CYB5R3

Chr 22

cytochrome b5 reductase 3

Also known as: B5R, DIA1

NCBI Gene: 1727 ENSG00000100243 UniProt: P00387

Cytochrome b5 reductase catalyzes the reduction of cytochrome b5 using NADH, with the membrane-bound form functioning in fatty acid metabolism and cholesterol biosynthesis, and the soluble erythrocyte form reducing methemoglobin. Mutations cause autosomal recessive methemoglobinemia, which can be limited to erythrocytes (type I) or involve multiple organ systems with neurological manifestations (type II). The gene shows low constraint against loss-of-function variants.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMethemoglobinemia CYB5R3-related

Clinical highlights

Gene-disease validity (ClinGen)

methemoglobinemia due to deficiency of methemoglobin reductase · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.85

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429