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Aliases for HPN Gene

Aliases for HPN Gene

  • Hepsin 2 3 5
  • Transmembrane Protease Serine 1 3 4
  • EC 4 56
  • TMPRSS1 3 4
  • Transmembrane Protease, Serine 1 2
  • Testicular Tissue Protein Li 85 3
  • Serine Protease Hepsin 3
  • EC 3.4.21 56

External Ids for HPN Gene

Previous GeneCards Identifiers for HPN Gene

  • GC19P036148
  • GC19P035980
  • GC19P040207
  • GC19P040223
  • GC19P035531
  • GC19P032039

Summaries for HPN Gene

Entrez Gene Summary for HPN Gene

  • This gene encodes a type II transmembrane serine protease that may be involved in diverse cellular functions, including blood coagulation and the maintenance of cell morphology. Expression of the encoded protein is associated with the growth and progression of cancers, particularly prostate cancer. The protein is cleaved into a catalytic serine protease chain and a non-catalytic scavenger receptor cysteine-rich chain, which associate via a single disulfide bond. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

GeneCards Summary for HPN Gene

HPN (Hepsin) is a Protein Coding gene. Diseases associated with HPN include Prostate Cancer and Deafness, Autosomal Recessive 24. Among its related pathways are Signaling by MST1 and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase activity and serine-type peptidase activity. An important paralog of this gene is TMPRSS3.

UniProtKB/Swiss-Prot for HPN Gene

  • Serine protease that cleaves extracellular substrates, and contributes to the proteolytic processing of growth factors, such as HGF and MST1/HGFL (PubMed:21875933, PubMed:15839837). Plays a role in cell growth and maintenance of cell morphology (PubMed:8346233, PubMed:21875933). Plays a role in the proteolytic processing of ACE2 (PubMed:24227843). Mediates the proteolytic cleavage of urinary UMOD that is required for UMOD polymerization (PubMed:26673890).

Gene Wiki entry for HPN Gene

Additional gene information for HPN Gene

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

Genomics for HPN Gene

GeneHancer (GH) Regulatory Elements for HPN Gene

Promoters and enhancers for HPN 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
GH19I035037 Promoter/Enhancer 2 EPDnew Ensembl ENCODE dbSUPER 550.8 +0.3 288 6.4 HDGF PKNOX1 CLOCK SMAD1 FOXA2 MLX ZFP64 ARID4B SIN3A DMAP1 HPN ZNF181 HAUS5 ZNF599 TMEM147-AS1 KMT2B ENSG00000267219 GRAMD1A LSM14A SDHAF1
GH19I035136 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE dbSUPER 11.2 +99.0 98952 5.4 HDGF FOXA2 MLX ARID4B SIN3A YBX1 ZNF2 YY1 ZNF143 ZNF548 ENSG00000221857 FXYD1 ENSG00000279619 ZNF599 TMEM147-AS1 LSM14A HAUS5 KIAA0355 ZNF792 KMT2B
GH19I035113 Promoter/Enhancer 2.1 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 11.1 +77.5 77514 8.1 SIN3A ZNF2 ZBTB7B TCF12 GLIS2 ZNF213 ZNF143 KLF7 ATF7 FOS FXYD3 LSM14A RBM42 PROSER3 KMT2B ENSG00000221857 LGI4 HAUS5 LOC101927572 HPN
GH19I035066 Enhancer 1.6 FANTOM5 Ensembl ENCODE dbSUPER 13.1 +27.5 27532 3.2 HDGF ARID4B SIN3A FEZF1 ZNF2 YY1 E2F8 ZNF207 ZNF143 KLF13 HPN TMEM147-AS1 SCN1B LSM14A RBM42 ENSG00000267049 KMT2B HAUS5 ZBTB32 ZNF599
GH19I034972 Enhancer 1.8 FANTOM5 Ensembl ENCODE dbSUPER 11.6 -66.4 -66444 2.5 HDGF PKNOX1 ARID4B SIN3A ZNF2 IRF4 YY1 SLC30A9 ZNF302 ZNF416 TMEM147-AS1 ZNF599 HAUS5 ZNF181 ENSG00000267049 PROSER3 LSM14A KMT2B KIAA0355 ZNF30
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around HPN on UCSC Golden Path with GeneCards custom track

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

Genomic Locations for HPN Gene

Genomic Locations for HPN Gene
26,072 bases
Plus strand

Genomic View for HPN Gene

Genes around HPN on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for HPN Gene

Proteins for HPN Gene

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

    Protein Symbol:
    Recommended name:
    Serine protease hepsin
    Protein Accession:
    Secondary Accessions:
    • B2RDS4

    Protein attributes for HPN Gene

    417 amino acids
    Molecular mass:
    45011 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for HPN Gene

neXtProt entry for HPN Gene

Selected DME Specific Peptides for HPN Gene


Post-translational modifications for HPN Gene

Domains & Families for HPN Gene

Gene Families for HPN Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Enzymes
  • Predicted intracellular proteins
  • Predicted membrane proteins

Suggested Antigen Peptide Sequences for HPN Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the peptidase S1 family.
  • Belongs to the peptidase S1 family.
genes like me logo Genes that share domains with HPN: view

Function for HPN Gene

Molecular function for HPN Gene

GENATLAS Biochemistry:
hepsin,cell membrane associated serine protease,activating factor VII
UniProtKB/Swiss-Prot CatalyticActivity:
Cleavage after basic amino-acid residues, with Arg strongly preferred to Lys.
UniProtKB/Swiss-Prot Function:
Serine protease that cleaves extracellular substrates, and contributes to the proteolytic processing of growth factors, such as HGF and MST1/HGFL (PubMed:21875933, PubMed:15839837). Plays a role in cell growth and maintenance of cell morphology (PubMed:8346233, PubMed:21875933). Plays a role in the proteolytic processing of ACE2 (PubMed:24227843). Mediates the proteolytic cleavage of urinary UMOD that is required for UMOD polymerization (PubMed:26673890).

Enzyme Numbers (IUBMB) for HPN Gene

Phenotypes From GWAS Catalog for HPN Gene

Gene Ontology (GO) - Molecular Function for HPN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity TAS --
GO:0005515 protein binding IPI 15614436
GO:0008233 peptidase activity IDA 16908524
GO:0008236 serine-type peptidase activity IDA,TAS 19911255
GO:0015269 calcium-activated potassium channel activity ISS --
genes like me logo Genes that share ontologies with HPN: view
genes like me logo Genes that share phenotypes with HPN: view

Animal Models for HPN Gene

MGI Knock Outs for HPN:

Animal Model Products

miRNA for HPN Gene

miRTarBase miRNAs that target HPN

Clone Products

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

Localization for HPN Gene

Subcellular locations from UniProtKB/Swiss-Prot for HPN Gene

Cell membrane; Single-pass type II membrane protein. Apical cell membrane; Single-pass type II membrane protein.

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 HPN gene
Compartment Confidence
plasma membrane 5
extracellular 5
endoplasmic reticulum 5
lysosome 1

Gene Ontology (GO) - Cellular Components for HPN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005789 endoplasmic reticulum membrane IDA 17918732
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IDA 1885621
GO:0005911 cell-cell junction ISS --
GO:0009986 cell surface IDA 8346233
genes like me logo Genes that share ontologies with HPN: view

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

Pathways & Interactions for HPN Gene

genes like me logo Genes that share pathways with HPN: view

Pathways by source for HPN Gene

1 KEGG pathway for HPN Gene

Gene Ontology (GO) - Biological Process for HPN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IDA,IEA 16908524
GO:0008360 regulation of cell shape IMP 8346233
GO:0010628 positive regulation of gene expression ISS --
GO:0010719 negative regulation of epithelial to mesenchymal transition IDA 19843851
GO:0010756 positive regulation of plasminogen activation IDA 16908524
genes like me logo Genes that share ontologies with HPN: view

No data available for SIGNOR curated interactions for HPN Gene

Drugs & Compounds for HPN Gene

(13) Drugs for HPN Gene - From: DrugBank, ClinicalTrials, DGIdb, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Coagulation factor VIIa Recombinant Human Approved Pharma Target 0
Sorbitol Approved Pharma 41
Taurine Approved Nutra Non-selective, endogenous glycine receptor partial agonist 31
6-Chloro-2-(2-Hydroxy-Biphenyl-3-Yl)-1h-Indole-5-Carboxamidine Experimental Pharma Target 0
Benzylsulfinic Acid Experimental Pharma Target 0

(1) Additional Compounds for HPN Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with HPN: view

Transcripts for HPN Gene

Unigene Clusters for HPN Gene

Representative Sequences:

Clone Products

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

ExUns: 1 ^ 2a · 2b · 2c ^ 3a · 3b ^ 4a · 4b ^ 5a · 5b ^ 6 ^ 7a · 7b ^ 8a · 8b · 8c ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15
SP1: - - - -
SP2: - - -
SP3: -
SP4: - - -
SP5: - -
SP6: - - - - - - -
SP7: -

Relevant External Links for HPN Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for HPN Gene

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

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

This gene is overexpressed in Liver (x28.3), Pancreas (x8.8), and Kidney - Cortex (x7.8).

Protein differential expression in normal tissues from HIPED for HPN Gene

This gene is overexpressed in Skin (36.5), Plasma (16.1), and Urine (9.6).

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

Protein tissue co-expression partners for HPN Gene

NURSA nuclear receptor signaling pathways regulating expression of HPN Gene:


SOURCE GeneReport for Unigene cluster for HPN Gene:


mRNA Expression by UniProt/SwissProt for HPN Gene:

Tissue specificity: Detected in liver and kidney.

Evidence on tissue expression from TISSUES for HPN Gene

  • Liver(4.7)
  • Pancreas(4.4)
  • Spleen(4)
  • Kidney(2.6)
  • Nervous system(2.1)
genes like me logo Genes that share expression patterns with HPN: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for HPN Gene

Orthologs for HPN Gene

This gene was present in the common ancestor of animals.

Orthologs for HPN Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia HPN 33 34
  • 99.84 (n)
(Canis familiaris)
Mammalia HPN 33 34
  • 90.33 (n)
(Bos Taurus)
Mammalia HPN 33 34
  • 90.09 (n)
(Monodelphis domestica)
Mammalia HPN 34
  • 88 (a)
(Mus musculus)
Mammalia Hpn 33 16 34
  • 84.67 (n)
(Rattus norvegicus)
Mammalia Hpn 33
  • 84.18 (n)
(Ornithorhynchus anatinus)
Mammalia HPN 34
  • 12 (a)
(Gallus gallus)
Aves HPN 34
  • 34 (a)
(Anolis carolinensis)
Reptilia HPN 34
  • 68 (a)
(Danio rerio)
Actinopterygii si:dkey-33i11.3 33
  • 59.04 (n)
HPN (1 of 2) 34
  • 51 (a)
HPN (2 of 2) 34
  • 50 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP004568 33
  • 48.54 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG4613 35
  • 41 (a)
CG11824 35
  • 40 (a)
CG3355 35
  • 39 (a)
CG11836 35
  • 38 (a)
mas 35
  • 38 (a)
Sb 35
  • 38 (a)
CG11192 35
  • 37 (a)
CG4386 35
  • 37 (a)
eegrTry 35
  • 37 (a)
CG6041 35
  • 36 (a)
zgrTry 35
  • 36 (a)
CG7829 35
  • 34 (a)
Tequila 35
  • 34 (a)
CG1299 35
  • 33 (a)
(Caenorhabditis elegans)
Secernentea C07G1.1 35
  • 36 (a)
Species where no ortholog for HPN was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • 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 squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • 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)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for HPN Gene

Gene Tree for HPN (if available)
Gene Tree for HPN (if available)

Paralogs for HPN Gene

Variants for HPN Gene

Sequence variations from dbSNP and Humsavar for HPN Gene

SNP ID Clin Chr 19 pos Variation AA Info Type
rs150721582 conflicting-interpretations-of-pathogenicity, likely-benign, not specified, Cardiovascular phenotype, Brugada syndrome 5 35,039,676(+) G/A upstream_transcript_variant
rs16969930 conflicting-interpretations-of-pathogenicity, benign, likely-benign, not specified, Cardiovascular phenotype, Cardiac conduction defect, nonspecific, Brugada syndrome, Generalized epilepsy with febrile seizures plus, Brugada syndrome 5 35,039,169(+) T/C upstream_transcript_variant
rs35478147 uncertain-significance, Brugada syndrome 5 35,039,190(+) C/A/T upstream_transcript_variant
rs72550247 pathogenic, uncertain-significance, Atrial fibrillation, familial, 13, not specified, Death in early adulthood 35,039,125(+) G/A upstream_transcript_variant
rs765269835 likely-benign, not specified, Brugada syndrome 5 35,039,139(+) C/A/T upstream_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for HPN Gene

Variant ID Type Subtype PubMed ID
esv2718489 CNV deletion 23290073
nsv1123248 CNV deletion 24896259
nsv1129392 OTHER inversion 24896259
nsv1147961 CNV deletion 26484159

Variation tolerance for HPN Gene

Residual Variation Intolerance Score: 39.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.52; 29.58% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HPN Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HPN Gene

Disorders for HPN Gene

MalaCards: The human disease database

(4) MalaCards diseases for HPN Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
prostate cancer
  • prostate cancer, susceptibility to
deafness, autosomal recessive 24
  • dfnb24
deafness, autosomal recessive 25
  • dfnb25
male reproductive organ cancer
  • male genital cancer
- elite association - COSMIC cancer census association via MalaCards
Search HPN in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HPN

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with HPN: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HPN Gene

Publications for HPN Gene

  1. Association of hepsin gene variants with prostate cancer risk and prognosis. (PMID: 20166135) Holt SK … Stanford JL (The Prostate 2010) 3 22 44 58
  2. Genes involved in the transforming growth factor beta signalling pathway and the risk of intracranial aneurysms. (PMID: 18487557) Ruigrok YM … Wijmenga C (Journal of neurology, neurosurgery, and psychiatry 2008) 3 22 44 58
  3. Variants in the HEPSIN gene are associated with prostate cancer in men of European origin. (PMID: 16783571) Pal P … Deka R (Human genetics 2006) 3 22 44 58
  4. Hepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers. (PMID: 15839837) Herter S … Austin RJ (The Biochemical journal 2005) 3 4 22 58
  5. Analysis of candidate genes for prostate cancer. (PMID: 15583422) Burmester JK … Catalona WJ (Human heredity 2004) 3 22 44 58

Products for HPN Gene

Sources for HPN Gene

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