POLH

Summary

POLH (DNA polymerase eta, HGNC:9181) is a protein-coding gene on chromosome 6p21.1, encoding DNA polymerase eta (Q9Y253). DNA polymerase specifically involved in the DNA repair by translesion synthesis (TLS).

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.

Source: NCBI Gene 5429 — RefSeq curated summary.

At a glance

• Gene–disease (curated): xeroderma pigmentosum variant type (Definitive, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 648 total — 48 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 22
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_006502

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9181
Approved symbol	POLH
Name	DNA polymerase eta
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	XPV, RAD30A, XP-V
Ensembl gene	ENSG00000170734
Ensembl biotype	protein_coding
OMIM	603968
Entrez	5429

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000372226, ENST00000372236, ENST00000443535, ENST00000901658, ENST00000921322, ENST00000953718

RefSeq mRNA: 3 — MANE Select: NM_006502 NM_001291969, NM_001291970, NM_006502

CCDS: CCDS4902, CCDS78147

Canonical transcript exons

ENST00000372236 — 11 exons

Exon	Start	End
ENSE00000481500	43597696	43597865
ENSE00000752927	43587272	43587489
ENSE00001172191	43610554	43610723
ENSE00001172195	43605254	43605319
ENSE00001172201	43604615	43604738
ENSE00001172207	43603892	43604011
ENSE00001172213	43600988	43601091
ENSE00001457304	43582316	43582456
ENSE00001717994	43576185	43576440
ENSE00001861041	43613660	43620523
ENSE00003481299	43583007	43583141

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 96.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.9051 / max 110.7990, expressed in 1755 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67915	8.2606	1748
67916	0.6445	398

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.30	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.60	gold quality
stromal cell of endometrium	CL:0002255	87.14	gold quality
trabecular bone tissue	UBERON:0002483	86.63	gold quality
lower lobe of lung	UBERON:0008949	86.58	gold quality
colonic epithelium	UBERON:0000397	84.80	gold quality
nipple	UBERON:0002030	84.54	gold quality
tonsil	UBERON:0002372	84.19	gold quality
cauda epididymis	UBERON:0004360	83.44	gold quality
ventricular zone	UBERON:0003053	83.43	gold quality
oral cavity	UBERON:0000167	83.24	gold quality
vena cava	UBERON:0004087	83.20	gold quality
mucosa of paranasal sinus	UBERON:0005030	83.14	gold quality
caput epididymis	UBERON:0004358	82.33	gold quality
corpus epididymis	UBERON:0004359	82.21	gold quality
gingiva	UBERON:0001828	82.09	gold quality
adrenal tissue	UBERON:0018303	81.96	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	81.75	gold quality
gingival epithelium	UBERON:0001949	81.70	gold quality
mammalian vulva	UBERON:0000997	81.39	gold quality
sperm	CL:0000019	81.38	gold quality
superior surface of tongue	UBERON:0007371	81.30	gold quality
cardia of stomach	UBERON:0001162	81.23	gold quality
pylorus	UBERON:0001166	80.59	gold quality
body of tongue	UBERON:0011876	80.46	gold quality
pharyngeal mucosa	UBERON:0000355	80.39	gold quality
ganglionic eminence	UBERON:0004023	80.33	gold quality
cerebellar vermis	UBERON:0004720	80.08	gold quality
pericardium	UBERON:0002407	80.00	gold quality
lymph node	UBERON:0000029	79.76	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6911	yes	194.43
E-ANND-3	no	4.49
E-MTAB-6678	no	3.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

217 targeting POLH, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• DNA polymerase fidelity and specificity (PMID:11554790)
• These results show that XPV cells develop DNA DSBs during the course of UV-induced replication arrest (PMID:11756691)
• Preferential misincorporation of purine nucleotides by human DNA polymerase eta opposite benzo[a]pyrene 7,8-diol 9,10-epoxide deoxyguanosine adducts (PMID:11821420)
• Translesion synthesis by human DNA polymerase eta across thymine glycol lesions. (PMID:11994004)
• Mutational analysis of nonproductive rearrangements from a patient with xeroderma pigmentosum variant finds that the contribution of defective pol eta to overall somatic hypermutation is not essential. (PMID:12244178)
• DNA polymerase eta targets DNA polymerase iota to the replication machinery. (PMID:12426396)
• DNA polymerase eta is involved in transcription-coupled nucleotide excision repair (PMID:12509472)
• DNA polymerase eta has a role in error-prone DNA synthesis in human cells (PMID:12584190)
• demonstration that an amino acid substitution within the active site enhances the fidelity of DNA synthesis by human DNA polymerase eta supports the hypothesis that even error-prone DNA polymerases function in base selection (PMID:12644469)
• results clearly show the protective role of DNA polymerase eta against UV-induced lesions and the activation by UV of DNA polymerase eta-independent mutagenic processes (PMID:12644471)
• study of efficiency and specificity of apurinic/apyrimidinic site bypass by human DNA polymerase eta (PMID:14523013)
• mechanistic basis of the low level of fidelity of human Poleta (PMID:14585988)
• by analyzing switched memory B cells from two xeroderma pigmentosum variant patients, pol eta is an A/T mutator during class switch recombination (PMID:14734526)
• Pol eta bypasses a dimer with low fidelity and with higher error rates at the 3’ thymine than at the 5’ thymine (PMID:14999287)
• C is preferentially mutated in vivo and pol eta generates hypermutation in the mu and gamma switch regions. (PMID:15051760)
• Data suggest that the properties of DNA polymerases eta and kappa are consistent with the mutagenic events attributed to estrogen-derived DNA adducts. (PMID:15147214)
• Monoubiquitinated PCNA but not unmodified PCNA specifically interacts with poleta, and we have identified two motifs in poleta that are involved in this interaction. (PMID:15149598)
• REV1 interacts with pol eta in translesion synthesis of damaged DNA (PMID:15380106)
• Catalyses translesion synthesis past cis-syn cyclobutane thymine dimers. (PMID:15569147)
• High mobility of flap endonuclease 1 and DNA polymerase eta associated with replication foci in S-phase nucleus. (PMID:15758026)
• Data suggest that DNA polymerase eta may be required for the efficient bypass of some bulky pol delta-blocking N2-guanine adducts in human cells. (PMID:16061253)
• incorporates dATP opposite the 5’ T of the cyclobutane pyrimidine dimers via Watson-Crick base pairing and not by Hoogsteen base pairing (PMID:16116089)
• identification of two previously unknown ubiquitin-binding domains in the Y-family translesion synthesis polymerases that enable them to interact with monoubiquitinated targets and undergo monoubiquitination in vivo (PMID:16357261)
• PolH has a novel role in the DNA damage checkpoint, and a p53 target can modulate the DNA damage response and subsequently regulate p53 activation. (PMID:16449651)
• Data show that ultraviolet (UV) radiation-induced ATR signaling is compromised in XPA-deficient human cells during S phase, and this signaling involves UV bypass polymerase eta. (PMID:16675950)
• DNA polymerases iota and eta interact noncovalently with free polyUb chains, as well as mono-ubiquitinated proliferating cell nuclear antigen (Ub-PCNA). (PMID:16763556)
• Neither mutations nor polymorphisms in the coding regions of POLH are required for the generation of human skin squamous cell carcinoma. (PMID:16823845)
• Differences in gene expression, rather than sequence changes may be the main mechanism by which POLH status varies between normal and skin tumours in the population under investigation. (PMID:17334634)
• The immunoprecipitation analysis of the POLH protein revealed a very useful method for screening the patients suspected of xeroderma pigmentosum variant type. Seven mutations in the POLH gene including three novel mutations were identified. (PMID:17344931)
• Results are consistent with a model in which nucleotide excision repair and polymerase eta are are involved in processing crosslinks and avoiding gamma-H2AX associated with double-strand breaks and single-stranded DNA in human cells. (PMID:18068156)
• findings suggest that Poleta may be involved in induction of various types of mutations through the erroneous and efficient incorporation of oxidized dNTPs into DNA in human cells (PMID:18242151)
• PCNA ubiquitylation at K164 of PCNA is not required in vitro for DNA polymerase eta to gain access to replication complexes at forks stalled by T (wedge)T and to catalyze translesion synthesis across this dimer (PMID:18321066)
• There is a wide spectrum of mutations in the POLH gene among xeroderma pigmentosum-variant patients in different countries, suggesting that many of these mutations arose independently. (PMID:18368133)
• Data show that showed that pol kappaDeltaC was more efficient than pol eta by incorporating dCMP opposite both 6alpha- and 6beta-isomeric dG-N(2)-6-E(2) adducts. (PMID:18512958)
• These results highlight the critical role of poleta in error-free translesion DNA synthesis across thymine-thymine cyclobutane pyrimidine dimer in human cells. (PMID:18634905)
• Four types of possible founder mutations of POLH are responsible for 87% of Japanese patients with Xeroderma pigmentosum variant type. (PMID:18703314)
• Data suggest that DNA polymerases eta and iota transiently probe DNA/chromatin; when DNA is exposed at replication forks, the polymerase residence times increase, and this is further facilitated by the ubiquitination of PCNA. (PMID:18799611)
• phosphorylation of pol eta increased after UV irradiation, and treatment with caffeine, siRNA against ATR, or an inhibitor of PKC, reduced the accumulation of pol eta at stalled replication forks after UV irradiation (PMID:18946034)
• The binding to PCNA via its PIP domain is a prerequisite for Poleta’s ability to function in translesion synthesis in human cells. (PMID:19001268)
• Hydroquinone could induce the expression of XPV in a dose- and time-dependent manner in L-02 hepatic cells. (PMID:19069642)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	polh	ENSDARG00000070231
mus_musculus	Polh	ENSMUSG00000023953
rattus_norvegicus	Polh	ENSRNOG00000019195
drosophila_melanogaster	PolH	FBGN0037141
caenorhabditis_elegans		WBGENE00018721

Paralogs (5): POLI (ENSG00000101751), POLK (ENSG00000122008), REV1 (ENSG00000135945), ESCO1 (ENSG00000141446), ESCO2 (ENSG00000171320)

Protein

Protein identifiers

DNA polymerase eta — Q9Y253 (reviewed: Q9Y253)

Alternative names: RAD30 homolog A, Xeroderma pigmentosum variant type protein

All UniProt accessions (2): Q9Y253, Q5JTF2

UniProt curated annotations — full annotation on UniProt →

Function. DNA polymerase specifically involved in the DNA repair by translesion synthesis (TLS). 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. Particularly important for the repair of UV-induced pyrimidine dimers. Although inserts the correct base, may cause base transitions and transversions depending upon the context. May play a role in hypermutation at immunoglobulin genes. 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. Targets POLI to replication foci.

Subunit / interactions. Interacts with REV1 (via C-terminal domain). Interacts with monoubiquitinated PCNA, but not unmodified PCNA. Interacts with POLI; this interaction targets POLI to the replication machinery. Interacts with PALB2 and BRCA2; the interactions are direct and are required to sustain the recruitment of POLH at blocked replication forks and to stimulate POLH-dependent DNA synthesis on D loop substrates. Interacts (via C-terminus) with TRAIP. Interacts with ubiquitin. Interacts with POLDIP2.

Subcellular location. Nucleus.

Post-translational modifications. Monoubiquitinated by RCHY1/PIRH2. Ubiquitination depends on integrity of the UBZ3-type zinc finger domain and is enhanced by TRAIP. Ubiquitination inhibits the ability of PolH to interact with PCNA and to bypass UV-induced lesions.

Disease relevance. Xeroderma pigmentosum variant type (XPV) [MIM:278750] An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. XPV shows normal nucleotide excision repair, but an exaggerated delay in recovery of replicative DNA synthesis. Most patients with the variant type of xeroderma pigmentosum do not develop clinical symptoms and skin neoplasias until a later age. Clinical manifestations are limited to photo-induced deterioration of the skin and eyes. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The enzyme in complex with the DNA substrate binds a third divalent metal cation. The binding of this third divalent cation, which is coordinated by water molecules and two oxygen atoms from DNA and dNTP, is essential for catalyzing the DNA synthesis.

Cofactor. Binds 2 Mg(2+). Prefers Mg(2+), but can also use Mn(2+). In vitro, can also utilize other divalent cations such as Ca(2+).

Domain organisation. The catalytic core consists of fingers, palm and thumb subdomains, but the fingers and thumb subdomains are much smaller than in high-fidelity polymerases; residues from five sequence motifs of the Y-family cluster around an active site cleft that can accommodate DNA and nucleotide substrates with relaxed geometric constraints, with consequently higher rates of misincorporation and low processivity. The UBZ3-type zinc finger domain and the PIP-box mediate the interaction with ubiquitinated PCNA and are both necessary for the enzymatic activity in translesion synthesis.

Similarity. Belongs to the DNA polymerase type-Y family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y253-1	1	yes
Q9Y253-2	2

RefSeq proteins (3): NP_001278898, NP_001278899, NP_006493* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001126	UmuC	Domain
IPR017961	DNA_pol_Y-fam_little_finger	Domain
IPR036775	DNA_pol_Y-fam_lit_finger_sf	Homologous_superfamily
IPR041298	UBZ3	Domain
IPR043128	Rev_trsase/Diguanyl_cyclase	Homologous_superfamily
IPR043502	DNA/RNA_pol_sf	Homologous_superfamily
IPR052230	DNA_polymerase_eta	Family

Pfam: PF00817, PF11799, PF18439, PF21704

Enzyme classification (BRENDA):

• EC 2.7.7.7 — DNA-directed DNA polymerase (BRENDA: 139 organisms, 372 substrates, 325 inhibitors, 281 Km, 239 kcat entries)

Substrate kinetics (BRENDA)

52 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DATP	0.0003–3.2	52
DCTP	0.0001–2.5	46
DTTP	0.0003–47.4	46
DGTP	0.0002–2.5	29
DEOXYNUCLEOSIDE TRIPHOSPHATE	0.0012–0.64	12
DNAN	—	7
7-DEAZA-2’-DEOXYADENOSINE 5’-TRIPHOSPHATE	0.0011–0.344	5
N1-METHYL-2’-DEOXYADENOSINE 5’-TRIPHOSPHATE	0.223–0.403	5
2-AMINOPURINE-2’-DEOXY-D-RIBOSE 5’-TRIPHOSPHATE	0.006–0.0144	2
2-THIO-DCTP	0.067–0.98	2
5-METHYL-DCTP	0.013–1.22	2
DAMP:DG	1.153–1.42	2
DCMP:DG	—	2
DGMP:DG	0.263–0.3511	2
DTMP:DG	1.26–1.43	2

Catalyzed reactions (Rhea), 1 shown:

• DNA(n) + a 2’-deoxyribonucleoside 5’-triphosphate = DNA(n+1) + diphosphate (RHEA:22508)

UniProt features (115 total): helix 26, strand 21, sequence variant 20, binding site 17, mutagenesis site 9, turn 7, cross-link 4, region of interest 4, compositionally biased region 2, chain 1, domain 1, zinc finger region 1, splice variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

241 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7M7N	X-RAY DIFFRACTION	1.31
5KFZ	X-RAY DIFFRACTION	1.44
5KFN	X-RAY DIFFRACTION	1.45
5KFS	X-RAY DIFFRACTION	1.46
7M7M	X-RAY DIFFRACTION	1.46
7M7T	X-RAY DIFFRACTION	1.46
7M84	X-RAY DIFFRACTION	1.47
7U7L	X-RAY DIFFRACTION	1.47
4ECQ	X-RAY DIFFRACTION	1.5
5KFC	X-RAY DIFFRACTION	1.5
5KFA	X-RAY DIFFRACTION	1.51
5KFO	X-RAY DIFFRACTION	1.52
5KFT	X-RAY DIFFRACTION	1.52
5KFX	X-RAY DIFFRACTION	1.52
7U74	X-RAY DIFFRACTION	1.52
8V7G	X-RAY DIFFRACTION	1.52
4ECV	X-RAY DIFFRACTION	1.52
4ED8	X-RAY DIFFRACTION	1.52
7U72	X-RAY DIFFRACTION	1.53
7U7U	X-RAY DIFFRACTION	1.54
4Q8E	X-RAY DIFFRACTION	1.55
5KFB	X-RAY DIFFRACTION	1.55
5KFE	X-RAY DIFFRACTION	1.55
5KFG	X-RAY DIFFRACTION	1.55
5KFQ	X-RAY DIFFRACTION	1.55
5KFU	X-RAY DIFFRACTION	1.55
5KG6	X-RAY DIFFRACTION	1.55
7M83	X-RAY DIFFRACTION	1.55
7M86	X-RAY DIFFRACTION	1.55
7U75	X-RAY DIFFRACTION	1.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y253-F1	77.73	0.62

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (17): 13; 13; 13; 13; 14; 14; 61; 115; 115; 115; 115; 116 …

Post-translational modifications (4): 682, 686, 694, 709

Mutagenesis-validated functional residues (9):

Position	Phenotype
52	reduces dna polymerase activity.
52	reduces dna polymerase activity. increases fidelity of replication and reduces translesion bypass.
61	reduces enzymatic activity by two-thirds.
62	increased dna polymerase activity and translesion bypass compared to wild-type.
68	severe reduction in thymine dimer translesion bypass.
324–326	reduces binding to chromatin and to monoubiquitinated pcna. abolishes binding to monoubiquitinated pcna; when associated
638	reduces cell resistance to uv-induced dna damage.
652	abolishes ubiquitin binding and localization to nuclear foci after uv-induced dna damage but does not affect catalytic a
705–713	reduces cell resistance to uv-induced dna damage. reduces binding to chromatin and to monoubiquitinated pcna. abolishes

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-110320	Translesion Synthesis by POLH
R-HSA-5656169	Termination of translesion DNA synthesis
R-HSA-5685942	HDR through Homologous Recombination (HRR)

MSigDB gene sets: 239 (showing top): GOBP_RESPONSE_TO_UV_C, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, WANG_CLIM2_TARGETS_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_CELLULAR_RESPONSE_TO_UV, CMYB_01, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, CGGAARNGGCNG_UNKNOWN, GOBP_DNA_DAMAGE_TOLERANCE, AP2_Q3, KAUFFMANN_DNA_REPAIR_GENES, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_ERROR_FREE_TRANSLESION_SYNTHESIS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, GOMF_DNA_POLYMERASE_ACTIVITY

GO Biological Process (13): DNA synthesis involved in DNA repair (GO:0000731), DNA replication (GO:0006260), DNA repair (GO:0006281), regulation of DNA repair (GO:0006282), pyrimidine dimer repair (GO:0006290), response to radiation (GO:0009314), response to UV-C (GO:0010225), error-prone translesion synthesis (GO:0042276), error-free translesion synthesis (GO:0070987), cellular response to UV-C (GO:0071494), DNA damage tolerance (GO:0006301), DNA damage response (GO:0006974), DNA biosynthetic process (GO:0071897)

GO Molecular Function (9): damaged DNA binding (GO:0003684), DNA-directed DNA polymerase activity (GO:0003887), zinc ion binding (GO:0008270), DNA binding (GO:0003677), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), DNA polymerase activity (GO:0034061), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), replication fork (GO:0005657), cytosol (GO:0005829), site of double-strand break (GO:0035861)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	2
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	4
DNA repair	3
DNA biosynthetic process	3
cellular anatomical structure	3
DNA damage response	2
translesion synthesis	2
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
response to abiotic stimulus	1
response to UV	1
response to UV-C	1
cellular response to UV	1
DNA replication	1
cellular response to stress	1
nucleic acid biosynthetic process	1
DNA binding	1
DNA polymerase activity	1
transition metal ion binding	1
nucleic acid binding	1
binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
nucleotidyltransferase activity	1
catalytic activity, acting on DNA	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
chromosome	1
cytoplasm	1
site of DNA damage	1

Protein interactions and networks

STRING

1562 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLH	POLM	Q9NP87	924
POLH	REV3L	O60673	919
POLH	MAD2L2	Q9UI95	811
POLH	RAD18	Q9NS91	807
POLH	UNG	P13051	799
POLH	REV1	Q9UBZ9	775
POLH	POLL	Q9UGP5	772
POLH	RAD51	Q06609	759
POLH	OGG1	P78554	736
POLH	UBE2V2	Q15819	735
POLH	LIG1	P18858	706
POLH	UBE2N	P61088	667
POLH	CADM1	Q9BY67	648
POLH	RAD52	P43351	644
POLH	TENT4A	Q5XG87	592

IntAct

40 interactions, top by confidence:

A	B	Type	Score
BRCA2	PALB2	psi-mi:“MI:0403”(colocalization)	0.970
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
POLH	BRCA2	psi-mi:“MI:0915”(physical association)	0.680
POLH	BRCA2	psi-mi:“MI:0407”(direct interaction)	0.680
POLH	BRCA2	psi-mi:“MI:0914”(association)	0.680
BRCA2	POLH	psi-mi:“MI:0407”(direct interaction)	0.680
POLH	PALB2	psi-mi:“MI:0403”(colocalization)	0.670
PALB2	POLH	psi-mi:“MI:0915”(physical association)	0.670
POLH	PALB2	psi-mi:“MI:0407”(direct interaction)	0.670
PALB2	POLH	psi-mi:“MI:0407”(direct interaction)	0.670
POLH	PALB2	psi-mi:“MI:0915”(physical association)	0.670
UBC	POLH	psi-mi:“MI:0407”(direct interaction)	0.660
POLH	UBC	psi-mi:“MI:0915”(physical association)	0.660
UBC	POLH	psi-mi:“MI:0915”(physical association)	0.660
LSM5	LSM1	psi-mi:“MI:0914”(association)	0.640
MAD2L2	REV3L	psi-mi:“MI:0915”(physical association)	0.640
PCNA	POLH	psi-mi:“MI:0915”(physical association)	0.530
PCNA	POLH	psi-mi:“MI:0407”(direct interaction)	0.530
AR	POLH	psi-mi:“MI:0915”(physical association)	0.470
POLH	REV1	psi-mi:“MI:0407”(direct interaction)	0.440
H2AX	PALB2	psi-mi:“MI:0403”(colocalization)	0.430
POLH	ENTREP1	psi-mi:“MI:0915”(physical association)	0.370
POLH	POLH	psi-mi:“MI:0915”(physical association)	0.370
POLH	DHX16	psi-mi:“MI:0914”(association)	0.350
PIP	RBM47	psi-mi:“MI:0914”(association)	0.350
PTX3	POLRMT	psi-mi:“MI:0914”(association)	0.350

BioGRID (187): POLH (Two-hybrid), POLH (Affinity Capture-RNA), POLH (Affinity Capture-Western), PALB2 (Affinity Capture-Western), POLH (Affinity Capture-Western), POLH (Reconstituted Complex), POLH (Reconstituted Complex), POLH (Co-localization), POLH (Co-localization), BRCA2 (Affinity Capture-Western), UBC (Reconstituted Complex), POLH (Affinity Capture-Western), POLH (Affinity Capture-Western), POLH (Affinity Capture-RNA), USP7 (Affinity Capture-Western)

ESM2 similar proteins: A0A0G2JV04, A2AP18, D4A1F2, F1M775, F1MF74, F1QWK4, F1RA39, O08808, O60524, O60610, O75038, O88509, O94851, P18858, P37913, P41111, P49916, P51400, P51432, P51892, P54276, P78563, P97386, Q01970, Q2VPA6, Q3T058, Q3TX08, Q3ULW8, Q4G056, Q5ZLV4, Q61749, Q63186, Q7SXA9, Q8BIP0, Q8BJ37, Q8BMI3, Q8BML1, Q8CCP0, Q8CDG1, Q8R0H9

Diamond homologs: A1JNY3, A1RMZ5, A1S8M3, A3D147, A3N148, A4TPK8, A5F5Y1, A6WRW5, A7FLI9, A7MEN4, A9L0T3, B0BPX9, B8F542, C3LQ59, O42917, Q086K1, Q12Q05, Q1C4D9, Q1CLD4, Q487H6, Q56NI9, Q5FWF5, Q5SPR8, Q65TG8, Q66DZ7, Q69Z69, Q6C668, Q6D1H8, Q7MID6, Q87MB4, Q8CIB9, Q8DBI7, Q8ZBZ9, Q9JJN0, Q9KPS5, Q9Y253, A0KHD5, A0KTR5, A0Q6K9, A1A7U2

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
ATR	up-regulates	POLH	phosphorylation
BRCA2	up-regulates	POLH	binding
PALB2	up-regulates	POLH	binding
POLH	up-regulates	DNA_repair
RCHY1	“down-regulates activity”	POLH	monoubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Translesion synthesis by REV1	5	148.7×	3e-08
Translesion synthesis by POLI	5	139.9×	3e-08
Translesion synthesis by POLK	5	132.2×	3e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

648 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	48
Likely pathogenic	15
Uncertain significance	232
Likely benign	236
Benign	60

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1119983	NM_006502.3(POLH):c.672_673insT (p.Leu225fs)	Pathogenic
1174862	NM_006502.3(POLH):c.890G>A (p.Trp297Ter)	Pathogenic
1459259	NM_006502.3(POLH):c.1066C>T (p.Arg356Ter)	Pathogenic
1696282	NM_006502.3(POLH):c.1078dup (p.Asp360fs)	Pathogenic
224063	NM_006502.3(POLH):c.907C>T (p.Arg303Ter)	Pathogenic
264680	NM_006502.3(POLH):c.725C>G (p.Ser242Ter)	Pathogenic
264682	NM_006502.2(POLH):c.1075-?_1244+?del	Pathogenic
2696420	NM_006502.3(POLH):c.388C>T (p.Gln130Ter)	Pathogenic
2697211	NM_006502.3(POLH):c.838C>T (p.Gln280Ter)	Pathogenic
2704821	NM_006502.3(POLH):c.1019G>A (p.Trp340Ter)	Pathogenic
2734866	NM_006502.3(POLH):c.353dup (p.Tyr118Ter)	Pathogenic
2734867	NM_006502.3(POLH):c.437dup (p.Tyr146Ter)	Pathogenic
2734868	NM_006502.3(POLH):c.499C>T (p.Arg167Ter)	Pathogenic
2734869	NM_006502.3(POLH):c.764+1G>C	Pathogenic
2734871	NM_006502.3(POLH):c.897T>G (p.Tyr299Ter)	Pathogenic
2734872	NM_006502.3(POLH):c.1657dup (p.Gln553fs)	Pathogenic
2756379	NM_006502.3(POLH):c.202dup (p.Ala68fs)	Pathogenic
2762706	NM_006502.3(POLH):c.1007del (p.Gln336fs)	Pathogenic
2766670	NM_006502.3(POLH):c.1671G>A (p.Trp557Ter)	Pathogenic
2865714	NM_006502.3(POLH):c.54del (p.Phe18fs)	Pathogenic
2866570	NM_006502.3(POLH):c.1195del (p.Ala399fs)	Pathogenic
2871625	NM_006502.3(POLH):c.381_384del (p.Glu127fs)	Pathogenic
2903313	NM_006502.3(POLH):c.1615del (p.Leu538_Leu539insTer)	Pathogenic
3008452	NM_006502.3(POLH):c.1244+1G>A	Pathogenic
3246201	NC_000006.11:g.(?43578271)(43578480_?)del	Pathogenic
3246202	NC_000006.11:g.(?43581377)(43582294_?)del	Pathogenic
3246203	NC_000006.11:g.(?43554989)(43555246_?)del	Pathogenic
3246204	NC_000006.11:g.(?43568705)(43568848_?)del	Pathogenic
3246205	NC_000006.11:g.(?43565413)(43568848_?)del	Pathogenic
3246206	NC_000006.11:g.(?43571609)(43573076_?)del	Pathogenic

SpliceAI

1756 predictions. Top by Δscore:

Variant	Effect	Δscore
6:43575770:T:TA	donor_gain	1.0000
6:43582409:G:GT	donor_gain	1.0000
6:43582425:GTT:G	donor_gain	1.0000
6:43582430:AC:A	donor_gain	1.0000
6:43582432:A:AG	donor_gain	1.0000
6:43582433:G:GG	donor_gain	1.0000
6:43582448:GGGTG:G	donor_gain	1.0000
6:43582449:GGTGG:G	donor_gain	1.0000
6:43582999:A:AG	acceptor_gain	1.0000
6:43583000:A:G	acceptor_gain	1.0000
6:43583005:A:AC	acceptor_loss	1.0000
6:43583005:A:AG	acceptor_gain	1.0000
6:43583006:G:GA	acceptor_gain	1.0000
6:43583006:GA:G	acceptor_gain	1.0000
6:43583006:GAA:G	acceptor_gain	1.0000
6:43583006:GAAT:G	acceptor_gain	1.0000
6:43583006:GAATA:G	acceptor_gain	1.0000
6:43583107:GTTC:G	donor_gain	1.0000
6:43583111:G:GG	donor_gain	1.0000
6:43583139:CAAGT:C	donor_loss	1.0000
6:43583140:AAGTA:A	donor_loss	1.0000
6:43583142:G:GG	donor_gain	1.0000
6:43583143:T:G	donor_loss	1.0000
6:43597823:G:GT	donor_gain	1.0000
6:43600978:A:AG	acceptor_gain	1.0000
6:43600978:AT:A	acceptor_gain	1.0000
6:43600979:T:G	acceptor_gain	1.0000
6:43600979:T:TA	acceptor_gain	1.0000
6:43600983:TCCAG:T	acceptor_loss	1.0000
6:43600985:CAGGT:C	acceptor_loss	1.0000

AlphaMissense

4656 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:43583020:A:C	S51R	0.997
6:43583022:T:A	S51R	0.997
6:43583022:T:G	S51R	0.997
6:43603984:T:C	L286P	0.997
6:43582426:T:A	V36D	0.996
6:43583045:T:A	V59D	0.996
6:43604659:T:A	V310D	0.996
6:43605300:T:C	L352P	0.996
6:43583014:G:C	A49P	0.994
6:43587336:A:C	S113R	0.994
6:43587338:C:A	S113R	0.994
6:43587338:C:G	S113R	0.994
6:43610722:T:A	W415R	0.994
6:43610722:T:C	W415R	0.994
6:43582375:T:A	V19D	0.993
6:43582423:C:A	A35E	0.993
6:43583009:T:A	I47K	0.993
6:43583033:G:C	R55P	0.993
6:43587285:A:C	S96R	0.993
6:43587287:T:A	S96R	0.993
6:43587287:T:G	S96R	0.993
6:43604623:T:C	L298P	0.993
6:43605288:T:C	L348P	0.993
6:43583072:C:A	A68D	0.992
6:43587277:G:C	R93P	0.992
6:43587348:G:C	A117P	0.992
6:43604638:G:C	R303P	0.992
6:43582362:G:C	D15H	0.991
6:43597785:G:C	A194P	0.991
6:43597808:A:C	R201S	0.991

dbSNP variants (sampled 300 via entrez): RS1000073215 (6:43603938 G>A,C), RS1000073916 (6:43594450 C>T), RS1000087577 (6:43596459 G>A), RS1000134367 (6:43613378 G>A,T), RS1000181077 (6:43582752 G>T), RS1000205819 (6:43578705 C>T), RS1000228471 (6:43582516 T>A,G), RS1000239048 (6:43590020 G>T), RS1000269751 (6:43596145 TA>T), RS1000286921 (6:43576248 G>A), RS1000352772 (6:43620539 A>G), RS1000500733 (6:43594187 A>G), RS1000577983 (6:43591434 C>G), RS1000673974 (6:43605464 T>G), RS1000725834 (6:43619257 A>C)

Disease associations

OMIM: gene MIM:603968 | disease phenotypes: MIM:278750, MIM:278700

GenCC curated gene-disease

Disease	Classification	Inheritance
xeroderma pigmentosum variant type	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
xeroderma pigmentosum variant type	Definitive	AR

Mondo (3): xeroderma pigmentosum variant type (MONDO:0010214), xeroderma pigmentosum (MONDO:0019600), breast cancer (MONDO:0007254)

Orphanet (2): Xeroderma pigmentosum variant (Orphanet:90342), Xeroderma pigmentosum (Orphanet:910)

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000491	Keratitis
HP:0000509	Conjunctivitis
HP:0000613	Photophobia
HP:0000621	Entropion
HP:0000656	Ectropion
HP:0000953	Hyperpigmentation of the skin
HP:0000958	Dry skin
HP:0000992	Cutaneous photosensitivity
HP:0001009	Telangiectasia
HP:0001010	Hypopigmentation of the skin
HP:0001029	Poikiloderma
HP:0001510	Growth delay
HP:0002671	Basal cell carcinoma
HP:0002860	Squamous cell carcinoma
HP:0002861	Melanoma
HP:0003593	Infantile onset
HP:0004334	Dermal atrophy
HP:0007603	Freckles in sun-exposed areas
HP:0012056	Cutaneous melanoma
HP:0034697	Cutaneous telangiectasia

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005956_58	Waist-to-hip ratio adjusted for BMI	7.000000e-26
GCST005957_1	Waist-to-hip ratio adjusted for BMI (age <50)	2.000000e-14
GCST005958_2	Waist-to-hip ratio adjusted for BMI (age >50)	2.000000e-19
GCST005962_2	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-31

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D014983	Xeroderma Pigmentosum	C04.834.867; C16.131.831.936; C16.320.850.970; C17.800.600.925; C17.800.621.936; C17.800.804.936; C17.800.827.970; C18.452.284.975
C536766	Xeroderma pigmentosum, variant type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5542 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 211,168 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL50	QUERCETIN	3	74,559
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL44	GENISTEIN	2	44,212
CHEMBL6246	ELLAGIC ACID	2	23,148
CHEMBL8260	BAICALEIN	2	8,592
CHEMBL150	KAEMPFEROL	1	25,940

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

10 potent at pChembl≥5 of 34 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.21	IC50	62	nM	ELLAGIC ACID
7.12	IC50	75	nM	AURINTRICARBOXYLIC ACID
5.30	IC50	5000	nM	CHEMBL457821
5.16	IC50	6900	nM	CHEMBL1917196
5.11	IC50	7700	nM	CHEMBL5398631
5.10	IC50	8000	nM	CHEMBL5433463
5.08	IC50	8400	nM	CHEMBL1917198
5.06	IC50	8700	nM	CHEMBL243677

PubChem BioAssay actives

10 with measured affinity, of 61 total; 8 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
6,7,13,14-tetrahydroxy-2,9-dioxatetracyclo[6.6.2.04,16.011,15]hexadeca-1(15),4,6,8(16),11,13-hexaene-3,10-dione	1315754: Inhibition of human recombinant DNA polymerase eta expressed in Baculovirus expression system using TAMRA/BHQ-2-labeled primer/template measured at 2 to 6 mins by reporter-strand displacement assay	ic50	0.0620	uM
5-[(3-carboxy-4-hydroxyphenyl)-(3-carboxy-4-oxocyclohexa-2,5-dien-1-ylidene)methyl]-2-hydroxybenzoic acid	1315754: Inhibition of human recombinant DNA polymerase eta expressed in Baculovirus expression system using TAMRA/BHQ-2-labeled primer/template measured at 2 to 6 mins by reporter-strand displacement assay	ic50	0.0750	uM
5,7-dihydroxy-2-(3-hydroxyphenyl)chromen-4-one	1973466: Inhibition of C-terminal 6xHis-tagged human DNA polymerase eta (1 to 511 residues) expressed in Escherichia coli BL21 DE3 using 5’-IRD700-GCAGGTCGACTCCAAAG-3’ primer/ 5’-TCGGTACCGGGTTAGCCTTTGGAGTCGACCTGC-3’ template as DNA substrate incubated for 60 mins in presence of Mg2+ by bromophenol blue staining based assay	ic50	5.0000	uM
(5,8-dioxonaphthalen-1-yl) dodecanoate	627962: Inhibition of C-terminal His6-tagged human DNA polymerase eta (amino acids 1 to 511) using poly(dA)/oligo(dT)18 (A/T = 2/1) and dTTP as the DNA template-primer and nucleotide substrate after 60 mins	ic50	6.9000	uM
5-(5,7-dihydroxy-4-oxochromen-2-yl)-2-hydroxybenzoic acid	1973466: Inhibition of C-terminal 6xHis-tagged human DNA polymerase eta (1 to 511 residues) expressed in Escherichia coli BL21 DE3 using 5’-IRD700-GCAGGTCGACTCCAAAG-3’ primer/ 5’-TCGGTACCGGGTTAGCCTTTGGAGTCGACCTGC-3’ template as DNA substrate incubated for 60 mins in presence of Mg2+ by bromophenol blue staining based assay	ic50	7.7000	uM
5-[[5-chloro-1-(naphthalen-2-ylmethyl)indol-3-yl]methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione	1973463: Inhibition of human DNA polymerase eta (1 to 437 residues) using 5’-TTT TTT TTG C-TAMRA-3’ reporter/5’-(FAM-TTT)-GGGGGAAGGATTC-3’ primer/5’-TCACGGAATCCTTCCCCC-3’ template as DNA substrate preincubated for 5 to 10 mins followed by DNA substrate addition measured immediately in presence of dTTP/MgCl2 by fluorescence based assay	ic50	8.0000	uM
(5,8-dioxonaphthalen-1-yl) (Z)-octadec-9-enoate	627962: Inhibition of C-terminal His6-tagged human DNA polymerase eta (amino acids 1 to 511) using poly(dA)/oligo(dT)18 (A/T = 2/1) and dTTP as the DNA template-primer and nucleotide substrate after 60 mins	ic50	8.4000	uM
2-(3,4-dihydroxyphenyl)-5-hydroxychromen-4-one	1973466: Inhibition of C-terminal 6xHis-tagged human DNA polymerase eta (1 to 511 residues) expressed in Escherichia coli BL21 DE3 using 5’-IRD700-GCAGGTCGACTCCAAAG-3’ primer/ 5’-TCGGTACCGGGTTAGCCTTTGGAGTCGACCTGC-3’ template as DNA substrate incubated for 60 mins in presence of Mg2+ by bromophenol blue staining based assay	ic50	8.7000	uM

CTD chemical–gene interactions

65 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	5
Aflatoxin B1	affects expression, increases expression	5
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	3
mercuric bromide	increases expression, affects cotreatment	2
pifithrin	decreases reaction, increases expression	2
Dactinomycin	decreases reaction, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
pradimicin-IRD	affects response to substance, increases response to substance, decreases expression	1
triphenyl phosphate	affects expression	1
quercitrin	increases expression	1
dimethylselenide	increases expression, increases oxidation	1
nitrosobenzylmethylamine	affects binding, decreases activity	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenz(a)anthracene	increases expression	1
benz(a)anthracene	increases expression	1
hydroquinone	affects reaction, increases expression, affects response to substance	1
mafosfamide	decreases response to substance, increases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	affects activity	1
fotemustine	decreases reaction, increases expression, affects binding, increases reaction, decreases response to substance	1
polyhexamethyleneguanidine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
benzo(a)pyrene diolepoxide I	affects binding, increases reaction, decreases expression, increases expression, decreases reaction (+1 more)	1
perfluorooctane sulfonic acid	decreases expression	1
N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	affects activity	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
2-amino-1-methyl-6-phenolimidazo(4,5-b)pyridine-DNA adduct	affects activity	1

ChEMBL screening assays

18 unique, capped per target: 16 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1023120	Binding	Inhibition of human DNA polymerase eta	Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases. — Bioorg Med Chem
CHEMBL1794569	Functional	PUBCHEM_BIOASSAY: qHTS for Inhibitors of Polymerase Eta. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID588636]	PubChem BioAssay data set

Cellosaurus cell lines

92 cell lines: 73 finite cell line, 10 cancer cell line, 8 transformed cell line, 1 telomerase immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1F47	XP98TMA	Finite cell line	Female
CVCL_1F48	XP98TMA LCL	Transformed cell line	Female
CVCL_2556	XP11BR LCL	Transformed cell line	Male
CVCL_3243	XP2SA	Finite cell line	Female
CVCL_7358	XP115LO 2	Finite cell line	Male
CVCL_7372	XP1CH [XP-V Cherevan]	Finite cell line	Male
CVCL_7395	XP30RO	Finite cell line	Male
CVCL_A1ZC	XPV1HM	Finite cell line	Male
CVCL_A1ZD	XPV2HM	Finite cell line	Male
CVCL_A1ZF	XPV6HM	Finite cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00014638	PHASE4	COMPLETED	Letrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
NCT00022386	PHASE4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00082277	PHASE4	COMPLETED	Anastrozole Biphosphonate Study in Postmenopausal Women With Hormone-Receptor-Positive Early Breast Cancer
NCT00087620	PHASE4	TERMINATED	A Study of Capecitabine In Combination With Docetaxel vs Capecitabine Followed by Docetaxel As First-Line Treatment For Metastatic Breast Cancer
NCT00121836	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer
NCT00126360	PHASE4	UNKNOWN	STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing Pilot)
NCT00127933	PHASE4	COMPLETED	XeNA Study - A Study of Xeloda (Capecitabine) in Patients With Invasive Breast Cancer
NCT00128297	PHASE4	COMPLETED	Pamidronate Administration in Breast Cancer Patients With Bone Metastases
NCT00129597	PHASE4	UNKNOWN	Effect of Ketalar to Prevent Postoperative Chronic Pain After Mastectomy
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NCT00699101	PHASE4	TERMINATED	Using the Conture® Multi-Lumen Balloon to Deliver Accelerated Partial Breast Brachytherapy
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