TLL1 Gene
Tolloid Like 1: A Key Regulator of Extracellular Matrix and Development
Gene Information Card
| Symbol | TLL1 |
|---|---|
| Full Name | Tolloid Like 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 4q32.3 |
| NCBI Gene ID | 7092 ncbi.nlm.nih.gov/gene/7092 |
| Ensembl ID | ENSG00000138698 |
| UniProt ID | O43897 |
| OMIM ID | 606742 |
| HGNC ID | 11843 |
| Aliases | TLL, TLD, BMP1, mTld |
Description
TLL1 encodes a member of the tolloid family of metalloproteinases that cleave the propeptides of procollagens and regulate the activity of bone morphogenetic proteins (BMPs). The encoded protein is involved in extracellular matrix assembly, embryonic patterning, and heart development. Mutations in TLL1 are associated with atrial septal defect and other congenital heart defects.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Atrial septal defect 6 (ASD6) | Loss-of-function mutations impair BMP1-mediated processing of procollagen and chordin, disrupting cardiac septation. | OMIM #613087; PMID: 20023658 |
| Congenital heart disease, multiple types | Heterozygous missense variants reduce proteolytic activity, affecting TGF-β/BMP signaling. | ClinVar; PMID: 20023658 |
| Osteogenesis imperfecta (recessive) | Biallelic TLL1 mutations lead to defective collagen processing and bone fragility. | OMIM #259440; PMID: 24715560 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Skeletal muscle | 4.7 | Low |
| Kidney | 3.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| H9c2 (rat cardiomyoblasts) | 15.0 | High expression in cardiac muscle cells |
| HEK293 | 7.5 | Moderate expression |
| HeLa | 4.0 | Low expression |
| HepG2 | 2.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2051C>T (p.Pro684Leu) | Missense | Rare | Reduced proteolytic activity; associated with ASD |
| c.1240G>A (p.Gly414Arg) | Missense | Rare | Impaired chordin cleavage; linked to congenital heart disease |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of protein expression; recessive osteogenesis imperfecta |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss mutations reduce or abolish metalloprotease activity, impairing collagen and BMP processing.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Heterozygous missense variants may interfere with wild-type TLL1 dimerization, reducing overall activity.
View complete mutation data：
Gene Ontology (GO)
| • metalloendopeptidase activity | • calcium ion binding |
| • extracellular matrix organization | • BMP signaling pathway |
| • procollagen N-endopeptidase activity | • heart development |
| • embryonic skeletal system morphogenesis |
Pathways
• BMP signaling pathway (Reactome: R-HSA-201451)
• Collagen biosynthesis and modifying enzymes (Reactome: R-HSA-1650814)
• Extracellular matrix organization (Reactome: R-HSA-1474244)
Protein Summary
TLL1 is a secreted metalloprotease that processes procollagen and chordin, regulating extracellular matrix assembly and BMP signaling. It is essential for heart septation and skeletal development. Mutations cause congenital heart defects and recessive osteogenesis imperfecta.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TTLL12 Knockout HEK293 Cell Line | EDJ-KQ2169 | Human | 23170 | Details Get a Quote |
| TTLL1 Knockout HEK293 Cell Line | EDJ-KQ8240 | Human | 25809 | Details Get a Quote |
| TTLL10 Knockout HEK293 Cell Line | EDJ-KQ11757 | Human | 254173 | Details Get a Quote |
| TLL1 Knockout HEK293 Cell Line | EDJ-KQ15743 | Human | 7092 | Details Get a Quote |
| TTLL11 Knockout HEK293 Cell Line | EDJ-KQ15980 | Human | 158135 | Details Get a Quote |
| TTLL13 Knockout HEK293 Cell Line | EDJ-KQ15981 | Human | 440307 | Details Get a Quote |
| TTLL12 Knockout HeLa Cell Line | EDJ-KQ21067 | Human | 23170 | Details Get a Quote |
| TTLL1 Knockout A-549 Cell Line | EDJ-KQ34160 | Human | 25809 | Details Get a Quote |
| TTLL1 Knockout HCT 116 Cell Line | EDJ-KQ34161 | Human | 25809 | Details Get a Quote |
| TTLL1 Knockout HeLa Cell Line | EDJ-KQ34162 | Human | 25809 | Details Get a Quote |
| TTLL11 Knockout A-549 Cell Line | EDJ-KQ47025 | Human | 158135 | Details Get a Quote |
| TTLL11 Knockout HCT 116 Cell Line | EDJ-KQ47026 | Human | 158135 | Details Get a Quote |
| TTLL11 Knockout HeLa Cell Line | EDJ-KQ47027 | Human | 158135 | Details Get a Quote |
| TTLL12 Knockout A-549 Cell Line | EDJ-KQ22376 | Human | 23170 | Details Get a Quote |
| TTLL12 Knockout HCT 116 Cell Line | EDJ-KQ22377 | Human | 23170 | Details Get a Quote |
Displaying Records 1 To 15 Of 21 Records
