HTRA1: HtrA Serine Peptidase 1
A multifunctional serine protease involved in TGF-β signaling, extracellular matrix homeostasis, and linked to cerebral small vessel disease and age-related macular degeneration.
Gene Information Card
| Symbol | HTRA1 |
|---|---|
| Full Name | HtrA serine peptidase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q26.13 |
| NCBI Gene ID | 5654 ncbi.nlm.nih.gov/gene/5654 |
| Ensembl ID | ENSG00000166033 |
| UniProt ID | Q92743 |
| OMIM ID | 602194 |
| HGNC ID | 9476 |
| Aliases | HtrA, L56, ORF480, PRSS11, ARMD7, CARASIL |
Description
HTRA1 encodes a member of the HtrA family of serine proteases. The protein is secreted and functions in the degradation of extracellular matrix components, regulation of transforming growth factor-beta (TGF-β) signaling, and cellular stress responses. Mutations in HTRA1 are associated with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) and age-related macular degeneration (AMD).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) | Loss-of-function mutations reduce protease activity, leading to impaired TGF-β signaling regulation and arterial wall degeneration. | OMIM #600142; multiple case reports |
| Age-related macular degeneration (AMD) | Increased HTRA1 expression in retinal pigment epithelium promotes complement activation and extracellular matrix remodeling, contributing to drusen formation. | GWAS and functional studies; OMIM #610149 |
| Osteoarthritis | HTRA1 degrades cartilage matrix components such as aggrecan and fibromodulin, contributing to joint degeneration. | Expression studies in cartilage tissue |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.2 | Medium |
| Retina | 12.5 | High |
| Artery | 6.8 | Medium |
| Liver | 4.1 | Low |
| Kidney | 5.3 | Low |
| Lung | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (retinal pigment epithelium) | 15.3 | High expression; relevant for AMD studies |
| HUVEC (umbilical vein endothelial) | 7.1 | Moderate expression |
| HeLa (cervical carcinoma) | 4.8 | Low expression |
| HEK293 (embryonic kidney) | 6.2 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.904C>T (p.Arg302*) | Nonsense | Rare | Loss of function; associated with CARASIL |
| c.110G>A (p.Arg37His) | Missense | Rare | Reduced protease activity; linked to CARASIL |
| rs11200638 (promoter variant) | Regulatory | Common (allele frequency ~0.3 in East Asians) | Increased HTRA1 expression; risk factor for AMD |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg302*, p.Arg37His) reduce or abolish protease activity, leading to CARASIL.
Gain of Function (GOF)
Promoter variant rs11200638 increases HTRA1 expression, contributing to AMD risk.
Dominant Negative (DN)
Not well documented for HTRA1; most disease-associated mutations are recessive or risk alleles.
View complete mutation data：
Gene Ontology (GO)
Pathways
• TGF-β signaling pathway (Reactome: R-HSA-170834)
• Extracellular matrix organization (Reactome: R-HSA-1474244)
• Cellular response to stress (Reactome: R-HSA-2262752)
Protein Summary
HTRA1 is a 480-amino acid secreted serine protease with a trypsin-like protease domain and a PDZ domain. It degrades extracellular matrix components (e.g., fibronectin, aggrecan) and modulates TGF-β signaling by cleaving TGF-β family members. The protein is implicated in vascular integrity, retinal health, and cartilage maintenance. Dysregulation leads to cerebral arteriopathy and AMD.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HTRA1 Knockout HEK293 Cell Line | EDJ-KQ1898 | Human | 5654 | Details Get a Quote |
| HTRA1 Knockout A-549 Cell Line | EDJ-KQ20503 | Human | 5654 | Details Get a Quote |
| HTRA1 Knockout HeLa Cell Line | EDJ-KQ21805 | Human | 5654 | Details Get a Quote |
| HTRA1 Knockout HCT 116 Cell Line | EDJ-KQ71198 | Human | 5654 | Details Get a Quote |
