PCDHGB5

Chr 5

protocadherin gamma subfamily B, 5

Also known as: PCDH-GAMMA-B5

NCBI Gene: 56101 ENSG00000276547 UniProt: Q9Y5G0

This gene is a member of the protocadherin gamma gene cluster, one of three related clusters tandemly linked on chromosome five. These gene clusters have an immunoglobulin-like organization, suggesting that a novel mechanism may be involved in their regulation and expression. The gamma gene cluster includes 22 genes divided into 3 subfamilies. Subfamily A contains 12 genes, subfamily B contains 7 genes and 2 pseudogenes, and the more distantly related subfamily C contains 3 genes. The tandem array of 22 large, variable region exons are followed by a constant region, containing 3 exons shared by all genes in the cluster. Each variable region exon encodes the extracellular region, which includes 6 cadherin ectodomains and a transmembrane region. The constant region exons encode the common cytoplasmic region. These neural cadherin-like cell 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. [provided by RefSeq, Jul 2008]

Active trials

Pathogenic / LP

998

ClinVar variants

Pubs (1 yr)

—

Missense Z

—

LOEUF

Clinical Summary— PCDHGB5

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ClinVar Variants

3 Pathogenic / Likely Pathogenic· 911 VUS of 998 total submissions

Some data sources returned errors (1)

gnomad: Error: Gene not found

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

DNGOF

Badonyi & Marsh 2024 ↗

0.84top 10%

GOF

0.78top 25%

LOF

0.2871th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.