TLL1

Chr 4AD

tolloid like 1

Also known as: ASD6, TLL

NCBI Gene: 7092 ENSG00000038295 UniProt: O43897 OMIM: 606742

This gene encodes a zinc-dependent metalloprotease that processes procollagen C-propeptides including chordin, pro-biglycan, and pro-lysyl oxidase, playing essential roles in cardiac development and formation of the interventricular septum. Mutations cause atrial septal defect 6, inherited in an autosomal dominant pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.37), suggesting some intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Atrial septal defect 6MIM #613087

Clinical highlights

Gene-disease validity (ClinGen)

congenital heart disease · ADLimitednot for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.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

0.37

LOEUF

Multiple*

Mechanism· predicted