The protein encoded by this gene belongs to the thrombospondin protein family. Thrombospondin family members are adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. This protein forms a pentamer and can bind to heparin and calcium. It is involved in local signaling in the developing and adult nervous system, and it contributes to spinal sensitizati... See more...

Aliases for THBS4 Gene

Aliases for THBS4 Gene

  • Thrombospondin 4 2 3 5
  • Thrombospondin-4 3 4
  • TSP4 3 4
  • TSP-4 3
  • THBS4 5

External Ids for THBS4 Gene

Previous GeneCards Identifiers for THBS4 Gene

  • GC05P078134
  • GC05P079570
  • GC05P079369
  • GC05P079415
  • GC05P079366
  • GC05P079287
  • GC05P074539

Summaries for THBS4 Gene

Entrez Gene Summary for THBS4 Gene

  • The protein encoded by this gene belongs to the thrombospondin protein family. Thrombospondin family members are adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. This protein forms a pentamer and can bind to heparin and calcium. It is involved in local signaling in the developing and adult nervous system, and it contributes to spinal sensitization and neuropathic pain states. This gene is activated during the stromal response to invasive breast cancer. It may also play a role in inflammatory responses in Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

GeneCards Summary for THBS4 Gene

THBS4 (Thrombospondin 4) is a Protein Coding gene. Diseases associated with THBS4 include Prostate Cancer and Nephroma. Among its related pathways are Signaling by GPCR and Focal Adhesion. Gene Ontology (GO) annotations related to this gene include calcium ion binding and heparin binding. An important paralog of this gene is THBS3.

UniProtKB/Swiss-Prot Summary for THBS4 Gene

  • Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions and is involved in various processes including cellular proliferation, migration, adhesion and attachment, inflammatory response to CNS injury, regulation of vascular inflammation and adaptive responses of the heart to pressure overload and in myocardial function and remodeling. Binds to structural extracellular matrix (ECM) proteins and modulates the ECM in response to tissue damage, contributing to cardioprotective and adaptive ECM remodeling. Plays a role in ER stress response, via its interaction with the activating transcription factor 6 alpha (ATF6) which produces adaptive ER stress response factors and protects myocardium from pressure overload. May contribute to spinal presynaptic hypersensitivity and neuropathic pain states after peripheral nerve injury. May play a role in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury in a NOTCH1-dependent manner (By similarity).

Gene Wiki entry for THBS4 Gene

Additional gene information for THBS4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for THBS4 Gene

Genomics for THBS4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for THBS4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH05J079989 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 600.7 -0.2 -196 2.6 HNRNPL TFE3 NFKBIZ KDM1A ZNF692 POLR2A LARP7 GABPA ZNF143 ZIC2 MTX3 THBS4 lnc-CMYA5-4 LINC01455 CMYA5
GH05J080035 Promoter 1 EPDnew Ensembl 611.1 +44.0 44005 1 RNF2 PRDM1 EZH2 BMI1 ZNF335 SMARCA4 TAF1 CBX8 THBS4 TRMT112P2 THBS4-AS1 MTX3 ENSG00000251675 SERINC5
GH05J079955 Enhancer 1 Ensembl ENCODE CraniofacialAtlas 38.2 -35.2 -35209 2.9 CEBPG ATF7 ZNF629 FOXA1 ZIC2 ZNF600 CEBPB RFX1 JUND CTBP1 THBS4 THBS4-AS1 LINC01455 MTX3 LOC105379048 CMYA5
GH05J079962 Enhancer 0.7 Ensembl ENCODE 36.7 -28.9 -28879 1.6 ZBTB33 PKNOX1 ZBTB17 POLR2A ZNF335 SPI1 JUND SMARCA4 ZBTB21 ESRRA THBS4 MTX3 LINC01455 LOC105379048 CMYA5
GH05J079974 Enhancer 0.7 Ensembl ENCODE 37.7 -16.6 -16595 2.6 PRDM1 JUND TSHZ1 FOS SMARCA4 POLR2A FOSL2 PKNOX1 THBS4 MTX3 LINC01455 LOC105379048 CMYA5
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around THBS4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for THBS4

Top Transcription factor binding sites by QIAGEN in the THBS4 gene promoter:
  • aMEF-2
  • AML1a
  • HSF1 (long)
  • HSF1short
  • MEF-2
  • MEF-2A
  • Pbx1a
  • RFX1

Genomic Locations for THBS4 Gene

Genomic Locations for THBS4 Gene
chr5:79,991,296-80,083,753
(GRCh38/hg38)
Size:
92,458 bases
Orientation:
Plus strand
chr5:79,287,134-79,379,110
(GRCh37/hg19)
Size:
91,977 bases
Orientation:
Plus strand

Genomic View for THBS4 Gene

Genes around THBS4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
THBS4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for THBS4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for THBS4 Gene

Proteins for THBS4 Gene

  • Protein details for THBS4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P35443-TSP4_HUMAN
    Recommended name:
    Thrombospondin-4
    Protein Accession:
    P35443
    Secondary Accessions:
    • B2R909
    • Q86TG2

    Protein attributes for THBS4 Gene

    Size:
    961 amino acids
    Molecular mass:
    105869 Da
    Quaternary structure:
    • Homopentamer; disulfide-linked. Interacts with PTBP3. Interacts with NOTCH1 (By similarity). Interacts (via EGF-like 3; calcium-binding domain) with ATF6 and facilitates its processing, activation and nuclear translocation.

neXtProt entry for THBS4 Gene

Post-translational modifications for THBS4 Gene

  • Glycosylation at Asn612 and Asn941
  • Modification sites at PhosphoSitePlus

Other Protein References for THBS4 Gene

No data available for DME Specific Peptides for THBS4 Gene

Domains & Families for THBS4 Gene

Gene Families for THBS4 Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for THBS4 Gene

InterPro:
Blocks:
  • EGF-like calcium-binding
  • Thrombospondin, N-terminal
  • Thrombospondin, C-terminal
ProtoNet:

Suggested Antigen Peptide Sequences for THBS4 Gene

GenScript: Design optimal peptide antigens:
  • Thrombospondin-4 (TSP4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P35443

UniProtKB/Swiss-Prot:

TSP4_HUMAN :
  • Belongs to the thrombospondin family.
Family:
  • Belongs to the thrombospondin family.
genes like me logo Genes that share domains with THBS4: view

Function for THBS4 Gene

Molecular function for THBS4 Gene

UniProtKB/Swiss-Prot Function:
Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions and is involved in various processes including cellular proliferation, migration, adhesion and attachment, inflammatory response to CNS injury, regulation of vascular inflammation and adaptive responses of the heart to pressure overload and in myocardial function and remodeling. Binds to structural extracellular matrix (ECM) proteins and modulates the ECM in response to tissue damage, contributing to cardioprotective and adaptive ECM remodeling. Plays a role in ER stress response, via its interaction with the activating transcription factor 6 alpha (ATF6) which produces adaptive ER stress response factors and protects myocardium from pressure overload. May contribute to spinal presynaptic hypersensitivity and neuropathic pain states after peripheral nerve injury. May play a role in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury in a NOTCH1-dependent manner (By similarity).
GENATLAS Biochemistry:
thrombospondin 4,cell adhesion molecule expressed in heart,skeletal muscle,bone tissues

Phenotypes From GWAS Catalog for THBS4 Gene

Gene Ontology (GO) - Molecular Function for THBS4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005178 integrin binding IDA 16099885
GO:0005509 calcium ion binding IEA,IDA 7852353
GO:0005515 protein binding IPI 22682248
GO:0008083 growth factor activity IEA --
GO:0008201 heparin binding IDA 7852353
genes like me logo Genes that share ontologies with THBS4: view
genes like me logo Genes that share phenotypes with THBS4: view

Animal Models for THBS4 Gene

MGI Knock Outs for THBS4:

Animal Model Products

  • Taconic Biosciences Mouse Models for THBS4

CRISPR Products

miRNA for THBS4 Gene

miRTarBase miRNAs that target THBS4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for THBS4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for THBS4 Gene

Localization for THBS4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for THBS4 Gene

Endoplasmic reticulum. Sarcoplasmic reticulum. Secreted. Secreted, extracellular space. Secreted, extracellular space, extracellular matrix.

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 THBS4 gene
Compartment Confidence
extracellular 5
endoplasmic reticulum 4
plasma membrane 3
cytoskeleton 2
mitochondrion 2
nucleus 2
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for THBS4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA,TAS --
GO:0005604 basement membrane IDA 17927980
GO:0005615 extracellular space IEA,IDA 12952849
GO:0005783 endoplasmic reticulum ISS --
GO:0016529 sarcoplasmic reticulum ISS --
genes like me logo Genes that share ontologies with THBS4: view

Pathways & Interactions for THBS4 Gene

genes like me logo Genes that share pathways with THBS4: view

Pathways by source for THBS4 Gene

1 BioSystems pathway for THBS4 Gene
2 Reactome pathways for THBS4 Gene
1 R&D Systems pathway for THBS4 Gene

Gene Ontology (GO) - Biological Process for THBS4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001938 positive regulation of endothelial cell proliferation IDA 12952849
GO:0006986 response to unfolded protein IEA --
GO:0007155 cell adhesion IEA --
GO:0007165 signal transduction IEA --
GO:0016525 negative regulation of angiogenesis IEP 18802666
genes like me logo Genes that share ontologies with THBS4: view

No data available for SIGNOR curated interactions for THBS4 Gene

Drugs & Compounds for THBS4 Gene

(6) Drugs for THBS4 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
genes like me logo Genes that share compounds with THBS4: view

Transcripts for THBS4 Gene

mRNA/cDNA for THBS4 Gene

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

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for THBS4

Alternative Splicing Database (ASD) splice patterns (SP) for THBS4 Gene

No ASD Table

Relevant External Links for THBS4 Gene

GeneLoc Exon Structure for
THBS4

Expression for THBS4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for THBS4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for THBS4 Gene

This gene is overexpressed in Heart - Left Ventricle (x6.9), Muscle - Skeletal (x5.5), and Nerve - Tibial (x5.4).

Protein differential expression in normal tissues from HIPED for THBS4 Gene

This gene is overexpressed in Synovial fluid (14.1), Monocytes (9.0), Colon (8.3), and Plasma (7.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for THBS4 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for THBS4

SOURCE GeneReport for Unigene cluster for THBS4 Gene:

Hs.211426

Evidence on tissue expression from TISSUES for THBS4 Gene

  • Heart(4.7)
  • Nervous system(4.6)
  • Muscle(3.6)
  • Blood(2.3)
  • Eye(2.2)
  • Intestine(2.2)
  • Bone marrow(2.1)
  • Skin(2)
genes like me logo Genes that share expression patterns with THBS4: view

No data available for Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for THBS4 Gene

Orthologs for THBS4 Gene

This gene was present in the common ancestor of animals.

Orthologs for THBS4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia THBS4 30 31
  • 98.89 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia THBS4 30 31
  • 90.27 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia THBS4 30 31
  • 88.75 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Thbs4 30
  • 87.34 (n)
Mouse
(Mus musculus)
Mammalia Thbs4 30 17 31
  • 87.3 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia THBS4 31
  • 87 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 36 (a)
ManyToMany
Chicken
(Gallus gallus)
Aves THBS4 30 31
  • 73.9 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia THBS4 31
  • 76 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia thbs4 30
  • 71.7 (n)
African clawed frog
(Xenopus laevis)
Amphibia LOC397943 30
Zebrafish
(Danio rerio)
Actinopterygii thbs4b 30 31
  • 68.24 (n)
OneToMany
thbs4a 31
  • 63 (a)
OneToMany
thbs4 30
Fruit Fly
(Drosophila melanogaster)
Insecta Tsp 31 32
  • 37 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 59 (a)
OneToMany
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.3131 30
Species where no ortholog for THBS4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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 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 THBS4 Gene

ENSEMBL:
Gene Tree for THBS4 (if available)
TreeFam:
Gene Tree for THBS4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for THBS4: view image

Paralogs for THBS4 Gene

Paralogs for THBS4 Gene

(5) SIMAP similar genes for THBS4 Gene using alignment to 2 proteins:

  • TSP4_HUMAN
  • E7ES19_HUMAN
genes like me logo Genes that share paralogs with THBS4: view

Variants for THBS4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for THBS4 Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
727042 Likely Benign: not provided 80,083,132(+) C/T SYNONYMOUS_VARIANT
749715 Likely Benign: not provided 80,082,449(+) G/A MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
779423 Benign: not provided 80,068,037(+) C/T MISSENSE_VARIANT
783438 Benign: not provided 80,055,915(+) A/G SYNONYMOUS_VARIANT
784051 Benign: not provided 80,076,898(+) G/A MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for THBS4 Gene

Structural Variations from Database of Genomic Variants (DGV) for THBS4 Gene

Variant ID Type Subtype PubMed ID
esv2287240 CNV deletion 18987734
esv3570228 CNV loss 25503493
esv3605549 CNV loss 21293372
esv3890662 CNV loss 25118596
nsv4894 CNV insertion 18451855
nsv598743 CNV loss 21841781

Variation tolerance for THBS4 Gene

Residual Variation Intolerance Score: 40% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.43; 77.27% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for THBS4 Gene

Human Gene Mutation Database (HGMD)
THBS4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
THBS4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for THBS4 Gene

Disorders for THBS4 Gene

MalaCards: The human disease database

(7) MalaCards diseases for THBS4 Gene - From: LncRNADisease, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
prostate cancer
  • prostate cancer, somatic
nephroma
  • benign nephroma
myocardial infarction
  • myocardial infarction, susceptibility to
mycetoma
  • madura foot
alzheimer disease
  • ad
- elite association - COSMIC cancer census association via MalaCards
Search THBS4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for THBS4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with THBS4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for THBS4 Gene

Publications for THBS4 Gene

  1. Characterization of human thrombospondin-4. (PMID: 7852353) Lawler J … Derick L (The Journal of biological chemistry 1995) 2 3 4 23
  2. Polymorphisms in genes involved in innate immunity predispose toward mycetoma susceptibility. (PMID: 17709521) van de Sande WW … van Belkum A (Journal of immunology (Baltimore, Md. : 1950) 2007) 3 23 41
  3. Association of common promoter polymorphisms of MCP1 with hepatitis B virus clearance. (PMID: 17202846) Park BL … Shin HD (Experimental & molecular medicine 2006) 3 23 41
  4. Thrombospondin-4 1186G>C (A387P) is a sex-dependent risk factor for myocardial infarction: a large replication study with increased sample size from the same population. (PMID: 16923428) Cui J … Xie YG (American heart journal 2006) 3 23 41
  5. Large scale association analysis for identification of genes underlying premature coronary heart disease: cumulative perspective from analysis of 111 candidate genes. (PMID: 15121769) McCarthy JJ … GeneQuest Investigators (Journal of medical genetics 2004) 3 23 41

Products for THBS4 Gene

Sources for THBS4 Gene