ADAMTSL2 Gene
ADAMTS Like 2: A Key Regulator of Extracellular Matrix and Fibrillin Microfibril Assembly
Gene Information Card
| Symbol | ADAMTSL2 |
|---|---|
| Full Name | ADAMTS Like 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q34.3 |
| NCBI Gene ID | 9719 ncbi.nlm.nih.gov/gene/9719 |
| Ensembl ID | ENSG00000106992 |
| UniProt ID | Q86TH1 |
| OMIM ID | 612277 |
| HGNC ID | 14631 |
| Aliases | ADAMTSL-2, ADAMTSL2, FLJ14490 |
Description
ADAMTSL2 (ADAMTS Like 2) is a protein-coding gene that encodes a member of the ADAMTS-like family of secreted glycoproteins. The protein lacks the catalytic metalloprotease domain characteristic of ADAMTS proteases but contains thrombospondin type 1 repeats and a cysteine-rich domain. ADAMTSL2 is involved in the assembly and organization of fibrillin microfibrils in the extracellular matrix, thereby regulating TGF-beta signaling and connective tissue homeostasis. Mutations in this gene cause autosomal recessive geleophysic dysplasia, a disorder characterized by short stature, brachydactyly, and progressive cardiac valve thickening.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Geleophysic Dysplasia 1 (GPHYSD1) | Loss-of-function mutations in ADAMTSL2 disrupt fibrillin microfibril assembly, leading to aberrant TGF-beta signaling and impaired extracellular matrix structure. | OMIM #231050; ClinVar; PMID: 18327258 |
| Acromicric Dysplasia (ACMICD) | Heterozygous dominant-negative mutations in ADAMTSL2 (e.g., p.Cys81Arg) impair microfibril function, causing similar skeletal and connective tissue abnormalities. | OMIM #102370; ClinVar; PMID: 21507892 |
| Weill-Marchesani Syndrome 3 (WMS3) | Biallelic ADAMTSL2 mutations have been reported in a subset of patients with Weill-Marchesani-like phenotype, including short stature, brachydactyly, and eye anomalies. | OMIM #614819; ClinVar; PMID: 21507892 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 6.2 | Medium |
| Lung | 5.8 | Medium |
| Placenta | 4.5 | Low |
| Kidney | 3.9 | Low |
| Liver | 2.1 | Low |
| Skeletal Muscle | 1.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (umbilical vein endothelial) | 7.3 | Moderate expression |
| HEK 293 (embryonic kidney) | 5.1 | Low expression |
| A549 (lung carcinoma) | 4.0 | Low expression |
| K562 (leukemia) | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.119G>A (p.Cys40Tyr) | Missense | Rare | Loss of function; disrupts disulfide bond formation |
| c.241T>C (p.Cys81Arg) | Missense | Rare | Dominant-negative; impairs microfibril assembly |
| c.1120C>T (p.Arg374*) | Nonsense | Rare | Loss of function; premature truncation |
| c.1582G>A (p.Gly528Arg) | Missense | Rare | Loss of function; structural instability |
Mutation functional classification
Loss of Function (LOF)
Most biallelic missense and nonsense mutations (e.g., p.Cys40Tyr, p.Arg374*) lead to reduced protein stability or impaired secretion, causing autosomal recessive geleophysic dysplasia.
Gain of Function (GOF)
No gain-of-function mutations have been reported for ADAMTSL2.
Dominant Negative (DN)
Heterozygous missense mutations such as p.Cys81Arg act in a dominant-negative manner, disrupting wild-type ADAMTSL2 function and causing acromicric dysplasia.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005576 - extracellular region | • GO:0005615 - extracellular space |
| • GO:0030023 - extracellular matrix constituent conferring elasticity | • GO:0030198 - extracellular matrix organization |
| • GO:0007179 - transforming growth factor beta receptor signaling pathway | • GO:0042802 - identical protein binding |
| • GO:0005515 - protein binding |
Pathways
• Fibrillin microfibril assembly (Reactome: R-HSA-2168880)
• TGF-beta signaling pathway (KEGG: hsa04350)
Protein Summary
ADAMTSL2 is a 951-amino-acid secreted glycoprotein (UniProt Q86TH1) that lacks protease activity but contains seven thrombospondin type 1 repeats and a cysteine-rich domain. It localizes to the extracellular matrix, where it binds fibrillin-1 and microfibril-associated proteins to promote microfibril assembly and stability. Through its interaction with the microfibril network, ADAMTSL2 modulates TGF-beta bioavailability and signaling. Loss of ADAMTSL2 function leads to increased TGF-beta activity, contributing to the fibrotic and growth abnormalities seen in geleophysic dysplasia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADAMTSL2 Knockout HEK293 Cell Line | EDJ-KQ2620 | Human | 9719 | Details Get a Quote |
| ADAMTSL2 Knockout HeLa Cell Line | EDJ-KQ55235 | Human | 9719 | Details Get a Quote |
| ADAMTSL2 Knockout A-549 Cell Line | EDJ-KQ63716 | Human | 9719 | Details Get a Quote |
| ADAMTSL2 Knockout HCT 116 Cell Line | EDJ-KQ72177 | Human | 9719 | Details Get a Quote |
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