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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CYGB
cytoglobin
Chromosome 17 · 17q25.1
NCBI Gene: 114757Ensembl: ENSG00000161544.10HGNC: HGNC:16505UniProt: Q8WWM9
88PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
removal of superoxide radicalscytosolnuclear speckcarbon monoxide bindingretinitis pigmentosaRetinal dystrophygenetic disorderPosterior column ataxia - retinitis pigmentosa
✦AI Summary

CYGB encodes cytoglobin, a multifunctional globin protein with diverse cellular roles dependent on oxygen availability and redox conditions. Under normoxic conditions, CYGB functions as a potent nitric oxide dioxygenase, rapidly consuming NO to regulate vascular tone and blood pressure 1. The protein exhibits superoxide dismutase activity with rates approaching those of classical SOD enzymes (1.6 × 10⁸ M⁻¹·s⁻¹), protecting cells against oxidative stress through iron redox cycling 2. Under hypoxic conditions, CYGB can switch function to nitrite reductase, generating NO from nitrite 1. The gene is transcriptionally regulated by hypoxia-inducible factor-1 (HIF-1) through hypoxia-responsive elements at positions -141, -144, and -448, with expression increasing ~1.6-1.7-fold under hypoxic stress 3. CYGB shows high co-expression with neuronal nitric oxide synthase in hippocampus and is stress-responsive 4. In cancer contexts, CYGB can function as both tumor suppressor and oncogene depending on cellular context, with roles in clearing reactive oxygen species and influencing drug resistance 56. The gene produces multiple alternatively spliced isoforms, with the canonical V-1 isoform predominant in most tissues, though V-3 isoform is prevalent in liver tissues 7.

Sources cited
1
CYGB functions as nitric oxide dioxygenase under normoxic conditions and can switch to nitrite reductase under hypoxic conditions
PMID: 31880165
2
CYGB has potent superoxide dismutase activity with rates of 1.6 × 10⁸ M⁻¹·s⁻¹ and protects against oxidative stress
PMID: 34930834
3
CYGB expression is regulated by HIF-1 through hypoxia-responsive elements and increases 1.6-1.7-fold under hypoxic stress
PMID: 17936249
4
CYGB shows high co-expression with neuronal nitric oxide synthase and is stress-responsive
PMID: 23696808
5
CYGB plays a role in clearing excess ROS and influences drug resistance in cancer
PMID: 35397613
6
CYGB functions in cancer progression through the DNMT3B/CYGB axis
PMID: 39227479
7
CYGB gene produces multiple alternatively spliced isoforms with V-1 predominant in most tissues and V-3 prevalent in liver
PMID: 38016326
Disease Associationsⓘ20
retinitis pigmentosaOpen Targets
0.54Moderate
Retinal dystrophyOpen Targets
0.51Moderate
genetic disorderOpen Targets
0.18Weak
Posterior column ataxia - retinitis pigmentosaOpen Targets
0.16Weak
diabetes mellitusOpen Targets
0.11Weak
type 1 diabetes mellitusOpen Targets
0.11Weak
melanomaOpen Targets
0.11Weak
neoplasmOpen Targets
0.10Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.09Suggestive
cancerOpen Targets
0.09Suggestive
Alzheimer diseaseOpen Targets
0.09Suggestive
neuropathyOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
atherosclerosisOpen Targets
0.08Suggestive
gestational diabetesOpen Targets
0.07Suggestive
infectionOpen Targets
0.07Suggestive
severe combined immunodeficiencyOpen Targets
0.07Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.07Suggestive
gliomaOpen Targets
0.06Suggestive
type 2 diabetes mellitusOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RHBDF2Protein interaction85%ADGBProtein interaction74%GPTProtein interaction71%NGBProtein interaction69%HAO1Shared pathway22%MBShared pathway22%
Tissue Expression6 tissues
Heart
100%
Lung
38%
Ovary
28%
Liver
21%
Brain
10%
Bone Marrow
8%
Gene Interaction Network
Click a node to explore
CYGBRHBDF2ADGBGPTNGBHAO1MB
PROTEIN STRUCTURE
Preparing viewer…
PDB2DC3 · 1.68 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.06LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.66 [0.43–1.06]
RankingsWhere CYGB stands among ~20K protein-coding genes
  • #5,406of 20,598
    Most Researched88
  • #10,608of 17,882
    Most Constrained (LOEUF)1.06
Genes detectedCYGB
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
SOX7 inhibits the malignant progression of bladder cancer via the DNMT3B/CYGB axis.
PMID: 39227479
Mol Biomed · 2024
1.00
2
Study of the hypoxia-dependent regulation of human CYGB gene.
PMID: 17936249
Biochem Biophys Res Commun · 2007
0.90
3
Insights into the function of cytoglobin.
PMID: 37721133
Biochem Soc Trans · 2023
0.80
4
A gene-environment study of cytoglobin in the human and rat hippocampus.
PMID: 23696808
PLoS One · 2013
0.70
5
Cytoglobin has potent superoxide dismutase function.
PMID: 34930834
Proc Natl Acad Sci U S A · 2021
0.60