ADAMTSL1

Chr 9

ADAMTS like 1

Also known as: ADAMTSL-1, ADAMTSR1, C9orf94, PUNCTIN

NCBI Gene: 92949 ENSG00000178031 UniProt: Q8N6G6 OMIM: 609198

The protein is a secreted extracellular matrix component that contains thrombospondin motifs but lacks the metalloproteinase domains typical of other ADAMTS family members. Mutations cause geleophysic dysplasia, a rare skeletal dysplasia characterized by short stature, joint contractures, distinctive facial features, and cardiac valve abnormalities, with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.531), indicating that complete loss of protein function is likely deleterious.

OMIM ResearchSummary from RefSeq

This gene encodes a secreted protein and member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) family. This protein lacks the metalloproteinase and disintegrin-like domains, which are typical of the ADAMTS family, but contains other ADAMTS domains, including the thrombospondin type 1 motif. This protein may have important functions in the extracellular matrix. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

A dominant-negative effect is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.53

LOEUF

Mechanism· G2P