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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PCDH18
protocadherin 18
Chromosome 4 · 4q28.3
NCBI Gene: 54510Ensembl: ENSG00000189184.12HGNC: HGNC:14268UniProt: Q9HCL0
25PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingbrain developmentplasma membranecell adhesion molecule bindinghypertensionessential hypertensioncardiovascular diseaseIncreased blood pressure
✦AI Summary

PCDH18 (protocadherin 18) is a non-clustered protocadherin that functions as a calcium-dependent cell adhesion molecule with critical roles in brain development and potential tumor suppression. As a member of the δ2 subgroup of non-clustered protocadherins, PCDH18 is predominantly expressed in the nervous system and exhibits region-specific expression patterns in cortical areas during early postnatal development and in mature brain structures including caudate putamen and hippocampal formation 1. The protein demonstrates homophilic/heterophilic cell-cell adhesion properties and interacts with mDab1 for intracellular signaling 1. PCDH18 plays important roles in neuronal circuit formation and maintenance, with haploinsufficiency potentially contributing to intellectual disability, as demonstrated in a patient with severe developmental delay, seizures, and brain malformations carrying a deletion encompassing only PCDH18 2. The gene is upregulated during early brain development (10-12 weeks gestation) alongside genes involved in sensory organ development 3. Beyond its neurological functions, PCDH18 acts as a tumor suppressor in colorectal cancer, where it is frequently silenced by promoter hypermethylation 4. Overexpression of PCDH18 suppresses cancer cell viability, colony formation, and migration, while its depletion promotes oncogenic behaviors through β-catenin pathway activation 4. PCDH18 deletions are also observed in aggressive pituitary adenomas and metastatic colorectal cancers 56.

Sources cited
1
PCDH18 belongs to δ2 subgroup of non-clustered protocadherins, shows nervous system expression patterns, and interacts with mDab1
PMID: 21173574
2
PCDH18 haploinsufficiency is associated with intellectual disability, seizures, and brain malformations
PMID: 22450339
3
PCDH18 is upregulated during early brain development (10-12 weeks gestation) alongside sensory organ genes
PMID: 24436137
4
PCDH18 functions as tumor suppressor in colorectal cancer, frequently silenced by methylation, and suppresses cancer cell behaviors
PMID: 28588296
5
PCDH18 deletions are associated with fast-growing pituitary adenomas
PMID: 29259037
6
PCDH18 deletions occur in metastatic colorectal cancer patients with chromothripsis
PMID: 31868331
Disease Associationsⓘ20
hypertensionOpen Targets
0.54Moderate
essential hypertensionOpen Targets
0.49Moderate
cardiovascular diseaseOpen Targets
0.42Moderate
Increased blood pressureOpen Targets
0.40Moderate
biliary tract diseaseOpen Targets
0.34Weak
response to xenobiotic stimulusOpen Targets
0.34Weak
atrial fibrillationOpen Targets
0.32Weak
smoking initiationOpen Targets
0.31Weak
bipolar disorderOpen Targets
0.30Weak
placenta praeviaOpen Targets
0.30Weak
tooth diseaseOpen Targets
0.30Weak
pituitary gland diseaseOpen Targets
0.30Weak
Abnormality of refractionOpen Targets
0.29Weak
nephritisOpen Targets
0.28Weak
bacterial pneumoniaOpen Targets
0.23Weak
cataractOpen Targets
0.22Weak
liver diseaseOpen Targets
0.21Weak
cervical carcinomaOpen Targets
0.21Weak
glomerulonephritisOpen Targets
0.21Weak
Abnormal nasolacrimal system morphologyOpen Targets
0.20Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DIPK2AProtein interaction76%CDHR4Shared pathway67%PCDH11YShared pathway67%PCDH20Shared pathway67%PCDH19Shared pathway67%PCDH11XShared pathway67%
Tissue Expression6 tissues
Ovary
100%
Heart
83%
Lung
38%
Brain
28%
Liver
18%
Bone Marrow
6%
Gene Interaction Network
Click a node to explore
PCDH18DIPK2ACDHR4PCDH11YPCDH20PCDH19PCDH11X
PROTEIN STRUCTURE
Preparing viewer…
PDB6VFR · 2.79 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.67LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.51 [0.39–0.67]
RankingsWhere PCDH18 stands among ~20K protein-coding genes
  • #13,035of 20,598
    Most Researched25
  • #4,979of 17,882
    Most Constrained (LOEUF)0.67
Genes detectedPCDH18
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Non-clustered protocadherin.
PMID: 21173574
Cell Adh Migr · 2011
1.00
2
Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors.
PMID: 35685361
Comput Struct Biotechnol J · 2022
0.90
3
A single gene deletion on 4q28.3: PCDH18--a new candidate gene for intellectual disability?
PMID: 22450339
Eur J Med Genet · 2012
0.80
4
PCDH18 is frequently inactivated by promoter methylation in colorectal cancer.
PMID: 28588296
Sci Rep · 2017
0.70
5
Differential changes in gene expression in human brain during late first trimester and early second trimester of pregnancy.
PMID: 24436137
Prenat Diagn · 2014
0.60