This gene encodes a member of the serine protease family. Serine proteases are known to be involved in a variety of biological processes, whose malfunction often leads to human diseases and disorders. This gene was identified as a gene overexpressed in pancreatic carcinoma. The encoded protein is membrane bound with a N-terminal anchor sequence and a glycosylated extracellular ... See more...

Aliases for TMPRSS4 Gene

Aliases for TMPRSS4 Gene

  • Transmembrane Serine Protease 4 2 3 5
  • Membrane-Type Serine Protease 2 2 3 4
  • TMPRSS3 2 3 4
  • MT-SP2 2 3 4
  • Channel-Activating Serine Protease 2 2 3
  • Type II Membrane Serine Protease 2 3
  • Transmembrane Protease, Serine 4 2 3
  • Transmembrane Serine Protease 3 2 3
  • Transmembrane Protease Serine 4 3 4
  • Channel-Activating Protease 2 3 4
  • CAPH2 3 4
  • CAP2 2 3
  • EC 3.4.21.43 50
  • EC 3.4.21.4 50
  • EC 3.4.21.- 4
  • EC 3.4.21 50
  • TMPRSS4 5

External Ids for TMPRSS4 Gene

Previous GeneCards Identifiers for TMPRSS4 Gene

  • GC11P120304
  • GC11P119459
  • GC11P117981
  • GC11P117485
  • GC11P117452
  • GC11P113881
  • GC11P117949

Summaries for TMPRSS4 Gene

Entrez Gene Summary for TMPRSS4 Gene

  • This gene encodes a member of the serine protease family. Serine proteases are known to be involved in a variety of biological processes, whose malfunction often leads to human diseases and disorders. This gene was identified as a gene overexpressed in pancreatic carcinoma. The encoded protein is membrane bound with a N-terminal anchor sequence and a glycosylated extracellular region containing the serine protease domain. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneCards Summary for TMPRSS4 Gene

TMPRSS4 (Transmembrane Serine Protease 4) is a Protein Coding gene. Diseases associated with TMPRSS4 include Autosomal Recessive Cerebral Atrophy and Deafness, Autosomal Recessive 8. Among its related pathways are Measles. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase activity and scavenger receptor activity. An important paralog of this gene is KLK2.

UniProtKB/Swiss-Prot Summary for TMPRSS4 Gene

  • Plasma membrane-anchored serine protease that directly induces processing of pro-uPA/PLAU into the active form through proteolytic activity (PubMed:24434139). Seems to be capable of activating ENaC (By similarity).
  • (Microbial infection) In gut epithelial cells, facilitates human coronavirus SARS-CoV-2 infection through, at least, the cleavage of coronavirus spike glycoproteins which activates the glycoprotein for host cell entry.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TMPRSS4 Gene

Genomics for TMPRSS4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TMPRSS4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TMPRSS4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TMPRSS4

Top Transcription factor binding sites by QIAGEN in the TMPRSS4 gene promoter:
  • AML1a
  • C/EBPalpha
  • CHOP-10
  • CREB
  • deltaCREB
  • GR
  • GR-alpha
  • Lmo2
  • POU3F2

Genomic Locations for TMPRSS4 Gene

Latest Assembly
chr11:118,077,012-118,125,505
(GRCh38/hg38)
Size:
48,494 bases
Orientation:
Plus strand

Previous Assembly
chr11:117,947,793-117,992,605
(GRCh37/hg19 by Entrez Gene)
Size:
44,813 bases
Orientation:
Plus strand

chr11:117,947,753-117,992,605
(GRCh37/hg19 by Ensembl)
Size:
44,853 bases
Orientation:
Plus strand

Genomic View for TMPRSS4 Gene

Genes around TMPRSS4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TMPRSS4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TMPRSS4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TMPRSS4 Gene

Proteins for TMPRSS4 Gene

  • Protein details for TMPRSS4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NRS4-TMPS4_HUMAN
    Recommended name:
    Transmembrane protease serine 4
    Protein Accession:
    Q9NRS4
    Secondary Accessions:
    • A8MU84
    • B0YJB0
    • B7Z8C5
    • E7ERX8
    • Q5XKQ6
    • Q6UX37
    • Q9NZA5

    Protein attributes for TMPRSS4 Gene

    Size:
    437 amino acids
    Molecular mass:
    48246 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=AAF31436.1; Type=Frameshift; Evidence={ECO:0000305};

    Alternative splice isoforms for TMPRSS4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TMPRSS4 Gene

Selected DME Specific Peptides for TMPRSS4 Gene

Q9NRS4:
  • PWQVSIQ
  • VLTAAHC
  • GDSGGPL
  • PGVYTKV
  • CQGDSGGP
  • WVLTAAHCFR
  • LTAAHCF
  • WVLTAAH

Post-translational modifications for TMPRSS4 Gene

  • Proteolytically processed; probably by an autocatalytic mechanism.
  • Glycosylation at Asn130 and Asn178
  • Modification sites at PhosphoSitePlus

Domains & Families for TMPRSS4 Gene

Gene Families for TMPRSS4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for TMPRSS4 Gene

InterPro:
Blocks:
  • Serine protease, trypsin family
  • Chymotrypsin serine protease family (S1) signature
  • Low density lipoprotein-receptor, class A

Suggested Antigen Peptide Sequences for TMPRSS4 Gene

GenScript: Design optimal peptide antigens:
  • Membrane-type serine protease 2 (TMPS4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9NRS4

UniProtKB/Swiss-Prot:

TMPS4_HUMAN :
  • Belongs to the peptidase S1 family.
Family:
  • Belongs to the peptidase S1 family.
genes like me logo Genes that share domains with TMPRSS4: view

Function for TMPRSS4 Gene

Molecular function for TMPRSS4 Gene

UniProtKB/Swiss-Prot Function:
Plasma membrane-anchored serine protease that directly induces processing of pro-uPA/PLAU into the active form through proteolytic activity (PubMed:24434139). Seems to be capable of activating ENaC (By similarity).
UniProtKB/Swiss-Prot Function:
(Microbial infection) In gut epithelial cells, facilitates human coronavirus SARS-CoV-2 infection through, at least, the cleavage of coronavirus spike glycoproteins which activates the glycoprotein for host cell entry.

Enzyme Numbers (IUBMB) for TMPRSS4 Gene

Phenotypes From GWAS Catalog for TMPRSS4 Gene

Gene Ontology (GO) - Molecular Function for TMPRSS4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity NAS 10825129
GO:0005044 scavenger receptor activity IEA --
GO:0005515 protein binding IEA,IPI 25416956
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity IEA,IDA 24434139
genes like me logo Genes that share ontologies with TMPRSS4: view
genes like me logo Genes that share phenotypes with TMPRSS4: view

Animal Models for TMPRSS4 Gene

MGI Knock Outs for TMPRSS4:

Animal Models for research

  • Taconic Biosciences Mouse Models for TMPRSS4

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TMPRSS4

Clone products for research

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TMPRSS4 Gene

Localization for TMPRSS4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TMPRSS4 Gene

Cell membrane. Single-pass type II membrane protein.
[Transmembrane protease serine 4 catalytic chain]: Secreted. Note=Activated by cleavage and secreted. {ECO:0000269 PubMed:24434139}.

Subcellular locations from

COMPARTMENTS
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 TMPRSS4 gene
Compartment Confidence
extracellular 5
plasma membrane 4
cytoskeleton 1
mitochondrion 1
nucleus 1
endoplasmic reticulum 1
endosome 1
cytosol 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TMPRSS4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IDA 24434139
GO:0005886 plasma membrane IEA --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA,NAS 10825129
genes like me logo Genes that share ontologies with TMPRSS4: view

Pathways & Interactions for TMPRSS4 Gene

PathCards logo

SuperPathways for TMPRSS4 Gene

SuperPathway Contained pathways
1 Measles
genes like me logo Genes that share pathways with TMPRSS4: view

Pathways by source for TMPRSS4 Gene

1 KEGG pathway for TMPRSS4 Gene

SIGNOR curated interactions for TMPRSS4 Gene

Activates:

Gene Ontology (GO) - Biological Process for TMPRSS4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA,NAS 10825129
GO:0006897 endocytosis IEA --
GO:0009611 response to wounding IEA --
GO:0010468 regulation of gene expression IDA 29529050
GO:0016485 protein processing IDA 24434139
genes like me logo Genes that share ontologies with TMPRSS4: view

Drugs & Compounds for TMPRSS4 Gene

(1) Drugs for TMPRSS4 Gene - From: ApexBio

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
PMSF Pharma Serine proteinases inhibitor, irreversible 0

(1) ApexBio Compounds for TMPRSS4 Gene

Compound Action Cas Number
PMSF Serine proteinases inhibitor, irreversible 329-98-6
genes like me logo Genes that share compounds with TMPRSS4: view

Drug products for research

Transcripts for TMPRSS4 Gene

mRNA/cDNA for TMPRSS4 Gene

7 REFSEQ mRNAs :
17 NCBI additional mRNA sequence :
19 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TMPRSS4

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for TMPRSS4 Gene

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

Relevant External Links for TMPRSS4 Gene

GeneLoc Exon Structure for
TMPRSS4

Expression for TMPRSS4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TMPRSS4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TMPRSS4 Gene

This gene is overexpressed in Esophagus - Mucosa (x16.7), Colon - Transverse (x11.5), and Bladder (x7.2).

Protein differential expression in normal tissues from HIPED for TMPRSS4 Gene

This gene is overexpressed in Rectum (37.5) and Colon (31.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for TMPRSS4 Gene



Protein tissue co-expression partners for TMPRSS4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TMPRSS4

SOURCE GeneReport for Unigene cluster for TMPRSS4 Gene:

Hs.161985

mRNA Expression by UniProt/SwissProt for TMPRSS4 Gene:

Q9NRS4-TMPS4_HUMAN
Tissue specificity: High levels in pancreatic, gastric, colorectal and ampullary cancer. Very weak expression in normal gastrointestinal and urogenital tract (PubMed:10825129). Coexpressed with ACE2 within mature enterocytes (PubMed:32404436).

Evidence on tissue expression from TISSUES for TMPRSS4 Gene

  • Intestine(4.8)
  • Pancreas(4.4)
  • Kidney(2.4)
  • Thyroid gland(2.3)
  • Lung(2.1)
  • Stomach(2.1)
  • Skin(2.1)
genes like me logo Genes that share expression patterns with TMPRSS4: view

Primer products for research

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for TMPRSS4 Gene

Orthologs for TMPRSS4 Gene

This gene was present in the common ancestor of animals.

Orthologs for TMPRSS4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TMPRSS4 29 30
  • 99.23 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TMPRSS4 29 30
  • 86.99 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TMPRSS4 29 30
  • 84.56 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Tmprss4 29 16 30
  • 81.61 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Tmprss4 29
  • 80.84 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia TMPRSS4 30
  • 61 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia TMPRSS4 30
  • 51 (a)
OneToOne
Chicken
(Gallus gallus)
Aves TMPRSS4 29 30
  • 63.19 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia TMPRSS4 30
  • 47 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia tmprss4 29
  • 50.87 (n)
Zebrafish
(Danio rerio)
Actinopterygii tmprss4a 29 30
  • 49.31 (n)
OneToMany
tmprss4b 30
  • 33 (a)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta lambdaTry 29
  • 47.06 (n)
CG18065 31
  • 41 (a)
&lgr;Try 31
  • 38 (a)
Try29F 31
  • 38 (a)
CG4613 31
  • 37 (a)
CG11192 31
  • 37 (a)
CG9372 31
  • 37 (a)
CG4914 31
  • 36 (a)
CG10405 31
  • 36 (a)
BEST:GH02921 31
  • 35 (a)
CG6865 31
  • 33 (a)
Species where no ortholog for TMPRSS4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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)
  • 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 Vase (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)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for TMPRSS4 Gene

ENSEMBL:
Gene Tree for TMPRSS4 (if available)
TreeFam:
Gene Tree for TMPRSS4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TMPRSS4: view image
Alliance of Genome Resources:
Additional Orthologs for TMPRSS4

Paralogs for TMPRSS4 Gene

Paralogs for TMPRSS4 Gene

genes like me logo Genes that share paralogs with TMPRSS4: view

Variants for TMPRSS4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TMPRSS4 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
rs142842357 Likely Benign: not provided 118,115,136(+) A/G
NM_019894.4(TMPRSS4):c.1010-2A>G
SPLICE_ACCEPTOR
rs12270001 -- p.Lys198Glu
rs1894176 -- p.Arg177Gln
rs1941635 -- p.Val208Gly

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for TMPRSS4 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for TMPRSS4 Gene

Variant ID Type Subtype PubMed ID
esv2745122 CNV deletion 23290073
esv275347 CNV loss 21479260
esv3892103 CNV gain 25118596
nsv1049373 CNV loss 25217958
nsv1159938 CNV duplication 26073780
nsv468878 CNV gain 19166990
nsv509444 CNV insertion 20534489
nsv515768 CNV loss 19592680
nsv556463 CNV loss 21841781
nsv556464 CNV gain 21841781

Variation tolerance for TMPRSS4 Gene

Residual Variation Intolerance Score: 54% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.43; 88.59% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TMPRSS4 Gene

Human Gene Mutation Database (HGMD)
TMPRSS4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TMPRSS4
Leiden Open Variation Database (LOVD)
TMPRSS4

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TMPRSS4 Gene

Disorders for TMPRSS4 Gene

MalaCards: The human disease database

(11) MalaCards diseases for TMPRSS4 Gene - From: ORP and COP

Additional Disease Information for TMPRSS4

genes like me logo Genes that share disorders with TMPRSS4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TMPRSS4 Gene

Publications for TMPRSS4 Gene

  1. A novel transmembrane serine protease (TMPRSS3) overexpressed in pancreatic cancer. (PMID: 10825129) Wallrapp C … Gress TM (Cancer research 2000) 2 3 4 22
  2. TMPRSS4: an emerging potential therapeutic target in cancer. (PMID: 25203520) de Aberasturi AL … Calvo A (British journal of cancer 2015) 2 3 4
  3. TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes. (PMID: 32404436) Zang R … Ding S (Science immunology 2020) 3 4
  4. TMPRSS4 induces cancer cell invasion through pro-uPA processing. (PMID: 24434139) Min HJ … Kim S (Biochemical and biophysical research communications 2014) 3 4
  5. A mutation in the serine protease TMPRSS4 in a novel pediatric neurodegenerative disorder. (PMID: 23957953) Lahiry P … Hegele RA (Orphanet journal of rare diseases 2013) 3 72

Products for TMPRSS4 Gene

Sources for TMPRSS4 Gene