PCDH12

Chr 5AR

protocadherin 12

Also known as: DMJDS1, VE-cadherin-2, VECAD2

PCDH12 encodes protocadherin-12, a cellular adhesion molecule that regulates cell-cell interactions and cell migration through calcium-dependent homotypic aggregation at intercellular junctions. Biallelic mutations cause diencephalic-mesencephalic junction dysplasia syndrome 1, an autosomal recessive disorder affecting brainstem development. The gene shows no significant constraint against loss-of-function variants (pLI near zero, LOEUF 0.98), consistent with the recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.981 OMIM phenotype
Clinical SummaryPCDH12
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.000
Z-score 1.65
OE 0.70 (0.510.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.78Z-score
OE missense 0.92 (0.860.98)
622 obs / 679.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.70 (0.510.98)
00.351.4
Missense OE0.92 (0.860.98)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 25 / 35.6Missense obs/exp: 622 / 679.5Syn Z: 1.02
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePCDH12-related diencephalic-mesencephalic junction dysplasia syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.77top 25%
GOF
0.81top 10%
LOF
0.3067th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PCDH12 · 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.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC