CYB5R1: Cytochrome b5 Reductase 1
A key enzyme in electron transfer and lipid metabolism, with implications in hereditary methemoglobinemia and cancer.
Gene Information Card
| Symbol | CYB5R1 |
|---|---|
| Full Name | Cytochrome b5 reductase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q32.1 |
| NCBI Gene ID | 51768 ncbi.nlm.nih.gov/gene/51768 |
| Ensembl ID | ENSG00000143178 |
| UniProt ID | Q9UHQ9 |
| OMIM ID | 608343 |
| HGNC ID | 2873 |
| Aliases | B5R1, B5R.1, CYB5R, DIA1, MGC117188 |
Description
CYB5R1 encodes a member of the cytochrome b5 reductase family, which functions as an electron transfer enzyme. It catalyzes the reduction of cytochrome b5 using NADH as an electron donor, playing a critical role in fatty acid desaturation, cholesterol biosynthesis, and drug metabolism. Mutations in this gene are associated with hereditary methemoglobinemia and have been implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary methemoglobinemia | Deficiency in CYB5R1 leads to reduced NADH-dependent reduction of methemoglobin, causing accumulation of oxidized hemoglobin and impaired oxygen delivery. | ClinVar, OMIM |
| Breast cancer | Altered CYB5R1 expression may influence estrogen metabolism and redox balance, contributing to tumor progression. | COSMIC, NCBI |
| Colorectal cancer | Somatic mutations and copy number alterations in CYB5R1 have been observed, potentially affecting lipid metabolism and cell proliferation. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Heart | 6.1 | Low |
| Brain | 4.2 | Low |
| Lung | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| HEK293 | 9.7 | Embryonic kidney cells |
| MCF7 | 7.4 | Breast cancer cell line |
| A549 | 5.1 | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.517C>T (p.Arg173Trp) | Missense | <0.01% | Reduced enzyme activity; associated with methemoglobinemia |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss of protein expression; pathogenic |
| c.682G>A (p.Gly228Arg) | Missense | <0.01% | Impaired NADH binding; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss mutations reduce or abolish NADH-cytochrome b5 reductase activity, leading to methemoglobinemia.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • NADH-cytochrome b5 reductase activity | • electron transfer activity |
| • FAD binding | • cytochrome b5 binding |
| • oxidation-reduction process | • lipid metabolic process |
| • fatty acid desaturation | • cholesterol biosynthetic process |
Pathways
• Fatty acid metabolism (Reactome: R-HSA-8978868)
• Cytochrome b5 reductase / cytochrome b5 electron transport (Reactome: R-HSA-1483191)
• Methemoglobin reduction (KEGG: map00982)
Protein Summary
Cytochrome b5 reductase 1 (CYB5R1) is a 34 kDa flavoprotein that localizes to the endoplasmic reticulum and outer mitochondrial membrane. It contains an N-terminal membrane anchor and a conserved FAD-binding domain. The enzyme transfers electrons from NADH to cytochrome b5, which then participates in desaturation of fatty acids, elongation of very long-chain fatty acids, and reduction of methemoglobin. Defects in CYB5R1 cause type I and type II hereditary methemoglobinemia, with neurological involvement in the severe form.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CYB5R1 Knockout HEK293 Cell Line | EDJ-KQ11196 | Human | 51706 | Details Get a Quote |
| CYB5R1 Knockout A-549 Cell Line | EDJ-KQ39254 | Human | 51706 | Details Get a Quote |
| CYB5R1 Knockout HCT 116 Cell Line | EDJ-KQ39255 | Human | 51706 | Details Get a Quote |
| CYB5R1 Knockout HeLa Cell Line | EDJ-KQ39256 | Human | 51706 | Details Get a Quote |
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