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HTT Gene(Protein Coding)

Huntingtin

GCID:
GC04P003076
GIFtS:
61
Genes Participants
UDN Logo

Aliases for HTT Gene

Aliases for HTT Gene

  • Huntingtin 2 3 3 5
  • Huntington Disease Protein 3 4
  • IT15 3 4
  • HD 3 4
  • Huntingtin (Huntington Disease) 2
  • HD Protein 4
  • LOMARS 3

External Ids for HTT Gene

Previous HGNC Symbols for HTT Gene

  • HD

Previous GeneCards Identifiers for HTT Gene

  • GC04P003046
  • GC04P003014

Summaries for HTT Gene

Entrez Gene Summary for HTT Gene

  • Huntingtin is a disease gene linked to Huntington's disease, a neurodegenerative disorder characterized by loss of striatal neurons. This is thought to be caused by an expanded, unstable trinucleotide repeat in the huntingtin gene, which translates as a polyglutamine repeat in the protein product. A fairly broad range of trinucleotide repeats (9-35) has been identified in normal controls, and repeat numbers in excess of 40 have been described as pathological. The huntingtin locus is large, spanning 180 kb and consisting of 67 exons. The huntingtin gene is widely expressed and is required for normal development. It is expressed as 2 alternatively polyadenylated forms displaying different relative abundance in various fetal and adult tissues. The larger transcript is approximately 13.7 kb and is expressed predominantly in adult and fetal brain whereas the smaller transcript of approximately 10.3 kb is more widely expressed. The genetic defect leading to Huntington's disease may not necessarily eliminate transcription, but may confer a new property on the mRNA or alter the function of the protein. One candidate is the huntingtin-associated protein-1, highly expressed in brain, which has increased affinity for huntingtin protein with expanded polyglutamine repeats. This gene contains an upstream open reading frame in the 5' UTR that inhibits expression of the huntingtin gene product through translational repression. [provided by RefSeq, Jul 2016]

GeneCards Summary for HTT Gene

HTT (Huntingtin) is a Protein Coding gene. Diseases associated with HTT include Huntington Disease and Spinocerebellar Ataxia 1. Among its related pathways are fMLP Pathway and Mesodermal Commitment Pathway. GO annotations related to this gene include identical protein binding and transcription factor binding.

UniProtKB/Swiss-Prot for HTT Gene

  • May play a role in microtubule-mediated transport or vesicle function.

Gene Wiki entry for HTT Gene

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

Genomics for HTT Gene

Products:

  1. Regulatory Element

Regulatory Elements for HTT Gene

Enhancers for HTT Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH04G003110 1.1 Ensembl ENCODE 20.3 +37.7 37715 3.4 PKNOX1 BMI1 RAD21 GATA2 RCOR1 FOS ZNF592 ZNF217 SREBF1 ZNF579 HTT HTT-AS RNU6-204P RNU7-33P MSANTD1 GC04P003121 GC04M003105
GH04G002857 1.5 Ensembl ENCODE dbSUPER 10.4 -214.0 -214032 5.7 PKNOX1 ATF1 ARID4B FEZF1 YY1 TCF12 ZNF121 CBX5 KLF7 FOS GRK4 NOP14-AS1 NOP14 TNIP2 HTT GC04P002843 GC04P002844 GC04P002845 PIR46708 GC04P002904
GH04G002930 1.4 ENCODE dbSUPER 10.4 -140.3 -140309 8.2 HDGF PKNOX1 FOXA2 MLX AGO1 WRNIP1 ARID4B SIN3A DMAP1 ZNF2 GRK4 NOP14-AS1 HTT HTT-AS MFSD10 GC04P002904 PIR46708
GH04G003037 1.1 Ensembl ENCODE 11.9 -36.6 -36587 1.8 ARNT ZSCAN4 ARID4B ZNF2 RAD21 ZNF143 ZNF207 CREM IKZF2 THAP11 HTT-AS HTT RNU7-33P GRK4 GC04P003044 GC04M003004
GH04G003106 0.9 ENCODE 11.6 +33.1 33102 2.8 HDGF PKNOX1 ATF1 WRNIP1 SIN3A ARID4B ZNF2 ZNF48 YY1 GATA2 RNU6-204P RNU7-33P HTT HTT-AS GC04M003105 GC04P003121
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around HTT on UCSC Golden Path with GeneCards custom track

Promoters for HTT Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000165041 190 2601 HDGF PKNOX1 FOXA2 MLX WRNIP1 ARID4B SIN3A DMAP1 YY1 ZNF207

Transcription factor binding sites by QIAGEN in the HTT gene promoter:

Genomic Location for HTT Gene

Chromosome:
4
Start:
3,074,510 bp from pter
End:
3,243,960 bp from pter
Size:
169,451 bases
Orientation:
Plus strand

Genomic View for HTT Gene

Genes around HTT on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for HTT Gene

Proteins for HTT Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

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

    Protein Symbol:
    P42858-HD_HUMAN
    Recommended name:
    Huntingtin
    Protein Accession:
    P42858
    Secondary Accessions:
    • Q9UQB7

    Protein attributes for HTT Gene

    Size:
    3142 amino acids
    Molecular mass:
    347603 Da
    Quaternary structure:
    • Interacts with PFN1 (PubMed:18573880). Interacts through its N-terminus with PRPF40A (PubMed:9700202). Interacts with PQBP1 (PubMed:10332029). Interacts with SETD2 (PubMed:9700202, PubMed:10958656, PubMed:11461154). Interacts with SH3GLB1 (By similarity). Interacts with SYVN (PubMed:17141218). Interacts with TPR; the interaction is inhibited by forms of Huntingtin with expanded polyglutamine stretch (PubMed:15654337). Interacts with ZDHHC13 (via ANK repeats) (PubMed:26198635). Interacts with ZDHHC17 (via ANK repeats) (PubMed:26198635).

    Three dimensional structures from OCA and Proteopedia for HTT Gene

neXtProt entry for HTT Gene

Protein Expression for HTT Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for HTT Gene

  • Cleaved by apopain downstream of the polyglutamine stretch. The resulting N-terminal fragment is cytotoxic and provokes apoptosis.
  • Forms with expanded polyglutamine expansion are specifically ubiquitinated by SYVN1, which promotes their proteasomal degradation.
  • Phosphorylation at Ser-1179 and Ser-1199 by CDK5 in response to DNA damage in nuclei of neurons protects neurons against polyglutamine expansion as well as DNA damage mediated toxicity.
  • Ubiquitination at posLast=12621262, posLast=14021402, posLast=14311431, and isoforms=2417
  • Modification sites at PhosphoSitePlus

Other Protein References for HTT Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for HTT (Huntingtin)

No data available for DME Specific Peptides for HTT Gene

Domains & Families for HTT Gene

Gene Families for HTT Gene

HGNC:

Protein Domains for HTT Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for HTT Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P42858

UniProtKB/Swiss-Prot:

HD_HUMAN :
  • The N-terminal Gln-rich and Pro-rich domain has great conformational flexibility and is likely to exist in a fluctuating equilibrium of alpha-helical, random coil, and extended conformations.
  • Belongs to the huntingtin family.
Domain:
  • The N-terminal Gln-rich and Pro-rich domain has great conformational flexibility and is likely to exist in a fluctuating equilibrium of alpha-helical, random coil, and extended conformations.
Family:
  • Belongs to the huntingtin family.
genes like me logo Genes that share domains with HTT: view

Function for HTT Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line
  7. Flow Cytometry

Molecular function for HTT Gene

UniProtKB/Swiss-Prot Function:
May play a role in microtubule-mediated transport or vesicle function.

Gene Ontology (GO) - Molecular Function for HTT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002039 p53 binding IPI 10823891
GO:0005515 protein binding IPI 7477378
GO:0005522 profilin binding IPI 18573880
GO:0008134 transcription factor binding IBA --
GO:0019900 kinase binding IPI 25686248
genes like me logo Genes that share ontologies with HTT: view
genes like me logo Genes that share phenotypes with HTT: view

Human Phenotype Ontology for HTT Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for HTT Gene

MGI Knock Outs for HTT:

Animal Model Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for HTT

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for HTT Gene

Localization for HTT Gene

Subcellular locations from UniProtKB/Swiss-Prot for HTT Gene

Cytoplasm. Nucleus. Note=The mutant Huntingtin protein colocalizes with AKAP8L in the nuclear matrix of Huntington disease neurons. Shuttles between cytoplasm and nucleus in a Ran GTPase-independent manner.

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

Gene Ontology (GO) - Cellular Components for HTT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA,IMP 17947297
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IMP,IDA 17947297
GO:0005770 late endosome IDA 17704510
GO:0005776 autophagosome IDA 17704510
genes like me logo Genes that share ontologies with HTT: view

Pathways & Interactions for HTT Gene

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

Pathways by source for HTT Gene

2 Cell Signaling Technology pathways for HTT Gene
2 BioSystems pathways for HTT Gene
1 KEGG pathway for HTT Gene
2 Qiagen pathways for HTT Gene

SIGNOR curated interactions for HTT Gene

Is activated by:
Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for HTT Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000132 establishment of mitotic spindle orientation IMP 20696378
GO:0006890 retrograde vesicle-mediated transport, Golgi to ER IMP 20515468
GO:0006915 apoptotic process IEA --
GO:0007030 Golgi organization IMP 20515468
GO:0031587 positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity IDA 12873381
genes like me logo Genes that share ontologies with HTT: view

Drugs & Compounds for HTT Gene

Products:

  1. Drug

(31) Drugs for HTT Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(22) Additional Compounds for HTT Gene - From: Novoseek

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

Transcripts for HTT Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone
  5. Flow Cytometry

mRNA/cDNA for HTT Gene

(1) REFSEQ mRNAs :
(6) Additional mRNA sequences :
(256) Selected AceView cDNA sequences:
(13) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for HTT Gene

Huntingtin:
Representative Sequences:

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for HTT

Flow Cytometry Products

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

No ASD Table

Relevant External Links for HTT Gene

GeneLoc Exon Structure for
HTT
ECgene alternative splicing isoforms for
HTT

Expression for HTT Gene

Products:

  1. Primer

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

mRNA expression in normal human tissues for HTT Gene
mRNA expression by BioGPS for HTT GenemRNA expression by GTEx for HTT Gene

Protein differential expression in normal tissues from HIPED for HTT Gene

This gene is overexpressed in Peripheral blood mononuclear cells (18.3).

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



Protein tissue co-expression partners for HTT Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of HTT Gene:

HTT

SOURCE GeneReport for Unigene cluster for HTT Gene:

Hs.518450

mRNA Expression by UniProt/SwissProt for HTT Gene:

P42858-HD_HUMAN
Tissue specificity: Expressed in the brain cortex (at protein level). Widely expressed with the highest level of expression in the brain (nerve fibers, varicosities, and nerve endings). In the brain, the regions where it can be mainly found are the cerebellar cortex, the neocortex, the striatum, and the hippocampal formation.

Evidence on tissue expression from TISSUES for HTT Gene

  • Nervous system(4.9)
  • Blood(4.5)
  • Eye(4.4)
  • Muscle(4.3)
  • Liver(4.2)
  • Lung(3)
  • Adrenal gland(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for HTT Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • nervous
  • skeletal muscle
  • skeleton
Organs:
Head and neck:
  • brain
  • cerebellum
  • eye
  • head
  • larynx
  • neck
  • vocal cord
General:
  • spinal cord
genes like me logo Genes that share expression patterns with HTT: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for HTT Gene

Orthologs for HTT Gene

This gene was present in the common ancestor of animals.

Orthologs for HTT Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia HTT 34 35
  • 98.62 (n)
dog
(Canis familiaris)
 Mammalia HD 35
  • 91 (a)
 OneToOne
HTT 34
  • 87.27 (n)
mouse
(Mus musculus)
 Mammalia Htt 34 16 35
  • 86.38 (n)
rat
(Rattus norvegicus)
 Mammalia Htt 34
  • 86.11 (n)
oppossum
(Monodelphis domestica)
 Mammalia HTT 35
  • 86 (a)
 OneToOne
cow
(Bos Taurus)
 Mammalia HTT 34 35
  • 84.14 (n)
platypus
(Ornithorhynchus anatinus)
 Mammalia HTT 35
  • 83 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves HTT 34 35
  • 75.5 (n)
lizard
(Anolis carolinensis)
 Reptilia -- 35
  • 87 (a)
 OneToMany
-- 35
  • 78 (a)
 OneToMany
tropical clawed frog
(Silurana tropicalis)
 Amphibia htt 34
  • 72.18 (n)
zebrafish
(Danio rerio)
 Actinopterygii htt 34 35
  • 69.1 (n)
hd 34
fruit fly
(Drosophila melanogaster)
 Insecta htt 35
  • 17 (a)
 OneToOne
sea squirt
(Ciona savignyi)
 Ascidiacea -- 35
  • 33 (a)
 OneToOne
Species where no ortholog for HTT 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)
  • 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 HTT Gene

ENSEMBL:
Gene Tree for HTT (if available)
TreeFam:
Gene Tree for HTT (if available)

Paralogs for HTT Gene

(1) SIMAP similar genes for HTT Gene using alignment to 2 proteins:

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

No data available for Paralogs for HTT Gene

Variants for HTT Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for HTT Gene

HD_HUMAN-P42858
The poly-Gln region of HTT is highly polymorphic (10 to 35 repeats) in the normal population and is expanded to about 36-120 repeats in Huntington disease patients. The repeat length usually increases in successive generations, but contracts also on occasion. The adjacent poly-Pro region is also polymorphic and varies between 7-12 residues. Polyglutamine expansion leads to elevated susceptibility to apopain cleavage and likely result in accelerated neuronal apoptosis (PubMed:8696339).

Sequence variations from dbSNP and Humsavar for HTT Gene

SNP ID Clin Chr 04 pos Sequence Context AA Info Type
rs587777899 untested 3,074,929(+) GCAGC(A/C)GCAGC upstream-variant-2KB, reference, missense
rs1000020655 -- 3,193,594(+) CACAA(C/T)TGAGG intron-variant
rs10000252 -- 3,214,757(+) AAGAT(C/T)CAGGG intron-variant
rs1000034843 -- 3,113,244(+) TATTA(A/T)TCCAA intron-variant
rs1000048838 -- 3,237,517(+) CCCAA(C/T)GCTAG intron-variant

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

Variant ID Type Subtype PubMed ID
esv2667257 CNV deletion 23128226
esv2726869 CNV deletion 23290073
esv2726870 CNV deletion 23290073
esv3376417 CNV duplication 20981092
esv3387920 CNV insertion 20981092
esv3599421 CNV loss 21293372
esv3599422 CNV loss 21293372
esv8475 CNV loss 19470904
nsv1123741 CNV deletion 24896259
nsv461163 CNV gain 19166990
nsv461164 CNV loss 19166990
nsv470003 CNV loss 18288195
nsv524211 CNV loss 19592680
nsv593437 CNV gain 21841781
nsv593439 CNV loss 21841781
nsv949760 CNV deletion 24416366

Variation tolerance for HTT Gene

Residual Variation Intolerance Score: 0.145% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 22.05; 99.38% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for HTT Gene

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

Disorders for HTT Gene

MalaCards: The human disease database

(14) MalaCards diseases for HTT Gene - From: OMIM, ClinVar, GeneTests, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
huntington disease
  • congenital anomalies of kidney and urinary tract 2
spinocerebellar ataxia 1
  • spinocerebellar ataxia type 1
spinal and bulbar muscular atrophy of kennedy
  • spinal and bulbar muscular atrophy, x-linked 1
choreatic disease
  • chorea
huntington disease-like 2
  • hdl2
- elite association - COSMIC cancer census association via MalaCards
Search HTT in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

HD_HUMAN
  • Huntington disease (HD) [MIM:143100]: A neurodegenerative disorder characterized by involuntary movements (chorea), general motor impairment, psychiatric disorders and dementia. Onset of the disease occurs usually in the third or fourth decade of life. Onset and clinical course depend on the degree of poly-Gln repeat expansion, longer expansions resulting in earlier onset and more severe clinical manifestations. Neuropathology of Huntington disease displays a distinctive pattern with loss of neurons, especially in the caudate and putamen. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for HTT

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

No data available for Genatlas for HTT Gene

Publications for HTT Gene

  1. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. (PMID: 8458085) Macdonald M. … Harper P.S. (Cell 1993) 2 3 4 22 64
  2. Normal and mutant HTT interact to affect clinical severity and progression in Huntington disease. (PMID: 19776381) Aziz N.A. … Roos R.A. (Neurology 2009) 3 22 46 64
  3. Phosphorylation of profilin by ROCK1 regulates polyglutamine aggregation. (PMID: 18573880) Shao J. … Diamond M.I. (Mol. Cell. Biol. 2008) 3 4 22 64
  4. Huntington CAG repeat size does not modify onset age in familial Parkinson's disease: the GenePD study. (PMID: 18649400) McNicoll C.F. … Myers R.H. (Mov. Disord. 2008) 3 22 46 64
  5. Ubiquitin ligase Hrd1 enhances the degradation and suppresses the toxicity of polyglutamine-expanded huntingtin. (PMID: 17141218) Yang H. … Fang S. (Exp. Cell Res. 2007) 3 4 22 64

Products for HTT Gene

  • Addgene plasmids for HTT

Sources for HTT Gene

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