PCDHGC4

Chr 5AR

protocadherin gamma subfamily C, 4

This gene encodes a neural protocadherin that functions as a calcium-dependent cell adhesion protein involved in establishing and maintaining specific neuronal connections in the brain. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with poor growth and skeletal anomalies. The gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.31), indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.311 OMIM phenotype
Clinical SummaryPCDHGC4
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.31LOEUF
pLI 0.980
Z-score 4.36
OE 0.14 (0.070.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.97Z-score
OE missense 0.76 (0.700.83)
422 obs / 552.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.14 (0.070.31)
00.351.4
Missense OE0.76 (0.700.83)
00.61.4
Synonymous OE0.82
01.21.6
LoF obs/exp: 4 / 29.6Missense obs/exp: 422 / 552.1Syn Z: 2.15
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongPCDHGC4-related neurodevelopmental disorder with microcephaly and seizuresOTHERAR

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

DN
0.6454th %ile
GOF
0.6443th %ile
LOF
0.57top 25%

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PCDHGC4 · 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