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8 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PCDHGA12
protocadherin gamma subfamily A, 12
Chromosome 5 · 5q31.3
NCBI Gene: 26025Ensembl: ENSG00000253159.3HGNC: HGNC:8699UniProt: O60330
14PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membranecell adhesion molecule bindingcell adhesioncell-cell junctionneurodevelopmental disorder with poor growth and skeletal anomaliesneurodegenerative diseasegenetic disorderatrial flutter
✦AI Summary

PCDHGA12 is a calcium-dependent cell-adhesion molecule belonging to the protocadherin gamma subfamily, predicted to function in establishing and maintaining neuronal connections [UniProt annotation]. The protein localizes to the plasma membrane and mediates cell-cell adhesion through calcium-dependent interactions [GO annotations]. Beyond its neurobiological role, PCDHGA12 has emerged as a significant biomarker in cancer biology. In lung cancer, PCDHGA12 expression is downregulated in both adenocarcinoma and squamous cell carcinoma tissues, with differential prognostic impact: high expression correlates with poor overall survival specifically in squamous cell carcinoma through altered DNA repair and immune infiltration pathways 1. PCDHGA12 was identified as one of 64 genes in a predictive signature for stage I NSCLC patient survival, associated with cancer metastasis processes 2. In breast cancer, PCDHGA12 represents one of ten genes in a cyclophosphamide-response prognostic signature 3. Epigenetically, PCDHGA12 promoter methylation serves as a diagnostic biomarker: methylation is associated with acute lymphoblastic leukemia detection 45, bladder cancer 6, and lung cancer diagnosis via bronchial washings, achieving 74.4% sensitivity and 91.9% specificity when combined with CDO1 methylation 7. These findings suggest PCDHGA12 functions dually as a cell-adhesion regulator in neural development and as an epigenetic biomarker for cancer detection and prognosis.

Sources cited
1
PCDHGA12 is downregulated in lung adenocarcinoma and squamous cell carcinoma; high expression correlates with poor survival in squamous cell carcinoma through altered DNA repair and immune pathways
PMID: 39067405
2
PCDHGA12 is one of 64 genes in a predictive signature for stage I NSCLC survival and is associated with cancer metastasis
PMID: 17194181
3
PCDHGA12 is one of ten genes in a cyclophosphamide-response prognostic signature for breast cancer
PMID: 34704810
4
PCDHGA12 DNA methylation is a biomarker for detecting B-cell acute lymphoblastic leukemia
PMID: 20224725
5
PCDHGA12 methylation is validated as a tumor marker in bladder cancer with significant differential methylation
PMID: 21788354
6
PCDHGA12 methylation in bronchial washing cytology achieves 74.4% sensitivity and 91.9% specificity for lung cancer diagnosis
PMID: 38225788
7
PCDHGA12 methylation is identified in acute lymphoblastic leukemia; methylation silences expression which can be reversed pharmacologically
PMID: 17363581
Disease Associationsⓘ20
neurodevelopmental disorder with poor growth and skeletal anomaliesOpen Targets
0.52Moderate
neurodegenerative diseaseOpen Targets
0.32Weak
genetic disorderOpen Targets
0.19Weak
atrial flutterOpen Targets
0.05Suggestive
age-related macular degenerationOpen Targets
0.05Suggestive
lung cancerOpen Targets
0.04Suggestive
colorectal adenocarcinomaOpen Targets
0.04Suggestive
psoriasisOpen Targets
0.04Suggestive
atrial fibrillationOpen Targets
0.03Suggestive
laryngotracheoesophageal cleftOpen Targets
0.02Suggestive
lung adenocarcinomaOpen Targets
0.02Suggestive
macular degenerationOpen Targets
0.01Suggestive
Ehlers-Danlos syndrome, musculocontractural typeOpen Targets
0.01Suggestive
cardiovascular diseaseOpen Targets
0.01Suggestive
infectionOpen Targets
0.01Suggestive
papillary thyroid carcinomaOpen Targets
0.01Suggestive
squamous cell carcinomaOpen Targets
0.01Suggestive
small cell lung carcinomaOpen Targets
0.00Suggestive
rheumatoid arthritisOpen Targets
0.00Suggestive
neoplasmOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PCDH10Shared pathway100%PCDHA1Shared pathway100%PCDHA2Shared pathway100%PCDHA3Shared pathway100%PCDHA4Shared pathway100%PCDHA5Shared pathway100%
Tissue Expression6 tissues
Brain
100%
Heart
84%
Lung
56%
Ovary
49%
Liver
16%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
PCDHGA12PCDH10PCDHA1PCDHA2PCDHA3PCDHA4PCDHA5
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt O60330
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.88LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.68 [0.53–0.88]
RankingsWhere PCDHGA12 stands among ~20K protein-coding genes
  • #15,951of 20,598
    Most Researched14
  • #7,781of 17,882
    Most Constrained (LOEUF)0.88
Genes detectedPCDHGA12
Sources retrieved8 papers
Response time—
📄 Sources
8▼
1
Differential prognostic impact and potential molecular mechanisms of PCDHGA12 expression in lung adenocarcinoma and squamous cell carcinoma.
PMID: 39067405
Int Immunopharmacol · 2024
1.00
2
Identification and Prognostic Value Exploration of Cyclophosphamide (Cytoxan)-Centered Chemotherapy Response-Associated Genes in Breast Cancer.
PMID: 34704810
DNA Cell Biol · 2021
0.88
3
A gene expression signature predicts survival of patients with stage I non-small cell lung cancer.
PMID: 17194181
PLoS Med · 2006
0.75
4
Molecular detection of B-cell neoplasms by specific DNA methylation biomarkers.
PMID: 20224725
Int J Clin Exp Pathol · 2010
0.63
5
Comprehensive genome methylation analysis in bladder cancer: identification and validation of novel methylated genes and application of these as urinary tumor markers.
PMID: 21788354
Clin Cancer Res · 2011
0.50