PARD6G

Chr 18

par-6 family cell polarity regulator gamma

Also known as: PAR-6G, PAR6gamma

NCBI Gene: 84552ENSG00000178184UniProt: Q9BYG4

The protein encoded by this gene is an adapter protein involved in asymmetrical cell division and cell polarization processes, and may play a role in epithelial tight junction formation. Mutations cause autosomal recessive lissencephaly with cerebellar hypoplasia, a severe brain malformation presenting in early infancy with developmental delays, seizures, and distinctive neuroimaging findings. The gene shows relatively low constraint to loss-of-function variation.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
6
Pubs (1 yr)
166
P/LP submissions
0%
P/LP missense
0.88
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— PARD6G
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
163 unique Pathogenic / Likely Pathogenic· 71 VUS of 243 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.88LOEUF
pLI 0.095
Z-score 1.82
OE 0.34 (0.15–0.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.84Z-score
OE missense 0.67 (0.58–0.76)
161 obs / 241.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.34 (0.15–0.88)
0≤0.351.4
Missense OE0.67 (0.58–0.76)
0≤0.61.4
Synonymous OE0.86
0≤1.21.6
LoF obs/exp: 3 / 8.9Missense obs/exp: 161 / 241.7Syn Z: 1.19
DN
0.7326th %ile
GOF
0.6932th %ile
LOF
0.4431th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

243 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic156
Likely Pathogenic7
VUS71
Likely Benign3
156
Pathogenic
7
Likely Pathogenic
71
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
156
0
156
Likely Pathogenic
0
0
7
0
7
VUS
0
57
14
0
71
Likely Benign
0
0
3
0
3
Benign
0
0
0
0
0
Total0571800237

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

View in ClinVar →

Protein Context — Lollipop Plot

PARD6G · protein map & ClinVar variants

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

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