CYB5R4 cytochrome b5 reductase 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CYB5R4provided by HGNC
Official Full Name: cytochrome b5 reductase 4provided by HGNC
Primary source: HGNC:HGNC:20147
See related: Ensembl:ENSG00000065615 MIM:608343; AllianceGenome:HGNC:20147
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NCB5OR; cb5/cb5R; dJ676J13.1
Summary: NCB5OR is a flavohemoprotein that contains functional domains found in both cytochrome b5 (CYB5A; MIM 613218) and CYB5 reductase (CYB5R3; MIM 613213) (Zhu et al., 1999 [PubMed 10611283]).[supplied by OMIM, Jan 2010]
Expression: Broad expression in testis (RPKM 17.2), appendix (RPKM 16.0) and 24 other tissues See more
Orthologs: all
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Genomic context

Location:: 6q14.2

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (83859689..83967423)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (85082972..85190710)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (84569408..84677142)

Chromosome 6 - NC_000006.12 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?

The N-terminal intrinsically disordered region of Ncb5or docks with the cytochrome b5 core to form a helical motif that is of ancient origin.
Title: The N-terminal intrinsically disordered region of Ncb5or docks with the cytochrome b(5) core to form a helical motif that is of ancient origin.
Cytosolic localization of NADH cytochrome b oxidoreductase
Title: Cytosolic localization of NADH cytochrome b₅ oxidoreductase (Ncb5or).
data provide first evidence for natural mutations in NCB5OR gene resulting in decreased protein levels and hence having potential implications in human pathology.
Title: Natural mutations lead to enhanced proteasomal degradation of human Ncb5or, a novel flavoheme reductase.
Mutation in cytochrome b5 reductase is associated with developmental delay and severe neurological problems.
Title: Methemoglobin reductase deficiency: novel mutation is associated with a disease phenotype of intermediate severity.
Study of the individual cytochrome b5 and cytochrome b5 reductase domains of Ncb5or reveals a unique heme pocket and a possible role of the CS domain.
Title: Study of the individual cytochrome b5 and cytochrome b5 reductase domains of Ncb5or reveals a unique heme pocket and a possible role of the CS domain.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Observational study of gene-disease association. (HuGE Navigator)
Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
Variaation in the coding region is not a major contributor in the pathogenesis of nonautoimmune diabetes.
Title: Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset diabetes of the young, and gestational diabetes mellitus.
NCB5OR is a novel soluble NAD(P)H reductase localized in the endoplasmic reticulum
Title: NCB5OR is a novel soluble NAD(P)H reductase localized in the endoplasmic reticulum.

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D6S1634 (e-PCR), detects polymorphism
- UniSTS:65296

A006A45 (e-PCR)
- UniSTS:27442

RH37476 (e-PCR)
- UniSTS:26462

Readthrough RIPPLY2-CYB5R4

Readthrough gene: RIPPLY2-CYB5R4, Included gene: RIPPLY2

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
NOT enables NAD(P)H oxidase H2O2-forming activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD(P)H oxidase H2O2-forming activity	IDA Inferred from Direct Assay more info	PubMed
enables cytochrome-b5 reductase activity, acting on NAD(P)H	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 heme binding	IBA Inferred from Biological aspect of Ancestor more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in bicarbonate transport	TAS Traceable Author Statement more info
involved_in cell development	ISS Inferred from Sequence or Structural Similarity more info
involved_in detection of oxygen	NAS Non-traceable Author Statement more info	PubMed
involved_in glucose homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in insulin secretion	ISS Inferred from Sequence or Structural Similarity more info
involved_in reactive oxygen species metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in response to antibiotic	ISS Inferred from Sequence or Structural Similarity more info
involved_in superoxide metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in superoxide metabolic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: cytochrome b5 reductase 4

Names: N-terminal cytochrome b5 and cytochrome b5 oxidoreductase domain-containing protein; NADPH cytochrome B5 oxidoreductase; cytochrome b-type NAD(P)H oxidoreductase; flavohemoprotein b5+b5R; flavohemoprotein b5/b5R

NP_057314.2

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.

mRNA and Protein(s)

NM_016230.4 → NP_057314.2 cytochrome b5 reductase 4

See identical proteins and their annotated locations for NP_057314.2

Status: VALIDATED

Source sequence(s)

AL034347, BC025380, BC029339, DA274558

Consensus CDS

CCDS5000.2

UniProtKB/Swiss-Prot

B1AEM2, Q5TGI9, Q7L1T6, Q9NUE4, Q9UHI9

Related

ENSP00000358695.3, ENST00000369681.10

Conserved Domains (3) summary

cd06183
Location:278 → 519

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 ...

cd06490
Location:170 → 256

p23_NCB5OR; p23_like domain found in NAD(P)H cytochrome b5 (NCB5) oxidoreductase (OR) and similar proteins. NCB5OR is widely expressed in human organs and tissues and is localized in the ER (endoplasmic reticulum). It appears to play a critical role in maintaining ...

pfam00173
Location:58 → 130

Cyt-b5; Cytochrome b5-like Heme/Steroid binding domain