PCDH17

Chr 13

protocadherin 17

Also known as: PCDH68, PCH68

NCBI Gene: 27253ENSG00000118946UniProt: O14917OMIM: 611760

The encoded protein is a calcium-dependent cell-adhesion protein with six extracellular cadherin domains that establishes specific cell-cell connections in the brain. Mutations cause autosomal recessive intellectual disability and neurodevelopmental disorders. This gene shows moderate constraint against loss-of-function variants, suggesting intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.40
Clinical Summary— PCDH17
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.64) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
62 unique Pathogenic / Likely Pathogenic· 158 VUS of 230 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
0.40LOEUF
pLI 0.641
Z-score 4.01
OE 0.20 (0.11–0.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.34Z-score
OE missense 0.86 (0.80–0.92)
591 obs / 690.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.20 (0.11–0.40)
0≤0.351.4
Missense OE0.86 (0.80–0.92)
0≤0.61.4
Synonymous OE1.18
0≤1.21.6
LoF obs/exp: 6 / 29.6Missense obs/exp: 591 / 690.5Syn Z: -2.46
DN
0.6453th %ile
GOF
0.7028th %ile
LOF
0.54top 25%

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

230 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic61
Likely Pathogenic1
VUS158
Likely Benign2
61
Pathogenic
1
Likely Pathogenic
158
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
61
0
61
Likely Pathogenic
0
0
1
0
1
VUS
0
142
16
0
158
Likely Benign
0
0
1
1
2
Benign
0
0
0
0
0
Total0142791222

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

View in ClinVar →

Protein Context — Lollipop Plot

PCDH17 · 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 5 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