CDH8

Chr 16

cadherin 8

Also known as: Nbla04261

NCBI Gene: 1006 ENSG00000150394 UniProt: P55286 OMIM: 603008

This protein is a type II cadherin that mediates calcium-dependent cell-cell adhesion in the brain and is involved in synaptic adhesion, axon outgrowth and guidance. Mutations cause autosomal dominant neurodevelopmental disorders including developmental and epileptic encephalopathy and autism spectrum disorder. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.30), indicating that even single functional copies may be insufficient for normal brain development.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a type II classical cadherin from the cadherin superfamily, integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. The extracellular domain consists of 5 subdomains, each containing a cadherin motif, and appears to determine the specificity of the protein's homophilic cell adhesion activity. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. This particular cadherin is expressed in brain and is putatively involved in synaptic adhesion, axon outgrowth and guidance. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

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.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.29

LOEUF· LoF intol.

Multiple*

Mechanism· predicted