ADAMTSL4 Gene
ADAMTS Like 4: A Key Regulator of Fibrillin Microfibril Assembly and Ectopia Lentis
Gene Information Card
| Symbol | ADAMTSL4 |
|---|---|
| Full Name | ADAMTS Like 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q21.2 |
| NCBI Gene ID | 54507 ncbi.nlm.nih.gov/gene/54507 |
| Ensembl ID | ENSG00000143384 |
| UniProt ID | Q6UY14 |
| OMIM ID | 610113 |
| HGNC ID | 19706 |
| Aliases | ADAMTSL-4, ADAMTSL4, FLJ90709, MGC119427, MGC119429, THSD4 |
Description
The ADAMTSL4 gene encodes a secreted glycoprotein belonging to the ADAMTS-like family. It lacks the catalytic metalloprotease domain found in ADAMTS proteases but contains thrombospondin type 1 repeats. ADAMTSL4 is essential for the proper assembly and anchoring of fibrillin-1 microfibrils in the extracellular matrix, particularly in the ocular zonule. Loss-of-function mutations cause isolated ectopia lentis and are associated with other connective tissue disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ectopia lentis, isolated, autosomal recessive | Disruption of microfibril assembly in the zonular fibers leads to lens dislocation | OMIM #225100; multiple homozygous/compound heterozygous mutations reported |
| Ectopia lentis et pupillae | Similar mechanism involving zonular and pupillary abnormalities | OMIM #225200; rare ADAMTSL4 variants identified |
| Weill-Marchesani syndrome 6 | Defective microfibril structure results in short stature, brachydactyly, and lens dislocation | OMIM #617811; biallelic ADAMTSL4 mutations |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Eye (retina, lens, ciliary body) | High | Tissue-specific enrichment |
| Heart | Moderate | GTEx median 10-20 nTPM |
| Skeletal muscle | Moderate | GTEx median 10-20 nTPM |
| Lung | Low | GTEx median <5 nTPM |
| Liver | Low | GTEx median <5 nTPM |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (retinal pigment epithelium) | 15.2 | Moderate expression |
| HUVEC (umbilical vein endothelial) | 8.5 | Low expression |
| HEK 293 (embryonic kidney) | 5.1 | Low expression |
| HepG2 (hepatocellular carcinoma) | 2.3 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.767_768del (p.Glu256Glyfs*5) | Frameshift | Found in multiple families | Loss of function; nonsense-mediated decay |
| c.1063C>T (p.Arg355*) | Nonsense | Rare | Premature stop; truncated protein |
| c.1282G>A (p.Gly428Arg) | Missense | Low frequency | Impaired secretion and microfibril binding |
| c.1735C>T (p.Arg579*) | Nonsense | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Majority of reported mutations are nonsense, frameshift, or splice-site leading to haploinsufficiency or complete loss of ADAMTSL4 function.
Gain of Function (GOF)
No evidence of gain-of-function mutations in ADAMTSL4.
Dominant Negative (DN)
Not reported; disease inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005576 - extracellular region | • GO:0005615 - extracellular space |
| • GO:0030023 - extracellular matrix constituent conferring tensile strength | • GO:0042802 - identical protein binding |
| • GO:0062023 - collagen-containing extracellular matrix |
Pathways
• Fibrillin microfibril assembly (Reactome: R-HSA-216083)
• Elastic fibre formation (Reactome: R-HSA-1566948)
Protein Summary
ADAMTSL4 is a 1075-amino-acid secreted protein with a signal peptide, a central ADAMTS spacer-like region, and seven thrombospondin type 1 repeats. It localizes to the extracellular matrix and interacts directly with fibrillin-1 to promote microfibril assembly and stability. The protein is critical for the structural integrity of the ocular zonule and other elastic tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADAMTSL4 Knockout HEK293 Cell Line | EDJ-KQ11445 | Human | 54507 | Details Get a Quote |
| ADAMTSL4 Knockout A-549 Cell Line | EDJ-KQ38386 | Human | 54507 | Details Get a Quote |
| ADAMTSL4 Knockout HCT 116 Cell Line | EDJ-KQ39725 | Human | 54507 | Details Get a Quote |
| ADAMTSL4 Knockout HeLa Cell Line | EDJ-KQ39726 | Human | 54507 | Details Get a Quote |
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