POLA1
Chr XXLRDNA polymerase alpha 1, catalytic subunit
Also known as: NSX, PDR, POLA, VEODS, p180
The POLA1 gene encodes the catalytic subunit of DNA polymerase alpha, which initiates DNA synthesis during replication by extending short RNA primers before transfer to other polymerases for processive synthesis. Mutations cause X-linked recessive Van Esch-O'Driscoll syndrome and pigmentary disorder with systemic manifestations, affecting multiple organ systems including skin pigmentation. This gene is extremely intolerant to loss-of-function variants (pLI ~1.0, LOEUF 0.051), indicating that functional copies are critical for normal cellular function.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
POLA1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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