HIF1A Gene - Hypoxia Inducible Factor 1 Subunit Alpha

HIF1A Gene

Pathway Diagram

```mermaid
flowchart TD
HIF1A["HIF1A"]
style HIF1A fill:#006494,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0
Microglial_Metabolic_Reprogram["Microglial Metabolic Reprogramming"]
HIF1A -->|"associated with"| Microglial_Metabolic_Reprogram
AEROBIC_GLYCOLYSIS["AEROBIC GLYCOLYSIS"]
HIF1A -->|"activates"| AEROBIC_GLYCOLYSIS
Bladder_Tumorigenesis["Bladder Tumorigenesis"]
HIF1A -->|"involved in"| Bladder_Tumorigenesis
Cancer_Stemness["Cancer Stemness"]
HIF1A -->|"associated with"| Cancer_Stemness
VEGF["VEGF"]
HIF1A -->|"regulates"| VEGF
BNIP3["BNIP3"]
HIF1A -->|"activates"| BNIP3
AGGF1["AGGF1"]
HIF1A -->|"upregulates"| AGGF1
Cancer["Cancer"]
HIF1A -->|"therapeutic target"| Cancer
IDH2["IDH2"]
IDH2 -->|"associated with"| HIF1A
BMAL1["BMAL1"]
BMAL1 -->|"regulates"| HIF1A
EGLN2["EGLN2"]
EGLN2 -->|"inhibits"| HIF1A
NLRP3_inhibition["NLRP3 inhibition"]
NLRP3_inhibition -->|"contributes to"| HIF1A
FOXO3["FOXO3"]
FOXO3 -->|"interacts with"| HIF1A
APOPTOSIS["APOPTOSIS"]
APOPTOSIS -->|"activates"| HIF1A
TNF["TNF"]
TNF -->|"associated with"| HIF1A
style Microglial_Metabolic_Reprogram fill:#006494,stroke:#888,color:#e0e0e0
style AEROBIC_GLYCOLYSIS fill:#006494,stroke:#888,color:#e0e0e0
style Bladder_Tumorigenesis fill:#006494,stroke:#888,color:#e0e0e0
style Cancer_Stemness fill:#ef5350,stroke:#ff8a65,color:#e0e0e0
style VEGF fill:#1b5e20,stroke:#81c784,color:#e0e0e0
style BNIP3 fill:#4a1a6b,stroke:#ce93d8,col

HIF1A Gene

Pathway Diagram

Introduction

Hif1A Gene Hypoxia Inducible Factor 1 Subunit Alpha is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

This page provides comprehensive information about HIF1A Gene, including its structure, normal function in the nervous system, and its role in neurodegenerative diseases.

<div class="infobox infobox-gene">
<div class="infobox-header">HIF1A</div>
<div class="infobox-content">
<table>
<tr><td><strong>Full Name</strong></td><td>Hypoxia Inducible Factor 1 Subunit Alpha</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>14q21.1</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td><a href="https://www.ncbi.nlm.nih.gov/gene/3091" target="_blank">3091</a></td></tr>
<tr><td><strong>OMIM</strong></td><td><a href="https://www.omim.org/entry/603348" target="_blank">603348</a></td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000100644</td></tr>
<tr><td><strong>UniProt ID</strong></td><td><a href="https://www.uniprot.org/uniprot/Q16665" target="_blank">Q16665</a></td></tr>
<tr><td><strong>Protein</strong></td><td>HIF-1α</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Alzheimer's Disease, Parkinson's Disease, Stroke, Vascular Dementia, ALS, Cancer</td></tr>
</table>
</div>
</div>

Function

The HIF1A gene encodes Hypoxia Inducible Factor 1 subunit alpha (HIF-1α), the oxygen-sensitive subunit of the heterodimeric transcription factor HIF-1. HIF-1 is a master regulator of cellular adaptation to hypoxia (low oxygen conditions). Under normoxic conditions, HIF-1α is hydroxylated by prolyl hydroxylases (PHD1-3), leading to its rapid degradation via the ubiquitin-proteasome pathway. Under hypoxic conditions, HIF-1α escapes hydroxylation, translocates to the nucleus, dimerizes with HIF-1β (ARNT), and activates transcription of hundreds of target genes involved in oxygen homeostasis.

In the central nervous system, HIF-1α plays critical roles in:

• Response to Ischemia: Activates genes that protect [neurons](/entities/neurons) from hypoxic injury
• Angiogenesis: Induces VEGF and other血管生成因子
• Metabolic Adaptation: Increases glycolytic enzyme expression
• Erythropoiesis: Stimulates EPO production
• Mitochondrial Function: Regulates mitochondrial biogenesis and dynamics
• Neuroprotection: Activates anti-apoptotic and antioxidant genes

Disease Associations

Alzheimer's Disease

• HIF-1α activation is reduced in AD brains despite chronic hypoxia
• Impaired HIF-1α response may contribute to [Aβ](/proteins/amyloid-beta) accumulation
• VEGF (HIF target) is dysregulated in AD
• Neurovascular dysfunction involves HIF-1α dysregulation
• Therapeutic strategies aim to enhance HIF-1α activity

Parkinson's Disease

• HIF-1α activity is reduced in PD substantia nigra
• Contributes to dopaminergic neuron vulnerability
• May affect mitophagy and mitochondrial function
• Loss of HIF-1α exacerbates MPTP-induced parkinsonism

Stroke and Vascular Dementia

• HIF-1α is acutely protective in ischemic stroke
• Activates survival pathways in penumbral tissue
• Prolyl hydroxylase inhibitors (PHI) are neuroprotective in stroke
• Chronic HIF-1α dysregulation contributes to vascular cognitive impairment

ALS

• HIF-1α response impaired in ALS motor neurons
• Contributes to excitotoxicity and oxidative stress
• Therapeutic potential of HIF-1α stabilizers

Expression

HIF1A is expressed in all brain regions with notable expression in:

• [Hippocampus](/brain-regions/hippocampus): Particularly in CA1 and dentate gyrus
• [Cortex](/brain-regions/cortex): All layers, especially pyramidal neurons
• Substantia Nigra: Dopaminergic neurons
• Cerebellum: Purkinje cells
• Brainstem: Various nuclei
• White Matter: Oligodendrocytes

• Oxygen tension (primary regulator)
• Growth factors (IGF-1, EGF)
• Inflammatory cytokines (IL-1β, TNF)
• Metabolic state (glucose, [ROS](/entities/reactive-oxygen-species))

Key Publications

Therapeutic Targeting

| Approach | Description | Status |
|----------|-------------|--------|
| PHD Inhibitors | Dimethyloxalylglycine (DMOG), roxadustat, vadadustat | FDA approved (anemia), trials for neuroprotection |
| HIF-1α Stabilizers | Natural compounds (e.g., salidroside) | Preclinical |
| Gene Therapy | AAV-delivered HIF-1α | Research |

Background

The study of Hif1A Gene Hypoxia Inducible Factor 1 Subunit Alpha has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

<sup>[[1]](https://pubmed.ncbi.nlm.nih.gov/11719428/)</sup> HIF-1alpha and cellular response to hypoxia. PMID: 11719428(https://pubmed.ncbi.nlm.nih.gov/11719428/)

See Also

• [Mitochondrial Dysfunction Pathway](/mechanisms/mitochondrial-dysfunction)
• VEGF Gene
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• Stroke and Neurodegeneration
• [Neurovascular Unit](/mechanisms/neurovascular-unit)

External Links

Brain Atlas Resources

• [Allen Human Brain Atlas - HIF1A Expression](https://human.brain-map.org/microarray/search/show?search_term=HIF1A)
• [Allen Cell Type Atlas - HIF1A](https://celltypes.brain-map.org/)
• [BrainSpan - HIF1A Developmental Expression](https://brainspan.org/)
• [Allen Mouse Brain Atlas - HIF1A](https://mouse.brain-map.org/)
• [NCBI Gene: HIF1A](https://www.ncbi.nlm.nih.gov/gene/3091)
• [UniProt: HIF1A](https://www.uniprot.org/uniprot/Q16665)
• [OMIM: HIF1A](https://www.omim.org/entry/603348)
• [GeneCards: HIF1A](https://www.genecards.org/cgi-bin/carddisp.pl?gene=HIF1A)

Pathway Diagram

The following diagram shows the key molecular relationships involving HIF1A Gene - Hypoxia Inducible Factor 1 Subunit Alpha discovered through SciDEX knowledge graph analysis: