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Features include always present findings: Hypertonia, Decreased erythrocyte nicotinamide adenine dinucleotide-cytochrome b5 reductase activity, Global developmental delay, and Methemoglobinemia and others. 15 total HPO annotations.
Organ System | Phenotype Count | Example Features |
|---|---|---|
Brain and nerves | 4 | Global developmental delay, Headache, Intellectual disability |
Bones and joints | 1 | Severe backward arching of the body (opisthotonus) |
Head and neck | 1 | Microcephaly |
Eyes | 1 | Strabismus |
Lab test results | 1 | Decreased erythrocyte nicotinamide adenine dinucleotide-cytochrome b5 reductase activity |
Growth and development | 1 | Growth delay |
Lungs and breathing | 1 | Exertional dyspnea |
CYB5R3 encodes cytochrome b5 reductase 3 (301 aa). Catalyzes the reduction of two molecules of cytochrome b5 using NADH as the electron donor Highest expression in Artery Aorta (741.7 TPM) and Artery Tibial (590.7 TPM).
Methemoglobinemia due to deficiency of methemoglobin reductase is caused by mutations in the CYB5R3 gene on chromosome 22.
The CYB5R3 protein participates in CYB5R3:FAD reduces CYB5A:ferriheme to CYB5A:heme and MARC1,MARC2 reduce N-hydroxylated compounds pathways.
CYB5R3 is classified as a druggable target (Druggable Genome and Enzyme categories) with score 1.7.
Genetic testing for CYB5R3 is available. Testing is considered confirmatory for diagnosis.
Phenotype severity distribution: 7 always present features.
No clinical trials have been registered for methemoglobinemia due to deficiency of methemoglobin reductase.
6 publications have been identified in PubMed for methemoglobinemia due to deficiency of methemoglobin reductase. Research spans Case Report / Case Series (100%).
Ouragini H (2025). [PMID: 40429944](https://pubmed.ncbi.nlm.nih.gov/40429944/). *International journal of molecular sciences*. [Case Report / Case Series]
Yang Y (2025). [PMID: 38781945](https://pubmed.ncbi.nlm.nih.gov/38781945/). *Acta haematologica*. [Case Report / Case Series]
He KY (2025). [PMID: 39154701](https://pubmed.ncbi.nlm.nih.gov/39154701/). *Clinica chimica acta; international journal of clinical chemistry*. [Case Report / Case Series]
Nagarajan B (2024). [PMID: 39264282](https://pubmed.ncbi.nlm.nih.gov/39264282/). *Movement disorders clinical practice*. [Case Report / Case Series]
Bai S (2024). [PMID: 39070456](https://pubmed.ncbi.nlm.nih.gov/39070456/). *Cureus*. [Case Report / Case Series]
Belgemen-Ozer T (2024). [PMID: 38439554](https://pubmed.ncbi.nlm.nih.gov/38439554/). *Clinical pediatrics*. [Case Report / Case Series]
Data assembled from 6 of 12 sources · Last updated Sep 20, 2026, 11:36 PM UTC
Online Mendelian Inheritance in Man
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