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): 663 total — 49 pathogenic, 20 likely-pathogenic (top 5% of genes corpus-wide)
• GTEx eGene: eQTL in 12 tissues, sQTL in 5 (q < 0.05)
• Phenotypes (HPO): 22
• ChEMBL bioactivity: 7 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.85 (unconstrained)
• 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: 14 — 11 protein_coding, 3 nonsense_mediated_decay

MANE Select: ENST00000372236

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1

ENST00000372236, ENST00000372226, ENST00000443535, ENST00000901658, ENST00000921322, ENST00000953718, ENST00000974791, ENST00000974792, ENST00000974793, ENST00000974794, ENST00001021644, ENST00001119896, ENST00001119897, ENST00001140538

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.

Highest expression (Bgee): buccal mucosa cell, skeletal muscle tissue of rectus abdominis, stromal cell of endometrium, trabecular bone tissue, lower lobe of lung.

Genetic regulation across tissues (GTEx eQTL / sQTL)

POLH is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

17 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	8.8e-16	+0.51	6:43560704:C:T
Cells EBV-transformed lymphocytes	sqtl	4.4e-12	-0.61	6:43626722:A:G
Artery Tibial	sqtl	1.9e-08	+0.41	6:43640649:C:T
Brain Cerebellum	eqtl	4.2e-07	+0.66	6:43494528:C:T
Thyroid	eqtl	1.7e-06	+0.32	6:43490712:A:G
Skin Not Sun Exposed Suprapubic	eqtl	2.0e-03	+0.29	6:44512340:G:A
Artery Aorta	sqtl	2.5e-03	+0.36	6:43686799:G:C
Lung	eqtl	4.1e-03	+0.20	6:43509029:G:C
Pancreas	eqtl	9.0e-03	+0.28	6:43475513:A:G
Cells Cultured fibroblasts	eqtl	2.4e-02	+0.24	6:43653008:T:TG
Brain Cerebellar Hemisphere	eqtl	2.5e-02	+0.45	6:43468868:C:CAG
Brain Anterior cingulate cortex BA24	eqtl	3.2e-02	+0.24	6:43137869:T:C
Testis	eqtl	3.3e-02	+0.10	6:43937300:T:C
Testis	sqtl	3.4e-02	-0.46	6:43984675:G:A
Nerve Tibial	eqtl	3.5e-02	+0.36	6:43521098:C:T
Skin Sun Exposed Lower leg	eqtl	3.7e-02	-0.10	6:43630572:G:A
Muscle Skeletal	eqtl	4.1e-02	-0.46	6:43890101:C:T

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 288 tissues 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
tongue	UBERON:0001723	79.67	gold quality
bronchial epithelial cell	CL:0002328	79.57	gold quality
myocardium	UBERON:0002349	78.98	gold quality
renal medulla	UBERON:0000362	78.93	gold quality
lateral globus pallidus	UBERON:0002476	78.90	gold quality
male germ cell	CL:0000015	78.76	gold quality
saphenous vein	UBERON:0007318	78.69	gold quality
inferior vagus X ganglion	UBERON:0005363	78.66	gold quality
cortical plate	UBERON:0005343	78.48	gold quality
subthalamic nucleus	UBERON:0001906	78.40	gold quality
bone marrow cell	CL:0002092	78.37	gold quality
lateral nuclear group of thalamus	UBERON:0002736	78.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.16	gold quality
visceral pleura	UBERON:0002401	78.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.13	gold quality
pons	UBERON:0000988	78.05	gold quality
jejunum	UBERON:0002115	78.02	gold quality
trachea	UBERON:0003126	78.00	gold quality
endometrium	UBERON:0001295	77.74	gold quality
islet of Langerhans	UBERON:0000006	77.67	gold quality
medulla oblongata	UBERON:0001896	77.67	gold quality
ventral tegmental area	UBERON:0002691	77.63	gold quality
bone marrow	UBERON:0002371	77.57	gold quality
secondary oocyte	CL:0000655	77.55	gold quality
mucosa of sigmoid colon	UBERON:0004993	77.43	gold quality
rectum	UBERON:0001052	77.33	gold quality
superior vestibular nucleus	UBERON:0007227	77.18	gold quality
amniotic fluid	UBERON:0000173	77.15	gold quality
substantia nigra pars reticulata	UBERON:0001966	77.15	gold quality
calcaneal tendon	UBERON:0003701	77.14	gold quality
trigeminal ganglion	UBERON:0001675	77.09	gold quality
tendon	UBERON:0000043	76.85	gold quality
caecum	UBERON:0001153	76.58	gold quality
jejunal mucosa	UBERON:0000399	76.55	gold quality
substantia nigra pars compacta	UBERON:0001965	76.34	gold quality
dorsal plus ventral thalamus	UBERON:0001897	76.29	gold quality
colonic mucosa	UBERON:0000317	76.19	gold quality
synovial joint	UBERON:0002217	76.18	gold quality
descending thoracic aorta	UBERON:0002345	75.95	gold quality
tendon of biceps brachii	UBERON:0008188	75.84	gold quality
mammary duct	UBERON:0001765	75.82	gold quality
skeletal muscle tissue	UBERON:0001134	75.81	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	75.79	gold quality
vermiform appendix	UBERON:0001154	75.59	gold quality
cartilage tissue	UBERON:0002418	75.57	gold quality
left ventricle myocardium	UBERON:0006566	75.52	gold quality
monocyte	CL:0000576	75.50	gold quality
parietal pleura	UBERON:0002400	75.49	gold quality
liver	UBERON:0002107	75.42	gold quality
penis	UBERON:0000989	75.34	gold quality
seminal vesicle	UBERON:0000998	75.32	gold quality
leukocyte	CL:0000738	75.31	gold quality
pancreas	UBERON:0001264	75.26	gold quality
pleura	UBERON:0000977	75.21	gold quality
blood	UBERON:0000178	75.09	gold quality
granulocyte	CL:0000094	75.07	gold quality
urethra	UBERON:0000057	75.04	gold quality
mononuclear cell	CL:0000842	74.96	gold quality
testis	UBERON:0000473	74.87	gold quality
skin of leg	UBERON:0001511	74.81	gold quality
heart right ventricle	UBERON:0002080	74.67	gold quality
uterus	UBERON:0000995	74.65	gold quality
muscle tissue	UBERON:0002385	74.65	gold quality
dorsal root ganglion	UBERON:0000044	74.58	gold quality
left testis	UBERON:0004533	74.55	gold quality
cardiac muscle of right atrium	UBERON:0003379	74.54	gold quality
nasal cavity mucosa	UBERON:0001826	74.50	gold quality
body of pancreas	UBERON:0001150	74.48	gold quality
superficial temporal artery	UBERON:0001614	74.48	gold quality
zone of skin	UBERON:0000014	74.40	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	15.8
Cerebellum	tissue	14.5	medium
Tonsil	tissue	13.3	medium
Lymph node	tissue	12.1	medium
Thymus	tissue	12.0
Testis	tissue	9.9	medium
Nucleus accumbens	tissue	8.8
Spinal cord	tissue	8.5
Olfactory bulb	tissue	8.3
Skin 1	tissue	8.0	medium
Skeletal muscle	tissue	8.0	medium
Hippocampus	tissue	8.0	medium
Superior colliculi	tissue	7.8
Cerebral cortex	tissue	7.6	medium
Ventral forebrain	tissue	7.6
Occipital cortex	tissue	7.6
Somatosensory cortex	tissue	7.4
Putamen	tissue	7.2
Locus coeruleus	tissue	7.2
Postcentral gyrus	tissue	7.2
Septum	tissue	7.2
Hippocampal formation	tissue	7.0
Entorhinal cortex	tissue	7.0
Retina	tissue	6.9
Basal ganglia	tissue	6.8	medium
Temporal cortex	tissue	6.8
Rectum	tissue	6.7	medium
Midbrain	tissue	6.6
Retrosplenial and cingulate cortex	tissue	6.6
Colon	tissue	6.5	medium
Appendix	tissue	6.5	medium
Motor cortex	tissue	6.4
Medulla oblongata	tissue	6.3
Thalamus	tissue	6.3
Thyroid gland	tissue	6.3	high
Prefrontal cortex	tissue	6.2
Corpus callosum	tissue	6.1
Insular cortex	tissue	6.1
Smooth muscle	tissue	5.9	medium
Retrosplenial cortex	tissue	5.9
Pons	tissue	5.7
Cervix	tissue	5.6	medium
Amygdala	tissue	5.6
Substantia nigra	tissue	5.6
Hypothalamus	tissue	5.5
Lung	tissue	5.4	high
Spleen	tissue	5.2	low
Liver	tissue	5.2	medium
Fallopian tube	tissue	5.2	medium
Esophagus	tissue	5.1	medium
Pancreas	tissue	5.1	high
Periaqueductal gray	tissue	5.0
Adipose tissue	tissue	4.7	not detected
Breast	tissue	4.5	medium
Urinary bladder	tissue	4.5	medium
Prostate	tissue	4.4	medium
Stomach 1	tissue	4.3	medium
Tongue	tissue	4.3
Kidney	tissue	4.3	medium
Duodenum	tissue	4.3	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Flocculonodular lobe (14.4), Vermis (13.6), Cerebellar cortex (13.0), Temporal white matter (11.6), Cerebellar white matter (11.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DBP, IRF1, TBP

miRNA regulators (miRDB)

Targeting POLH by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 217 miRNAs:

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

gnomAD constraint: pLI 3.06e-09, LOEUF 0.846, missense Z 1.6 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000372236 — one region, missense o/e 0.89.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1891457) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 7 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal B cell physiology	2
increased incidence of tumors by UV-induction	2
abnormal ear pigmentation	1
skin photosensitivity	1
increased sensitivity to skin irradiation	1
increased squamous cell carcinoma incidence	1
increased skin tumor incidence	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Arabidopsis thaliana	Q8H2D5	41.6%	Diamond
Schizosaccharomyces pombe 972h-	O42917	33.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GTPBP2	protein-coding	54676
XPO5	protein-coding	57510
POLR1C	protein-coding	9533
MAD2L1BP	protein-coding	9587
YIPF3	protein-coding	25844
RSPH9	protein-coding	221421
MRPS18A	protein-coding	55168
LRRC73	protein-coding	221424

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)

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

UniProt features (117 total): helix 28, 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)

showing 30 of 241 structures by resolution:

PDB	Title	Method	Resolution (Å)
7M7N	Human DNA Pol eta with 2’-FA-ended primer and dAMPNPP	X-RAY DIFFRACTION	1.31
5KFZ	Human DNA polymerase eta-DNA ternary complex: reaction first with 1 mM Mn2+ for 1800s …	X-RAY DIFFRACTION	1.44
5KFN	Human DNA polymerase eta-DNA ternary complex with Sp-dATP-alpha-S: reaction with 1 mM …	X-RAY DIFFRACTION	1.45
5KFS	Human DNA polymerase eta R61A-DNA ternary complex: ground state at pH7.0 (K+ MES) with 1 …	X-RAY DIFFRACTION	1.46
7M7M	Human DNA Pol eta with rA-ended primer and dAMPNPP	X-RAY DIFFRACTION	1.46
7M7T	Human DNA Pol eta S113A with dT-ended primer and dATP: in crystallo reaction for 0 s	X-RAY DIFFRACTION	1.46
7M84	Human DNA Pol eta S113A with dA-ended primer and dATP: in crystallo reaction for 40 s	X-RAY DIFFRACTION	1.47
7U7L	Human DNA polymerase eta-DNA ternary mismatch complex:reaction with 1.0 mM Mg2+ for 300s …	X-RAY DIFFRACTION	1.47
4ECQ	Human DNA polymerase eta- DNA ternary complex: AT crystal at pH6.8(K+ MES) with 1 Ca2+ ion	X-RAY DIFFRACTION	1.5
5KFC	Human DNA polymerase eta-DNA ternary complex: reaction with 1 mM Mn2+ for 180s	X-RAY DIFFRACTION	1.5
5KFA	Human DNA polymerase eta-DNA ternary complex: ground state at pH7.0 (K+ MES) with 1 Ca2+ …	X-RAY DIFFRACTION	1.51
5KFO	Human DNA polymerase eta-DNA ternary complex with Sp-dATP-alpha-S: reaction with 1 mM …	X-RAY DIFFRACTION	1.52
5KFT	Human DNA polymerase eta R61A-DNA ternary complex: reaction with 1 mM Mg2+ for 40s	X-RAY DIFFRACTION	1.52
5KFX	Human DNA polymerase eta R61A-DNA ternary complex: reaction with 1 mM Mg2+ for 300s	X-RAY DIFFRACTION	1.52
7U74	Human DNA polymerase eta-DNA ternary mismatch complex:reaction with 0.5 mM Mn2+ for 1800s …	X-RAY DIFFRACTION	1.52
8V7G	Human DNA polymerase eta-DNA-gemC-ended primer-dAMPNPP ternary complex with Mg2+	X-RAY DIFFRACTION	1.52
4ECV	Human DNA polymerase eta - DNA ternary complex: Reaction in the AT crystal at pH 7.0 for …	X-RAY DIFFRACTION	1.52
4ED8	Human DNA polymerase eta - DNA ternary complex: Reaction in the TG crystal at pH 7.0 …	X-RAY DIFFRACTION	1.52
7U72	Human DNA polymerase eta-DNA ternary mismatch complex:ground state at pH7.0 (K+ MES) with …	X-RAY DIFFRACTION	1.53
7U7U	Human DNA polymerase eta-DNA-dGMPNPP ternary mismatch complex in 0.1 mM Mg2+ for 600s	X-RAY DIFFRACTION	1.54
4Q8E	Human DNA polymerase eta inserting dCMPNPP opposite a phenanthriplatin adducted G	X-RAY DIFFRACTION	1.55
5KFB	Human DNA polymerase eta-DNA ternary complex: reaction with 1 mM Mn2+ for 90s	X-RAY DIFFRACTION	1.55
5KFE	Human DNA polymerase eta-DNA ternary complex: reaction with 1 mM Mn2+ for 600s	X-RAY DIFFRACTION	1.55
5KFG	Human DNA polymerase eta-DNA ternary complex: reaction with 10 mM Mn2+ for 30s	X-RAY DIFFRACTION	1.55
5KFQ	Human DNA polymerase eta-DNA ternary complex with Sp-dATP-alpha-S: reaction with 10 mM …	X-RAY DIFFRACTION	1.55
5KFU	Human DNA polymerase eta R61A-DNA ternary complex: reaction with 1 mM Mg2+ for 80s	X-RAY DIFFRACTION	1.55
5KG6	Human DNA polymerase eta-DNA ternary complex: reaction first with 1 mM Mn2+ for 1800s …	X-RAY DIFFRACTION	1.55
7M83	Human DNA Pol eta S113A with dA-ended primer and dATP: in crystallo reaction for 0 s	X-RAY DIFFRACTION	1.55
7M86	Human DNA Pol eta S113A with dA-ended primer and dATP: in crystallo reaction for 140 s	X-RAY DIFFRACTION	1.55
7U75	Human DNA polymerase eta-DNA ternary mismatch complex:reaction with 0.5 mM Mn2+ for 1800s …	X-RAY DIFFRACTION	1.55

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Congenital malformations of skin, Other congenital malformations

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · IF enhanced

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)

Position	Role
13	Mg(2+)
13	Mn(2+)
14	Mg(2+)
14	Mn(2+)
61	a 2’-deoxyribonucleoside 5’-triphosphate
115	Mg(2+)
115	Mn(2+)
116	Mg(2+)
116	Mn(2+)
635	Zn(2+)
638	Zn(2+)
650	Zn(2+)
654	Zn(2+)

Post-translational modifications (4)

Type	Positions
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)	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 with 705-e–h-713 …
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 activity.
705–713	reduces cell resistance to uv-induced dna damage. reduces binding to chromatin and to monoubiquitinated pcna. abolishes binding to …

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

ID	Pathway	Evidence
R-HSA-5685942	HDR through Homologous Recombination (HRR)	curated
R-HSA-9968295	Somatic hypermutation of immunoglobulin genes by error-prone mismatch repair (MMR)	curated
R-HSA-5656169	Termination of translesion DNA synthesis	curated
R-HSA-110320	Translesion Synthesis by POLH	curated
R-HSA-73893	DNA Damage Bypass	—
R-HSA-5693532	DNA Double-Strand Break Repair	—
R-HSA-73894	DNA Repair	—
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	—
R-HSA-5693538	Homology Directed Repair	—
R-HSA-9968297	Somatic hypermutation of immunoglobulin genes by error-prone base excision repair (BER)	electronic
R-HSA-110313	Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	—

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 (12): DNA synthesis involved in DNA repair (GO:0000731), DNA repair (GO:0006281), regulation of DNA repair (GO:0006282), response to radiation (GO:0009314), response to UV-C (GO:0010225), translesion synthesis (GO:0019985), error-prone translesion synthesis (GO:0042276), error-free translesion synthesis (GO:0070987), DNA replication (GO:0006260), 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 (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), replication fork (GO:0005657), site of double-strand break (GO:0035861)

Reactome top-level categories

7 top-level categories:

Category	Pathways
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	2
Somatic hypermutation of immunoglobulin genes	2
DNA Repair	2
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
DNA Damage Bypass	1
DNA Double-Strand Break Repair	1
Homology Directed Repair	1

GO top-level categories

29 GO namespaces:

Category	Terms
DNA metabolic process	4
DNA biosynthetic process	3
DNA repair	2
DNA damage response	2
translesion synthesis	2
cellular anatomical structure	2
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
response to abiotic stimulus	1
response to UV	1
DNA damage tolerance	1
DNA synthesis involved in DNA replication	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
site of DNA damage	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 25 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
DNA synthesis involved in DNA repair	BP	direct assay
response to UV-C	BP	direct assay
translesion synthesis	BP	direct assay
nucleoplasm	CC	direct assay
DNA-directed DNA polymerase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 888 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLH	REV3L	O60673	969
POLH	MAD2L2	Q9UI95	920
POLH	RAD18	Q9NS91	915
POLH	POLM	Q9NP87	906
POLH	UBE2V2	Q15819	870
POLH	PCNA	P12004	859
POLH	UBE2N	P61088	843
POLH	UNG	P13051	791
POLH	RAD51	Q06609	717
POLH	POLL	Q9UGP5	711
POLH	LIG1	P18858	696
POLH	OGG1	P78554	693
POLH	SUMO1	P55856	663
POLH	CADM1	Q9BY67	661
POLH	REV1	Q9UBZ9	627

IntAct

Human interaction partners of POLH in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

9 partners by confidence:

Partner	Interaction type	MIscore	Records
BRCA2	physical association	0.680	5
PALB2	colocalization	0.670	5
UBC	direct interaction	0.660	4
PCNA	physical association	0.530	3
AR	physical association	0.470	1
REV1	direct interaction	0.440	1
ENTREP1	physical association	0.370	1
DHX16	association	0.350	1
POTEI	association	0.350	1

BioGRID (190 interactions; top human partners by supporting records): PCNA (Affinity Capture-Western; 31 records), REV1 (Affinity Capture-MS; 13 records), RAD18 (Affinity Capture-Western; 10 records), UBC (Two-hybrid; 7 records), USP7 (Affinity Capture-Western; 6 records), POLI (Two-hybrid; 5 records), BRCA2 (Affinity Capture-Western; 4 records), HSP90AA1 (Affinity Capture-MS; 4 records), PALB2 (Affinity Capture-Western; 4 records), RCHY1 (Biochemical Activity; 4 records), TRAIP (Two-hybrid; 4 records), DTL (Biochemical Activity; 3 records), FANCD2 (Affinity Capture-Western; 3 records), MLH1 (Two-hybrid; 3 records), OGT (Affinity Capture-MS; 3 records)

SIGNOR signaling

showing 5 of 8 signaling 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

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
CTF18-cohesion-RFC-POLH complex	8	DSCC1, POLH, RFC2, RFC3, RFC4, RFC5, CHTF18, CHTF8

Disease & clinical

Genetic variants

Variant evidence for POLH: 663 ClinVar records (69 pathogenic / likely pathogenic); 4 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	49
Likely pathogenic	20
Uncertain significance	238
Likely benign	237
Benign	58

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 69 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
224063	NM_006502.3(POLH):c.907C>T (p.Arg303Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1119983	NM_006502.3(POLH):c.672_673insT (p.Leu225fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
2734868	NM_006502.3(POLH):c.499C>T (p.Arg167Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1459259	NM_006502.3(POLH):c.1066C>T (p.Arg356Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1696282	NM_006502.3(POLH):c.1078dup (p.Asp360fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2734872	NM_006502.3(POLH):c.1657dup (p.Gln553fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2682158	NM_006502.3(POLH):c.571A>C (p.Thr191Pro)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
3593649	NM_006502.3(POLH):c.533_534del (p.Leu178fs)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
5884	NM_006502.3(POLH):c.106_118del (p.Val36fs)	Pathogenic	criteria provided, single submitter	2
5889	NM_006502.3(POLH):c.376C>T (p.Gln126Ter)	Pathogenic	criteria provided, single submitter	2
5890	NM_006502.3(POLH):c.1117C>T (p.Gln373Ter)	Pathogenic	criteria provided, single submitter	2
5892	NM_006502.3(POLH):c.207del (p.Lys70fs)	Pathogenic	criteria provided, single submitter	2
264680	NM_006502.3(POLH):c.725C>G (p.Ser242Ter)	Pathogenic	criteria provided, single submitter	2
449225	NM_006502.3(POLH):c.1318_1322del (p.Ile440fs)	Pathogenic	criteria provided, single submitter	1
520989	NM_006502.3(POLH):c.512del (p.Leu171fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore POLH’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 957):

Position(s)	Effect	Δscore	Sites
6:43583000	acceptor_gain	1.0000
6:43583005–43583006	acceptor_loss	1.0000	5
6:43583142–43583143	donor_loss	1.0000	5
6:43600979	acceptor_gain	1.0000
6:43600987	acceptor_loss	1.0000
6:43603883	acceptor_gain	1.0000
6:43603888	acceptor_gain	1.0000
6:43604012–43604013	donor_loss	1.0000	5
6:43604603–43604604	acceptor_gain	1.0000	2
6:43604613–43604614	acceptor_loss	1.0000	4

AlphaMissense

930 missense substitutions predicted likely pathogenic (of 4,656 scored), across 260 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D115	8	0.978	0.990
D15	8	0.975	0.991
D13	8	0.967	0.984
F325	8	0.868	0.977
D652	8	0.867	0.951
D355	8	0.786	0.936
F18	7	0.969	0.990
F17	7	0.948	0.989
W415	7	0.940	0.994
K231	7	0.939	0.989
E116	7	0.933	0.974
C72	7	0.921	0.973
W340	7	0.917	0.973
F247	7	0.898	0.958
C16	7	0.879	0.988
E22	7	0.879	0.946
S113	7	0.875	0.994
W174	7	0.873	0.972
C635	7	0.860	0.945
W42	7	0.857	0.932

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (validation)	favorable	2e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000186

Disease associations

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

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
xeroderma pigmentosum variant type	Definitive	Autosomal recessive	6

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
xeroderma pigmentosum variant type	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (3 panels, 3 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

3 panels:

Panel	Rating
Adult solid tumours cancer susceptibility	green
Childhood solid tumours	green
Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome	green

Mondo (2): xeroderma pigmentosum variant type (MONDO:0010214), xeroderma pigmentosum (MONDO:0019600)

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

HPO phenotypes

22 phenotypes (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:

Study	Trait	p-value
GCST005962_28	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3e-31
GCST005956_15	Waist-to-hip ratio adjusted for BMI	7e-26
GCST005958_10	Waist-to-hip ratio adjusted for BMI (age >50)	2e-19
GCST005957_3	Waist-to-hip ratio adjusted for BMI (age <50)	2e-14

EFO canonical traits (from GWAS)

3 canonical traits:

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 disease descriptors:

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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 213,649 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

7 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,240
CHEMBL50	QUERCETIN	3	75,572
CHEMBL8260	BAICALEIN	2	8,718
CHEMBL6246	ELLAGIC ACID	2	23,439
CHEMBL44	GENISTEIN	2	44,589
CHEMBL151	LUTEOLIN	2	23,845
CHEMBL150	KAEMPFEROL	1	26,246

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

24 measured of 35 human assays (47 total across all organisms); most potent 24 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Naringenin, 18	IC50	710 nM
cid_5280863	IC50	1050 nM
Prunetol	IC50	2210 nM
MLS002153482	IC50	3200 nM
TCV-116	IC50	5000 nM
CHEMBL457821	IC50	5000 nM
2-(3,4-dihydroxyphenyl)-4H-chromen-4-one	IC50	5700 nM
CHEMBL5398631	IC50	7700 nM
CHEMBL5433463	IC50	8000 nM
CHEMBL243677	IC50	8700 nM
2-(3,4-dihydroxyphenyl)-7-hydroxy-5-meth-oxy-4H-chromen-4-one	IC50	10200 nM
2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-methoxy-4H-chromen-4-one	IC50	10800 nM
CHEMBL5418159	IC50	13800 nM
CHEMBL5272459	IC50	14700 nM
CHEMBL4584525	IC50	16000 nM
5,7-Dihydroxy-2-(4-hydroxy-phenyl)-3-methoxy-chromen-4-one	IC50	16100 nM
CHEMBL5279962	IC50	26500 nM
CHEMBL3326852	IC50	33500 nM
CHEMBL3593571	IC50	50000 nM
CHEMBL3326854	IC50	62400 nM
CHEMBL5280903	IC50	84600 nM
CHEMBL5271510	IC50	87100 nM
CHEMBL5284680	IC50	87500 nM
CHEMBL5440374	IC50	98300 nM

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	increases abundance, increases expression, decreases expression, affects cotreatment	3
mercuric bromide	increases expression, affects cotreatment	2
pifithrin	decreases reaction, increases expression	2
Dactinomycin	affects cotreatment, increases expression, decreases reaction	2
Phenylmercuric Acetate	increases expression, affects cotreatment	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	increases expression, decreases response to substance	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00014638	Phase 4	COMPLETED	Letrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
NCT00022386	Phase 4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00029224	Phase 4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00030758	Phase 4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00082277	Phase 4	COMPLETED	Anastrozole Biphosphonate Study in Postmenopausal Women With Hormone-Receptor-Positive Early Breast Cancer
NCT00087620	Phase 4	TERMINATED	A Study of Capecitabine In Combination With Docetaxel vs Capecitabine Followed by Docetaxel As First-Line Treatment For Metastatic Breast Cancer
NCT00121836	Phase 4	COMPLETED	A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer
NCT00126360	Phase 4	UNKNOWN	STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing Pilot)
NCT00127933	Phase 4	COMPLETED	XeNA Study - A Study of Xeloda (Capecitabine) in Patients With Invasive Breast Cancer
NCT00128297	Phase 4	COMPLETED	Pamidronate Administration in Breast Cancer Patients With Bone Metastases
NCT00129597	Phase 4	UNKNOWN	Effect of Ketalar to Prevent Postoperative Chronic Pain After Mastectomy
NCT00131170	Phase 4	COMPLETED	Paravertebral Block for Breast Surgery
NCT00156039	Phase 4	COMPLETED	Randomized Trial of Follow-up Strategies in Breast Cancer
NCT00160901	Phase 4	COMPLETED	Complementary Therapies for the Reduction of Side Effects During Chemotherapy for Breast Cancer
NCT00171847	Phase 4	TERMINATED	Study of the Efficacy and Safety of Letrozole Combined With Trastuzumab in Patients With Metastatic Breast Cancer
NCT00176046	Phase 4	COMPLETED	Mistletoe Extract in Early or Advanced Breast Cancer, A Feasibility Study
NCT00190697	Phase 4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00234195	Phase 4	COMPLETED	Wellbutrin XL, Major Depressive Disorder and Breast Cancer
NCT00237133	Phase 4	COMPLETED	Treatment of Locally Advanced Breast Cancer With Letrozole in Postmenopausal Women
NCT00237224	Phase 4	COMPLETED	Open Label Study of Postmenopausal Women With ER and /or PgR Positive Breast Cancer Treated With Letrozole
NCT00241046	Phase 4	TERMINATED	Letrozole in the Treatment of 1st and 2nd Line Hormone Receptor Positive Breast Cancer: Pre-therapeutic Risk Assessment
NCT00277160	Phase 4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00323479	Phase 4	COMPLETED	Arthralgia During Anastrozole Therapy for Breast Cancer
NCT00334139	Phase 4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00356148	Phase 4	COMPLETED	The Efficacy of Prophylactic Antibiotic Administration During Breast Cancer Surgery in Overweight Patients.
NCT00372476	Phase 4	COMPLETED	Efficacy and Safety of Imatinib and Vinorelbine in Patients With Advanced Breast Cancer
NCT00413491	Phase 4	UNKNOWN	National Screening in Denmark With MR Versus Mammography and Ultrasound of Women With BRCA1 or BRCA2 Mutations
NCT00484614	Phase 4	UNKNOWN	Study the Role of Positron Emission Mammography in Pre-surgical Planning for Breast Cancer
NCT00485953	Phase 4	COMPLETED	Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
NCT00496678	Phase 4	COMPLETED	Trial of Patient Navigation-Activation
NCT00531973	Phase 4	UNKNOWN	A Study of Liposomal Doxorubicin in Women With Breast Cancer Exploiting Tissue Doppler Imaging
NCT00537771	Phase 4	COMPLETED	Liver Safety Under Upfront Arimidex vs Tamoxifen
NCT00544986	Phase 4	COMPLETED	A Prospective,Open-label Study of Anastrozole in Post-menopausal Women With Hormone Sensitive Advanced Breast Cancer
NCT00613275	Phase 4	COMPLETED	Patient Navigation in the Safety Net:CONNECTeDD
NCT00638599	Phase 4	COMPLETED	Comparison of Laryngeal Mask Airway (LMA®) and Tracheal Tube in Modified Radical Mastectomy on Breast Cancer
NCT00647075	Phase 4	UNKNOWN	Yunzhi as Dietary Supplement in Breast Cancer
NCT00688909	Phase 4	COMPLETED	Rheumatological Evaluation of Anastrozole and Letrozole as Adjuvant Treatment in Post-menopausal Women With Breast Cancer
NCT00699101	Phase 4	TERMINATED	Using the Conture® Multi-Lumen Balloon to Deliver Accelerated Partial Breast Brachytherapy
NCT00742222	Phase 4	COMPLETED	Electronic Xoft Intersociety Brachytherapy Trial: Electronic Brachytherapy (EBT) For Treatment of Early Stage Breast Cancer
NCT00754767	Phase 4	TERMINATED	L-Carnitine L-Tartrate in Preventing Peripheral Neuropathy Caused By Chemotherapy in Women With Metastatic Breast Cancer
NCT00756717	Phase 4	COMPLETED	Study Of MK-0752 In Combination With Tamoxifen Or Letrozole to Treat Early Stage Breast Cancer
NCT00766532	Phase 4	COMPLETED	Do Aromatase Inhibitors (AIs) Decrease Intestinal Calcium Absorption?
NCT00768222	Phase 4	COMPLETED	Coated VICRYL* Plus Suture Compared to Chinese Silk in Scheduled Breast Cancer Surgery
NCT00772824	Phase 4	COMPLETED	Study of the Effect of Glutamine Supplementation on Chemotherapy Induced Toxicities in Breast Cancer Patients
NCT00774241	Phase 4	WITHDRAWN	PRIMADOS Study:A Study of Avastin (Bevacizumab) Plus Docetaxel for First Line Treatment of Patients With Metastatic Breast Cancer
NCT00812864	Phase 4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00872859	Phase 4	COMPLETED	The BREASTrial:Breast Reconstruction Evaluation Using Acellular Dermal Matrix as a Sling Trial
NCT00882089	Phase 4	COMPLETED	Use of the Contura™ Catheter in Intermediate-Risk, Pathological Stage 0, I, or II (Up to 3.0 cm) Breast Cancer Patients
NCT00882596	Phase 4	COMPLETED	Use of the Contura™ Catheter to Deliver Accelerated Partial Breast Irradiation to Low-risk Breast Cancer Patients
NCT00904410	Phase 4	COMPLETED	Early Assessment of the Response to Neo-adjuvant Chemotherapy in Breast Cancer Patients With FDG-PET
NCT00912639	Phase 4	UNKNOWN	A Clinical Trial of Paclitaxel Loaded Polymeric Micelle in Patients With Taxane-Pretreated Recurrent Breast Cancer
NCT00912938	Phase 4	UNKNOWN	Evaluate the Relationship of Bone Remodeling Markers for Skeletal Complications in Metastatic Breast Cancer Patients
NCT01035099	Phase 4	COMPLETED	RCT of Fixed vs Titrated Letrozole in Breast Cancer Patient Undergoing IVF
NCT01049295	Phase 4	UNKNOWN	Omega-3 Fatty Acids and Chemotherapy-induced Neuropathy and Inflammation in Breast Cancer
NCT01072318	Phase 4	UNKNOWN	Extended Adjuvant Treatment With Letrozole in Breast Cancer Who Complete 5 Years of Toremifene
NCT01094184	Phase 4	COMPLETED	A Study of Bevacizumab With Taxane Therapy in Participants With Triple Negative Breast Cancer
NCT01156961	Phase 4	WITHDRAWN	A Study of The Safety Profile of First-line Avastin (Bevacizumab) in Combination With Paclitaxel in Patients With Locally Recurrent or Metastatic Her2-negative Breast Cancer (AVATAX)
NCT01199432	Phase 4	COMPLETED	Comparative Efficiency of Three Regimen, CEFci, CEF and EC as Neoadjuvant Chemotherapy for Primary Breast Cancer
NCT01216254	Phase 4	UNKNOWN	Clinical Trial Comparing Outcomes of Breast Conserving Operations With Classic v High-frequency Electrocoagulation
NCT01231204	Phase 4	COMPLETED	Prevention of Post-Mastectomy Breast Pain Using Ambulatory Continuous Paravertebral Blocks

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for POLH across ~30M SureChEMBL compounds — explore on Sugi Predict.