This gene encodes protocadherin-9, a calcium-dependent cell adhesion protein that mediates cell adhesion in neural tissues and may function in signaling at neuronal synaptic junctions. Mutations cause neurodevelopmental disorders with intellectual disability, and the gene shows autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants, reflecting its critical role in nervous system development and function.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOEUF 0.37
Clinical SummaryPCDH9
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.81) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
63 unique Pathogenic / Likely Pathogenic· 150 VUS of 243 total submissions
📖
GeneReview available — PCDH9
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.37LOEUF
pLI 0.809
Z-score 4.25
OE 0.19 (0.100.37)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.33Z-score
OE missense 0.75 (0.690.80)
495 obs / 663.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.19 (0.100.37)
00.351.4
Missense OE0.75 (0.690.80)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 6 / 31.9Missense obs/exp: 495 / 663.9Syn Z: -0.34

ClinVar Variant Classifications

243 submitted variants in ClinVar

Classification Summary

Pathogenic63
VUS150
Likely Benign13
Benign7
Conflicting1
63
Pathogenic
150
VUS
13
Likely Benign
7
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
63
0
63
Likely Pathogenic
0
0
0
0
0
VUS
0
127
23
0
150
Likely Benign
0
5
5
3
13
Benign
0
0
5
2
7
Conflicting
1
Total0132965234

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

View in ClinVar →

Protein Context — Lollipop Plot

PCDH9 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →