POLH

Chr 6p21.1

DNA polymerase eta

Aliases:: XPV, RAD30A, XP-V
MANE:: ENST00000372236.9

OMIM: 603968 ↗NCBI: 5429 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

POLH · Q9Y253

v62025-08-01

Predicted Aligned Error matrix for POLH — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

76.9/ 100

Confident

713 residues

Confidence breakdown

Very high(≥ 90)61%
Confident(70–90)5%
Low(50–70)4%
Very low(< 50)29%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Adult solid tumours cancer susceptibility
BIALLELIC, autosomal or pseudoautosomal
Childhood solid tumours
BIALLELIC, autosomal or pseudoautosomal
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome
BIALLELIC, autosomal or pseudoautosomal
Anophthalmia or microphthalmia
Monogenic hearing loss
Structural eye disease
BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

xeroderma pigmentosum variant type
0.82
Xeroderma pigmentosum variant
0.66
xeroderma pigmentosum
0.51
hereditary disease
0.42
disease of peritoneum
0.16
breast cancer
0.08
hepatocellular carcinoma
0.08
breast carcinoma
0.08
acute myeloid leukemia
0.08
neoplasm
0.04

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

DNA polymerase eta

DNA polymerase specifically involved in the DNA repair by translesion synthesis (TLS) (PubMed:10385124, PubMed:11743006, PubMed:16357261, PubMed:20388628, PubMed:24449906, PubMed:24553286, PubMed:38212351). Due to low processivity on both damaged and normal DNA, cooperates with the heterotetrameric (REV3L, REV7, POLD2 and POLD3) POLZ complex for complete bypass of DNA lesions. Inserts one or 2 nucleotide(s) opposite the lesion, the primer is further extended by the tetrameric POLZ complex. In the case of 1,2-intrastrand d(GpG)-cisplatin cross-link, inserts dCTP opposite the 3' guanine (PubMed:24449906). Particularly important for the repair of UV-induced pyrimidine dimers (PubMed:10385124, PubMed:11743006). Although inserts the correct base, may cause base transitions and transversions depending upon the context. May play a role in hypermutation at immunoglobulin genes (PubMed:11376341, PubMed:14734526). Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have any lyase activity, preventing the release of the 5'-deoxyribose phosphate (5'-dRP) residue. This covalent trapping of the enzyme by the 5'-dRP residue inhibits its DNA synthetic activity during base excision repair, thereby avoiding high incidence of mutagenesis (PubMed:14630940). Targets POLI to replication foci (PubMed:12606586)