PCDHA@

Summary

PCDHA@ (protocadherin alpha cluster, complex locus, HGNC:8662) is a protein-coding gene on chromosome 5q31.

The protocadherin alpha gene cluster is one of three related clusters tandemly linked on chromosome five. The clusters have a genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 genes and 1 pseudogene, which are members of the cadherin superfamily and related to the mouse CNR genes. The sequence of the 13 upstream genes and the pseudogene are highly similar to one another, while a subfamily (C) contains two more distantly related coding sequences. The alpha cluster genes are organized in a tandem array of 15 large, variable region exons followed by a constant region, which contains 3 exons shared by all genes in the cluster. Each variable region exon encodes an extracellular domain comprised of 6 cadherin ectodomains and a transmembrane region. The constant region exons encode a common cytoplasmic tail. These neural adhesion proteins most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been described for the alpha cluster genes.

Source: NCBI Gene 56117 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 20 total

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8662
Approved symbol	PCDHA@
Name	protocadherin alpha cluster, complex locus
Location	5q31
Locus type	gene with protein product
Status	Approved
Aliases	CNR1
OMIM	604966
Entrez	56117

Gene structure

Transcript identifiers

Ensembl transcripts: 0

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

None — 0 exons

Expression profiles

Top tissues by expression

0 total, by Bgee expression score (0-100, higher = more expressed):

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• PCDHs are candidate tumor suppressors that modulate regulatory pathways critical in development and disease, such as canonical Wnt signaling (PMID:19956686)
• Results provide evidence of PCDHA as a potential candidate gene for autism (PMID:23031252)
• Association between Genetic Variants in DUSP15, CNTNAP2, and PCDHA Genes and Risk of Childhood Autism Spectrum Disorder. (PMID:34257739)
• Decreased Levels of DNA Methylation in the PCDHA Gene Cluster as a Risk Factor for Early-Onset High Myopia in Young Children. (PMID:36036911)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Canonical reviewed UniProt: None (reviewed: )

All UniProt accessions (0):

RefSeq proteins (0): (*=MANE)

Domains & families (InterPro)

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 275 (showing top): chr6q15, TGGTGCT_MIR29A_MIR29B_MIR29C, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, RRAGTTGT_UNKNOWN, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_NEURON_RECOGNITION, MODULE_64, GOBP_NEUROGENESIS, HASLINGER_B_CLL_WITH_11Q23_DELETION, GOBP_CELL_CELL_SIGNALING, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, MODULE_205, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOCC_MITOCHONDRIAL_ENVELOPE

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

20 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

Disease associations

OMIM: gene MIM:604966 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.