HTRA3 Gene

Name HtrA serine peptidase 3
Description Enables endopeptidase activity; identical protein binding activity; and serine-type peptidase activity. Involved in proteolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Mar 2025]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HtrA3 is a multifunctional serine protease belonging to the HtrA family that is expressed in a highly tissue‐ and context‐dependent manner. In reproductive tissues it is best known for its roles in placental development and ovarian function. Two alternatively spliced isoforms—a long form containing a PDZ domain and a short form lacking this domain—are produced, and both appear to be active proteases. HtrA3 is highly expressed in the placenta, where it is involved in regulating trophoblast differentiation and invasiveness, thereby contributing to proper implantation and placentation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In the primate and rodent ovary HtrA3 has been implicated in folliculogenesis and luteinization, with altered expression potentially affecting fertility and reproductive outcomes."}, {"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 addition to its reproductive functions, HtrA3 has emerged as a key player in cancer biology. Loss or epigenetic downregulation of HtrA3 is observed in several malignancies such as lung, breast, endometrial, ovarian, and gastric cancers, where its diminished expression is associated with increased cell survival, chemoresistance, metastasis, and poor prognosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "11"}]}, {"type": "t", "text": " In contrast, in some contexts—for example, in oral squamous cell carcinoma—upregulation of HtrA3 has been linked to the acquisition of an invasive phenotype."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Furthermore, experimental inhibition of HtrA3 proteolytic activity using dominant‐negative mutants or specific monoclonal antibodies enhanced trophoblast and cancer cell invasion, suggesting that HtrA3 normally acts to restrain invasive behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural and biochemical studies have further delineated the regulatory mechanisms of HtrA3 activity. Crystal structures reveal that although the PDZ domain is not essential for substrate binding and protease activity, its presence modulates oligomerization and may contribute to substrate specificity and stability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " As a secreted protease with a complex domain organization, HtrA3 also shows promise as a diagnostic marker; for instance, elevated serum levels have been suggested as an early indicator for preeclampsia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its roles in reproduction and cancer, HtrA3 has been identified as a candidate gene in neurodevelopmental disorders"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": ", highlighting its broader significance in cell signaling and apoptosis. Collectively, these data support the notion that HtrA3 functions as a critical regulator of cell fate and tissue homeostasis, with its dysregulation contributing to pathologies ranging from placental dysfunction and infertility to tumor progression and chemoresistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": " \n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gui-Ying Nie, Anne Hampton, Ying Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and cloning of two isoforms of human high-temperature requirement factor A3 (HtrA3), characterization of its genomic structure and comparison of its tissue distribution with HtrA1 and HtrA2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20021569"}], "href": "https://doi.org/10.1042/BJ20021569"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12513693"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12513693"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Gui-Ying Nie, Ying Li, Hiroyuki Minoura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel serine protease of the mammalian HtrA family is up-regulated in mouse uterus coinciding with placentation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Hum Reprod (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/molehr/gag036"}], "href": "https://doi.org/10.1093/molehr/gag036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12728021"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12728021"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "H Singh, S-i Makino, Y Endo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of HTRA3 stimulates trophoblast invasion during human placental development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Placenta (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.placenta.2010.10.003"}], "href": "https://doi.org/10.1016/j.placenta.2010.10.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21035848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21035848"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Marissa A Bowden, Ann E Drummond, Peter J Fuller, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Molecular Cloning of the Porcine HTRA3 Gene and Association of a SNP with Litter Size Traits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Folia Biol (Praha) (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14712/fb2017063050217"}], "href": "https://doi.org/10.14712/fb2017063050217"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29687776"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29687776"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Marissa A Bowden, Ying Li, Yi-Xun Liu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "HtrA3 Is Downregulated in Cancer Cell Lines and Significantly Reduced in Primary Serous and Granulosa Cell Ovarian Tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cancer (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/jca.5702"}], "href": "https://doi.org/10.7150/jca.5702"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23412729"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23412729"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yujiro Moriya, Narikazu Uzawa, Takuma Morita, et al. 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Synonyms PRSP
Proteins HTRA3_HUMAN
NCBI Gene ID 94031
API
Download Associations
Predicted Functions View HTRA3's ARCHS4 Predicted Functions.
Co-expressed Genes View HTRA3's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View HTRA3's ARCHS4 Predicted Functions.

Functional Associations

HTRA3 has 3,521 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 82 datasets.

Click the + buttons to view associations for HTRA3 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles tissues with high or low expression of HTRA3 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 HTRA3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray tissue samples with high or low expression of HTRA3 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 HTRA3 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 HTRA3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
BioGPS Human Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of HTRA3 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 HTRA3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of HTRA3 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 HTRA3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of HTRA3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of HTRA3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing HTRA3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 cellular components containing HTRA3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with HTRA3 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 HTRA3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of HTRA3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with HTRA3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Disease Associations diseases associated with HTRA3 gene/protein from the curated CTD Gene-Disease Associations dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by HTRA3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with HTRA3 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 HTRA3 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 HTRA3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with HTRA3 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 HTRA3 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 HTRA3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of HTRA3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
ESCAPE Omics Signatures of Genes and Proteins for Stem Cells PubMedIDs of publications reporting gene signatures containing HTRA3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GAD Gene-Disease Associations diseases associated with HTRA3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
GAD High Level Gene-Disease Associations diseases associated with HTRA3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with HTRA3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing HTRA3 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of HTRA3 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of HTRA3 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of HTRA3 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of HTRA3 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of HTRA3 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of HTRA3 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving HTRA3 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2025 biological processes involving HTRA3 gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2015 cellular components containing HTRA3 protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by HTRA3 gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by HTRA3 gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx eQTL 2025 SNPs regulating expression of HTRA3 gene from the GTEx eQTL 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of HTRA3 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Sample Gene Expression Profiles tissue samples with high or low expression of HTRA3 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
GTEx Tissue-Specific Aging Signatures tissue samples with high or low expression of HTRA3 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset.
GWASdb SNP-Phenotype Associations phenotypes associated with HTRA3 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles cell lines with high or low expression of HTRA3 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
HPA Cell Line Gene Expression Profiles cell lines with high or low expression of HTRA3 gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of HTRA3 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
HPA Tissue Protein Expression Profiles tissues with high or low expression of HTRA3 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
HPA Tissue Sample Gene Expression Profiles tissue samples with high or low expression of HTRA3 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
HPM Cell Type and Tissue Protein Expression Profiles cell types and tissues with high or low expression of HTRA3 protein relative to other cell types and tissues from the HPM Cell Type and Tissue Protein Expression Profiles dataset.
HuGE Navigator Gene-Phenotype Associations phenotypes associated with HTRA3 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for HTRA3 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of HTRA3 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of HTRA3 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles cell lines with HTRA3 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of HTRA3 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain HTRA3 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MiRTarBase microRNA Targets microRNAs targeting HTRA3 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of HTRA3 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations gene perturbations changing expression of HTRA3 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset.
NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles drug perturbations changing expression of HTRA3 gene from the NIBR DRUG-seq U2OS MoA Box dataset.
NURSA Protein Complexes protein complexs containing HTRA3 protein recovered by IP-MS from the NURSA Protein Complexes dataset.
PFOCR Pathway Figure Associations 2023 pathways involving HTRA3 protein from the PFOCR Pathway Figure Associations 2023 dataset.
PFOCR Pathway Figure Associations 2024 pathways involving HTRA3 protein from the Wikipathways PFOCR 2024 dataset.
Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles cell types and tissues with high or low DNA methylation of HTRA3 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset.
Roadmap Epigenomics Cell and Tissue Gene Expression Profiles cell types and tissues with high or low expression of HTRA3 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue Gene Expression Profiles dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at HTRA3 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of HTRA3 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of HTRA3 gene from the RummaGEO Gene Perturbation Signatures dataset.
Sanger Dependency Map Cancer Cell Line Proteomics cell lines associated with HTRA3 protein from the Sanger Dependency Map Cancer Cell Line Proteomics dataset.
TargetScan Predicted Conserved microRNA Targets microRNAs regulating expression of HTRA3 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of HTRA3 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of HTRA3 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores tissues with high expression of HTRA3 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of HTRA3 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores tissues with high expression of HTRA3 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 tissues with high expression of HTRA3 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with HTRA3 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with HTRA3 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.