PARD6A
Chr 16par-6 family cell polarity regulator alpha
Also known as: PAR-6A, PAR6, PAR6C, PAR6alpha, TAX40, TIP-40
The protein functions as an adapter protein that controls asymmetrical cell division, cell polarization, and centrosome organization by linking GTP-bound Rho small GTPases to atypical protein kinase C proteins and recruiting key centrosomal proteins that regulate microtubule organization. Mutations in PARD6A cause disease through a gain-of-function mechanism, though specific associated neurological conditions are not established in the provided data. The gene shows tolerance to loss-of-function variants (pLI 0.006, LOEUF 1.016), consistent with the gain-of-function disease mechanism.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
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.
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
83 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 25 | 0 | 25 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 37 | 7 | 0 | 44 |
Likely Benign | 0 | 1 | 0 | 2 | 3 |
Benign | 0 | 1 | 0 | 1 | 2 |
| Total | 0 | 39 | 35 | 3 | 77 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PARD6A · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools