PCDH11Y

Chr Y

protocadherin 11 Y-linked

Also known as: PCDH-PC, PCDH22, PCDHX, PCDHY

NCBI Gene: 83259 ENSG00000099715 UniProt: Q9BZA8 OMIM: 400022

The protein is a calcium-dependent cell-adhesion molecule with seven cadherin repeats that mediates cell-cell recognition during central nervous system development. This Y-linked gene follows patrilineal inheritance and has extremely low constraint against loss-of-function variants (pLI near zero), suggesting mutations may be well-tolerated. Clinical significance of PCDH11Y variants in pediatric neurological disorders remains unclear.

OMIM ResearchSummary from RefSeq, UniProt

This gene belongs to the protocadherin family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing seven cadherin repeats, a transmembrane domain, and a cytoplasmic tail that differs from those of the classical cadherins. This gene is located on the Y chromosome in a block of X/Y homology and is very closely related to its paralog on the X chromosome. The protein is thought to play a role in cell-cell recognition during development of the central nervous system. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.66

Clinical Summary— PCDH11Y

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

13 total variants — no pathogenic classifications of 13 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.66LOEUF

pLI 0.000

Z-score 0.29

OE 0.88 (0.48–1.66)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.14Z-score

OE missense 1.03 (0.91–1.17)

175 obs / 169.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.88 (0.48–1.66)

0≤0.351.4

Missense OE?1.03 (0.91–1.17)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 6 / 6.8Missense obs/exp: 175 / 169.9Syn Z: 0.88

This gene — mechanism propensity

0.75top 25%

GOF

0.76top 25%

LOF

0.3648th %ile

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

GOFprediction above median

DNprediction 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.

ClinVar Variant Classifications

13 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Benign1

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	—	—	—	—	0
Likely Pathogenic	—	—	—	—	0
VUS	—	—	—	—	0
Likely Benign	—	—	—	—	1
Benign	—	—	—	—	0
Total	—				1

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

58 pathogenic / likely-pathogenic (of 72) ClinVar copy-number / structural variants overlap PCDH11Y — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →