POLH

Chr 6AR

DNA polymerase eta

Also known as: RAD30, RAD30A, XP-V, XPV

NCBI Gene: 5429 ENSG00000170734 UniProt: Q9Y253 OMIM: 603968

This gene encodes DNA polymerase eta, which performs translesion synthesis to repair UV-damaged DNA by accurately replicating across pyrimidine dimers and other DNA lesions. Mutations cause xeroderma pigmentosum variant type, an autosomal recessive disorder characterized by extreme sun sensitivity and increased cancer risk due to defective DNA repair. The gene is highly constrained against loss-of-function variants (pLI near zero), indicating that complete loss of function is likely incompatible with normal development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the Y family of specialized DNA polymerases. It copies undamaged DNA with a lower fidelity than other DNA-directed polymerases. However, it accurately replicates UV-damaged DNA; when thymine dimers are present, this polymerase inserts the complementary nucleotides in the newly synthesized DNA, thereby bypassing the lesion and suppressing the mutagenic effect of UV-induced DNA damage. This polymerase is thought to be involved in hypermutation during immunoglobulin class switch recombination. Mutations in this gene result in XPV, a variant type of xeroderma pigmentosum. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Xeroderma pigmentosum, variant typeMIM #278750

Clinical highlights

Gene-disease validity (ClinGen)

xeroderma pigmentosum variant type · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.84

LOEUF

LOF

Mechanism· G2P

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GeneReview available — POLH