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Aliases for TLL1 Gene

Aliases for TLL1 Gene

  • Tolloid Like 1 2 3 5
  • TLL 3 4
  • Tolloid-Like Protein 1 3
  • EC 56
  • EC 3.4.24.- 4
  • EC 3.4.24 56
  • ASD6 3

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 Collagen chain trimerization and Degradation of the extracellular matrix. 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 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

Additional gene information for TLL1 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TLL1 Gene

Genomics for TLL1 Gene

GeneHancer (GH) Regulatory Elements for TLL1 Gene

Promoters and enhancers for TLL1 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04I165872 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE 550.8 +0.6 565 3 MXI1 USF1 ZNF777 SUZ12 MAX HIC1 ZNF335 E2F1 ZFHX2 ZNF213 TLL1 RNA5SP170
GH04I165111 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 10.6 -760.3 -760267 2.3 HDGF PKNOX1 FOXA2 MLX ZFP64 ARID4B SIN3A DMAP1 ZBTB7B YY1 TMEM192 KLHL2 TLL1 TRIM75P
GH04I165476 Enhancer 0.9 ENCODE 10.6 -396.5 -396547 1.2 PKNOX1 ATF1 ARNT NCOA2 TCF12 POLR2B ZNF766 CBX5 GATA2 FOS TLL1 CPE GC04P165491 GC04M165414
GH04I165579 Enhancer 0.8 Ensembl ENCODE 10.1 -292.6 -292571 2.4 PKNOX1 JUN ZIC2 ZNF335 HIC1 CTBP1 JUND ZNF547 FOSL2 TRIM28 TLL1 NOL8P1 GC04M165628
GH04I165502 Enhancer 0.8 ENCODE 10 -370.1 -370095 1.7 FOXA2 RARA ATF7 FOS CREM MIXL1 CEBPB PPARG KLF16 CEBPA TLL1 LOC105377520 GC04P165491
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around TLL1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TLL1 gene promoter:

Genomic Locations for TLL1 Gene

Genomic Locations for TLL1 Gene
231,941 bases
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:
    Recommended name:
    Tolloid-like protein 1
    Protein Accession:
    Secondary Accessions:
    • B2RMU2
    • Q96AN3
    • Q9NQS4

    Protein attributes for TLL1 Gene

    1013 amino acids
    Molecular mass:
    114709 Da
    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


neXtProt entry for TLL1 Gene

Selected DME Specific Peptides for TLL1 Gene


Post-translational modifications for TLL1 Gene

  • Glycosylation at isoforms=2169, posLast=359359, posLast=390390, and posLast=626626

Domains & Families for TLL1 Gene

Gene Families for TLL1 Gene

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

Suggested Antigen Peptide Sequences for TLL1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the peptidase M12A family.
  • Belongs to the peptidase M12A family.
genes like me logo Genes that share domains with TLL1: view

Function for TLL1 Gene

Molecular function for TLL1 Gene

GENATLAS Biochemistry:
tolloid-like gene 1,astacin-like matalloprotease necessary for normal septation and positioning of the heart
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.

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 TAS,IEA --
GO:0004252 serine-type endopeptidase activity TAS --
GO:0005509 calcium ion binding IEA --
GO:0008233 peptidase activity IEA --
GO:0008237 metallopeptidase activity 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:

Clone Products

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


Subcellular locations from

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 1
peroxisome 1
cytosol 1
lysosome 1

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

Interacting Proteins for TLL1 Gene

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

Unigene Clusters for TLL1 Gene

Tolloid-like 1:
Representative Sequences:

Clone Products

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: -

Relevant External Links for TLL1 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for TLL1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP 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, PaxDb, MaxQB, and MOPED for TLL1 Gene

Protein tissue co-expression partners for TLL1 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of TLL1 Gene:


SOURCE GeneReport for Unigene cluster for TLL1 Gene:


Evidence on tissue expression from TISSUES for TLL1 Gene

  • Heart(4.2)

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

Germ Layers:
  • mesoderm
  • cardiovascular
Head and neck:
  • ear
  • 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
(Pan troglodytes)
Mammalia TLL1 33 34
  • 99.31 (n)
(Canis familiaris)
Mammalia TLL1 33 34
  • 91.07 (n)
(Bos Taurus)
Mammalia TLL1 33 34
  • 91.02 (n)
(Monodelphis domestica)
Mammalia TLL1 34
  • 91 (a)
(Ornithorhynchus anatinus)
Mammalia TLL1 34
  • 89 (a)
(Mus musculus)
Mammalia Tll1 33 16 34
  • 88.7 (n)
(Rattus norvegicus)
Mammalia Tll1 33
  • 87.78 (n)
(Gallus gallus)
Aves TLL1 33 34
  • 82.9 (n)
(Anolis carolinensis)
Reptilia TLL1 34
  • 88 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100495742 33
  • 79.28 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.16598 33
(Danio rerio)
Actinopterygii tll1 33 34
  • 73.67 (n)
bmp1 33
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003702 33
  • 56.71 (n)
fruit fly
(Drosophila melanogaster)
Insecta tok 35 33 34
  • 54.88 (n)
tld 35 34
  • 45 (a)
(Caenorhabditis elegans)
Secernentea nas-39 33 34
  • 51.94 (n)
F38E9.2 35
  • 41 (a)
T04G9.2 35
  • 39 (a)
F09E8.6 35
  • 38 (a)
C07D10.4 35
  • 35 (a)
Y95B8A.1 35
  • 34 (a)
K04E7.3 35
  • 30 (a)
toh-2 35
  • 30 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 51 (a)
Species where no ortholog for TLL1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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 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

Gene Tree for TLL1 (if available)
Gene Tree for TLL1 (if available)

Paralogs for TLL1 Gene

Paralogs for TLL1 Gene Pseudogenes for TLL1 Gene

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

Variants for TLL1 Gene

Sequence variations from dbSNP and Humsavar for TLL1 Gene

SNP ID Clin Chr 04 pos Variation AA Info Type
rs137852951 pathogenic, uncertain-significance, Atrial septal defect 6, not specified, Atrial septal defect 6 (ASD6) [MIM:613087] 165,995,090(+) A/C/G coding_sequence_variant, missense_variant
rs137852952 pathogenic, Atrial septal defect 6, Atrial septal defect 6 (ASD6) [MIM:613087] 166,003,471(+) T/C coding_sequence_variant, missense_variant
rs137852953 pathogenic, Atrial septal defect 6, Atrial septal defect 6 (ASD6) [MIM:613087] 166,060,066(+) A/G coding_sequence_variant, genic_downstream_transcript_variant, missense_variant
VAR_036142 A breast cancer sample p.Leu688Val
rs1057524197 uncertain-significance, not specified 166,099,481(+) G/A coding_sequence_variant, genic_downstream_transcript_variant, missense_variant

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

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

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)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

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

Disorders for TLL1 Gene

MalaCards: The human disease database

(5) MalaCards diseases for TLL1 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, 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
patent ductus arteriosus 1
  • pda1
atrial heart septal defect
  • atrial septal defect
- elite association - COSMIC cancer census association via MalaCards
Search TLL1 in MalaCards View complete list of genes associated with diseases


  • 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
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
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 22 58
  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 22 58
  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 44 58
  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 58
  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 58

Products for TLL1 Gene

Sources for TLL1 Gene

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