PCDH11X

Chr X

protocadherin 11 X-linked

Also known as: PCDH-X, PCDH-Y, PCDH11, PCDH11Y, PCDH22, PCDHX, PPP1R119

NCBI Gene: 27328ENSG00000102290UniProt: Q9BZA7

The encoded protein is a calcium-dependent cell-adhesion protein with an extracellular domain containing 7 cadherin repeats that functions in cell-cell recognition essential for segmental development and function of the central nervous system. Mutations cause developmental dyslexia affecting language and reading abilities. This X-linked gene follows X-linked inheritance patterns and is not highly constrained against loss-of-function variants.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
3
P/LP submissions
0%
P/LP missense
0.56
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— PCDH11X
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
3 unique Pathogenic / Likely Pathogenic· 26 VUS of 100 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.56LOEUF
pLI 0.016
Z-score 3.25
OE 0.31 (0.18–0.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.30Z-score
OE missense 0.71 (0.65–0.78)
356 obs / 500.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.31 (0.18–0.56)
0≤0.351.4
Missense OE0.71 (0.65–0.78)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 8 / 25.8Missense obs/exp: 356 / 500.7Syn Z: -0.88
DN
0.79top 25%
GOF
0.82top 10%
LOF
0.2774th %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

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
VUS26
Likely Benign1
3
Pathogenic
26
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
3
0
3
Likely Pathogenic
0
0
0
0
0
VUS
0
24
2
0
26
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total0255030

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PCDH11X · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients