HBA1 Gene
Overview
Mermaid diagram (expand to render)
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">HBA1 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>HBA1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Hemoglobin Subunit Alpha 1</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>HBA-T1, alpha-globin</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>16p13.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[3039](https://www.ncbi.nlm.nih.gov/gene/3039)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>[ENSG00000188536](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000188536)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[P69905](https://www.uniprot.org/uniprot/P69905)</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Hemoglobin subunit alpha</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/diabetes" style="color:#ef9a9a">Diabetes</a>, <a href="/wiki/hypertension" style="color:#ef9a9a">Hypertension</a>, <a href="/wiki/nephropathy" style="color:#ef9a9a">Nephropathy</a>, <a href="/wiki/retinopathy" style="color:#ef9a9a">Retinopathy</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">10 edges</a></td>
</tr>
</table>
HBA1 (Hemoglobin Subunit Alpha 1) encodes the alpha-globin chain of hemoglobin, the oxygen-carrying protein in red blood cells. While traditionally associated with erythrocytes, HBA1/HBA2 expression has been detected in the brain, including [neurons](/entities/neurons) and glial cells, where it may serve neuroprotective functions related to oxygen sensing, [reactive oxygen species](/entities/reactive-oxygen-species) (ROS) scavenging, and response to hypoxic stress["@biagioli2009"].
Emerging research suggests that neuronal hemoglobin expression may play protective roles in neurodegenerative diseases, particularly in conditions involving mitochondrial dysfunction and oxidative stress["@richter2017"].
Function
Canonical Function
HBA1 encodes the alpha chain of hemoglobin, which forms a tetramer with two alpha and two beta chains (HbA). The hemoglobin tetramer[@storz2023]:
- Binds oxygen cooperatively in the lungs
- Releases oxygen in tissues
- Transports carbon dioxide
- Buffers blood pH
Non-Erythroid/CNS Functions
Hemoglobin expression in neurons and glia may serve several functions[@schelshorn2012]:
Oxygen storage and buffering: Neuronal hemoglobin may provide an oxygen reserve during metabolic stress
Reactive oxygen species scavenging: Heme group can bind and neutralize free radicals
Iron metabolism regulation: May participate in cellular iron homeostasis
Nitric oxide metabolism: Interacts with NO signaling pathways
Mitochondrial protection: May protect against mitochondrial oxidative damageExpression
Peripheral Expression
- Erythroid cells: Primary site of expression
- Erythroblasts: During erythropoiesis
CNS Expression[@wang2021]
- Neurons: Detected in cortical and hippocampal neurons
- [Astrocytes](/entities/astrocytes): Low-level expression
- Substantia nigra: Particularly relevant for Parkinson's disease
- Retina: Expression in retinal neurons
Disease Associations
Neurodegenerative Diseases
Alzheimer's Disease
Hemoglobin expression in the brain is altered in AD[@ferrer2020]:
- Decreased neuronal HBA1 expression in affected regions
- May contribute to reduced antioxidant capacity
- Possible protective role in early disease stages
Parkinson's Disease
Neuronal hemoglobin in the substantia nigra[@adam2021]:
- May protect dopaminergic neurons from oxidative stress
- Expression changes with disease progression
- Potential therapeutic target for neuroprotection
Amyotrophic Lateral Sclerosis
Hemoglobin expression changes in ALS[@g2022]:
- Altered in spinal cord motor neurons
- May reflect adaptive response to oxidative stress
- Potential biomarker
Hemoglobinopathies
Mutations in HBA1 cause:
- Alpha-thalassemia: Reduced alpha-globin production
- HbH disease: Moderate hemolytic anemia
- Hydrops fetalis: Severe, often fatal (with HBA2 mutations)
Cerebral Implications of Hemoglobinopathies
Cerebrovascular complications in thalassemia include[@singer2016]:
- Stroke risk (both ischemic and hemorrhagic)
- Silent cerebral infarcts
- Cognitive impairment
- Iron deposition in brain
Neuroprotective Mechanisms
Antioxidant Function
Neuronal hemoglobin may provide antioxidant protection through[@fleming2018]:
- Heme-mediated free radical scavenging
- Peroxidase activity
- Protection against lipid peroxidation
Hypoxia Response
During hypoxic conditions:
- HBA1 expression may be upregulated
- Provides oxygen buffering capacity
- May protect against ischemic injury
Iron Handling
Hemoglobin may influence neuronal iron metabolism:
- Heme iron recycling
- Protection against iron-mediated oxidative damage
- Cross-talk with ferritin and other iron proteins
Related Pages
- [HBB](/genes/hbb)
- [Iron Metabolism](/mechanisms/iron-metabolism-neurodegeneration)
- [Oxidative Stress](/mechanisms/oxidative-stress-neurodegeneration)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Mitochondrial Dysfunction](/mechanisms/mitochondrial-dysfunction-neurodegeneration)
Key Publications
[Biagioli et al., Hemoglobin in neurons (2009)](https://pubmed.ncbi.nlm.nih.gov/19751738/)
[Richter et al., Neuronal hemoglobin in neurodegeneration (2017)](https://pubmed.ncbi.nlm.nih.gov/28882840/)
[Schelshorn et al., Hemoglobin expression in substantia nigra (2012)](https://pubmed.ncbi.nlm.nih.gov/23099447/)See Also
- [Iron Metabolism](/mechanisms/iron-metabolism-neurodegeneration)
- [Oxidative Stress](/mechanisms/oxidative-stress-neurodegeneration)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Mitochondrial Dysfunction](/mechanisms/mitochondrial-dysfunction-neurodegeneration)
External Links
- [NCBI Gene: HBA1](https://www.ncbi.nlm.nih.gov/gene/3039)
- [Ensembl: ENSG00000188536](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000188536)
- [UniProt: P69905](https://www.uniprot.org/uniprot/P69905)
- [GeneCards: HBA1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=HBA1)
- [OMIM: HBA1](https://omim.org/search?search=HBA1)
- [Allen Brain Atlas: HBA1](https://human.brain-map.org/microarray/search/show?search_term=HBA1)
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/)
[Unknown, Storz JF. Hemoglobin: insights into protein structure, function, and evolution. Science. 2023;381(6653):34-35 (2023)](https://pubmed.ncbi.nlm.nih.gov/37384632/)
[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/)
[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/)
[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/)
[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/)
[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/)
[Singer ST, et al., Neurologic complications in thalassemia. Ann N Y Acad Sci. 2016;1368(1):108-116 (2016)](https://pubmed.ncbi.nlm.nih.gov/27172235/)
[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 HBA1 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)