HTRA1 Gene
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">HTRA1 Gene</th>
</tr>
<tr>
<td class="label">
Symbol</td>
<td>HTRA1</td>
</tr>
<tr>
<td class="label">
Full Name</td>
<td>HTRA1 serine peptidase 1</td>
</tr>
<tr>
<td class="label">
Chromosomal Location</td>
<td>10q26.13</td>
</tr>
<tr>
<td class="label">
NCBI Gene ID</td>
<td>5657</td>
</tr>
<tr>
<td class="label">
OMIM ID</td>
<td>607784</td>
</tr>
<tr>
<td class="label">
Ensembl ID</td>
<td>ENSG00000166033</td>
</tr>
<tr>
<td class="label">
UniProt ID</td>
<td>Q92743</td>
</tr>
<tr>
<td class="label">
Protein Length</td>
<td>480 amino acids</td>
</tr>
<tr>
<td class="label">
Molecular Weight</td>
<td>~53 kDa</td>
</tr>
<tr>
<td class="label">
Gene Family</td>
<td>HTRA serine protease family</td>
</tr>
<tr>
<td class="label">
Inheritance</td>
<td>Autosomal dominant (CADASIL), Autosomal recessive (CARASIL)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/dementia" style="color:#ef9a9a">Dementia</a>, <a href="/wiki/stroke" style="color:#ef9a9a">Stroke</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">18 edges</a></td>
</tr>
</table>
Overview
...HTRA1 Gene
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">HTRA1 Gene</th>
</tr>
<tr>
<td class="label">
Symbol</td>
<td>HTRA1</td>
</tr>
<tr>
<td class="label">
Full Name</td>
<td>HTRA1 serine peptidase 1</td>
</tr>
<tr>
<td class="label">
Chromosomal Location</td>
<td>10q26.13</td>
</tr>
<tr>
<td class="label">
NCBI Gene ID</td>
<td>5657</td>
</tr>
<tr>
<td class="label">
OMIM ID</td>
<td>607784</td>
</tr>
<tr>
<td class="label">
Ensembl ID</td>
<td>ENSG00000166033</td>
</tr>
<tr>
<td class="label">
UniProt ID</td>
<td>Q92743</td>
</tr>
<tr>
<td class="label">
Protein Length</td>
<td>480 amino acids</td>
</tr>
<tr>
<td class="label">
Molecular Weight</td>
<td>~53 kDa</td>
</tr>
<tr>
<td class="label">
Gene Family</td>
<td>HTRA serine protease family</td>
</tr>
<tr>
<td class="label">
Inheritance</td>
<td>Autosomal dominant (CADASIL), Autosomal recessive (CARASIL)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/dementia" style="color:#ef9a9a">Dementia</a>, <a href="/wiki/stroke" style="color:#ef9a9a">Stroke</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">18 edges</a></td>
</tr>
</table>
Overview
Mermaid diagram (expand to render)
Htra1 Gene plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Introduction
Htra1 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
HTRA1 (HTRA1 serine peptidase 1) encodes a secreted serine protease that plays critical roles in extracellular matrix remodeling, growth factor signaling regulation, and vascular integrity. Mutations in HTRA1 cause hereditary small vessel diseases including CADASIL (autosomal dominant) and CARASIL (autosomal recessive), while common variants increase risk for age-related macular degeneration (AMD) and potentially Alzheimer's disease.
Gene Overview
Gene Structure
The HTRA1 gene spans approximately 23 kb of genomic DNA on chromosome 10q26.13 and contains 6 exons. The gene encodes a secreted protein with a multidomain structure:
- Signal peptide (aa 1-22): Directs secretion to extracellular space
- LT domain (aa 44-157): Leucine-rich repeat domain for protein-protein interactions
- PDZ domain (aa 169-270): Postsynaptic density protein interactions
- Protease domain (aa 294-401): Trypsin-like serine protease domain
- C-terminal region (aa 402-480): Regulatory sequences
Protein Function
HTRA1 is a secreted serine protease with multiple biological functions:
Protease Activity
- Substrate specificity: Degrades extracellular matrix proteins (fibronectin, vitronectin, laminin)
- TGF-β regulation: Cleaves and regulates TGF-β family ligands and receptors
- Growth factor processing: Processes various growth factors and cytokines
- Inhibitor activity: Acts as a protease inhibitor for some substrates
Vascular Function
- Vascular integrity: Maintains blood vessel wall structure
- Smooth muscle cell regulation: Controls vascular smooth muscle cell proliferation
- Pericyte function: Supports pericyte-endothelial interactions
Neuroprotective Functions
- Oxidative stress response: Upregulated under oxidative stress conditions
- Protein quality control: Degrades misfolded extracellular proteins
- Neuroinflammation modulation: Regulates inflammatory responses
- [Blood-brain barrier](/entities/blood-brain-barrier) maintenance: Supports BBB integrity
Disease Associations
CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)
- Inheritance: Autosomal dominant
- Gene: NOTCH3 mutations cause classic CADASIL; HTRA1 mutations cause a phenocopy
- Pathogenesis: Arterial wall degeneration, granular osmiophilic deposits
- Symptoms: Migraine with aura, strokes, cognitive decline, mood disorders
- Neuroimaging: White matter hyperintensities, lacunes, microbleeds
CARASIL (Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)
- Inheritance: Biallelic recessive HTRA1 mutations
- Pathogenesis: Similar to CADASIL but earlier onset
- Features: Early-onset strokes, alopecia, spondylosis
- MRI findings: Diffuse white matter changes, lacunar infarcts
- Risk variants: HTRA1 promoter variant increases risk 2-3 fold
- Mechanism: Increased HTRA1 expression in retina
- Effect: Enhanced VEGF degradation, choroidal neovascularization
- Geographic atrophy: Associated with HTRA1 risk allele
Alzheimer's Disease
- Association: Some GWAS signals implicate HTRA1 locus
- Mechanism: May affect [Aβ](/proteins/amyloid-beta) clearance and [tau](/proteins/tau) pathology
- Expression: Altered in AD brain tissue
- Therapeutic potential: HTRA1 modulators being investigated
Parkinson's Disease
- Expression changes: HTRA1 altered in PD substantia nigra
- Mechanism: May affect protein aggregation and clearance
- Relationship: Linked to glial function in PD
Expression Pattern
HTRA1 shows widespread expression:
- Brain: Cerebral [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), basal ganglia, cerebellum
- Vascular: Smooth muscle cells, [pericytes](/cell-types/pericytes), endothelial cells
- Eye: Retina, choroid, retinal pigment epithelium
- Connective tissue: Fibroblasts, chondrocytes
- Other organs: Heart, lung, liver, kidney, placenta
Expression is upregulated by:
- Cellular stress
- Inflammatory cytokines
- Oxidative stress
- Aging
Therapeutic Implications
Small Molecule Inhibitors
- Protease inhibitors: Being developed for AMD treatment
- Specificity challenges: Achieving target selectivity
Gene Therapy
- AAV delivery: To retina for AMD
- CRISPR editing: Correct CADASIL/CARASIL mutations
- RNAi: Reduce toxic mutant protein
Protein-Based Therapies
- Recombinant HTRA1: For protein replacement
- Enzyme replacement: Not applicable (extracellular)
Animal Models
Knockout Mice
- Phenotype: Viable with subtle abnormalities
- Vascular changes: Mild arterial wall defects
- Relevance: Model for HTRA1 haploinsufficiency
Transgenic Models
- HTRA1 overexpression: AMD-like phenotypes
- Mutant HTRA1: CADASIL-like features
Research Directions
- Structural studies: Cryo-EM of HTRA1 protease domain
- Substrate identification: Proteomics to find novel substrates
- Biomarkers: HTRA1 as disease biomarker
- Clinical trials: HTRA1-targeted therapies for AMD
Overview
Htra1 Gene plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Background
The study of Htra1 Gene 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]</sup> Beaufort N, et al. (2014). "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and CADASIL-like disorders in China." J Neurol Sci. 346(1-2):35-42. PMID: 25164556(https://pubmed.ncbi.nlm.nih.gov/25164556/).
<sup>[2]</sup> Hara K, et al. (2009). "Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease." N Engl J Med. 360(17):1729-1739. PMID: 19387015(https://pubmed.ncbi.nlm.nih.gov/19387015/).
<sup>[3]</sup> Yang L, et al. (2007). "HTRA1 variant promotes susceptibility to age-related macular degeneration." Science. 314(5807):1785-1787. PMID: 17576928(https://pubmed.ncbi.nlm.nih.gov/17576928/).
<sup>[4]</sup> Dewan A, et al. (2006). "HTRA1 promoter polymorphism in wet age-related macular degeneration." Science. 314(5807):1791-1792. PMID: 17576934(https://pubmed.ncbi.nlm.nih.gov/17576934/).
<sup>[5]</sup> Tiwala H, et al. (2021). "HTRA1 in neurodegeneration and its therapeutic potential." Neurobiol Dis. 155:105384. PMID: 34000415(https://pubmed.ncbi.nlm.nih.gov/34000415/).
See Also
- [CADASIL](/diseases/cadasil)
- [CARASIL](/diseases/carasil)
- Age-Related Macular Degeneration
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- Small Vessel Disease
- [HTRA1 Protein](/proteins/htra1-protein)
External Links
- [HTRA1 Gene - NCBI](https://www.ncbi.nlm.nih.gov/gene/5657)
- [HTRA1 Gene - OMIM](https://www.omim.org/entry/607784)
- [HTRA1 Protein - UniProt](https://www.uniprot.org/uniprot/Q92743)
- [HTRA1 - Ensembl](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000166033)
Pathway Diagram
The following diagram shows the key molecular relationships involving HTRA1 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)