HTRA1 Gene

HGNC Family	Proteases, serine (PRSS)
Name	HtrA serine peptidase 1
Description	This gene encodes a member of the trypsin family of serine proteases. This protein is a secreted enzyme that is proposed to regulate the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. It has also been suggested to be a regulator of cell growth. Variations in the promoter region of this gene are the cause of susceptibility to age-related macular degeneration type 7. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HtrA1 is an ATP‐independent serine protease characterized by a trypsin–like catalytic domain coupled with one or more C‐terminal PDZ domains that function in substrate recognition and regulatory “fine‐tuning” of its proteolytic activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In its role in cellular protein quality control, HtrA1 not only degrades misfolded or damaged proteins but also performs chaperone functions, thereby contributing to the overall maintenance of proteostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, HtrA1 acts as a potent antagonist of transforming growth factor–β (TGF‑β) signaling by binding and proteolytically processing certain TGF‑β family members and their receptors; this inhibition of TGF‑β signaling has implications in tissue homeostasis, bone formation, and extracellular matrix remodeling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the nervous system, HtrA1 participates in the clearance of beta‐amyloid peptides, suggesting a role in preventing protein aggregation associated with Alzheimer’s disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, reduced expression of HtrA1 in cancer, particularly in ovarian and endometrial tumors, has been linked to impaired apoptosis and altered responses to chemotherapeutic agents, indicating that HtrA1 may also function as a metastasis suppressor by modulating cell death pathways and cell motility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic studies have identified that variants within the 10q26 locus—including those affecting HtrA1—are strongly associated with age‐related macular degeneration (AMD) and polypoidal choroidal vasculopathy, thereby implicating HtrA1 in the regulation of the extracellular milieu in ocular tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": " Structural insights further support a model in which substrate binding provides a conformational “switch” that activates its proteolytic function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies reveal that HtrA1 is a multifaceted protease involved in quality control, modulation of key signaling cascades, extracellular matrix turnover, and cell motility. Dysregulation of HtrA1—whether through genetic mutations, altered expression, or impaired functional activation—can contribute to diverse pathologies including cerebrovascular small‐vessel disease, neurodegeneration, AMD, and various malignancies. As such, HtrA1 represents not only a central modulator of cellular homeostasis but also a potential therapeutic target in diseases characterized by aberrant proteolysis and extracellular remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_fs", "start_ref": "11", "end_ref": "13"}, {"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tim Clausen, Chris Southan, Michael Ehrmann "}, {"type": "b", "children": [{"type": "t", "text": "The HtrA family of proteases: implications for protein composition and cell fate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1097-2765(02)00658-5"}], "href": "https://doi.org/10.1016/s1097-2765(02"}, {"type": "t", "text": "00658-5) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12408815"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12408815"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Charles Eigenbrot, Mark Ultsch, Michael T Lipari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural and functional analysis of HtrA1 and its subdomains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Structure (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.str.2012.03.021"}], "href": "https://doi.org/10.1016/j.str.2012.03.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22578544"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22578544"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Linda Truebestein, Annette Tennstaedt, Timon Mönig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Substrate-induced remodeling of the active site regulates human HTRA1 activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.2013"}], "href": "https://doi.org/10.1038/nsmb.2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21297635"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21297635"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kenju Hara, Atsushi Shiga, Toshio Fukutake, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "N Engl J Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1056/NEJMoa0801560"}], "href": "https://doi.org/10.1056/NEJMoa0801560"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19387015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19387015"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Chio Oka, Rumi Tsujimoto, Miwa Kajikawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HtrA1 serine protease inhibits signaling mediated by Tgfbeta family proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.00999"}], "href": "https://doi.org/10.1242/dev.00999"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14973287"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14973287"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Julie R Graham, Angela Chamberland, Qingcong Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serine protease HTRA1 antagonizes transforming growth factor-β signaling by cleaving its receptors and loss of HTRA1 in vivo enhances bone formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0074094"}], "href": "https://doi.org/10.1371/journal.pone.0074094"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24040176"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24040176"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sandra Grau, Alfonso Baldi, Rossana Bussani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Implications of the serine protease HtrA1 in amyloid precursor protein processing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0501823102"}], "href": "https://doi.org/10.1073/pnas.0501823102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15855271"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15855271"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jeremy Chien, Giovanni Aletti, Alfonso Baldi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serine protease HtrA1 modulates chemotherapy-induced cytotoxicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI27698"}], "href": "https://doi.org/10.1172/JCI27698"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16767218"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16767218"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jeremy Chien, Takayo Ota, Giovanni Aletti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serine protease HtrA1 associates with microtubules and inhibits cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00035-09"}], "href": "https://doi.org/10.1128/MCB.00035-09"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19470753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19470753"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Joanna Narkiewicz, Sylwia Lapinska-Szumczyk, Dorota Zurawa-Janicka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of human HtrA1, HtrA2, HtrA3 and TGF-beta1 genes in primary endometrial cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or_00000385"}], "href": "https://doi.org/10.3892/or_00000385"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19424634"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19424634"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Michael K Lin, Jin Yang, Chun Wei Hsu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HTRA1, an age-related macular degeneration protease, processes extracellular matrix proteins EFEMP1 and TSP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging Cell (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/acel.12710"}], "href": "https://doi.org/10.1111/acel.12710"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29730901"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29730901"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Naoshi Kondo, Shigeru Honda, Kazuki Ishibashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LOC387715/HTRA1 variants in polypoidal choroidal vasculopathy and age-related macular degeneration in a Japanese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Ophthalmol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajo.2007.06.003"}], "href": "https://doi.org/10.1016/j.ajo.2007.06.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17692272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17692272"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Julie Bergeron-Sawitzke, Bert Gold, Adam Olsh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Multilocus analysis of age-related macular degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2009.23"}], "href": "https://doi.org/10.1038/ejhg.2009.23"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19259132"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19259132"}]}]}]}
Synonyms	CADASIL2, PRSS11, HTRA, ARMD7, L56, ORF480, CARASIL
Proteins	HTRA1_HUMAN
NCBI Gene ID	5654
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HTRA1 has 10,125 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 127 datasets.

Click the + buttons to view associations for HTRA1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HTRA1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of HTRA1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of HTRA1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of HTRA1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of HTRA1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of HTRA1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of HTRA1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of HTRA1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of HTRA1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of HTRA1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of HTRA1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HTRA1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of HTRA1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with HTRA1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HTRA1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of HTRA1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HTRA1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of HTRA1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with HTRA1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with HTRA1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing HTRA1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of HTRA1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HTRA1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HTRA1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with HTRA1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with HTRA1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HTRA1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HTRA1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HTRA1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with HTRA1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by HTRA1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving HTRA1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving HTRA1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with HTRA1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with HTRA1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with HTRA1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with HTRA1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with HTRA1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HTRA1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at HTRA1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of HTRA1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.