POLA1

Chr X

DNA polymerase alpha 1, catalytic subunit

Also known as: NSX, PDR, POLA, VEODS, p180

NCBI Gene: 5422 ENSG00000101868 UniProt: P09884

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the catalytic subunit of DNA polymerase, which together with a regulatory and two primase subunits, forms the DNA polymerase alpha complex. The catalytic subunit plays an essential role in the initiation of DNA replication. [provided by RefSeq, Mar 2010]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPigmentary disorder, reticulate, with systemic manifestations, X-linked

UniProtVan Esch-O'Driscoll syndrome

Clinical highlights

Gene-disease validity (ClinGen)

X-linked reticulate pigmentary disorder · XLModerateconsider for supplementary testing

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.05

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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