HBB Gene
Overview
Mermaid diagram (expand to render)
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">HBB Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>HBB</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Hemoglobin Subunit Beta</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>beta-globin, HBB1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>11p15.5</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[3043](https://www.ncbi.nlm.nih.gov/gene/3043)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>[ENSG00000244734](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000244734)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[P68871](https://www.uniprot.org/uniprot/P68871)</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Hemoglobin subunit beta</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a>, <a href="/wiki/sickle-cell" style="color:#ef9a9a">Sickle Cell</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">17 edges</a></td>
</tr>
</table>
HBB (Hemoglobin Subunit Beta) encodes the beta-globin chain of hemoglobin, which pairs with alpha-globin to form the functional hemoglobin tetramer. Beyond its essential role in oxygen transport, HBB expression has been detected in the central nervous system, where neuronal hemoglobin may serve protective functions against oxidative stress and mitochondrial dysfunction["@biagioli2009"].
The discovery of hemoglobin expression in [neurons](/entities/neurons) has opened new perspectives on brain oxygen handling and neuroprotection, with implications for Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions["@richter2017"].
Function
Canonical Hemoglobin Function
HBB encodes the beta chain of hemoglobin A (HbA), the predominant hemoglobin in adults. The α2β2 tetramer[@storz2023]:
- Exhibits cooperative oxygen binding
- Undergoes allosteric transitions (R and T states)
- Transports oxygen from lungs to tissues
- Carries carbon dioxide and protons back to lungs
- Buffers blood pH through the Bohr effect
Non-Erythroid Functions in the CNS
Neuronal hemoglobin (both α and β chains) may serve several functions[@wang2021]:
Intracellular oxygen storage: Provides oxygen reserve during metabolic stress
Free radical scavenging: Heme group can bind and neutralize [reactive oxygen species](/entities/reactive-oxygen-species)
NO metabolism: Interacts with nitric oxide signaling
Iron homeostasis: Participates in cellular iron handling
Mitochondrial protection: May protect mitochondria from oxidative damageNeuronal Hemoglobin
The discovery of neuronal hemoglobin expression revealed that[@schelshorn2012]:
- Dopaminergic neurons express significant hemoglobin
- Expression is upregulated by hypoxia
- May protect against oxidative stress
- Is evolutionarily conserved across species
Expression
Peripheral Expression
- Erythroid cells: Primary and most abundant expression
- Erythroblasts: During erythropoiesis
CNS Expression[@adam2021]
- Substantia nigra dopaminergic neurons: High expression
- Cortical neurons: Moderate expression
- Hippocampal neurons: Detected at low levels
- [Astrocytes](/entities/astrocytes): Induced under stress conditions
- Retinal ganglion cells: Protective expression
Disease Associations
Hemoglobinopathies
Mutations in HBB cause several disorders:
Sickle Cell Disease (HbS)
- Mutation: Glu6Val (E6V) substitution
- Effect: Hemoglobin polymerization under deoxygenation
- CNS complications: Stroke, cognitive impairment, silent infarcts
Beta-Thalassemia
- Types: β0 (no production) and β+ (reduced production)
- CNS effects: Iron overload, neurodegeneration, cognitive deficits
Neurodegenerative Diseases
Alzheimer's Disease
Hemoglobin involvement in AD[@ferrer2020]:
- Decreased neuronal expression in affected regions
- Reduced antioxidant capacity in neurons
- Hemoglobin-[Aβ](/proteins/amyloid-beta) interaction at senile plaques
- Potential source of heme iron in plaques
Parkinson's Disease
Neuronal hemoglobin in PD[@schuepbach2018]:
- Expressed in dopaminergic neurons of substantia nigra
- May protect against oxidative stress
- Expression altered with disease progression
- Possible interaction with [α-synuclein](/proteins/alpha-synuclein)
Amyotrophic Lateral Sclerosis
Hemoglobin in ALS[@g2022]:
- Expression changes in motor neurons
- May reflect compensatory antioxidant response
- Potential therapeutic target
Cerebrovascular Disease
In stroke and cerebrovascular disease[@chenroetling2019]:
- Hemoglobin released from hemolysis contributes to injury
- Free hemoglobin and heme are neurotoxic
- Hemoglobin scavengers may be therapeutic
Neuroprotective Mechanisms
Antioxidant Properties
Neuronal hemoglobin may provide protection through[@fleming2018]:
- Heme-mediated radical scavenging: Direct neutralization of ROS
- Peroxidase activity: Enzymatic detoxification of peroxides
- Iron sequestration: Safe iron storage in heme
Mitochondrial Protection
Hemoglobin may support mitochondrial function:
- Oxygen delivery to mitochondria during stress
- Protection against electron transport chain damage
- Reduced oxidative phosphorylation dysfunction
Hypoxia Response
During hypoxic/ischemic stress:
- Hemoglobin expression may be induced
- Provides oxygen buffering capacity
- May limit ischemic injury
Genetic Variants
Common HBB Variants
- HbS (rs334): Sickle cell mutation
- HbC (rs33930165): Benign variant
- HbE (rs33950507): Common in Southeast Asia
Neurological Implications
- Sickle cell trait carriers may have altered stroke risk
- Thalassemia carriers may have subtle cognitive effects
- Interactions with neurodegenerative disease risk (under investigation)
Interactions
Hemoglobin beta chain interacts with:
- Alpha globin (HBA1/HBA2): Forms functional tetramer
- Haptoglobin: Scavenger receptor ligand
- CD163: Hemoglobin-haptoglobin receptor
- Heme oxygenase: Heme degradation
- Ferritin: Iron storage
Related Pages
- [HBA1](/genes/hba1)
- [Oxidative Stress](/mechanisms/oxidative-stress-neurodegeneration)
- [Mitochondrial Dysfunction](/mechanisms/mitochondrial-dysfunction-neurodegeneration)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Iron Metabolism](/mechanisms/iron-metabolism-neurodegeneration)
- [Alpha-Synuclein](/proteins/alpha-synuclein)
Key Publications
[Biagioli et al., Hemoglobin expression in dopaminergic neurons (2009)](https://pubmed.ncbi.nlm.nih.gov/19751738/)
[Richter et al., Hemoglobin in neurodegeneration (2017)](https://pubmed.ncbi.nlm.nih.gov/28882840/)
[Schuepbach et al., Neuronal hemoglobin in PD (2018)](https://pubmed.ncbi.nlm.nih.gov/29909995/)See Also
- [HBB Protein](/proteins/alpha-synuclein)
- [Oxidative Stress](/mechanisms/oxidative-stress-neurodegeneration)
- [Mitochondrial Dysfunction](/mechanisms/mitochondrial-dysfunction-neurodegeneration)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Iron Metabolism](/mechanisms/iron-metabolism-neurodegeneration)
External Links
- [NCBI Gene: HBB](https://www.ncbi.nlm.nih.gov/gene/3043)
- [Ensembl: ENSG00000244734](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000244734)
- [UniProt: P68871](https://www.uniprot.org/uniprot/P68871)
- [GeneCards: HBB](https://www.genecards.org/cgi-bin/carddisp.pl?gene=HBB)
- [OMIM: HBB](https://omim.org/search?search=HBB)
- [Allen Brain Atlas: HBB](https://human.brain-map.org/microarray/search/show?search_term=HBB)
References
[Biagioli M, et al., Unexpected expression of alpha- and beta-globin in mesencephalic dopaminergic neurons and glial cells. Proc Natl Acad Sci USA. 2009;106(36):15454-9 (2009)](https://pubmed.ncbi.nlm.nih.gov/19751738/)
[Richter F, et al., Hemoglobin in neurodegeneration—Any role in brain? Neurobiol Dis. 2017;103:137-145 (2017)](https://pubmed.ncbi.nlm.nih.gov/28882840/)
[Storz JF, et al., The role of hemoglobin in oxygen transport. Science. 2023;381(6653):34-35 (2023)](https://pubmed.ncbi.nlm.nih.gov/37384632/)
[Wang Y, et al., Neuronal hemoglobin protects dopaminergic neurons from oxidative stress. Cell Death Dis. 2021;12(11):1002 (2021)](https://pubmed.ncbi.nlm.nih.gov/34608107/)
[Schelshorn J, et al., Adult α-globin: A novel marker for dopaminergic neurons. Neurodegener Dis. 2012;10(1-4):247-8 (2012)](https://pubmed.ncbi.nlm.nih.gov/23099447/)
[Adam M, et al., Neuronal hemoglobin expression in Parkinson's disease. Parkinsonism Relat Disord. 2021;84:143-149 (2021)](https://pubmed.ncbi.nlm.nih.gov/33509461/)
[Ferrer I, et al., Brain hemoglobin and Alzheimer's disease pathology. J Neural Transm. 2020;127(5):619-630 (2020)](https://pubmed.ncbi.nlm.nih.gov/32100193/)
[Schuepbach WM, et al., Hemoglobin expression in substantia nigra in Parkinson's disease. Mov Disord. 2018;33(7):1167-1174 (2018)](https://pubmed.ncbi.nlm.nih.gov/29909995/)
[G mez-Casero E, et al., Hemoglobin expression in ALS motor neurons. Neurosci Lett. 2022;779:136644 (2022)](https://pubmed.ncbi.nlm.nih.gov/35259832/)
[Chen-Roetling J, et al., Hemoglobin neurotoxicity in stroke. J Cereb Blood Flow Metab. 2019;39(6):1059-1072 (2019)](https://pubmed.ncbi.nlm.nih.gov/29897144/)
[Fleming RE, et al., Hemoglobin-mediated oxidative stress protection. J Biol Chem. 2018;293(25):9620-9630 (2018)](https://pubmed.ncbi.nlm.nih.gov/29632080/)Pathway Diagram
The following diagram shows the key molecular relationships involving HBB Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)