This gene belongs to the TIMP gene family. The proteins encoded by this gene family are inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix. The secreted, netrin domain-containing protein encoded by this gene is involved in regulation of platelet aggregation and recruitment and may play role in hormonal regulati... See more...

Aliases for TIMP4 Gene

Aliases for TIMP4 Gene

  • TIMP Metallopeptidase Inhibitor 4 2 3 5
  • Tissue Inhibitor Of Metalloproteinases 4 3 4
  • Tissue Inhibitor Of Metalloproteinase 4 2 3
  • Metalloproteinase Inhibitor 4 3 4
  • TIMP-4 3 4
  • TIMP4 5

External Ids for TIMP4 Gene

Previous GeneCards Identifiers for TIMP4 Gene

  • GC03M012123
  • GC03M012038
  • GC03M012169

Summaries for TIMP4 Gene

Entrez Gene Summary for TIMP4 Gene

  • This gene belongs to the TIMP gene family. The proteins encoded by this gene family are inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix. The secreted, netrin domain-containing protein encoded by this gene is involved in regulation of platelet aggregation and recruitment and may play role in hormonal regulation and endometrial tissue remodeling. [provided by RefSeq, Jul 2008]

GeneCards Summary for TIMP4 Gene

TIMP4 (TIMP Metallopeptidase Inhibitor 4) is a Protein Coding gene. Diseases associated with TIMP4 include Corneal Neovascularization and Patella, Chondromalacia Of. Among its related pathways are Nanog in Mammalian ESC Pluripotency and Apoptotic Pathways in Synovial Fibroblasts. Gene Ontology (GO) annotations related to this gene include protease binding and metalloendopeptidase inhibitor activity. An important paralog of this gene is TIMP2.

UniProtKB/Swiss-Prot Summary for TIMP4 Gene

  • Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9.

Gene Wiki entry for TIMP4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TIMP4 Gene

Genomics for TIMP4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TIMP4 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
GH03J012158 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 256.7 0.0 -46 1.9 POLR2A ZIC2 CEBPB ETS1 MAX GABPB1 TBP NFE2 MCM5 NRF1 TIMP4 ENSG00000271716 PPARG MTCO1P5 lnc-TIMP4-3 SYN2
GH03J012170 Promoter/Enhancer 1.3 EPDnew FANTOM5 Ensembl dbSUPER 250.4 -11.6 -11589 2.6 NFE2 SPI1 MAFG MAFF NFE2L2 FOS IKZF1 PKNOX1 TIMP4 PPARG SYN2 MTCO1P5 lnc-TIMP4-3 piR-53306
GH03J012286 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE dbSUPER 18.3 -132.3 -132308 8.8 ZNF600 ZIC2 ZBTB10 ZNF341 ZEB1 CTCF KMT2B KLF9 SP2 RAD21 PPARG SYN2 TIMP4 NONHSAG034457.2 L13713-145 TSEN2
GH03J012458 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 16.3 -301.9 -301888 8.4 CEBPA ATF3 ZIC2 YY1 CEBPB MAX EP300 FOXA2 SMAD4 RXRA TSEN2 TIMP4 TAMM41 VGLL4 PPARG SYN2 MKRN2 CAND2 HSALNG0024218 lnc-TSEN2-1
GH03J012482 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 9.5 -325.3 -325319 3.5 ZNF207 MYC ZNF600 ZNF580 POLR2A ZNF10 ZSCAN16 NFIC YY1 MXD4 TSEN2 HSALNG0024220 lnc-MKRN2OS-3 TAMM41 VGLL4 ENSG00000271716 RPL32 TIMP4 SYN2 MKRN2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TIMP4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TIMP4

Top Transcription factor binding sites by QIAGEN in the TIMP4 gene promoter:
  • CUTL1
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5
  • HNF-1
  • HNF-1A
  • Lmo2

Genomic Locations for TIMP4 Gene

Latest Assembly
chr3:12,153,068-12,158,912
(GRCh38/hg38)
Size:
5,845 bases
Orientation:
Minus strand

Previous Assembly
chr3:12,194,568-12,200,412
(GRCh37/hg19 by Entrez Gene)
Size:
5,845 bases
Orientation:
Minus strand

chr3:12,194,551-12,200,851
(GRCh37/hg19 by Ensembl)
Size:
6,301 bases
Orientation:
Minus strand

Genomic View for TIMP4 Gene

Genes around TIMP4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TIMP4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TIMP4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TIMP4 Gene

Proteins for TIMP4 Gene

  • Protein details for TIMP4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99727-TIMP4_HUMAN
    Recommended name:
    Metalloproteinase inhibitor 4
    Protein Accession:
    Q99727
    Secondary Accessions:
    • B2R7K6

    Protein attributes for TIMP4 Gene

    Size:
    224 amino acids
    Molecular mass:
    25503 Da
    Quaternary structure:
    No Data Available

neXtProt entry for TIMP4 Gene

Post-translational modifications for TIMP4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for TIMP4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for TIMP4 Gene

Domains & Families for TIMP4 Gene

Gene Families for TIMP4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted secreted proteins

Protein Domains for TIMP4 Gene

InterPro:
Blocks:
  • Tissue inhibitor of metalloproteinase

Suggested Antigen Peptide Sequences for TIMP4 Gene

GenScript: Design optimal peptide antigens:
  • Tissue inhibitor of metalloproteinases 4 (TIMP4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q99727

UniProtKB/Swiss-Prot:

TIMP4_HUMAN :
  • Belongs to the protease inhibitor I35 (TIMP) family.
Family:
  • Belongs to the protease inhibitor I35 (TIMP) family.
genes like me logo Genes that share domains with TIMP4: view

Function for TIMP4 Gene

Molecular function for TIMP4 Gene

UniProtKB/Swiss-Prot Function:
Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9.
GENATLAS Biochemistry:
matrix metalloproteinase,tissue inhibitor 4,abundantly expressed only in adult heart maybe embedded in intron V of SYN2

Phenotypes From GWAS Catalog for TIMP4 Gene

Gene Ontology (GO) - Molecular Function for TIMP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IBA 21873635
GO:0004857 enzyme inhibitor activity IEA --
GO:0005515 protein binding IEA --
GO:0008191 metalloendopeptidase inhibitor activity IBA,NAS 8939999
GO:0030414 peptidase inhibitor activity IEA --
genes like me logo Genes that share ontologies with TIMP4: view
genes like me logo Genes that share phenotypes with TIMP4: view

Animal Models for TIMP4 Gene

MGI Knock Outs for TIMP4:

Animal Models for research

  • Taconic Biosciences Mouse Models for TIMP4

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TIMP4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for TIMP4 Gene

Localization for TIMP4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TIMP4 Gene

Secreted.

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 TIMP4 gene
Compartment Confidence
extracellular 5
plasma membrane 2
cytoskeleton 2
mitochondrion 2
nucleus 2
cytosol 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for TIMP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IEA,IBA 21873635
GO:0030017 sarcomere IEA --
GO:0031012 extracellular matrix IBA 21873635
genes like me logo Genes that share ontologies with TIMP4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TIMP4 Gene

Pathways & Interactions for TIMP4 Gene

PathCards logo

SuperPathways for TIMP4 Gene

SuperPathway Contained pathways
1 Apoptotic Pathways in Synovial Fibroblasts
.85
.85
.84
.84
.74
.72
.66
.65
.64
.62
.61
.60
.57
.57
2 GPCR Pathway
.73
.73
.62
.59
.58
.58
.55
3 ERK Signaling
.61
.61
.58
.51
.49
4 Nanog in Mammalian ESC Pluripotency
.61
.61
.59
.48
5 CREB Pathway
.68
.68
.63
.50
genes like me logo Genes that share pathways with TIMP4: view

Pathways by source for TIMP4 Gene

1 BioSystems pathway for TIMP4 Gene
55 Qiagen pathways for TIMP4 Gene
  • 14-3-3 Induced Intracellular Signaling
  • Actin-Based Motility by Rho Family GTPases
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • Activation of PKC through GPCR

Gene Ontology (GO) - Biological Process for TIMP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007219 Notch signaling pathway IEA --
GO:0007417 central nervous system development IEA --
GO:0008150 biological_process ND --
GO:0009725 response to hormone IEA,IBA 21873635
GO:0010033 response to organic substance IBA 21873635
genes like me logo Genes that share ontologies with TIMP4: view

No data available for SIGNOR curated interactions for TIMP4 Gene

Drugs & Compounds for TIMP4 Gene

(2) Drugs for TIMP4 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for TIMP4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TIMP4: view

Transcripts for TIMP4 Gene

mRNA/cDNA for TIMP4 Gene

1 REFSEQ mRNAs :
4 NCBI additional mRNA sequence :
1 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 TIMP4

Alternative Splicing Database (ASD) splice patterns (SP) for TIMP4 Gene

No ASD Table

Relevant External Links for TIMP4 Gene

GeneLoc Exon Structure for
TIMP4

Expression for TIMP4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TIMP4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TIMP4 Gene

This gene is overexpressed in Adipose - Visceral (Omentum) (x10.6), Adipose - Subcutaneous (x7.2), and Breast - Mammary Tissue (x4.7).

Protein differential expression in normal tissues from HIPED for TIMP4 Gene

This gene is overexpressed in Milk (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for TIMP4 Gene



Protein tissue co-expression partners for TIMP4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TIMP4

SOURCE GeneReport for Unigene cluster for TIMP4 Gene:

Hs.591665

mRNA Expression by UniProt/SwissProt for TIMP4 Gene:

Q99727-TIMP4_HUMAN
Tissue specificity: Abundant in heart and present at low levels in many other tissues.

Evidence on tissue expression from TISSUES for TIMP4 Gene

  • Nervous system(4.6)
  • Heart(4.6)
  • Muscle(3.1)
  • Kidney(2.2)
genes like me logo Genes that share expression patterns with TIMP4: view

Primer products for research

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for TIMP4 Gene

Orthologs for TIMP4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TIMP4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TIMP4 29 30
  • 98.96 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TIMP4 29 30
  • 91.07 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TIMP4 29 30
  • 89.43 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Timp4 29
  • 87.8 (n)
Mouse
(Mus musculus)
Mammalia Timp4 29 16 30
  • 87.65 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia TIMP4 30
  • 69 (a)
OneToOne
Chicken
(Gallus gallus)
Aves TIMP4 29 30
  • 76.05 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia TIMP4 30
  • 68 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii TIMP4 30
  • 37 (a)
OneToOne
Species where no ortholog for TIMP4 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)
  • Fruit Fly (Drosophila melanogaster)
  • 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)
  • Platypus (Ornithorhynchus anatinus)
  • 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)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for TIMP4 Gene

ENSEMBL:
Gene Tree for TIMP4 (if available)
TreeFam:
Gene Tree for TIMP4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TIMP4: view image
Alliance of Genome Resources:
Additional Orthologs for TIMP4

Paralogs for TIMP4 Gene

Paralogs for TIMP4 Gene

(3) SIMAP similar genes for TIMP4 Gene using alignment to 1 proteins:

  • TIMP4_HUMAN

Pseudogenes.org Pseudogenes for TIMP4 Gene

genes like me logo Genes that share paralogs with TIMP4: view

Variants for TIMP4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TIMP4 Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
rs145556365 Likely Benign: not provided 12,154,402(-) G/A
NM_003256.4(TIMP4):c.402C>T (p.Ile134=)
SYNONYMOUS_VARIANT,INTRON
rs148699109 Benign: not provided 12,158,778(-) C/T
NM_003256.4(TIMP4):c.63G>A (p.Leu21=)
SYNONYMOUS_VARIANT,INTRON

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for TIMP4 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 TIMP4 Gene

Variant ID Type Subtype PubMed ID
dgv763e201 CNV deletion 23290073
dgv850e199 CNV deletion 23128226
esv1007552 CNV deletion 20482838
esv1015927 CNV deletion 17803354
esv2193425 CNV deletion 18987734
esv2724931 CNV deletion 23290073
esv2724932 CNV deletion 23290073
esv3030297 CNV deletion 24192839
esv3561484 CNV deletion 23714750
nsv1073205 CNV deletion 25765185
nsv1112379 CNV deletion 24896259
nsv1139090 CNV deletion 24896259
nsv1147269 CNV deletion 26484159
nsv236830 CNV deletion 16902084
nsv7351 OTHER inversion 18451855

Variation tolerance for TIMP4 Gene

Residual Variation Intolerance Score: 20.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.53; 11.38% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TIMP4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
TIMP4
Leiden Open Variation Database (LOVD)
TIMP4

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TIMP4 Gene

Disorders for TIMP4 Gene

MalaCards: The human disease database

(5) MalaCards diseases for TIMP4 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
corneal neovascularization
patella, chondromalacia of
  • chondromalacia patellae
sorsby fundus dystrophy
  • sfd
dedifferentiated liposarcoma
  • ddls
fundus dystrophy
  • retinal dystrophy
- elite association - COSMIC cancer census association via MalaCards
Search TIMP4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TIMP4

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with TIMP4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TIMP4 Gene

Publications for TIMP4 Gene

  1. Cloning of the human tissue inhibitor of metalloproteinase-4 gene (TIMP4) and localization of the TIMP4 and Timp4 genes to human chromosome 3p25 and mouse chromosome 6, respectively. (PMID: 9693046) Olson TM … Apte SS (Genomics 1998) 2 3 4 22
  2. Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4. (PMID: 8939999) Greene J … Shi YE (The Journal of biological chemistry 1996) 2 3 4 22
  3. Promoter polymorphism (rs3755724, -55C/T) of tissue inhibitor of metalloproteinase 4 (TIMP4) as a risk factor for Kawasaki disease with coronary artery lesions in a Korean population. (PMID: 19048177) Ban JY … Chung JH (Pediatric cardiology 2009) 3 22 40
  4. Polymorphisms of MMP-3 and TIMP-4 genes affect angiographic coronary plaque progression in non-diabetic and type 2 diabetic patients. (PMID: 19376102) Chen QJ … Shen WF (Clinica chimica acta; international journal of clinical chemistry 2009) 3 22 40
  5. Association of TIMP-4 gene polymorphism with the risk of osteoarthritis in the Korean population. (PMID: 18301898) Lee HJ … Kim S (Rheumatology international 2008) 3 22 40

Products for TIMP4 Gene

Sources for TIMP4 Gene