CYB5R3 Gene - Cytochrome b5 Reductase 3
Key enzyme in methemoglobin reduction and fatty acid desaturation
Gene Information Card
| Symbol | CYB5R3 |
|---|---|
| Full Name | Cytochrome b5 reductase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q13.2 |
| NCBI Gene ID | 1727 ncbi.nlm.nih.gov/gene/1727 |
| Ensembl ID | ENSG00000100243 |
| UniProt ID | P00387 |
| OMIM ID | 250790 |
| HGNC ID | 2573 |
| Aliases | DIA1, B5R, NADH-cytochrome b5 reductase, diaphorase 1 |
Description
The CYB5R3 gene encodes cytochrome b5 reductase 3, a flavoprotein that catalyzes the reduction of cytochrome b5 using NADH. This enzyme is essential for methemoglobin reduction in erythrocytes and participates in fatty acid desaturation, cholesterol biosynthesis, and drug metabolism. Mutations in CYB5R3 cause recessive congenital methemoglobinemia (RCM), characterized by reduced oxygen-carrying capacity of hemoglobin.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Recessive congenital methemoglobinemia (RCM) type I | Deficiency of soluble CYB5R3 in erythrocytes leads to accumulation of methemoglobin | ClinVar, OMIM |
| Recessive congenital methemoglobinemia (RCM) type II | Deficiency of both soluble and membrane-bound CYB5R3 isoforms causing neurological involvement | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 28.6 | High |
| Adipose tissue | 22.1 | High |
| Heart | 18.4 | Medium |
| Brain | 12.3 | Medium |
| Skeletal muscle | 9.8 | Medium |
| Blood | 6.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 35.2 | Hepatocellular carcinoma cell line |
| K562 | 12.8 | Chronic myelogenous leukemia cell line |
| SH-SY5Y | 15.1 | Neuroblastoma cell line |
| HeLa | 20.3 | Cervical carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.808C>T (p.Arg270Cys) | Missense | Common in RCM type I | Reduced enzyme activity in erythrocytes |
| c.1058G>A (p.Arg353Gln) | Missense | Rare | Decreased catalytic efficiency |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of protein expression |
| c.517delG (p.Ala173Profs*12) | Frameshift | Rare | Loss of function, associated with RCM type II |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations reduce or abolish NADH-cytochrome b5 reductase activity, leading to methemoglobinemia.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Methemoglobin reduction (Reactome: R-HSA-1237044)
• Fatty acid metabolism (KEGG: hsa00071)
• Cholesterol biosynthesis (KEGG: hsa00100)
Protein Summary
Cytochrome b5 reductase 3 (UniProt P00387) is a 34 kDa flavoprotein that exists in two isoforms: a soluble form in erythrocytes and a membrane-bound form in other tissues. The enzyme contains an FAD-binding domain and an NADH-binding domain. It transfers electrons from NADH to cytochrome b5, which then reduces methemoglobin (Fe3+) to hemoglobin (Fe2+). The membrane-bound isoform is anchored to the endoplasmic reticulum and outer mitochondrial membrane, participating in lipid metabolism.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CYB5R3 Knockout HEK293 Cell Line | EDJ-KQ4440 | Human | 1727 | Details Get a Quote |
| CYB5R3 Knockout A-549 Cell Line | EDJ-KQ26989 | Human | 1727 | Details Get a Quote |
| CYB5R3 Knockout HCT 116 Cell Line | EDJ-KQ26990 | Human | 1727 | Details Get a Quote |
| CYB5R3 Knockout HeLa Cell Line | EDJ-KQ26991 | Human | 1727 | Details Get a Quote |
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