from Mutant Phenotype more info	PubMed
contributes_to nitrite reductase (NO-forming) activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in blood circulation	TAS Traceable Author Statement more info	PubMed
involved_in cholesterol biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in nitric oxide biosynthetic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in azurophil granule lumen	TAS Traceable Author Statement more info
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info
is_active_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
part_of hemoglobin complex	TAS Traceable Author Statement more info	PubMed
located_in lipid droplet	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	HDA more info	PubMed
located_in mitochondrial membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial outer membrane	TAS Traceable Author Statement more info
located_in mitochondrion	HDA more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
part_of nitric-oxide synthase complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: NADH-cytochrome b5 reductase 3

Names: NADH-cytochrome b5 reductase 3 membrane-bound form; NADH-cytochrome b5 reductase 3 soluble form; diaphorase-1; mutant NADH-cytochrome b5 reductase

NP_000389.1

EC 1.6.2.2

NP_001123291.1

EC 1.6.2.2

NP_001165131.1

EC 1.6.2.2

NP_001165132.1

EC 1.6.2.2

NP_015565.1

EC 1.6.2.2

XP_047297139.1

EC 1.6.2.2

XP_054181199.1

EC 1.6.2.2

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.

Genomic

NG_012194.1 RefSeqGene

Range

5008..36560

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000398.7 → NP_000389.1 NADH-cytochrome b5 reductase 3 isoform 1

See identical proteins and their annotated locations for NP_000389.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the membrane-bound form (isoform 1) of the enzyme. This isoform (1) is referred to in the literature as isoform m.

Source sequence(s)

BC004821, BX334220, Z93241

Consensus CDS

CCDS33658.1

UniProtKB/Swiss-Prot

B1AHF2, B7Z7L3, O75675, P00387, Q8TDL8, Q8WTS8, Q9UEN4, Q9UEN5, Q9UL55, Q9UL56

UniProtKB/TrEMBL

A0A8J8Z3C6

Related

ENSP00000338461.6, ENST00000352397.10

Conserved Domains (2) summary

cd06183
Location:45 → 301

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 ...

PTZ00319
Location:11 → 301

PTZ00319; NADH-cytochrome B5 reductase; Provisional
NM_001129819.2 → NP_001123291.1 NADH-cytochrome b5 reductase 3 isoform 2

See identical proteins and their annotated locations for NP_001123291.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) has an alternate 5' exon, as compared to variant 1. The resulting isoform (2) is the soluble form of the enzyme, which has a shorter N-terminus when it is compared to the membrane-bound form. This isoform (2) is referred to in the literature as isoform s.

Source sequence(s)

AJ310900, DA268749, DA548643, Z93241

Consensus CDS

CCDS14040.1

UniProtKB/TrEMBL

A0A8J8Z3C6

Related

ENSP00000384834.3, ENST00000407623.8

Conserved Domains (2) summary

cd06183
Location:22 → 278

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 ...

PTZ00319
Location:3 → 278

PTZ00319; NADH-cytochrome B5 reductase; Provisional
NM_001171660.2 → NP_001165131.1 NADH-cytochrome b5 reductase 3 isoform 3

See identical proteins and their annotated locations for NP_001165131.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and 5' coding region and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (3) is longer and has a distinct N-terminus, compared to isoform 1.

Source sequence(s)

AK302204, Z93241

Consensus CDS

CCDS54535.1

UniProtKB/TrEMBL

A0A8J8Z3C6

Related

ENSP00000509015.1, ENST00000688117.1

Conserved Domains (2) summary

cd06183
Location:78 → 334

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 ...

PTZ00319
Location:44 → 334

PTZ00319; NADH-cytochrome B5 reductase; Provisional
NM_001171661.1 → NP_001165132.1 NADH-cytochrome b5 reductase 3 isoform 2

See identical proteins and their annotated locations for NP_001165132.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate exon in the 5' UTR and 5' coding region, compared to variant 1. The resulting isoform (2) is the soluble form of the enzyme, which has a shorter N-terminus when it is compared to the membrane-bound form. This isoform (2) is referred to in the literature as isoform s.

Source sequence(s)

BM564146, Z93241

Consensus CDS

CCDS14040.1

UniProtKB/TrEMBL

A0A8J8Z3C6

Related

ENSP00000385679.1, ENST00000402438.6

Conserved Domains (2) summary

cd06183
Location:22 → 278

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 ...

PTZ00319
Location:3 → 278

PTZ00319; NADH-cytochrome B5 reductase; Provisional
NM_007326.4 → NP_015565.1 NADH-cytochrome b5 reductase 3 isoform 2

See identical proteins and their annotated locations for NP_015565.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate exon in the 5' UTR and 5' coding region, compared to variant 1. The resulting isoform (2) is the soluble form of the enzyme, which has a shorter N-terminus when it is compared to the membrane-bound form. This isoform (2) is referred to in the literature as isoform s.

Source sequence(s)

AJ310900, DB029897, Z93241

Consensus CDS

CCDS14040.1

UniProtKB/TrEMBL

A0A8J8Z3C6

Related

ENSP00000508492.1, ENST00000687198.1

Conserved Domains (2) summary

cd06183
Location:22 → 278

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 ...

PTZ00319
Location:3 → 278

PTZ00319; NADH-cytochrome B5 reductase; Provisional