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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NGB
neuroglobin
Chromosome 14 · 14q24.3
NCBI Gene: 58157Ensembl: ENSG00000165553.5HGNC: HGNC:14077UniProt: A0M8W9
117PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nitrite reductase activityGDP-dissociation inhibitor activityprotein bindingoxygen bindingdiabetes mellitusneuroinflammatory disordergliomaneoplasm
✦AI Summary

Neuroglobin (NGB) is a monomeric 17-kDa globin protein with a bis-histidyl six-coordinate heme-iron center that binds oxygen, carbon monoxide, and nitric oxide 12. While NGB's canonical role in oxygen transport remains uncertain due to its high oxygen affinity and low tissue abundance 13, it functions primarily as an endogenous neuroprotectant. Cerebral hypoxia and ischemia induce NGB expression, and neuronal overexpression reduces hypoxic-ischemic injury while knockdown exacerbates damage 4. NGB expression increases with aging, correlating with HIF-1α induction 5. Beyond oxygen binding, deoxygenated NGB exhibits nitrite reductase activity producing neuroprotective nitric oxide during hypoxia 6, and functions as a guanine nucleotide dissociation inhibitor toward G-alpha proteins, facilitating hypoxia-responsive neuroprotection 37. Recent evidence demonstrates NGB protects dopaminergic neurons in Parkinson's disease models by directly interacting with mitochondrial Complex I subunit NDUFA10, restoring its activity and inhibiting apoptosis 8. NGB overexpression also protects against Alzheimer's disease and mitochondrial dysfunction 9, though paradoxically facilitates cancer cell survival 9, positioning NGB as a critical cellular switch between death and survival pathways.

Sources cited
1
NGB binds oxygen, carbon monoxide, and nitric oxide; uncertain oxygen transport role due to high affinity and low tissue abundance
PMID: 11473128
2
NGB structural characterization and ligand binding properties
PMID: 12962627
3
NGB GDI activity toward G-alpha proteins and neuroprotection mechanisms
PMID: 12860983
4
Deoxygenated NGB exhibits nitrite reductase activity producing nitric oxide during hypoxia
PMID: 21296891
5
NGB GDI activity in signal transduction and neuroprotection
PMID: 18302932
6
NGB functions as endogenous neuroprotectant; hypoxia/ischemia induce expression and provide protection
PMID: 17942367
7
NGB and HIF-1α expression increases with aging in carotid bodies
PMID: 23080171
8
NGB interacts with Complex I subunit NDUFA10 and protects dopaminergic neurons in Parkinson's disease models
PMID: 39454716
9
NGB overexpression protects against Alzheimer's disease and mitochondrial dysfunction but facilitates cancer cell survival
PMID: 28707399
Disease Associationsⓘ20
diabetes mellitusOpen Targets
0.30Weak
neuroinflammatory disorderOpen Targets
0.28Weak
gliomaOpen Targets
0.10Suggestive
neoplasmOpen Targets
0.10Suggestive
breast cancerOpen Targets
0.09Suggestive
strokeOpen Targets
0.09Suggestive
glioblastoma multiformeOpen Targets
0.09Suggestive
cancerOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
biliary tract diseaseOpen Targets
0.05Suggestive
neuroblastomaOpen Targets
0.05Suggestive
obstructive sleep apneaOpen Targets
0.04Suggestive
Cerebral ischemiaOpen Targets
0.04Suggestive
Alzheimer diseaseOpen Targets
0.03Suggestive
subarachnoid hemorrhageOpen Targets
0.03Suggestive
ischemiaOpen Targets
0.03Suggestive
central nervous system cancerOpen Targets
0.03Suggestive
astrocytomaOpen Targets
0.03Suggestive
glioblastomaOpen Targets
0.03Suggestive
neurodegenerative diseaseOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MBProtein interaction96%CYCSProtein interaction94%FLOT1Protein interaction83%ADGBProtein interaction74%CYGBProtein interaction69%COXFA4L2Shared pathway67%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
1%
Liver
0%
Heart
0%
Ovary
0%
Lung
0%
Gene Interaction Network
Click a node to explore
NGBMBCYCSFLOT1ADGBCYGBCOXFA4L2
PROTEIN STRUCTURE
Preparing viewer…
PDB7VQG · 1.35 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.45LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.86 [0.53–1.45]
RankingsWhere NGB stands among ~20K protein-coding genes
  • #4,053of 20,598
    Most Researched117 · top quartile
  • #14,868of 17,882
    Most Constrained (LOEUF)1.45
Genes detectedNGB
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Neuroglobin and friends.
PMID: 28707399
J Mol Recognit · 2017
1.00
2
AAV gene therapy for hereditary spastic paraplegia type 50: a phase 1 trial in a single patient.
PMID: 38942994
Nat Med · 2024
0.90
3
Human carotid body HIF and NGB expression during human development and aging.
PMID: 23080171
Adv Exp Med Biol · 2012
0.80
4
Phospholamban antisense oligonucleotides improve cardiac function in murine cardiomyopathy.
PMID: 34462437
Nat Commun · 2021
0.70
5
Neuroglobin: an endogenous neuroprotectant.
PMID: 17942367
Curr Opin Pharmacol · 2008
0.60