PCDHG@

Summary

PCDHG@ (protocadherin gamma cluster, HGNC:8695) is a protein-coding gene on chromosome 5q31.

The protocadherin gamma gene cluster is one of three related clusters tandemly linked on chromosome five. The clusters have an immunoglobulin-like organization, suggesting that a novel mechanism may be involved in their regulation and expression. The gamma cluster includes 22 genes divided into 3 subfamilies, all part of the cadherin superfamily. Subfamily A contains 12 genes, subfamily B contains 7 genes and 2 pseudogenes, and the more distantly related subfamily C contains 3 genes. In addition, ORNT2 and TAF2F are included in the cluster due to their localization between protocadherin clusters beta and gamma on chromosome five. The protocadherin genes are organized in a tandem array of 22 large, variable region exons followed by a constant region, which contains 3 exons shared by all protocadherin 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 gamma cluster genes.

Source: NCBI Gene 56115 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 2,768 total — 3 pathogenic, 3 likely-pathogenic

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8695
Approved symbol	PCDHG@
Name	protocadherin gamma cluster
Location	5q31
Locus type	gene with protein product
Status	Approved
Aliases	PCDH2, PCDH4
OMIM	604968
Entrez	56115

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 1)

• PCDHs are candidate tumor suppressors that modulate regulatory pathways critical in development and disease, such as canonical Wnt signaling (PMID:19956686)

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: 0 (showing top):

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

2768 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	2580
Likely benign	164
Benign	13

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1687019	NM_018928.3(PCDHGC4):c.118C>T (p.Gln40Ter)	Pathogenic
1687021	NM_018928.3(PCDHGC4):c.324del (p.Phe108fs)	Pathogenic
1687022	NM_018928.3(PCDHGC4):c.1243C>T (p.Arg415Ter)	Pathogenic
1693119	NM_018928.3(PCDHGC4):c.2139dup (p.Lys714Ter)	Likely pathogenic
1802232	NM_018928.3(PCDHGC4):c.683_762del (p.Leu228fs)	Likely pathogenic
3255523	NM_018928.3(PCDHGC4):c.194_195del (p.Gln65fs)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

Disease associations

OMIM: gene MIM:604968 | disease phenotypes: MIM:619880

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder with poor growth and skeletal anomalies (MONDO:0859252)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006218_17	Erosive tooth wear (severe vs non-severe)	2.000000e-08

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.