CELSR1

Chr 22

cadherin EGF LAG seven-pass G-type receptor 1

Also known as: ADGRC1, CDHF9, FMI2, HFMI2, LMPHM9, ME2, YNS

NCBI Gene: 9620 ENSG00000075275 UniProt: Q9NYQ6

CELSR1 encodes a cell surface receptor with cadherin and EGF-like domains that mediates cell-to-cell signaling during nervous system development. Mutations cause lymphatic malformation 9 and yellow nail syndrome through both autosomal dominant and autosomal recessive inheritance patterns. The gene is extremely intolerant to loss-of-function variants (pLI >0.99), indicating that complete protein loss is likely incompatible with normal development.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the flamingo subfamily, part of the cadherin superfamily. The flamingo subfamily consists of nonclassic-type cadherins; a subpopulation that does not interact with catenins. The flamingo cadherins are located at the plasma membrane and have nine cadherin domains, seven epidermal growth factor-like repeats and two laminin A G-type repeats in their ectodomain. They also have seven transmembrane domains, a characteristic unique to this subfamily. It is postulated that these proteins are receptors involved in contact-mediated communication, with cadherin domains acting as homophilic binding regions and the EGF-like domains involved in cell adhesion and receptor-ligand interactions. This particular member is a developmentally regulated, neural-specific gene which plays an unspecified role in early embryogenesis. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeural tube defects

UniProtLymphatic malformation 9

UniProtYellow nail syndrome

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.25

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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