This gene encodes an astacin-like, zinc-dependent, metalloprotease that belongs to the peptidase M12A family. This protease processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase. Studies in mice suggest that this gene plays multiple roles in the development of mammalian heart, and is essential for the formation of the interventricular septum. ... See more...

Aliases for TLL1 Gene

Aliases for TLL1 Gene

  • Tolloid Like 1 2 3 5
  • Tolloid-Like Protein 1 3 4
  • TLL 3 4
  • EC 3.4.24.19 51
  • EC 3.4.24.- 4
  • EC 3.4.24 51
  • ASD6 3
  • TLL1 5

External Ids for TLL1 Gene

Previous GeneCards Identifiers for TLL1 Gene

  • GC04P167646
  • GC04P167222
  • GC04P167372
  • GC04P167152
  • GC04P167013
  • GC04P166794
  • GC04P162546

Summaries for TLL1 Gene

Entrez Gene Summary for TLL1 Gene

  • This gene encodes an astacin-like, zinc-dependent, metalloprotease that belongs to the peptidase M12A family. This protease processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase. Studies in mice suggest that this gene plays multiple roles in the development of mammalian heart, and is essential for the formation of the interventricular septum. Allelic variants of this gene are associated with atrial septal defect type 6. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

GeneCards Summary for TLL1 Gene

TLL1 (Tolloid Like 1) is a Protein Coding gene. Diseases associated with TLL1 include Atrial Septal Defect 6 and Atrial Septal Defect Ostium Primum. Among its related pathways are Degradation of the extracellular matrix and Collagen chain trimerization. Gene Ontology (GO) annotations related to this gene include calcium ion binding and metallopeptidase activity. An important paralog of this gene is TLL2.

UniProtKB/Swiss-Prot Summary for TLL1 Gene

  • Protease which processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase. Required for the embryonic development. Predominant protease, which in the development, influences dorsal-ventral patterning and skeletogenesis.

Gene Wiki entry for TLL1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TLL1 Gene

Genomics for TLL1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TLL1 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
GH04J165872 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE CraniofacialAtlas 600.7 +0.9 901 3.6 FOXA1 EZH2 MNT USF1 ZBTB48 E2F1 ZBTB26 E2F6 ZBTB17 MYC TLL1 piR-56883-138
GH04J165111 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 10.6 -760.4 -760353 2.7 SP1 HNRNPL CREB1 GATAD2A CTCF PRDM10 ZNF629 REST TFE3 IKZF1 TMEM192 KLHL2 TLL1 piR-47162-115 lnc-TRIM75P-3 TRIM60
GH04J165476 Enhancer 1.1 Ensembl ENCODE 10.6 -396.4 -396369 1.3 CREB1 LEF1 IKZF1 JUND MTA2 PKNOX1 BRD9 DPF2 HDAC1 SOX6 CPE TLL1 RF00017-4449 lnc-CPE-1
GH04J165502 Enhancer 1.1 FANTOM5 Ensembl ENCODE 10 -369.6 -369601 2.6 GATAD2A ATF7 ZNF629 RXRB CEBPA SOX13 TCF7 FOXA1 CEBPB FOXA2 HSALNG0038351 LOC105377520 TLL1 lnc-CPE-1 CPE
GH04J165579 Enhancer 0.7 Ensembl ENCODE 10.1 -292.5 -292457 2.4 ZIC2 JUN FOSL2 ZNF335 HIC1 TRIM28 JUND CTBP1 ZNF547 SP7 TLL1 lnc-CPE-2 LOC646995 CPE
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TLL1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TLL1

Top Transcription factor binding sites by QIAGEN in the TLL1 gene promoter:
  • aMEF-2
  • AML1a
  • AREB6
  • COMP1
  • FOXO4
  • GR
  • GR-alpha
  • HNF-3beta
  • MEF-2A
  • Pax-4a

Genomic Locations for TLL1 Gene

Genomic Locations for TLL1 Gene
chr4:165,873,124-166,105,178
(GRCh38/hg38)
Size:
232,055 bases
Orientation:
Plus strand
chr4:166,794,410-167,025,609
(GRCh37/hg19)
Size:
231,200 bases
Orientation:
Plus strand

Genomic View for TLL1 Gene

Genes around TLL1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TLL1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TLL1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TLL1 Gene

Proteins for TLL1 Gene

  • Protein details for TLL1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43897-TLL1_HUMAN
    Recommended name:
    Tolloid-like protein 1
    Protein Accession:
    O43897
    Secondary Accessions:
    • B2RMU2
    • Q96AN3
    • Q9NQS4

    Protein attributes for TLL1 Gene

    Size:
    1013 amino acids
    Molecular mass:
    114709 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for TLL1 Gene

    Alternative splice isoforms for TLL1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TLL1 Gene

Selected DME Specific Peptides for TLL1 Gene

O43897:
  • SVTPGEKI
  • IGQRTRLS
  • CGCCSYVGRRG
  • LNFTTMDL
  • DSRMWIEFRSSSNWVGKGFAAVYEAICGGEI
  • WEKHTCV
  • YLEVRDG
  • KDNGGCQ
  • FELEGNEVCKYDYVE
  • YEAICGG
  • FQSFEIERH
  • GGCEQRC
  • CGSGPPEE
  • FEIERHD
  • HSTECGG
  • IVFTYRPCGCCSYVGRRG
  • KYPSRKECTW
  • IQSPNYPDDYRP
  • KLHGKFCG
  • LWMKFVSDG
  • EFRSSSN
  • RENIQPGQEYNFLKME
  • YDFDSIMHYARNTFSRGMFLDTILPSRD
  • ECGGRLKAE
  • GFWHEHTRPDR
  • EFKSDNTVSK
  • CAYDYLE
  • KLYRCPACGETLQ
  • SVQRKGFQA
  • SDASVQRKGFQA
  • EQHQECAYDHLE
  • SPNWPDKYPS
  • GKNCDKFG
  • CPACGETLQ
  • ECAYDHLEVFDG
  • TFEVEEEADCGYD
  • WGDIALD
  • CEAACGG
  • SHAQFGDNNYP
  • PGWPKEYP
  • SIMHYARNTFSRG

Post-translational modifications for TLL1 Gene

  • Glycosylation at Asn169, Asn359, Asn390, and Asn626
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

Domains & Families for TLL1 Gene

Gene Families for TLL1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins
  • Predicted secreted proteins

Suggested Antigen Peptide Sequences for TLL1 Gene

GenScript: Design optimal peptide antigens:
  • TLL1 protein (B7ZLW3_HUMAN)
  • Tolloid-like protein 1 (TLL1_HUMAN)
genes like me logo Genes that share domains with TLL1: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for TLL1 Gene

Function for TLL1 Gene

Molecular function for TLL1 Gene

UniProtKB/Swiss-Prot Function:
Protease which processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase. Required for the embryonic development. Predominant protease, which in the development, influences dorsal-ventral patterning and skeletogenesis.
GENATLAS Biochemistry:
tolloid-like gene 1,astacin-like matalloprotease necessary for normal septation and positioning of the heart

Enzyme Numbers (IUBMB) for TLL1 Gene

Phenotypes From GWAS Catalog for TLL1 Gene

Gene Ontology (GO) - Molecular Function for TLL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004222 metalloendopeptidase activity IEA --
GO:0005509 calcium ion binding IEA --
GO:0008233 peptidase activity IEA --
GO:0008237 metallopeptidase activity IEA --
GO:0008270 zinc ion binding IEA --
genes like me logo Genes that share ontologies with TLL1: view
genes like me logo Genes that share phenotypes with TLL1: view

Human Phenotype Ontology for TLL1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TLL1 Gene

MGI Knock Outs for TLL1:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TLL1

No data available for Transcription Factor Targets and HOMER Transcription for TLL1 Gene

Localization for TLL1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TLL1 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 TLL1 gene
Compartment Confidence
extracellular 5
plasma membrane 2
cytoskeleton 1
mitochondrion 1
nucleus 1
endoplasmic reticulum 1
cytosol 1
lysosome 1
golgi apparatus 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for TLL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with TLL1: view

Pathways & Interactions for TLL1 Gene

genes like me logo Genes that share pathways with TLL1: view

Gene Ontology (GO) - Biological Process for TLL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001501 skeletal system development TAS 8661043
GO:0006508 proteolysis IEA --
GO:0007275 multicellular organism development IEA --
GO:0022617 extracellular matrix disassembly TAS --
GO:0030154 cell differentiation IEA --
genes like me logo Genes that share ontologies with TLL1: view

No data available for SIGNOR curated interactions for TLL1 Gene

Drugs & Compounds for TLL1 Gene

No Compound Related Data Available

Transcripts for TLL1 Gene

mRNA/cDNA for TLL1 Gene

2 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
6 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 TLL1

Alternative Splicing Database (ASD) splice patterns (SP) for TLL1 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23
SP1: - -
SP2: -
SP3:

Relevant External Links for TLL1 Gene

GeneLoc Exon Structure for
TLL1

Expression for TLL1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TLL1 Gene

mRNA differential expression in normal tissues according to GTEx for TLL1 Gene

This gene is overexpressed in Brain - Cerebellar Hemisphere (x7.2) and Brain - Cerebellum (x6.0).

Protein differential expression in normal tissues from HIPED for TLL1 Gene

This gene is overexpressed in Heart (66.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TLL1 Gene



Protein tissue co-expression partners for TLL1 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TLL1

SOURCE GeneReport for Unigene cluster for TLL1 Gene:

Hs.106513

Evidence on tissue expression from TISSUES for TLL1 Gene

  • Heart(4.3)
  • Nervous system(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for TLL1 Gene

Germ Layers:
  • mesoderm
Systems:
  • cardiovascular
Regions:
Head and neck:
  • ear
Thorax:
  • heart
  • heart valve
genes like me logo Genes that share expression patterns with TLL1: view

No data available for mRNA Expression by UniProt/SwissProt for TLL1 Gene

Orthologs for TLL1 Gene

This gene was present in the common ancestor of animals.

Orthologs for TLL1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TLL1 30 31
  • 99.31 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TLL1 30 31
  • 91.07 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TLL1 30 31
  • 91.02 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia TLL1 31
  • 91 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia TLL1 31
  • 89 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Tll1 30 17 31
  • 88.7 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Tll1 30
  • 87.78 (n)
Chicken
(Gallus gallus)
Aves TLL1 30 31
  • 82.9 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia TLL1 31
  • 88 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC100495742 30
  • 79.28 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.16598 30
Zebrafish
(Danio rerio)
Actinopterygii tll1 30 31
  • 73.67 (n)
OneToOne
bmp1 30
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003702 30
  • 56.71 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta tok 30 31 32
  • 54.88 (n)
ManyToMany
tld 31 32
  • 40 (a)
ManyToMany
Worm
(Caenorhabditis elegans)
Secernentea nas-39 30 31
  • 51.94 (n)
OneToMany
F38E9.2 32
  • 41 (a)
T04G9.2 32
  • 39 (a)
F09E8.6 32
  • 38 (a)
C07D10.4 32
  • 35 (a)
Y95B8A.1 32
  • 34 (a)
toh-2 32
  • 30 (a)
K04E7.3 32
  • 30 (a)
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 51 (a)
OneToMany
Species where no ortholog for TLL1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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 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)

Evolution for TLL1 Gene

ENSEMBL:
Gene Tree for TLL1 (if available)
TreeFam:
Gene Tree for TLL1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TLL1: view image

Paralogs for TLL1 Gene

(12) SIMAP similar genes for TLL1 Gene using alignment to 6 proteins:

  • TLL1_HUMAN
  • B7ZLW3_HUMAN
  • D6RAK5_HUMAN
  • D6RBI6_HUMAN
  • D6RCE0_HUMAN
  • E9PD25_HUMAN

Pseudogenes.org Pseudogenes for TLL1 Gene

genes like me logo Genes that share paralogs with TLL1: view

Variants for TLL1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TLL1 Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
690359 Pathogenic: Atrial septal defect 6 166,043,272(+) A/G SPLICE_ACCEPTOR_VARIANT
710956 Benign: not provided 166,065,748(+) A/G SYNONYMOUS_VARIANT
710957 Benign: not provided 166,074,933(+) G/A SYNONYMOUS_VARIANT
711124 Benign: not provided 166,008,057(+) C/T INTRON_VARIANT
711125 Likely Benign: not provided 166,057,177(+) T/C INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for TLL1 Gene

Structural Variations from Database of Genomic Variants (DGV) for TLL1 Gene

Variant ID Type Subtype PubMed ID
dgv155n73 CNV deletion 24416366
dgv2935n106 CNV deletion 24896259
dgv9371n54 CNV loss 21841781
esv1005389 CNV insertion 20482838
esv22616 CNV loss 19812545
esv2673253 CNV deletion 23128226
esv2728689 CNV deletion 23290073
esv3297606 CNV deletion 24192839
esv3564942 CNV deletion 23714750
esv3569805 CNV loss 25503493
esv3569806 CNV loss 25503493
esv3603029 CNV gain 21293372
esv3603030 CNV loss 21293372
esv3603031 CNV loss 21293372
esv4074 CNV loss 18987735
esv7036 CNV loss 19470904
nsv1016754 CNV loss 25217958
nsv1074767 CNV deletion 25765185
nsv1128108 CNV deletion 24896259
nsv1131841 CNV deletion 24896259
nsv1151253 CNV deletion 26484159
nsv291079 CNV insertion 16902084
nsv292670 CNV deletion 16902084
nsv4590 CNV insertion 18451855
nsv513176 CNV loss 21212237
nsv821532 CNV deletion 20802225
nsv821638 CNV loss 15273396
nsv830142 CNV loss 17160897

Variation tolerance for TLL1 Gene

Residual Variation Intolerance Score: 15.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.74; 57.77% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TLL1 Gene

Human Gene Mutation Database (HGMD)
TLL1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TLL1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TLL1 Gene

Disorders for TLL1 Gene

MalaCards: The human disease database

(6) MalaCards diseases for TLL1 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
atrial septal defect 6
  • asd6
atrial septal defect ostium primum
  • asd ostium primum type
patent foramen ovale
  • atrial septal defect within oval fossa
atrial septal defect 4
  • asd4
atrial septal defect 5
  • asd5
- elite association - COSMIC cancer census association via MalaCards
Search TLL1 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TLL1_HUMAN
  • Atrial septal defect 6 (ASD6) [MIM:613087]: A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria. {ECO:0000269 PubMed:18830233}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for TLL1

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 TLL1: view

No data available for Genatlas for TLL1 Gene

Publications for TLL1 Gene

  1. Mutations in mammalian tolloid-like 1 gene detected in adult patients with ASD. (PMID: 18830233) Stańczak P … Sieroń AL (European journal of human genetics : EJHG 2009) 3 4 23
  2. Structural basis for the substrate specificity of bone morphogenetic protein 1/tolloid-like metalloproteases. (PMID: 18824173) Mac Sweeney A … Gerhartz B (Journal of molecular biology 2008) 3 4 23
  3. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4
  5. Multiple bone morphogenetic protein 1-related mammalian metalloproteinases process pro-lysyl oxidase at the correct physiological site and control lysyl oxidase activation in mouse embryo fibroblast cultures. (PMID: 11313359) Uzel MI … Trackman PC (The Journal of biological chemistry 2001) 3 4

Products for TLL1 Gene

  • Signalway ELISA kits for TLL1

Sources for TLL1 Gene