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Aliases for HTRA4 Gene

Aliases for HTRA4 Gene

  • HtrA Serine Peptidase 4 2 3 5
  • High-Temperature Requirement Factor A4 4
  • EC 56
  • EC 3.4.21.- 4
  • EC 3.4.21 56

External Ids for HTRA4 Gene

Previous GeneCards Identifiers for HTRA4 Gene

  • GC08P038831
  • GC08P037364

Summaries for HTRA4 Gene

Entrez Gene Summary for HTRA4 Gene

  • This gene encodes a member of the HtrA family of proteases. The encoded protein contains a putative signal peptide, an insulin growth factor binding domain, a Kazal protease inhibitor domain, a conserved trypsin domain and a PDZ domain. Based on studies on other related family members, this enzyme may function as a secreted oligomeric chaperone protease to degrade misfolded secretory proteins. Other human HtrA proteins have been implicated in arthritis, tumor suppression, unfolded stress response, apoptosis, and aging. [provided by RefSeq, Oct 2008]

GeneCards Summary for HTRA4 Gene

HTRA4 (HtrA Serine Peptidase 4) is a Protein Coding gene. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase activity and insulin-like growth factor binding. An important paralog of this gene is HTRA1.

UniProtKB/Swiss-Prot for HTRA4 Gene

  • Serine protease.

Additional gene information for HTRA4 Gene

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HTRA4 Gene

Genomics for HTRA4 Gene

GeneHancer (GH) Regulatory Elements for HTRA4 Gene

Promoters and enhancers for HTRA4 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH08I038973 Promoter/Enhancer 1.5 EPDnew Ensembl ENCODE dbSUPER 550.8 +0.4 352 2.6 CTCF ZNF687 SUZ12 BACH1 SIN3A ZBTB33 EZH2 ZBTB20 ENSG00000253645 HTRA4 TM2D2 PLEKHA2 GC08M038869
GH08I038995 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 12.3 +26.6 26647 10.8 HDGF PKNOX1 FOXA2 SMAD1 MLX ARID4B SIN3A FEZF1 DMAP1 ZNF2 TM2D2 ADAM32 HTRA4 ENSG00000253645 PLEKHA2 ENSG00000272128 ADAM9 SNORD38D GC08M039019 GC08M038869
GH08I038898 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 11 -72.0 -71955 6.8 HDGF PKNOX1 FEZF1 GTF3C2 ZNF121 ZNF766 ZNF143 ATF7 FOS RUNX3 PLEKHA2 ENSG00000253645 HTRA4 TM2D2 ADAM9 TACC1 DDHD2 C8orf86 GC08M038869
GH08I038910 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 11 -61.2 -61186 4.7 TFAP4 TEAD4 BACH1 TEAD3 FOSL1 CTBP1 POLR2A ATF7 FOSL2 FOS ENSG00000253645 HTRA4 TM2D2 ADAM9 PLEKHA2 GC08M038869
GH08I038923 Enhancer 1.3 Ensembl ENCODE dbSUPER 11.8 -47.3 -47332 6.6 PKNOX1 FOXA2 SIN3A YY1 GTF3C2 FOS RXRA REST SMARCB1 MAFF PLEKHA2 HTRA4 ENSG00000253645 GC08M038869
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around HTRA4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the HTRA4 gene promoter:

Genomic Locations for HTRA4 Gene

Genomic Locations for HTRA4 Gene
14,514 bases
Plus strand

Genomic View for HTRA4 Gene

Genes around HTRA4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HTRA4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HTRA4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HTRA4 Gene

Proteins for HTRA4 Gene

  • Protein details for HTRA4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Serine protease HTRA4
    Protein Accession:
    Secondary Accessions:
    • Q542Z4
    • Q6PF13

    Protein attributes for HTRA4 Gene

    476 amino acids
    Molecular mass:
    50979 Da
    Quaternary structure:
    No Data Available

neXtProt entry for HTRA4 Gene

Selected DME Specific Peptides for HTRA4 Gene


Post-translational modifications for HTRA4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for HTRA4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for HTRA4 Gene

Gene Families for HTRA4 Gene

Human Protein Atlas (HPA):
  • Enzymes
  • Predicted secreted proteins

Suggested Antigen Peptide Sequences for HTRA4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the peptidase S1C family.
  • Belongs to the peptidase S1C family.
genes like me logo Genes that share domains with HTRA4: view

Function for HTRA4 Gene

Molecular function for HTRA4 Gene

UniProtKB/Swiss-Prot Function:
Serine protease.

Enzyme Numbers (IUBMB) for HTRA4 Gene

Phenotypes From GWAS Catalog for HTRA4 Gene

Gene Ontology (GO) - Molecular Function for HTRA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004175 endopeptidase activity IDA 18387192
GO:0004252 serine-type endopeptidase activity IEA --
GO:0005520 insulin-like growth factor binding IEA --
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity IEA --
genes like me logo Genes that share ontologies with HTRA4: view
genes like me logo Genes that share phenotypes with HTRA4: view

Animal Models for HTRA4 Gene

MGI Knock Outs for HTRA4:

Animal Model Products

  • Taconic Biosciences Mouse Models for HTRA4

CRISPR Products

miRNA for HTRA4 Gene

miRTarBase miRNAs that target HTRA4

Inhibitory RNA Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HTRA4 Gene

Localization for HTRA4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HTRA4 Gene


Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HTRA4 gene
Compartment Confidence
extracellular 4
peroxisome 1
lysosome 1

Gene Ontology (GO) - Cellular Components for HTRA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
genes like me logo Genes that share ontologies with HTRA4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for HTRA4 Gene

Pathways & Interactions for HTRA4 Gene

SuperPathways for HTRA4 Gene

No Data Available

Gene Ontology (GO) - Biological Process for HTRA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001558 regulation of cell growth IEA --
GO:0006508 proteolysis IDA 18387192
GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway ISS --
genes like me logo Genes that share ontologies with HTRA4: view

No data available for Pathways by source and SIGNOR curated interactions for HTRA4 Gene

Drugs & Compounds for HTRA4 Gene

No Compound Related Data Available

Transcripts for HTRA4 Gene

mRNA/cDNA for HTRA4 Gene

Unigene Clusters for HTRA4 Gene

HtrA serine peptidase 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Alternative Splicing Database (ASD) splice patterns (SP) for HTRA4 Gene

No ASD Table

Relevant External Links for HTRA4 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for HTRA4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for HTRA4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HTRA4 Gene

This gene is overexpressed in Lung (x6.7) and Adipose - Subcutaneous (x5.4).

Protein differential expression in normal tissues from HIPED for HTRA4 Gene

This gene is overexpressed in Cervix (53.9) and Placenta (15.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for HTRA4 Gene

Protein tissue co-expression partners for HTRA4 Gene

NURSA nuclear receptor signaling pathways regulating expression of HTRA4 Gene:


SOURCE GeneReport for Unigene cluster for HTRA4 Gene:

genes like me logo Genes that share expression patterns with HTRA4: view

No data available for mRNA Expression by UniProt/SwissProt , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for HTRA4 Gene

Orthologs for HTRA4 Gene

This gene was present in the common ancestor of animals.

Orthologs for HTRA4 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia HTRA4 33 34
  • 99.65 (n)
(Canis familiaris)
Mammalia LOC475580 33
  • 80.39 (n)
HTRA4 34
  • 71 (a)
(Bos Taurus)
Mammalia HTRA4 33 34
  • 78.57 (n)
(Mus musculus)
Mammalia Htra4 33 16 34
  • 76.17 (n)
(Rattus norvegicus)
Mammalia Htra4 33
  • 75.13 (n)
(Ornithorhynchus anatinus)
Mammalia -- 34
  • 73 (a)
(Monodelphis domestica)
Mammalia HTRA4 34
  • 55 (a)
(Anolis carolinensis)
Reptilia HTRA4 34
  • 60 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100488607 33
  • 61.75 (n)
(Danio rerio)
Actinopterygii LOC100334257 33
  • 58.6 (n)
htra4 34
  • 52 (a)
fruit fly
(Drosophila melanogaster)
Insecta HtrA2 34
  • 37 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 39 (a)
Species where no ortholog for HTRA4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for HTRA4 Gene

Gene Tree for HTRA4 (if available)
Gene Tree for HTRA4 (if available)

Paralogs for HTRA4 Gene

Paralogs for HTRA4 Gene

(3) SIMAP similar genes for HTRA4 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with HTRA4: view

Variants for HTRA4 Gene

Sequence variations from dbSNP and Humsavar for HTRA4 Gene

SNP ID Clin Chr 08 pos Variation AA Info Type
rs1000349657 -- 38,979,986(+) T/G coding_sequence_variant, intron_variant, missense_variant
rs1000460634 -- 38,973,390(+) G/A upstream_transcript_variant
rs1000470868 -- 38,979,589(+) T/G intron_variant
rs1000748323 -- 38,973,709(+) T/A upstream_transcript_variant
rs1001061892 -- 38,984,185(+) G/A genic_downstream_transcript_variant, intron_variant

Variation tolerance for HTRA4 Gene

Residual Variation Intolerance Score: 56.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.12; 38.64% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HTRA4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for HTRA4 Gene

Disorders for HTRA4 Gene

Additional Disease Information for HTRA4

No disorders were found for HTRA4 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for HTRA4 Gene

Publications for HTRA4 Gene

  1. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4 58
  2. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 58
  3. Architecture of the human interactome defines protein communities and disease networks. (PMID: 28514442) Huttlin EL … Harper JW (Nature 2017) 3 58
  4. GATA3 inhibits GCM1 activity and trophoblast cell invasion. (PMID: 26899996) Chiu YH … Chen H (Scientific reports 2016) 3 58
  5. Human HtrA4 Expression Is Restricted to the Placenta, Is Significantly Up-Regulated in Early-Onset Preeclampsia, and High Levels of HtrA4 Cause Endothelial Dysfunction. (PMID: 25946029) Singh H … Nie G (The Journal of clinical endocrinology and metabolism 2015) 3 58

Products for HTRA4 Gene

Sources for HTRA4 Gene

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