POLB

Summary

POLB (DNA polymerase beta, HGNC:9174) is a protein-coding gene on chromosome 8p11.21, encoding DNA polymerase beta (P06746). Repair polymerase that plays a key role in base-excision repair.

The protein encoded by this gene is a DNA polymerase involved in base excision and repair, also called gap-filling DNA synthesis. The encoded protein, acting as a monomer, is normally found in the cytoplasm, but it translocates to the nucleus upon DNA damage. Several transcript variants of this gene exist, but the full-length nature of only one has been described to date.

Source: NCBI Gene 5423 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 37 total
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈10% of expected missense variation)
• GTEx eGene: eQTL in 17 tissues, sQTL in 11 (q < 0.05)
• ChEMBL bioactivity: 117 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.03 (LoF-tolerant), LOEUF 1.77 (unconstrained)
• MANE Select transcript: NM_002690

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9174
Approved symbol	POLB
Name	DNA polymerase beta
Location	8p11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000070501
Ensembl biotype	protein_coding
OMIM	174760
Entrez	5423

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 22 protein_coding, 5 retained_intron, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000265421

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 4, TSL 3: 4, TSL 4: 1, TSL 5: 7

ENST00000265421, ENST00000517393, ENST00000518579, ENST00000518925, ENST00000519094, ENST00000519524, ENST00000519771, ENST00000520008, ENST00000521290, ENST00000521418, ENST00000521492, ENST00000522297, ENST00000522610, ENST00000523465, ENST00000524208, ENST00000530566, ENST00000532157, ENST00000929417, ENST00000987804, ENST00000987805, ENST00000987806, ENST00001014834, ENST00001063950, ENST00001063951, ENST00001063952, ENST00001063953, ENST00001091329, ENST00001091330, ENST00001091331, ENST00001091332, ENST00001091333, ENST00001091334, ENST00001134121

RefSeq mRNA: 1 — MANE Select: NM_002690 NM_002690

CCDS: CCDS6129

Canonical transcript exons

ENST00000265421 — 14 exons

Exon	Start	End
ENSE00002128274	42338494	42338685
ENSE00003586441	42361295	42361365
ENSE00003594528	42339012	42339069
ENSE00003601815	42350007	42350065
ENSE00003603058	42355516	42355567
ENSE00003615001	42349016	42349090
ENSE00003616864	42357169	42357223
ENSE00003620941	42369849	42369988
ENSE00003647857	42371563	42371808
ENSE00003658673	42369271	42369335
ENSE00003672168	42362612	42362698
ENSE00003673286	42357320	42357392
ENSE00003688632	42352519	42352568
ENSE00003691204	42344953	42345019

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.3990 / max 314.6333, expressed in 1811 samples.

Highest expression (Bgee): oocyte, cerebellar hemisphere, cerebellar cortex, secondary oocyte, hemisphere of cerebellum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

POLB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 17 tissues and its splicing (sQTL) in 11 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 28 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	1.1e-155	-1.20	8:42336930:T:C
Skin Not Sun Exposed Suprapubic	eqtl	2.2e-123	-1.09	8:42329061:T:C
Esophagus Mucosa	eqtl	1.3e-119	-1.00	8:42329061:T:C
Muscle Skeletal	sqtl	6.0e-26	-0.68	8:42336876:A:G
Brain Frontal Cortex BA9	sqtl	3.4e-17	-1.21	8:42343629:AAGG:A
Muscle Skeletal	eqtl	5.2e-16	+0.27	8:42337408:AAAG:A
Brain Cortex	sqtl	5.6e-14	-1.04	8:42338923:C:T
Testis	sqtl	3.7e-12	-1.29	8:42360252:C:T
Brain Cerebellar Hemisphere	sqtl	1.3e-08	-0.83	8:42300384:T:C
Testis	eqtl	1.4e-07	+0.28	8:42245804:C:T
Cells Cultured fibroblasts	sqtl	6.9e-06	+0.47	8:42230058:T:C
Lung	eqtl	1.1e-05	+0.22	8:42324723:A:C
Brain Cerebellum	sqtl	3.0e-05	-1.07	8:42338923:C:T
Adrenal Gland	eqtl	3.9e-04	-0.43	8:42275305:G:A
Adipose Subcutaneous	eqtl	5.2e-04	-0.22	8:42219231:A:G
Nerve Tibial	eqtl	9.4e-04	+0.22	8:42324723:A:C
Minor Salivary Gland	eqtl	2.1e-03	-1.52	8:42864810:A:C
Esophagus Mucosa	sqtl	3.8e-03	+0.59	8:42244730:G:A
Pituitary	eqtl	3.9e-03	+0.13	8:41745091:AACAG:A
Brain Hippocampus	sqtl	4.1e-03	-0.58	8:41666769:A:G

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
88681	16.4509	1809
88680	0.7760	485
88682	0.1256	36
88683	0.0465	12

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.16	gold quality
cerebellar hemisphere	UBERON:0002245	99.09	gold quality
cerebellar cortex	UBERON:0002129	99.08	gold quality
secondary oocyte	CL:0000655	98.92	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.85	gold quality
cerebellum	UBERON:0002037	98.79	gold quality
sperm	CL:0000019	98.51	gold quality
cortical plate	UBERON:0005343	97.19	gold quality
male germ cell	CL:0000015	96.99	gold quality
cerebellar vermis	UBERON:0004720	96.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.50	gold quality
ganglionic eminence	UBERON:0004023	96.37	gold quality
left testis	UBERON:0004533	95.75	gold quality
right testis	UBERON:0004534	95.69	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.36	gold quality
biceps brachii	UBERON:0001507	95.35	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.22	gold quality
embryo	UBERON:0000922	95.07	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.97	gold quality
diaphragm	UBERON:0001103	94.93	gold quality
testis	UBERON:0000473	94.92	gold quality
parotid gland	UBERON:0001831	94.80	gold quality
gingival epithelium	UBERON:0001949	94.39	gold quality
paraflocculus	UBERON:0005351	94.21	gold quality
monocyte	CL:0000576	94.02	gold quality
mononuclear cell	CL:0000842	93.80	gold quality
pons	UBERON:0000988	93.78	gold quality
leukocyte	CL:0000738	93.72	gold quality
palpebral conjunctiva	UBERON:0001812	93.53	gold quality
gingiva	UBERON:0001828	93.52	gold quality
body of tongue	UBERON:0011876	93.49	gold quality
gastrocnemius	UBERON:0001388	93.32	gold quality
epithelium of nasopharynx	UBERON:0001951	93.32	gold quality
periodontal ligament	UBERON:0008266	93.28	gold quality
muscle of leg	UBERON:0001383	93.24	gold quality
pituitary gland	UBERON:0000007	93.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.99	gold quality
granulocyte	CL:0000094	92.91	gold quality
squamous epithelium	UBERON:0006914	92.90	gold quality
triceps brachii	UBERON:0001509	92.86	gold quality
adenohypophysis	UBERON:0002196	92.73	gold quality
esophagus squamous epithelium	UBERON:0006920	92.53	gold quality
tonsil	UBERON:0002372	92.48	gold quality
muscle organ	UBERON:0001630	92.43	gold quality
gluteal muscle	UBERON:0002000	92.40	gold quality
mucosa of urinary bladder	UBERON:0001259	92.25	gold quality
epithelium of esophagus	UBERON:0001976	92.24	gold quality
adult organism	UBERON:0007023	92.23	gold quality
middle temporal gyrus	UBERON:0002771	92.17	gold quality
tongue	UBERON:0001723	91.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.69	gold quality
cervix squamous epithelium	UBERON:0006922	91.66	gold quality
blood	UBERON:0000178	91.64	gold quality
right frontal lobe	UBERON:0002810	91.59	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.47	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.36	gold quality
esophagus mucosa	UBERON:0002469	91.35	gold quality
nucleus accumbens	UBERON:0001882	91.18	gold quality
oral cavity	UBERON:0000167	91.13	gold quality
amygdala	UBERON:0001876	91.10	gold quality
islet of Langerhans	UBERON:0000006	91.08	gold quality
right lobe of liver	UBERON:0001114	91.05	gold quality
bone marrow	UBERON:0002371	91.05	gold quality
vastus lateralis	UBERON:0001379	91.03	gold quality
tongue squamous epithelium	UBERON:0006919	91.02	gold quality
skeletal muscle tissue	UBERON:0001134	90.88	gold quality
prefrontal cortex	UBERON:0000451	90.87	gold quality
brain	UBERON:0000955	90.86	gold quality
prostate gland	UBERON:0002367	90.86	gold quality
central nervous system	UBERON:0001017	90.85	gold quality
spinal cord	UBERON:0002240	90.71	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.52	gold quality
cervix epithelium	UBERON:0004801	90.48	gold quality
hypothalamus	UBERON:0001898	90.41	gold quality
skin of abdomen	UBERON:0001416	90.39	gold quality
heart left ventricle	UBERON:0002084	90.32	gold quality
cardiac ventricle	UBERON:0002082	90.28	gold quality
substantia nigra pars compacta	UBERON:0001965	90.24	gold quality
mammary duct	UBERON:0001765	90.12	gold quality
hair follicle	UBERON:0002073	90.08	gold quality
cingulate cortex	UBERON:0003027	90.06	gold quality
body of pancreas	UBERON:0001150	90.05	gold quality
superior surface of tongue	UBERON:0007371	90.05	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.98	gold quality
uterine cervix	UBERON:0000002	89.93	gold quality
forebrain	UBERON:0001890	89.93	gold quality
epithelium of mammary gland	UBERON:0003244	89.93	gold quality
skin of leg	UBERON:0001511	89.91	gold quality
anterior cingulate cortex	UBERON:0009835	89.91	gold quality
vagina	UBERON:0000996	89.89	gold quality
bone marrow cell	CL:0002092	89.85	gold quality
apex of heart	UBERON:0002098	89.85	gold quality
caudate nucleus	UBERON:0001873	89.84	gold quality
pharyngeal mucosa	UBERON:0000355	89.82	gold quality
upper leg skin	UBERON:0004262	89.82	gold quality
left ovary	UBERON:0002119	89.78	gold quality
putamen	UBERON:0001874	89.73	gold quality
zone of skin	UBERON:0000014	89.70	gold quality
saliva-secreting gland	UBERON:0001044	89.69	gold quality
ovary	UBERON:0000992	89.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.81

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	80.0	medium
Putamen	tissue	75.2
Tongue	tissue	65.3
Basal ganglia	tissue	62.6	low
Thalamus	tissue	57.7
Frontal cortex	tissue	56.5
Pons	tissue	54.7
Superior colliculi	tissue	54.7
Ventral forebrain	tissue	54.7
Cerebral cortex	tissue	52.6	medium
Somatosensory cortex	tissue	52.6
Midbrain	tissue	50.1
Testis	tissue	49.6	high
Bone marrow	tissue	48.4	low
Septum	tissue	48.1
Cerebellum	tissue	47.3	medium
Occipital cortex	tissue	47.3
Motor cortex	tissue	47.0
Medulla oblongata	tissue	46.5
Hypothalamus	tissue	46.5
Hippocampal formation	tissue	46.5
Spinal cord	tissue	46.3
Substantia nigra	tissue	45.7
Entorhinal cortex	tissue	44.9
Prefrontal cortex	tissue	44.5
Temporal cortex	tissue	43.5
Retrosplenial and cingulate cortex	tissue	43.2
Retrosplenial cortex	tissue	42.1
Caudate putamen	tissue	41.3
Insular cortex	tissue	39.3
Periaqueductal gray	tissue	36.7
Amygdala	tissue	35.9
Olfactory bulb	tissue	35.6
Corpus callosum	tissue	35.1
Liver	tissue	31.7	medium
Urinary bladder	tissue	28.8	high
Salivary gland	tissue	28.5	high
Pituitary gland	tissue	26.0
Breast	tissue	25.7	high
Heart muscle	tissue	24.5	not detected
Esophagus	tissue	24.1	medium
Thymus	tissue	23.1
Skin 1	tissue	21.7	medium
Prostate	tissue	21.6	medium
Ovary	tissue	21.3	medium
Postcentral gyrus	tissue	21.3
Tonsil	tissue	20.8	high
Vagina	tissue	19.1	low
Lymph node	tissue	18.9	medium
Epididymis	tissue	18.6	medium
Nucleus accumbens	tissue	18.4
Locus coeruleus	tissue	17.8
Parathyroid gland	tissue	17.6	medium
Retina	tissue	16.7
Adrenal gland	tissue	16.5	medium
Gallbladder	tissue	16.3	high
Spleen	tissue	15.9	medium
Hippocampus	tissue	15.5	low
Kidney	tissue	14.1	medium
Pancreas	tissue	14.0	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Cerebellar cortex (134.1), Vermis (121.0), Flocculonodular lobe (119.3), Dorsal hippocampus (46.5), Ventral spinal cord (46.3).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APEX1, ATF2, MYC, SP1, TBXT

miRNA regulators (miRDB)

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

17 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-655-5P	98.74	65.93	888
HSA-MIR-633	98.35	69.45	1167
HSA-MIR-4432	97.80	67.87	705
HSA-MIR-376C-3P	97.63	68.88	1263
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-346	97.01	66.97	662

Functional genomics

gnomAD constraint: pLI 0.0262, LOEUF 1.77, missense Z 0.676 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000265421 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈10% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
8:42,338,625–42,344,985	54 / 63.4	0.85	no
8:42,344,986–42,349,090	13 / 39.8	0.33	yes (p 2.2e-05)
8:42,350,007–42,371,654	246 / 297.6	0.83	no

Literature-anchored findings (GeneRIF, showing 40)

• To determine the role of Lys-280, site-directed mutants were constructed at this position, and the proteins were expressed and purified, and their catalytic efficiency and fidelity were assessed (PMID:11756435)
• dL residues may not be readily repaired by “short-patch” base excision repair but instead function as suicide substrates in the formation of protein-DNA cross-links that may require alternative modes of repair. (PMID:11805079)
• lowers replication fidelity and results in a modified error-specificity; occurs during synthesis of the lagging strand (PMID:11827474)
• dynamics of gapped DNA recognition (PMID:11912205)
• Repair of clustered DNA lesions (PMID:11923315)
• polymerase beta simulations suggest that Arg258 rotation is a slow step rather than large subdomain motions per se (PMID:11955015)
• Deregulated DNA polymerase beta induces chromosome instability and tumorigenesis. (PMID:12067997)
• To elucidate the molecular basis of microsatellite mutation, the in vitro error frequencies for DNA polymerase beta have been determined at template sequences representative of those found in the human genome: [GT/CA]10, [TC/AG]11, and [TTCC/AAGG]9. (PMID:12173936)
• readily expands triplet repeats at strand breaks under physiological dNTP and salt concentrations (PMID:12196536)
• analysis of the efficiency of dNTP (correct and incorrect) insertion for a low fidelity mutant of DNA polymerase beta shows that a strong correlation exists between the ability to synthesize DNA and the probability that the polymerase will make a mistake (PMID:12370169)
• Acetylation of Polbeta acts as an intranuclear regulatory mechanism and implies that p300 plays a critical regulatory role in base excision repair (PMID:12453427)
• Data report the first structure of a polymerase, DNA polymerase beta, with a promutagenic lesion in its active site. (PMID:12517346)
• The Werner syndrome protein stimulates this enzyme’s strand didsplacement DNA synthesis via its helicase activity (PMID:12665521)
• human RNA polymerase II (RNAP II) pausing and transcript cleavage is controlled by transcription factor IIF, hepatitis delta antigen, and stimulatory factor II (PMID:14506279)
• majority of single-strand DNA interruptions produced during the repair of alkylated DNA bases are repaired by the pathway mediated by Pol beta and either Lig I or Lig III (PMID:14627836)
• To probe molecular interactions in the dNTP-binding pocket, we analyzed the kinetic behavior of wild-type pol beta on modified DNA substrates that alter the structure of the DNA terminus and represent mutagenic intermediates. (PMID:15145936)
• identified a sequence in APC that binds DNA polymerase beta and blocks DNA polymerase beta-mediated strand-displacement synthesis in long patch BER without affecting short patch BER (PMID:15548520)
• pol beta cooperates with FEN1 to remove DNA damage via a “Hit and Run” mechanism, involving alternating short gap production by FEN1 and gap filling by pol beta (PMID:15561706)
• Splice variations of DNA polymerase beta may be caused by aberrant splicing. (PMID:15601998)
• Interplay between APE1, DNA polymerase beta and poly(ADP-ribose) polymerase-1 during base excision repair. (PMID:15731342)
• blockade of pol II-mediated transcription induces p53 accumulation in mitochondria and is the critical factor for eliciting p53-dependent but transcription-independent apoptosis (PMID:15753095)
• DNA polymerase beta variant (pol betadelta208-236) is ubiquitous and not breast cancer specific. (PMID:15764500)
• ectopic expression of TEIF in HeLa cells could upregulate both levels of endogenous beta-pol mRNA and protein, and consequently increases resistance to the oxidative stress of H2O2 (PMID:15963946)
• Following incision by AP endonuclease, DNA pol beta recognizes and binds to the incised abasic site and promotes recruitment of the DNA ligase III alpha-X-ray cross-complementing protein 1 (XRCC1) through its interaction with XRCC1. (PMID:16060670)
• cell-free extracts incubated with Ape1-incised 2-deoxyribonolactone substrates under non-repair conditions give rise to DNA-protein cross-links, with a major species dependent on the presence of polbeta (PMID:16188889)
• DNA pol-beta is an essential component of the DNA replication machinery in neuronal cell death in Alzheimer’s disease. (PMID:17065437)
• down-regulation of the normal base excision repair gap-filling DNA polymerase, pol beta, accompanies induced somatic hypermutation (PMID:17127106)
• Both pol-beta and Fen-1 interact with a 138-amino-acid peptide from adenomatosis polyposis coli protein at the DNA repair inhibitory domain. (PMID:17176113)
• use dGTP analogues replacing the beta,gamma-bridging O with CH2, CHF, CF2, or CCl2 to explore leaving-group effects on the nucleotidyl transfer mechanism and fidelity of DNA polymerase (pol) beta (PMID:17209556)
• The correlation coefficients show that the strength of the H-bond between dCTP and Asn279 is a strong predictor of the mutation-induced changes in the catalytic efficiency of pol beta. (PMID:17286973)
• The erroneous nucleotide incorporations catalyzed by DNA polymerases lambda and beta as well as the subsequent ligation catalyzed by a DNA ligase during base excision repair are a threat to genomic integrity. (PMID:17321545)
• results indicate step-by-step coordination in single-nucleotide base excision repair can rely on DNA binding specificity inherent in APE and Pol beta; coordination also may be facilitated by APE.Pol beta.DNA ternary complex formation (PMID:17355977)
• The E295K gastric carcinoma pol beta variant acts in a dominant-negative manner by interfering with base excision repair. (PMID:17526740)
• The Leu22Pro DNA polymerase beta variant has very little dRP lyase activity but retains its polymerase activity. (PMID:18039710)
• The fidelity of DNA polymerase beta was studied by analysing the chemical transition state of its catalytic site using analogues of dGTP. (PMID:18161950)
• Data show that CHIP-mediated degradation and DNA damage-dependent stabilization regulate base excision repair proteins XRCC1, DNA polymerase beta, and DNA ligase III. (PMID:18313385)
• Data report the crystallographic structures of DNA polymerase beta with dG-dAMPCPP and dC-dAMPCPP mismatches in the active site. (PMID:18471977)
• Results show that HPV16 is able to specifically stimulate the expression of DNA polB in human epithelial cells through interaction with the core upstream regulatory sequences of DNA polB promoter. (PMID:18686630)
• the mispaired primer terminus affects the geometry of the dNTP binding pocket such that the I260Q variant has a higher affinity for the incoming dNTP than wild-type polymerase beta. (PMID:18937502)
• replication protein A and proliferating cell nuclear antigen act as molecular switches to activate the DNA pol lambda- dependent highly efficient and faithful repair of A:8-oxo-G mismatches in human cells and to repress DNA pol beta activity. (PMID:19104052)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	polb	ENSDARG00000003749
mus_musculus	Polb	ENSMUSG00000031536
rattus_norvegicus	Polb	ENSRNOG00000019150

Paralogs (3): DNTT (ENSG00000107447), POLM (ENSG00000122678), POLL (ENSG00000166169)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97740) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 85 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased neuron apoptosis	2
increased splenocyte apoptosis	2
abnormal interatrial septum morphology	1
decreased cell proliferation	1
adrenal gland hypoplasia	1
abnormal forebrain morphology	1
abnormal cerebral cortex morphology	1
abnormal hindbrain morphology	1
small superior cervical ganglion	1
abnormal vagus ganglion morphology	1
small superior vagus ganglion	1
atelectasis	1
dermatitis	1
dermal cyst	1
decreased body size	1
cyanosis	1
salivary gland inflammation	1
respiratory failure	1
abnormal reflex	1
abnormal pulmonary alveolus morphology	1
abnormal spleen germinal center morphology	1
increased IgG level	1
increased mean platelet volume	1
glomerulonephritis	1
small thyroid gland	1

+60 more (showing top 25).

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
Bos taurus	Q27958	98.2%	Diamond
Macaca fascicularis	Q4R380	96.9%	Diamond
Xenopus laevis	O57383	83.9%	Diamond
Oryza sativa Japonica Group	Q67VC8	61.1%	Diamond
Arabidopsis thaliana	Q9FNY4	60.2%	Diamond
Acanthamoeba polyphaga mimivirus	Q7T6Y4	33.4%	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
IKBKB-DT	ncRNA	101929897
DKK4	protein-coding	27121
IKBKB	protein-coding	3551
VDAC3	protein-coding	7419
PLAT	protein-coding	5327
CHRNB3	protein-coding	1142
SMIM19	protein-coding	114926
SLC20A2	protein-coding	6575

Protein

Protein identifiers

DNA polymerase beta — P06746 (reviewed: P06746)

Alternative names: 5’-deoxyribose-phosphate lyase, AP lyase

All UniProt accessions (11): E5RG65, E5RHZ4, E5RIJ0, E5RJ55, E7EW18, E9PIC6, P06746, H0YAV8, H0YB29, H0YBJ0, H0YBX1

UniProt curated annotations — full annotation on UniProt →

Function. Repair polymerase that plays a key role in base-excision repair. During this process, the damaged base is excised by specific DNA glycosylases, the DNA backbone is nicked at the abasic site by an apurinic/apyrimidic (AP) endonuclease, and POLB removes 5’-deoxyribose-phosphate from the preincised AP site acting as a 5’-deoxyribose-phosphate lyase (5’-dRP lyase); through its DNA polymerase activity, it adds one nucleotide to the 3’ end of the arising single-nucleotide gap. Conducts ‘gap-filling’ DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases. It is also able to cleave sugar-phosphate bonds 3’ to an intact AP site, acting as an AP lyase.

Subunit / interactions. Monomer. Binds single-stranded DNA (ssDNA). Interacts with APEX1, LIG1, LIG3, FEN1, PCNA and XRCC1. Interacts with HUWE1/ARF-BP1, STUB1/CHIP and USP47. Interacts with FAM168A.

Subcellular location. Nucleus. Cytoplasm.

Post-translational modifications. Methylation by PRMT6 stimulates the polymerase activity by enhancing DNA binding and processivity. Ubiquitinated at Lys-41, Lys-61 and Lys-81: monoubiquitinated by HUWE1/ARF-BP1. Monoubiquitinated protein is then the target of STUB1/CHIP, which catalyzes polyubiquitination from monoubiquitin, leading to degradation by the proteasome. USP47 mediates the deubiquitination of monoubiquitinated protein, preventing polyubiquitination by STUB1/CHIP and its subsequent degradation.

Cofactor. Binds 2 magnesium ions per subunit.

Domain organisation. Residues 239-252 form a flexible loop which appears to affect the polymerase fidelity.

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

RefSeq proteins (1): NP_002681* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002008	DNA_pol_X_beta-like	Family
IPR002054	DNA-dir_DNA_pol_X	Domain
IPR003583	Hlx-hairpin-Hlx_DNA-bd_motif	Domain
IPR010996	HHH_MUS81	Domain
IPR018944	DNA_pol_lambd_fingers_domain	Domain
IPR019843	DNA_pol-X_BS	Binding_site
IPR022312	DNA_pol_X	Family
IPR027421	DNA_pol_lamdba_lyase_dom_sf	Homologous_superfamily
IPR028207	DNA_pol_B_palm_palm	Domain
IPR029398	PolB_thumb	Domain
IPR037160	DNA_Pol_thumb_sf	Homologous_superfamily
IPR043519	NT_sf	Homologous_superfamily

Pfam: PF10391, PF14716, PF14791, PF14792

Enzyme classification (BRENDA)

• EC 2.7.7.7 — DNA-directed DNA polymerase (BRENDA: 139 organisms, 372 substrates, 325 inhibitors, 281 Km, 239 kcat entries)
• EC 4.2.99.B1 — (BRENDA: organisms, substrates, inhibitors, Km, 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)
• 2’-deoxyribonucleotide-(2’-deoxyribose 5’-phosphate)-2’-deoxyribonucleotide-DNA = a 3’-end 2’-deoxyribonucleotide-(2,3-dehydro-2,3-deoxyribose 5’-phosphate)-DNA + a 5’-end 5’-phospho-2’-deoxyribonucleoside-DNA + H(+) (RHEA:66592)
• a 5’-end 2’-deoxyribose-2’-deoxyribonucleotide-DNA = (2E,4S)-4-hydroxypenten-2-al-5-phosphate + a 5’-end 5’-phospho-2’-deoxyribonucleoside-DNA + H(+) (RHEA:76255)

UniProt features (126 total): binding site 38, helix 25, mutagenesis site 24, strand 14, sequence variant 11, sequence conflict 4, modified residue 3, cross-link 3, chain 1, region of interest 1, active site 1, turn 1

Structure

Experimental structures (PDB)

showing 30 of 435 structures by resolution:

PDB	Title	Method	Resolution (Å)
8VFG	Binary DNA Polymerase Beta bound to DNA containing primer terminal FapydG base-paired …	X-RAY DIFFRACTION	1.54
9Y1J	S180R human DNA polymerase beta, Ternary complex dT:dAmpCpp	X-RAY DIFFRACTION	1.55
4KLI	DNA polymerase beta matched product complex with Mg2+, 90 s	X-RAY DIFFRACTION	1.6
5WO0	DNA polymerase beta substrate complex with incoming 5-FodUTP	X-RAY DIFFRACTION	1.6
9Y1E	S180R human DNA polymerase beta, Binary complex templating dG	X-RAY DIFFRACTION	1.6
9Y1G	S180R human DNA polymerase beta, Binary complex templating dC	X-RAY DIFFRACTION	1.6
2FMP	DNA Polymerase beta with a terminated gapped DNA substrate and ddCTP with sodium in the …	X-RAY DIFFRACTION	1.65
8VFF	Binary DNA Polymerase Beta bound to DNA containing primer terminal FapydG base-paired …	X-RAY DIFFRACTION	1.69
5VS3	Human DNA polymerase beta 8-oxoG:dA extension with dTTP after 90 s	X-RAY DIFFRACTION	1.7
9Y1D	S180R human DNA polymerase beta, Binary complex templating dA	X-RAY DIFFRACTION	1.7
9Y1K	S180R human DNA polymerase beta, Ternary complex dC:dGmpCpp	X-RAY DIFFRACTION	1.7
4KLG	DNA polymerase beta matched product complex with Mg2+, 40 s	X-RAY DIFFRACTION	1.7
7S9N	Binary complex of DNA Polymerase Beta with Fapy-dG in the template position	X-RAY DIFFRACTION	1.71
4KLM	DNA polymerase beta matched product complex with Mg2+, 11 h	X-RAY DIFFRACTION	1.75
6BTF	DNA Polymerase Beta I260Q Ternary Complex	X-RAY DIFFRACTION	1.75
7RBH	Human DNA polymerase beta crosslinked ternary complex 2	X-RAY DIFFRACTION	1.75
8VFI	Ternary DNA Polymerase Beta bound to DNA containing primer terminal FapydG base-paired …	X-RAY DIFFRACTION	1.77
5U2T	Pre-catalytic ternary complex of Human DNA Polymerase Beta With Gapped DNA substrate …	X-RAY DIFFRACTION	1.79
5V1G	DNA polymerase beta binary complex with 8-oxoG at the primer terminus	X-RAY DIFFRACTION	1.8
4KLJ	DNA polymerase beta matched product complex with Mg2+, 5 min	X-RAY DIFFRACTION	1.8
4F5N	Open ternary complex of R283K DNA polymerase beta with a metal free dCTP analog	X-RAY DIFFRACTION	1.8
4TUP	Structure of human DNA polymerase beta complexed with GG as the template (GG0b) in a …	X-RAY DIFFRACTION	1.8
5U2R	PRECATALYTIC TERNARY COMPLEX OF HUMAN DNA POLYMERASE BETA WITH GAPPED DNA SUBSTARTE …	X-RAY DIFFRACTION	1.8
6CR4	Ternary complex crystal structure of DNA polymerase Beta with a dideoxy terminated primer …	X-RAY DIFFRACTION	1.8
9Y16	WT human DNA polymerase beta, Binary complex templating dG	X-RAY DIFFRACTION	1.8
9Y18	WT human DNA polymerase beta, Binary complex templating dC	X-RAY DIFFRACTION	1.8
9Y1F	S180R human DNA polymerase beta, Binary complex templating dT	X-RAY DIFFRACTION	1.8
5V1O	DNA polymerase beta product complex with 8-oxoG:A and inserted dCTP	X-RAY DIFFRACTION	1.8
7RBF	Human DNA polymerase beta crosslinked binary complex - B	X-RAY DIFFRACTION	1.84
4KLL	DNA polymerase beta matched product complex with Mg2+, 45 min	X-RAY DIFFRACTION	1.84

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06746-F1	94.30	0.91

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; vesicles

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

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

Catalytic / active sites (1)

Position	Role
72	nucleophile; schiff-base intermediate with dna; for 5’-drp lyase activity

Ligand- & substrate-binding residues (38)

Position	Role
101	Na(+)
103	K(+)
103	Na(+)
106	K(+)
106	Na(+)
149	dATP
149	dCTP
149	dGTP
149	dTTP
180	dATP
180	dCTP
180	dGTP
180	dTTP
183	dATP
183	dCTP
183	dGTP
183	dTTP
189	dATP
189	dCTP
189	dGTP
60	K(+)
189	dTTP
190	dATP
190	dCTP
190	dGTP
190	dTTP
190	Mg(2+)
192	dGTP
192	Mg(2+)
60	Na(+)
256	Mg(2+)
62	K(+)
62	Na(+)
65	K(+)
65	Na(+)
101	K(+)

Post-translational modifications (6)

Type	Positions
N6-acetyllysine	72
Omega-n-methylarginine	83, 152
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)	41, 61, 81

Mutagenesis-validated functional residues (24)

Position	Phenotype
25	no effect on 5’-drp lyase activity. decreased ssdna binding.
34	decreased 5’-drp lyase activity. decreased ssdna binding.
35	decreased 5’-drp lyase activity. decreased ssdna binding. loss of 5’-drp lyase activity; when associated with a-68 and a-72. decreased …
35	reduces 5’-drp lyase activity slightly.
35	no effect on 5’-drp lyase activity.
39	no effect on 5’-drp lyase activity.
39	abolishes dna polymerase and 5’-drp lyase activity.
41	abolishes ubiquitination; when associated with r-61 and r-81.
60	decreased 5’-drp lyase activity. decreased ssdna binding.
61	abolishes ubiquitination; when associated with r-41 and r-81.
68	no effect on 5’-drp lyase activity. decreased ssdna binding. loss of 5’-drp lyase activity; when associated with a-35 and a-72. decreased …
68	slightly reduces 5’-drp lyase activity.
71	no effect on 5’-drp lyase activity. no effect on structure shown by circular dichroism. no effect on ssdna binding.
72	severely reduced 5’-drp lyase activity. does not affect ssdna binding. loss of 5’-drp lyase activity; when associated with a-35 and a-68 …
72	abolishes 5’-drp lyase activity. no effect on dna polymerase activity.
75	slightly decreased 5’-drp lyase activity. decreased ssdna binding. no effect on structure shown by circular dichroism.
81	abolishes ubiquitination; when associated with r-41 and r-61.
83	slight effect. abolishes methylation by prmt6 and impairs the polymerase activity; when associated with k-152.
84	no effect on structure shown by circular dichroism. no effect on ssdna binding.
84	no effect on 5’-drp lyase activity.
152	severely decreased function in base-excision repair. severely decreased dna-directed dna polymerase activity. no effect on 5’-drp lyase …
152	slight effect. abolishes methylation by prmt6 and impairs the polymerase activity; when associated with k-83.
285	affects dna-directed dna polymerase activity; contrary to wild-type enzyme, the mutant efficiently extends mispaired termini in gapped dna …
288	changed dna-directed dna polymerase activity; in complex with the dna template and the incoming dntp, it assumes a close conformation …

Function

Pathways and Gene Ontology

Reactome pathways

7 curated (TAS) of 13; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

13 pathways:

ID	Pathway	Evidence
R-HSA-5649702	APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway	curated
R-HSA-73930	Abasic sugar-phosphate removal via the single-nucleotide replacement pathway	curated
R-HSA-5651801	PCNA-Dependent Long Patch Base Excision Repair	curated
R-HSA-110362	POLB-Dependent Long Patch Base Excision Repair	curated
R-HSA-110373	Resolution of AP sites via the multiple-nucleotide patch replacement pathway	curated
R-HSA-110381	Resolution of AP sites via the single-nucleotide replacement pathway	curated
R-HSA-5689880	Ub-specific processing proteases	curated
R-HSA-73884	Base Excision Repair	—
R-HSA-73894	DNA Repair	—
R-HSA-5688426	Deubiquitination	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-73933	Resolution of Abasic Sites (AP sites)	—

MSigDB gene sets: 261 (showing top): GOBP_RESPONSE_TO_ETHANOL, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOMF_ENDONUCLEASE_ACTIVITY, GOBP_GLAND_MORPHOGENESIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_SALIVARY_GLAND_DEVELOPMENT, GOMF_NUCLEASE_ACTIVITY, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_LYMPH_NODE_DEVELOPMENT, SCIBETTA_KDM5B_TARGETS_UP, RAMJAUN_APOPTOSIS_BY_TGFB1_VIA_SMAD4_UP, KAUFFMANN_DNA_REPAIR_GENES

GO Biological Process (13): DNA-templated DNA replication (GO:0006261), DNA repair (GO:0006281), regulation of DNA repair (GO:0006282), base-excision repair (GO:0006284), base-excision repair, gap-filling (GO:0006287), pyrimidine dimer repair (GO:0006290), double-strand break repair via nonhomologous end joining (GO:0006303), DNA damage response (GO:0006974), response to gamma radiation (GO:0010332), response to ethanol (GO:0045471), response to hyperoxia (GO:0055093), DNA replication (GO:0006260), DNA biosynthetic process (GO:0071897)

GO Molecular Function (14): damaged DNA binding (GO:0003684), DNA-directed DNA polymerase activity (GO:0003887), DNA-(apurinic or apyrimidinic site) endonuclease activity (GO:0003906), microtubule binding (GO:0008017), lyase activity (GO:0016829), enzyme binding (GO:0019899), metal ion binding (GO:0046872), 5’-deoxyribose-5-phosphate lyase activity (GO:0051575), class I DNA-(apurinic or apyrimidinic site) endonuclease activity (GO:0140078), DNA binding (GO:0003677), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), DNA polymerase activity (GO:0034061)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule (GO:0005874), spindle microtubule (GO:0005876), protein-containing complex (GO:0032991), site of DNA damage (GO:0090734)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Resolution of Abasic Sites (AP sites)	3
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	2
Deubiquitination	1
Resolution of AP sites via the single-nucleotide replacement pathway	1
Post-translational protein modification	1
Metabolism of proteins	1
DNA Repair	1
Base Excision Repair	1

GO top-level categories

40 GO namespaces:

Category	Terms
DNA metabolic process	4
cellular anatomical structure	4
DNA repair	3
DNA biosynthetic process	2
catalytic activity	2
carbon-oxygen lyase activity	2
catalytic activity, acting on DNA	2
DNA replication	1
DNA damage response	1
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
base-excision repair	1
double-strand break repair	1
cellular response to stress	1
response to ionizing radiation	1
response to alcohol	1
response to stress	1
response to increased oxygen levels	1
nucleic acid biosynthetic process	1
DNA binding	1
DNA polymerase activity	1
DNA endonuclease activity	1
tubulin binding	1
protein binding	1
cation binding	1
DNA-(apurinic or apyrimidinic site) endonuclease activity	1
nucleic acid binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
nucleotidyltransferase activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
spindle	1
microtubule	1
cellular_component	1
chromosome	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 14 of 35 annotations. The rest are phylogenetic / computational / electronic (IEA).

14 experimentally-supported GO terms:

GO term	NS	Evidence
DNA damage response	BP	mutant phenotype
base-excision repair	BP	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
microtubule	CC	direct assay
nucleus	CC	direct assay
protein-containing complex	CC	direct assay
spindle microtubule	CC	direct assay
5’-deoxyribose-5-phosphate lyase activity	MF	direct assay
DNA-directed DNA polymerase activity	MF	direct assay
class I DNA-(apurinic or apyrimidinic site) endonuclease activity	MF	direct assay
enzyme binding	MF	physical interaction
lyase activity	MF	direct assay
microtubule binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 976 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLB	LIG3	P49916	966
POLB	XRCC1	P18887	952
POLB	APEX1	P27695	902
POLB	FEN1	P39748	846
POLB	PARP2	Q9UGN5	814
POLB	OGG1	P78554	809
POLB	PNKP	Q96T60	792
POLB	APTX	Q7Z2E3	782
POLB	UNG	P13051	771
POLB	LIG1	P18858	754
POLB	SMUG1	Q53HV7	749
POLB	POLM	Q9NP87	700
POLB	TAF1D	Q9H5J8	692
POLB	NEIL1	Q96FI4	679
POLB	POLE	Q07864	669

IntAct

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

12 partners by confidence:

Partner	Interaction type	MIscore	Records
TPP2	physical association	0.780	8
XRCC1	physical association	0.740	2
TDP1	association	0.640	1
WFS1	physical association	0.560	3
TAF1D	physical association	0.540	4
H2AC11	association	0.530	1
PARP1	association	0.530	1
SRPK2	phosphorylation reaction	0.440	1
HMGB1	association	0.350	2
HSD17B7	association	0.350	2
KAT7	physical association	0.000	1
TLE1	physical association	0.000	1

BioGRID (158 interactions; top human partners by supporting records): XRCC1 (Affinity Capture-MS; 20 records), PARP1 (Affinity Capture-MS; 6 records), PNKP (Affinity Capture-MS; 6 records), BRCA1 (Affinity Capture-Western; 5 records), EP300 (Affinity Capture-Western; 5 records), APEX1 (Two-hybrid; 4 records), LIG3 (Affinity Capture-MS; 4 records), PCNA (Affinity Capture-Western; 4 records), TDP1 (Affinity Capture-MS; 4 records), APLF (Affinity Capture-MS; 3 records), APTX (Affinity Capture-MS; 3 records), BCKDHA (Affinity Capture-MS; 3 records), BCKDHB (Affinity Capture-MS; 3 records), HIST1H2AG (Affinity Capture-MS; 3 records), HSD17B7 (Affinity Capture-MS; 3 records)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
ATF2	“up-regulates quantity by expression”	POLB	“transcriptional regulation”
clofarabine	“down-regulates activity”	POLB	“chemical inhibition”

Protein complexes (CORUM) (5)

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

5 complexes by size:

Complex	Subunits	Members
DNA repair complex (NEIL2-PNK-Pol(beta)-LigIII(alpha)-XRCC1)	5	LIG3, NEIL2, PNKP, POLB, XRCC1
DNA repair complex NEIL1-PNK-Pol(beta)-LigIII(alpha)-XRCC1	5	PDXK, POLB, XRCC1, LIG3, NEIL1
★ DNA base excision repair complex	5	LIG3, PARP1, PARP2, POLB, XRCC1
9-1-1-POLB complex	4	HUS1, POLB, RAD1, RAD9A
DNA ligase III-XRCC1-PNK-DNA-pol III multiprotein complex	4	LIG3, PNKP, POLB, XRCC1

Disease & clinical

Genetic variants

Variant evidence for POLB: 37 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 1,085):

Position(s)	Effect	Δscore	Sites
8:42338686	donor_loss	1.0000	2
8:42357319	acceptor_loss	1.0000
8:42357393–42357394	donor_loss	1.0000	5
8:42371556	acceptor_gain	1.0000
8:42371561–42371562	acceptor_loss	1.0000	4
8:42338686–42338687	donor_loss	0.9900	2
8:42344950	acceptor_gain	0.9900
8:42344951–42344952	acceptor_loss	0.9900	6
8:42349011	acceptor_gain	0.9900
8:42349091–42349092	donor_loss	0.9900	6

AlphaMissense

1,054 missense substitutions predicted likely pathogenic (of 2,224 scored), across 239 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
M236	9	0.927	0.997
D192	8	0.998	0.999
D256	8	0.998	0.999
D190	8	0.996	0.998
F320	8	0.979	0.997
F272	8	0.978	1.000
S180	8	0.975	0.998
F278	8	0.953	0.994
N279	8	0.936	0.997
D276	8	0.919	0.982
F146	8	0.900	0.985
H135	8	0.878	0.987
M155	8	0.858	0.993
F223	8	0.849	0.994
H197	8	0.823	0.964
D226	8	0.774	0.952
D145	8	0.757	0.901
N28	8	0.742	0.959
R283	7	0.996	1.000
E295	7	0.992	0.998

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 Papillary Cell Carcinoma (TCGA)	unfavorable	0.000399
Glioblastoma Multiforme (validation)	favorable	0.000511

Disease associations

OMIM: gene MIM:174760 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST002374_3	Plasma plasminogen activator levels	1e-9
GCST006431_8	Plasma parathyroid hormone levels	3e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2392 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 937,089 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 117 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1330792	ACETARSONE	4	2,078
CHEMBL1569	AMANTADINE HYDROCHLORIDE	4	11,279
CHEMBL174	AMPICILLIN	4	336,569
CHEMBL1200758	AMPICILLIN SODIUM	4	5,652
CHEMBL388590	BENZBROMARONE	4	8,286
CHEMBL1528134	BENZYDAMINE HYDROCHLORIDE	4	9,588
CHEMBL290106	BITHIONOL	4	6,490
CHEMBL113	CAFFEINE	4	202,768
CHEMBL1201236	CARBIDOPA ANHYDROUS	4	25,411
CHEMBL1200974	CARBINOXAMINE MALEATE	4	2,810
CHEMBL1010	CEFOTAXIME SODIUM	4	4,963
CHEMBL1200530	CEFOXITIN SODIUM	4	4,550
CHEMBL2146124	CEFUROXIME SODIUM	4	56
CHEMBL1632	CEPHALOTHIN SODIUM	4	3,094
CHEMBL1201043	CEPHAPIRIN SODIUM	4	3,320
CHEMBL1713	CHLORPROMAZINE HYDROCHLORIDE	4	13,271
CHEMBL311498	CIANIDANOL	4	60,179
CHEMBL42	CLOZAPINE	4	37,868
CHEMBL160	CYCLOSPORINE	4	169,776
CHEMBL1563	DAUNORUBICIN HYDROCHLORIDE	4	29,081
CHEMBL1200474	DEMECLOCYCLINE HYDROCHLORIDE	4
CHEMBL121663	DEQUALINIUM CHLORIDE	4
CHEMBL231884	DIOSMIN	4
CHEMBL421701	DITHIAZANINE IODIDE	4
CHEMBL1200561	DOXAZOSIN MESYLATE	4
CHEMBL359744	DOXORUBICIN HYDROCHLORIDE	4
CHEMBL1108	DROPERIDOL	4
CHEMBL1752	DYPHYLLINE	4
CHEMBL1523964	EPHEDRINE SULFATE	4
CHEMBL1511	ESTRADIOL VALERATE	4
CHEMBL1441	ETHIONAMIDE	4
CHEMBL1622	FOLIC ACID	4
CHEMBL562	GRISEOFULVIN	4
CHEMBL496	HEXACHLOROPHENE	4
CHEMBL1117	IDARUBICIN	4
CHEMBL1282	IMIQUIMOD	4
CHEMBL1711	ISOPROTERENOL HYDROCHLORIDE	4
CHEMBL5315124	LEVOFLOXACIN	4
CHEMBL1201119	LIOTHYRONINE SODIUM	4
CHEMBL313972	MASOPROCOL	4
CHEMBL1201139	MEGESTROL ACETATE	4
CHEMBL2146123	METHACYCLINE HYDROCHLORIDE	4
CHEMBL34259	METHOTREXATE	4
CHEMBL459	METHYLDOPA	4
CHEMBL405110	METHYLENE BLUE ANHYDROUS	4
CHEMBL606	MISOPROSTOL	4
CHEMBL1417019	MITOXANTRONE HYDROCHLORIDE	4
CHEMBL57	NEVIRAPINE	4
CHEMBL1256842	NOMIFENSINE MALEATE	4
CHEMBL2107797	NORGESTREL	4
CHEMBL1517	OXYTETRACYCLINE	4
CHEMBL1223	PENICILLIN G POTASSIUM	4
CHEMBL361506	PENTAMIDINE ISETHIONATE	4
CHEMBL856	PRIMIDONE	4
CHEMBL772	RESERPINE	4
CHEMBL850	SPARFLOXACIN	4
CHEMBL991	STAVUDINE	4
CHEMBL1200348	SULCONAZOLE NITRATE	4
CHEMBL1109	SULFAPHENAZOLE	4
CHEMBL117785	TETRABENAZINE	4

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — DNA polymerases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
oleanolic acid	Inhibition	5.6	pIC50

Binding affinities (BindingDB)

76 measured of 195 human assays (198 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5284382	IC50	5 nM
CHEMBL483492	IC50	15 nM
CHEMBL5557939	IC50	204 nM
CHEMBL2441983	KI	400 nM
CHEMBL5431041	IC50	400 nM
CHEMBL2441974	KI	450 nM
CHEMBL2092833	IC50	480 nM
[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)oxolan-2-yl]methyl {[(phosphonatooxy)phosphinato]methyl}phosphonate	KI	600 nM
(1S,2R,4aS,6aS,6bR,8aR,10R,11R,12aR,12bR,14bS)-10,11-dihydroxy-1,2,6a,6b,9,9,12a-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxylic acid	IC50	810 nM
gallic acid 5,6-dihydroxy-3-carboxyphenylester	KI	830 nM
[(2R,3S,5R)-5-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl {[(phosphonatooxy)phosphinato]methyl}phosphonate	KI	900 nM
1-(2-CYCLOPROPYLETHYL)-3-(1,1-DIOXIDO-2H-1,2,4-BENZOTHIADIAZIN-3-YL)-6-FLUORO-4-HYDROXYQUINOLIN-2(1H)-ONE	IC50	1000 nM
({({[(2R,3S,4R,5R)-3,4-dihydroxy-5-(5-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)oxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxyphosphoryl}oxy)phosphonic acid	IC50	1000 nM
[(2R,3S,5R)-5-(2-amino-6-oxo-6,9-dihydro-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methyl {[(phosphonatooxy)phosphinato]methyl}phosphonate	KI	1000 nM
sodium ((2S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl trihydrogentriphosphate	IC50	1300 nM
thymidine 5’-(tetrahydrogen triphosphate)	IC50	1400 nM
CHEMBL2441980	KI	1500 nM
3beta-hydroxyurs-12-en-28-oic acid	IC50	1900 nM
6,13-di(hydroxymethyl)-2,6-dimethyl-(1S,2S,5R,6R,7R,10S,12R,13R)-tetracyclo[10.3.1.01,10.02,7]hexadecane-5,13-diol (Aphidicolin)	EC50	2000 nM
1beta-hydroxyaleuritolic acid 3-p-hydroxybenzoate	IC50	2200 nM
(3aS,4S,7R,7aR)-1,6-dihexadecyl-2,7-bis(methoxycarbonyl)-3-oxo-3a,4,7,7a-tetrahydro-3H-indene-4-carboxylic acid	IC50	2500 nM
({({[2-(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)ethoxy]methyl}(hydroxy)phosphoryl)oxyphosphoryl}oxy)phosphonic acid	IC50	2500 nM
(E)-methyl-3,6-dioxo-4-docosenoate	IC50	3700 nM
CHEMBL1162297	KI	5000 nM
CHEMBL1977402	IC50	5000 nM
CHEMBL1985644	IC50	5000 nM
CHEMBL5290566	IC50	5160 nM
cid_64971	IC50	7280 nM
protolichesterinic acid	IC50	7400 nM
2’,3’-Dideoxyadenosine Triphosphate (Ddatp)	IC50	8400 nM
(3aS,4S,7R,7aR)-1,6-didodecyl-2,7-bis(methoxycarbonyl)-3-oxo-3a,4,7,7a-tetrahydro-3H-indene-4-carboxylic acid	IC50	8600 nM
(4aS,6aS,6bR,10S,12aR,14bS)-10-Hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-octadecahydro-2H-picene-4a-carboxylic acid	IC50	8800 nM
MLS000028605	IC50	9000 nM
CHEMBL2092835	IC50	10400 nM
Combivir	IC50	11000 nM
Mahureone D	IC50	12000 nM
armenin-B	IC50	12300 nM
3beta,16beta,23-triacetoxyolean-12-en-28-oic acid	IC50	13000 nM
PUSILATIN B	IC50	13000 nM
MARCHANTIN B	IC50	14400 nM
CHEBI:6693	IC50	14400 nM
CHEMBL5279154	IC50	14400 nM
PERROTETTIN F	IC50	14400 nM
(7S,8R,1’S,5’S,6’R)-delta 2’,8’-5’,6’-Dihydroxy-3’-methoxy-3,4-methylenedioxy-4’-oxo-8.1’,7.5’-neolignan	IC50	15300 nM
Untenone A	IC50	16000 nM
2,4-Dimethoxy-5,6-methylenedioxy-1-(2-propenyl)benzene	IC50	18600 nM
CHEBI:41846	IC50	19000 nM
(3aS,4S,7R,7aR)-1,6-dihexadecyl-2,7-bis(isopropoxycarbonyl)-3-oxo-3a,4,7,7a-tetrahydro-3H-indene-4-carboxylic acid	IC50	20000 nM
CHEMBL5431393	KD	20100 nM
CHEMBL4088430	IC50	20200 nM

ChEMBL bioactivities

5355 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.70	Potency	20	nM	CHEMBL1473350
7.65	Potency	22.4	nM	AURINTRICARBOXYLIC ACID
7.65	Potency	22.4	nM	CHEMBL1569550
7.60	Potency	25.1	nM	CHEMBL1344856
7.60	Potency	25.1	nM	CHEMBL1328025
7.45	Potency	35.5	nM	CHEMBL1336244
7.40	Potency	39.8	nM	CHEMBL1402560
7.20	Potency	63.1	nM	CHEMBL1334116
7.20	Potency	63.1	nM	CHEMBL3195346
7.20	Potency	63.1	nM	CHEMBL56393
7.15	Potency	70.8	nM	CHEMBL1490125
7.15	Potency	70.8	nM	CHEMBL3195250
7.10	Potency	79.4	nM	CHEMBL1329268
7.10	Potency	79.4	nM	CHEMBL1514546
7.10	Potency	79.4	nM	CHEMBL1436700
7.10	Potency	79.4	nM	CHEMBL1494689
7.10	Potency	79.4	nM	CHEMBL1444978
7.05	Potency	89.1	nM	CHEMBL1361558
7.05	Potency	89.1	nM	CHEMBL3196556
7.05	Potency	89.1	nM	CHEMBL1316953
7.05	Potency	89.1	nM	CHEMBL1409626
7.05	Potency	89.1	nM	CHEMBL2000202
7.05	Potency	89.1	nM	CHEMBL1468933
7.05	Potency	89.1	nM	CHEMBL1446452
7.05	Potency	89.1	nM	CHEMBL1424074
7.05	Potency	89.1	nM	CHEMBL1407370
7.05	Potency	89.1	nM	CHEMBL1496953
7.00	Potency	100	nM	CHEMBL1500886
7.00	Potency	100	nM	CHEMBL460518
7.00	Potency	100	nM	CHEMBL1354805
7.00	Potency	100	nM	CHEMBL1516808
7.00	Potency	100	nM	CHEMBL1477564
7.00	Potency	100	nM	CHEMBL1458407
7.00	Potency	100	nM	CHEMBL1449056
7.00	Potency	100	nM	CHEMBL1340515
7.00	Potency	100	nM	CHEMBL1300861
7.00	Potency	100	nM	CHEMBL1359927
7.00	Potency	100	nM	CHEMBL1528373
7.00	Potency	100	nM	CHEMBL1459623
7.00	Potency	100	nM	CHEMBL1460488
7.00	Potency	100	nM	CHEMBL1526395
7.00	Potency	100	nM	CHEMBL1486484
7.00	Potency	100	nM	CHEMBL220869
7.00	Potency	100	nM	CHEMBL3209829
7.00	Potency	100	nM	CHEMBL1299713
7.00	Potency	100	nM	CHEMBL1339797
7.00	Potency	100	nM	CHEMBL3211365
7.00	Potency	100	nM	CHEMBL1594479
7.00	Potency	100	nM	CHEMBL1399230
7.00	Potency	100	nM	CHEMBL1320223

PubChem BioAssay actives

37 with measured affinity, of 307 total; 34 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
[(2S,3R,5R)-3-[[5-(4-chlorophenyl)-2-(trifluoromethyl)furan-3-carbonyl]amino]-5-[5-[[(4,7-dibromo-3-hydroxynaphthalene-2-carbonyl)amino]methyl]-2,4-dioxopyrimidin-1-yl]oxolan-2-yl]methyl [(2S,3S,5R)-2,5-dihydroxyoxolan-3-yl]methyl hydrogen phosphate	2076427: Inhibition of DNA polymerase beta (unknown origin) measured after 30 mins	ic50	0.2040	uM
3,4-dihydroxy-5-(3,4,5-trihydroxybenzoyl)oxybenzoic acid	397114: Inhibition of DNA polymerase beta from human KB3 cells	ki	0.3900	uM
[(2R,3S,5R)-3-[(E)-(2,6-dichloro-3-hydroxy-4-methoxyphenyl)methylideneamino]oxy-5-[5-[[(3,8-dihydroxynaphthalene-2-carbonyl)amino]methyl]-2,4-dioxopyrimidin-1-yl]oxolan-2-yl]methyl [(3S)-2,5-dihydroxyoxolan-3-yl]methyl hydrogen phosphate	1993592: Inhibition of DNA polymerase beta (unknown origin)	ic50	0.4000	uM
[hydroxy-[[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphoryl]methyl-phosphonooxyphosphinic acid	391154: Inhibition of human DNA polymerase beta	ki	0.6000	uM
[(2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy-[[hydroxy(phosphonooxy)phosphoryl]methyl]phosphinic acid	391154: Inhibition of human DNA polymerase beta	ki	0.9000	uM
[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-[[hydroxy(phosphonooxy)phosphoryl]methyl]phosphinic acid	391154: Inhibition of human DNA polymerase beta	ki	1.0000	uM
[[(2S,3R,5S)-5-(4-amino-2-oxopyrimidin-1-yl)-3-fluorooxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	53486: Compound was evaluated for the inhibition of cellular DNA polymerase (beta)	ic50	1.0000	uM
[[(2S,3R,5S)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-fluorooxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	53486: Compound was evaluated for the inhibition of cellular DNA polymerase (beta)	ic50	1.0000	uM
sodium [(2S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [hydroxy(phosphonooxy)phosphoryl] phosphate	402635: Inhibition of human recombinant DNA polymerase beta assessed as fluorescein-12-dCTP incorporation by fluorimetry	ic50	1.3000	uM
[hydroxy-[[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphoryl] phosphono hydrogen phosphate	1443139: Inhibition of human DNA polymerase-beta	ic50	1.4000	uM
2-(2-amino-6-oxo-1H-purin-9-yl)ethoxymethyl-[hydroxy(phosphonooxy)phosphoryl]oxyphosphinic acid	560429: Inhibition of human DNA polymerase beta by microplate reader analysis	ic50	1.6000	uM
7-O-ethyl 2-O,4-O-dimethyl (3aR,4R,7S,7aS)-3,5-dihexadecyl-1-oxo-3a,4,7,7a-tetrahydroindene-2,4,7-tricarboxylate	265077: Inhibition of DNA polymerase beta	ic50	1.9000	uM
(4aS,6aS,6bR,8aS,10S,12R,12aR,14aS,14bR)-12-hydroxy-10-(4-hydroxybenzoyl)oxy-2,2,6b,9,9,12a,14a-heptamethyl-1,3,4,5,6a,7,8,8a,10,11,12,13,14,14b-tetradecahydropicene-4a-carboxylic acid	398466: Inhibition of DNA polymerase beta	ic50	2.2000	uM
[[(2S,3R,5S)-3-fluoro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	53486: Compound was evaluated for the inhibition of cellular DNA polymerase (beta)	ic50	2.2000	uM
(3aS,4S,7R,7aR)-1,6-didodecyl-2,7-bis(methoxycarbonyl)-3-oxo-3a,4,7,7a-tetrahydroindene-4-carboxylic acid	265077: Inhibition of DNA polymerase beta	ic50	2.3000	uM
7-O-ethyl 2-O,4-O-dimethyl (3aR,4S,7S,7aS)-3,5-dihexadecyl-1-oxo-3a,4,7,7a-tetrahydroindene-2,4,7-tricarboxylate	265077: Inhibition of DNA polymerase beta	ic50	2.4000	uM
(4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid	697027: Inhibition of DNA polymerase beta	ic50	3.0000	uM
[[(2S,3R,5S)-5-(2,4-dioxopyrimidin-1-yl)-3-fluorooxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	53486: Compound was evaluated for the inhibition of cellular DNA polymerase (beta)	ic50	3.0000	uM
(3aS,4S,7R,7aR)-1,6-dihexadecyl-2,7-bis(methoxycarbonyl)-3-oxo-3a,4,7,7a-tetrahydroindene-4-carboxylic acid	265077: Inhibition of DNA polymerase beta	ic50	3.2000	uM
(3aS,4S,7R,7aR)-1,6-dihexadecyl-3-oxo-2,7-bis(propan-2-yloxycarbonyl)-3a,4,7,7a-tetrahydroindene-4-carboxylic acid	265077: Inhibition of DNA polymerase beta	ic50	4.4000	uM
[(2R,3S,5R)-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-[[hydroxy(phosphonooxy)phosphoryl]methyl]phosphinic acid	391154: Inhibition of human DNA polymerase beta	ki	5.0000	uM
2,4,5-trimethyl-N-[5-(4-methylanilino)-1H-1,2,4-triazol-3-yl]benzenesulfonamide	1923837: Inhibition of human DNA polymerase beta by fluorescence anisotropy	ic50	5.0000	uM
4-chloro-N-[5-(4-chloroanilino)-1H-1,2,4-triazol-3-yl]-5-methyl-2-sulfanylbenzenesulfonamide	1993590: Inhibition of human DNA polymerase beta incubated for 30 mins in presence of dNTP by PAGE based assay	ic50	5.0000	uM
4-chloro-5-methyl-N-[5-(naphthalen-2-ylamino)-1H-1,2,4-triazol-3-yl]-2-sulfanylbenzenesulfonamide	1993590: Inhibition of human DNA polymerase beta incubated for 30 mins in presence of dNTP by PAGE based assay	ic50	5.0000	uM
4-(5,16,24-trihydroxy-14-oxapentacyclo[20.2.2.210,13.115,19.02,7]nonacosa-1(24),2(7),3,5,10(29),11,13(28),15(27),16,18,22,25-dodecaen-17-yl)-14-oxapentacyclo[20.2.2.210,13.115,19.02,7]nonacosa-1(24),2,4,6,10(29),11,13(28),15,17,19(27),22,25-dodecaene-5,16,24-triol	1959329: Inhibition of DNA polymerase beta (unknown origin)	ic50	5.1600	uM
(2S,3R)-4-methylidene-5-oxo-2-tridecyloxolane-3-carboxylic acid	398466: Inhibition of DNA polymerase beta	ic50	7.4000	uM
[[(2S,5R)-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	1614343: Inhibition of human DNA polymerase beta using 5-end radiolabeled 24nt to 48nt DNA as primer template after 5 mins in presence of dCTP/dGTP/dTTP/dATP by PAGE analysis	ic50	8.4000	uM
methyl (2S,3S,4R,5E)-2-ethyl-4-hydroxy-5-(2-oxononadecylidene)-1-(2-phenylethyl)pyrrolidine-3-carboxylate	265077: Inhibition of DNA polymerase beta	ic50	8.7000	uM
dimethyl (3aR,4R,7S,7aS)-3,5-dihexadecyl-1-oxo-7-(2-phenylethylcarbamoyl)-3a,4,7,7a-tetrahydroindene-2,4-dicarboxylate	265077: Inhibition of DNA polymerase beta	ic50	8.7000	uM
methyl (2R,3S,4R,5E)-4-hydroxy-5-(2-oxononadecylidene)-2-phenyl-1-(2-phenylethyl)pyrrolidine-3-carboxylate	265077: Inhibition of DNA polymerase beta	ic50	8.8000	uM
methyl (E)-3,6-dioxodocos-4-enoate	265077: Inhibition of DNA polymerase beta	ic50	8.8000	uM
4-[(3-carboxy-2-hydroxynaphthalen-1-yl)methyl]-3-hydroxynaphthalene-2-carboxylic acid	754124: Inhibition of DNA polymerase beta (unknown origin)	ic50	9.0000	uM
methyl (2R,3S,4R,5E)-4-hydroxy-1-[2-(1H-indol-3-yl)ethyl]-5-(2-oxotetradecylidene)-2-phenylpyrrolidine-3-carboxylate	265077: Inhibition of DNA polymerase beta	ic50	10.0000	uM
[[(R)-[(2S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]-fluoromethoxy]-hydroxyphosphoryl] phosphono hydrogen phosphate	547084: Inhibition of human DNA polymerase beta assessed as incorporation of [alpha-32P]dCTP up to 1mM preincubated for 30 mins by whatman DE81 paper binding assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	4
arsenite	increases expression, affects expression, affects binding, increases reaction	3
sodium arsenite	increases abundance, increases expression, decreases expression, increases activity, affects expression (+2 more)	3
bisphenol A	decreases expression, decreases reaction	2
Temozolomide	decreases reaction, increases reaction, increases response to substance, decreases response to substance	2
Arsenic	increases abundance, increases expression, decreases expression, decreases reaction, affects cotreatment	2
Curcumin	decreases expression, decreases reaction	2
Methyl Methanesulfonate	increases expression	2
N6-(2-hydroxy-3-buten-1-yl)-2’-deoxyadenosine	decreases activity	1
bisphenol F	increases expression	1
6-thio-2’-deoxyguanosine-5’-triphosphate	affects binding, increases metabolic processing	1
5-formyldeoxycytosine-5’-triphosphate	affects binding, increases metabolic processing	1
dicrotophos	decreases expression	1
methoxyamine	decreases reaction, increases reaction, increases response to substance	1
triphenyl phosphate	affects expression	1
honokiol	decreases activity	1
1,12-benzoperylene	increases expression	1
diepoxybutane	affects binding, decreases activity	1
5-chlorouracil	affects metabolic processing	1
trichostatin A	affects expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
4-hydroxy-2-nonenal	decreases expression	1
methyl tert-butyl ether	affects response to substance	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
beta-methylcholine	affects expression	1
2’-deoxyadenosine	decreases activity, affects binding	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
azoxystrobin	increases expression	1
cylindrospermopsin	decreases expression	1

ChEMBL screening assays

86 unique, capped per target: 75 binding, 6 admet, 5 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000069	Binding	Inhibition of human DNA polymerase beta	Anti-AIDS agents, 1. Isolation and characterization of four new tetragalloylquinic acids as a new class of HIV reverse transcriptase inhibitors from tannic acid. — *J Nat Prod*
CHEMBL1614079	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of DNA Polymerase Beta. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL4008261	ADMET	Inhibition of recombinant human DNA polymerase beta preincubated with enzyme followed by addition of dATP/dGTP/TTP as substrate in presence of [gamma-33P]TTP by phosphorimaging assay	Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses. — *J Med Chem*

Cellosaurus cell lines

9 cell lines: 7 cancer cell line, 1 transformed cell line, 1 hybrid cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4IJ	NALM-6 POLB (-/-)	Cancer cell line	Male
CVCL_B2BD	Abcam HeLa POLB KO	Cancer cell line	Female
CVCL_D9NX	Ubigene HEK293 POLB KO	Transformed cell line	Female
CVCL_E2H4	HAP1 POLB (-) 3	Cancer cell line	Male
CVCL_E2H5	HAP1 POLB (-) 4	Cancer cell line	Male
CVCL_E2H6	HAP1 POLB (-) 5	Cancer cell line	Male
CVCL_F4FD	HyCyte AC16 [Human hybrid cardiomyocyte] KO-hPOLB	Hybrid cell line
CVCL_TE88	HAP1 POLB (-) 1	Cancer cell line	Male
CVCL_TE89	HAP1 POLB (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

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