HTRA1 Gene

📖 Wiki Page

gene986 wordssynced 2026-04-02

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

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

Age-Related Macular Degeneration (AMD)

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

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

[1] 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/).

[2] 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/).

[3] 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/).

[4] 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/).

[5] 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/).

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)

📖 View canonical wiki page →

HTRA1 Gene

HTRA1 Gene

Overview

HTRA1 Gene

Overview

Introduction

Gene Overview

Gene Structure

Protein Function

Protease Activity

Vascular Function

Neuroprotective Functions

Disease Associations

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)

CARASIL (Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)

Age-Related Macular Degeneration (AMD)

Alzheimer's Disease

Parkinson's Disease

Expression Pattern

Therapeutic Implications

Small Molecule Inhibitors

Gene Therapy

Protein-Based Therapies

Animal Models

Knockout Mice

Transgenic Models

Research Directions

Overview

Background

References

See Also

External Links

Pathway Diagram