PCDH12

Chr 5AR

protocadherin 12

Also known as: DMJDS1, VE-cadherin-2, VECAD2

NCBI Gene: 51294 ENSG00000113555 UniProt: Q9NPG4 OMIM: 605622

PCDH12 encodes protocadherin-12, a cellular adhesion molecule that regulates cell-cell interactions and cell migration through calcium-dependent homotypic aggregation at intercellular junctions. Biallelic mutations cause diencephalic-mesencephalic junction dysplasia syndrome 1, an autosomal recessive disorder affecting brainstem development. The gene shows no significant constraint against loss-of-function variants (pLI near zero, LOEUF 0.98), consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 6 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene localizes to the region on chromosome 5 where the protocadherin gene clusters reside. The exon organization of this transcript is similar to that of the gene cluster transcripts, notably the first large exon, but no significant sequence homology exists. The function of this cellular adhesion protein is undetermined but mouse protocadherin 12 does not bind catenins and appears to have no affect on cell migration or growth. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Diencephalic-mesencephalic junction dysplasia syndrome 1MIM #251280

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.98

LOEUF

LOF

Mechanism· G2P