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POLB

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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
  • Druggable target: yes — 117 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_002690

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:9174
Approved symbolPOLB
NameDNA polymerase beta
Location8p11.21
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000070501
Ensembl biotypeprotein_coding
OMIM174760
Entrez5423

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 9 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000265421, ENST00000517393, ENST00000518579, ENST00000518925, ENST00000519094, ENST00000519524, ENST00000519771, ENST00000520008, ENST00000521290, ENST00000521418, ENST00000521492, ENST00000522297, ENST00000522610, ENST00000523465, ENST00000524208, ENST00000530566, ENST00000532157, ENST00000929417

RefSeq mRNA: 1 — MANE Select: NM_002690 NM_002690

CCDS: CCDS6129

Canonical transcript exons

ENST00000265421 — 14 exons

ExonStartEnd
ENSE000021282744233849442338685
ENSE000035864414236129542361365
ENSE000035945284233901242339069
ENSE000036018154235000742350065
ENSE000036030584235551642355567
ENSE000036150014234901642349090
ENSE000036168644235716942357223
ENSE000036209414236984942369988
ENSE000036478574237156342371808
ENSE000036586734236927142369335
ENSE000036721684236261242362698
ENSE000036732864235732042357392
ENSE000036886324235251942352568
ENSE000036912044234495342345019

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.

FANTOM5 promoters (4 alternative TSS)

Promoter IDTPM avgSamples expressed
8868116.45091809
886800.7760485
886820.125636
886830.046512

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
oocyteCL:000002399.16gold quality
cerebellar hemisphereUBERON:000224599.09gold quality
cerebellar cortexUBERON:000212999.08gold quality
secondary oocyteCL:000065598.92gold quality
right hemisphere of cerebellumUBERON:001489098.85gold quality
cerebellumUBERON:000203798.79gold quality
spermCL:000001998.51gold quality
cortical plateUBERON:000534397.19gold quality
male germ cellCL:000001596.99gold quality
cerebellar vermisUBERON:000472096.98gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099196.50gold quality
ganglionic eminenceUBERON:000402396.37gold quality
left testisUBERON:000453395.75gold quality
right testisUBERON:000453495.69gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450295.36gold quality
biceps brachiiUBERON:000150795.35gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451195.22gold quality
embryoUBERON:000092295.07gold quality
hindlimb stylopod muscleUBERON:000425294.97gold quality
diaphragmUBERON:000110394.93gold quality
testisUBERON:000047394.92gold quality
parotid glandUBERON:000183194.80gold quality
gingival epitheliumUBERON:000194994.39gold quality
paraflocculusUBERON:000535194.21gold quality
monocyteCL:000057694.02gold quality
mononuclear cellCL:000084293.80gold quality
ponsUBERON:000098893.78gold quality
leukocyteCL:000073893.72gold quality
palpebral conjunctivaUBERON:000181293.53gold quality
gingivaUBERON:000182893.52gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes6.81

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

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

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-318599.9968.121959
HSA-MIR-548P99.9872.253784
HSA-MIR-365899.9673.874379
HSA-MIR-548AJ-5P99.7871.123085
HSA-MIR-548F-5P99.7871.023093
HSA-MIR-548G-5P99.7871.123085
HSA-MIR-548X-5P99.7871.123085
HSA-MIR-377-5P99.7065.28712
HSA-MIR-608699.7065.38699
HSA-MIR-329-5P99.2768.111597
HSA-MIR-1213598.9970.261814
HSA-MIR-655-5P98.7465.93888
HSA-MIR-63398.3569.451167
HSA-MIR-443297.8067.87705
HSA-MIR-376C-3P97.6368.881263
HSA-MIR-428897.1167.231636
HSA-MIR-34697.0166.97662

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

OrganismSymbolGene ID
danio_reriopolbENSDARG00000003749
mus_musculusPolbENSMUSG00000031536
rattus_norvegicusPolbENSRNOG00000019150

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

Protein

Protein identifiers

DNA polymerase beta — P06746 (reviewed: P06746)

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

All UniProt accessions (11): P06746, E5RG65, E5RHZ4, E5RIJ0, E5RJ55, E7EW18, E9PIC6, 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)

IDNameType
IPR002008DNA_pol_X_beta-likeFamily
IPR002054DNA-dir_DNA_pol_XDomain
IPR003583Hlx-hairpin-Hlx_DNA-bd_motifDomain
IPR010996HHH_MUS81Domain
IPR018944DNA_pol_lambd_fingers_domainDomain
IPR019843DNA_pol-X_BSBinding_site
IPR022312DNA_pol_XFamily
IPR027421DNA_pol_lamdba_lyase_dom_sfHomologous_superfamily
IPR028207DNA_pol_B_palm_palmDomain
IPR029398PolB_thumbDomain
IPR037160DNA_Pol_thumb_sfHomologous_superfamily
IPR043519NT_sfHomologous_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.

SubstrateKm (mM)Measurements
DATP0.0003–3.252
DCTP0.0001–2.546
DTTP0.0003–47.446
DGTP0.0002–2.529
DEOXYNUCLEOSIDE TRIPHOSPHATE0.0012–0.6412
DNAN—7
7-DEAZA-2’-DEOXYADENOSINE 5’-TRIPHOSPHATE0.0011–0.3445
N1-METHYL-2’-DEOXYADENOSINE 5’-TRIPHOSPHATE0.223–0.4035
2-AMINOPURINE-2’-DEOXY-D-RIBOSE 5’-TRIPHOSPHATE0.006–0.01442
2-THIO-DCTP0.067–0.982
5-METHYL-DCTP0.013–1.222
DAMP:DG1.153–1.422
DCMP:DG—2
DGMP:DG0.263–0.35112
DTMP:DG1.26–1.432

Catalyzed reactions (Rhea), 3 shown:

  • 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 (120 total): binding site 38, mutagenesis site 24, helix 19, 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)

434 structures, top 30 by resolution.

PDBMethodResolution (Å)
8VFGX-RAY DIFFRACTION1.54
9Y1JX-RAY DIFFRACTION1.55
4KLIX-RAY DIFFRACTION1.6
5WO0X-RAY DIFFRACTION1.6
9Y1EX-RAY DIFFRACTION1.6
9Y1GX-RAY DIFFRACTION1.6
2FMPX-RAY DIFFRACTION1.65
8VFFX-RAY DIFFRACTION1.69
5VS3X-RAY DIFFRACTION1.7
9Y1DX-RAY DIFFRACTION1.7
9Y1KX-RAY DIFFRACTION1.7
4KLGX-RAY DIFFRACTION1.7
7S9NX-RAY DIFFRACTION1.71
4KLMX-RAY DIFFRACTION1.75
6BTFX-RAY DIFFRACTION1.75
7RBHX-RAY DIFFRACTION1.75
8VFIX-RAY DIFFRACTION1.77
5U2TX-RAY DIFFRACTION1.79
5V1GX-RAY DIFFRACTION1.8
4KLJX-RAY DIFFRACTION1.8
4F5NX-RAY DIFFRACTION1.8
4TUPX-RAY DIFFRACTION1.8
5U2RX-RAY DIFFRACTION1.8
6CR4X-RAY DIFFRACTION1.8
9Y16X-RAY DIFFRACTION1.8
9Y18X-RAY DIFFRACTION1.8
9Y1FX-RAY DIFFRACTION1.8
5V1OX-RAY DIFFRACTION1.8
7RBFX-RAY DIFFRACTION1.84
4KLLX-RAY DIFFRACTION1.84

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P06746-F194.300.91

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): 72 (nucleophile; schiff-base intermediate with dna; for 5’-drp lyase activity)

Ligand- & substrate-binding residues (38): 101; 103; 103; 106; 106; 149; 149; 149; 149; 180; 180; 180 …

Post-translational modifications (6): 72, 83, 152, 41, 61, 81

Mutagenesis-validated functional residues (24):

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

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

IDPathway
R-HSA-110362POLB-Dependent Long Patch Base Excision Repair
R-HSA-110373Resolution of AP sites via the multiple-nucleotide patch replacement pathway
R-HSA-110381Resolution of AP sites via the single-nucleotide replacement pathway
R-HSA-5649702APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway
R-HSA-5651801PCNA-Dependent Long Patch Base Excision Repair
R-HSA-5689880Ub-specific processing proteases
R-HSA-73930Abasic sugar-phosphate removal via the single-nucleotide replacement pathway

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 (24): in utero embryonic development (GO:0001701), DNA-templated DNA replication (GO:0006261), DNA repair (GO:0006281), 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), inflammatory response (GO:0006954), DNA damage response (GO:0006974), salivary gland morphogenesis (GO:0007435), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), response to gamma radiation (GO:0010332), somatic hypermutation of immunoglobulin genes (GO:0016446), response to ethanol (GO:0045471), lymph node development (GO:0048535), spleen development (GO:0048536), homeostasis of number of cells (GO:0048872), neuron apoptotic process (GO:0051402), response to hyperoxia (GO:0055093), immunoglobulin heavy chain V-D-J recombination (GO:0071707), DNA replication (GO:0006260), apoptotic process (GO:0006915), somatic diversification of immunoglobulins (GO:0016445), 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 (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), microtubule (GO:0005874), spindle microtubule (GO:0005876), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-4 pathways:

CategoryPathways
Resolution of Abasic Sites (AP sites)3
Resolution of AP sites via the multiple-nucleotide patch replacement pathway2
Deubiquitination1
Resolution of AP sites via the single-nucleotide replacement pathway1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
DNA metabolic process2
DNA damage response2
DNA repair2
hematopoietic or lymphoid organ development2
catalytic activity2
carbon-oxygen lyase activity2
catalytic activity, acting on DNA2
cellular anatomical structure2
chordate embryonic development1
DNA replication1
base-excision repair1
double-strand break repair1
defense response1
cellular response to stress1
salivary gland development1
gland morphogenesis1
intrinsic apoptotic signaling pathway1
response to ionizing radiation1
somatic diversification of immune receptors via somatic mutation1
somatic diversification of immunoglobulins1
response to alcohol1
multicellular organismal-level homeostasis1
apoptotic process1
response to stress1
response to increased oxygen levels1
immunoglobulin V(D)J recombination1
DNA binding1
DNA polymerase activity1
DNA endonuclease activity1
tubulin binding1
protein binding1
cation binding1
DNA-(apurinic or apyrimidinic site) endonuclease activity1
nucleic acid binding1
binding1
transferase activity, transferring phosphorus-containing groups1
nucleotidyltransferase activity1
DNA biosynthetic process1
intracellular membrane-bounded organelle1
nuclear lumen1

Protein interactions and networks

STRING

1062 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
POLBXRCC1P18887999
POLBLIG3P49916999
POLBPARP2Q9UGN5976
POLBAPEX1P27695971
POLBLIG1P18858964
POLBPARP1P09874963
POLBPNKPQ96T60903
POLBOGG1P78554882
POLBFEN1P39748857
POLBTP53P04637839
POLBNEIL1Q96FI4826
POLBAPTXQ7Z2E3823
POLBWRNQ14191816
POLBUNGP13051799
POLBXRCC6P12956794

IntAct

55 interactions, top by confidence:

ABTypeScore
TPP2POLBpsi-mi:“MI:0915”(physical association)0.780
POLBTPP2psi-mi:“MI:0915”(physical association)0.780
XRCC1POLBpsi-mi:“MI:0915”(physical association)0.740
POLBXRCC1psi-mi:“MI:0914”(association)0.740
TDP1POLBpsi-mi:“MI:0914”(association)0.640
WFS1POLBpsi-mi:“MI:0915”(physical association)0.560
TAF1DPOLBpsi-mi:“MI:0915”(physical association)0.540
POLBTAF1Dpsi-mi:“MI:0915”(physical association)0.540
TAF1DPOLBpsi-mi:“MI:0403”(colocalization)0.540
POLBPARP1psi-mi:“MI:0914”(association)0.530
POLBH2AC11psi-mi:“MI:0914”(association)0.530
Hmgb1POLBpsi-mi:“MI:0914”(association)0.460
POLBSRPK2psi-mi:“MI:0217”(phosphorylation reaction)0.440
POLBApex1psi-mi:“MI:0914”(association)0.350
POLBHMGB1psi-mi:“MI:0914”(association)0.350
HMGB1POLBpsi-mi:“MI:0914”(association)0.350
Ktn1ESYT2psi-mi:“MI:0914”(association)0.350
JunbRGPD3psi-mi:“MI:0914”(association)0.350
XRCC3DERL1psi-mi:“MI:0914”(association)0.350
EMC2TBL2psi-mi:“MI:0914”(association)0.350
MMGT1DERL1psi-mi:“MI:0914”(association)0.350

BioGRID (153): TPP2 (Two-hybrid), POLB (Two-hybrid), POLB (Reconstituted Complex), POLB (Affinity Capture-Western), POLB (Reconstituted Complex), EP300 (Reconstituted Complex), POLB (Biochemical Activity), XPC (Affinity Capture-MS), SUPT16H (Affinity Capture-MS), XRCC1 (Affinity Capture-MS), LIG3 (Affinity Capture-MS), TDP1 (Affinity Capture-MS), PARP2 (Affinity Capture-MS), PARP1 (Affinity Capture-MS), SSRP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0K9RL25, A0A7U2QYM2, A0JN39, B9N1F9, D2SW95, F4JGR5, O55236, O57383, O60942, O80526, P06746, P06766, P23514, P43490, P53618, P54577, Q27958, Q28EX9, Q29465, Q2KJD7, Q2QNG7, Q2QZ86, Q4KM49, Q5FWT7, Q5R4A0, Q5R4C4, Q5R8R4, Q5R8T5, Q5R922, Q5ZIA5, Q5ZID6, Q5ZJ08, Q5ZJJ8, Q66HV4, Q69YN2, Q6DI37, Q6DRD3, Q6NYG8, Q6TGS6, Q7ZVX6

Diamond homologs: O57383, P06746, P06766, Q27958, Q4R380, Q5RKI3, Q67VC8, Q6DRD3, Q7T6Y4, Q8K409, Q9FNY4, Q9QXE2, Q9UGP5, P09838, Q9JIW4, Q9NP87, A8N936

SIGNOR signaling

2 interactions.

AEffectBMechanism
ATF2“up-regulates quantity by expression”POLB“transcriptional regulation”
clofarabine“down-regulates activity”POLB“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

PathwayPartnersFoldFDR
B-WICH complex positively regulates rRNA expression516.0×1e-03
NoRC negatively regulates rRNA expression513.8×2e-03

GO biological processes:

GO termPartnersFoldFDR
double-strand break repair730.9×1e-06
DNA repair79.7×6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance16
Likely benign0
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1900 predictions. Top by Δscore:

VariantEffectΔscore
8:42338682:ACAGG:Adonor_loss1.0000
8:42338683:CAGG:Cdonor_loss1.0000
8:42338684:AGGT:Adonor_loss1.0000
8:42338685:GGTT:Gdonor_loss1.0000
8:42338686:G:GAdonor_loss1.0000
8:42344951:A:AGacceptor_gain1.0000
8:42344952:G:GGacceptor_gain1.0000
8:42344952:GA:Gacceptor_gain1.0000
8:42352517:A:AGacceptor_gain1.0000
8:42352518:G:GAacceptor_gain1.0000
8:42352518:GTCC:Gacceptor_gain1.0000
8:42355565:GAA:Gdonor_gain1.0000
8:42355568:G:GGdonor_gain1.0000
8:42357220:GCAA:Gdonor_gain1.0000
8:42357224:G:GGdonor_gain1.0000
8:42357314:TATTA:Tacceptor_loss1.0000
8:42357315:ATTAG:Aacceptor_gain1.0000
8:42357317:TAGG:Tacceptor_loss1.0000
8:42357318:A:AGacceptor_gain1.0000
8:42357319:G:GGacceptor_gain1.0000
8:42357388:AAGAG:Adonor_loss1.0000
8:42357389:AGAG:Adonor_loss1.0000
8:42357390:GAGGT:Gdonor_loss1.0000
8:42357391:AG:Adonor_loss1.0000
8:42357392:GGTAA:Gdonor_loss1.0000
8:42357393:G:Adonor_loss1.0000
8:42357394:T:Gdonor_loss1.0000
8:42362596:A:AGacceptor_gain1.0000
8:42369269:AG:Aacceptor_gain1.0000
8:42369270:GG:Gacceptor_gain1.0000

AlphaMissense

2224 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
8:42369889:T:CF272L1.000
8:42369891:C:AF272L1.000
8:42369891:C:GF272L1.000
8:42369923:G:TR283M1.000
8:42350065:G:AG107D0.999
8:42357376:T:GC178W0.999
8:42357377:G:CG179R0.999
8:42357378:G:AG179D0.999
8:42357378:G:TG179V0.999
8:42357387:G:CR182T0.999
8:42357388:A:CR182S0.999
8:42357388:A:TR182S0.999
8:42357390:G:CR183T0.999
8:42357391:A:CR183S0.999
8:42357391:A:TR183S0.999
8:42361318:G:CD192H0.999
8:42361319:A:CD192A0.999
8:42361319:A:GD192G0.999
8:42361319:A:TD192V0.999
8:42361320:T:AD192E0.999
8:42361320:T:GD192E0.999
8:42369271:G:CG237R0.999
8:42369323:G:CR254T0.999
8:42369324:A:CR254S0.999
8:42369324:A:TR254S0.999
8:42369328:G:CD256H0.999
8:42369329:A:CD256A0.999
8:42369329:A:TD256V0.999
8:42369330:T:AD256E0.999
8:42369330:T:GD256E0.999

dbSNP variants (sampled 300 via entrez): RS1000021062 (8:42366839 G>A), RS1000062336 (8:42363477 G>A), RS1000078616 (8:42370857 C>A,G), RS1000119191 (8:42354286 C>T), RS1000243697 (8:42357686 A>G), RS1000280290 (8:42349153 G>A), RS1000433344 (8:42363806 A>G), RS1000488476 (8:42351189 T>C,G), RS1000548631 (8:42359092 G>T), RS1000581135 (8:42358695 A>T), RS1000775930 (8:42351444 T>C,G), RS1000876971 (8:42341386 T>C), RS1000903814 (8:42354200 AACAT>A), RS1000935749 (8:42354522 G>A,T), RS1000944713 (8:42346089 T>C)

Disease associations

OMIM: gene MIM:174760 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

StudyTraitp-value
GCST002374_3Plasma plasminogen activator levels1.000000e-09
GCST006431_8Plasma parathyroid hormone levels3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2392 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

117 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 559,044 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1010CEFOTAXIME SODIUM44,928
CHEMBL1108DROPERIDOL416,888
CHEMBL1109SULFAPHENAZOLE44,065
CHEMBL1117IDARUBICIN4136,065
CHEMBL113CAFFEINE4200,591
CHEMBL117785TETRABENAZINE49,645
CHEMBL1200348SULCONAZOLE NITRATE43,129
CHEMBL1200474DEMECLOCYCLINE HYDROCHLORIDE41,867
CHEMBL1200530CEFOXITIN SODIUM44,514
CHEMBL1200561DOXAZOSIN MESYLATE411,917
CHEMBL1200758AMPICILLIN SODIUM45,602
CHEMBL1200974CARBINOXAMINE MALEATE42,796
CHEMBL1201043CEPHAPIRIN SODIUM43,301
CHEMBL1201119LIOTHYRONINE SODIUM43,058
CHEMBL1201139MEGESTROL ACETATE498,000
CHEMBL1201236CARBIDOPA ANHYDROUS425,180
CHEMBL121663DEQUALINIUM CHLORIDE44,224
CHEMBL1223PENICILLIN G POTASSIUM419,982
CHEMBL1256400XYLOMETAZOLINE HYDROCHLORIDE42,662
CHEMBL1256842NOMIFENSINE MALEATE4630
CHEMBL1282IMIQUIMOD4
CHEMBL1330792ACETARSONE4
CHEMBL1417019MITOXANTRONE HYDROCHLORIDE4
CHEMBL1441ETHIONAMIDE4
CHEMBL1511ESTRADIOL VALERATE4
CHEMBL1517OXYTETRACYCLINE4
CHEMBL1523964EPHEDRINE SULFATE4
CHEMBL1528134BENZYDAMINE HYDROCHLORIDE4
CHEMBL1563DAUNORUBICIN HYDROCHLORIDE4
CHEMBL1569AMANTADINE HYDROCHLORIDE4

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

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:

LigandActionAffinityParameter
oleanolic acidInhibition5.6pIC50

Binding affinities (BindingDB)

2 measured of 27 human assays (27 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
(7S,8R,1’S,5’S,6’R)-delta 2’,8’-3’,6’-dihydroxy-5’-methoxy-3,4-methylenedioxy-4’-oxo-8.1’,7.5’-neolignanIC5021600 nM
canellin CIC5032400 nM

ChEMBL bioactivities

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

pChemblTypeValueUnitMolecule
7.70Potency20nMCHEMBL1473350
7.65Potency22.4nMAURINTRICARBOXYLIC ACID
7.65Potency22.4nMCHEMBL1569550
7.60Potency25.1nMCHEMBL1344856
7.60Potency25.1nMCHEMBL1328025
7.45Potency35.5nMCHEMBL1336244
7.40Potency39.8nMCHEMBL1402560
7.20Potency63.1nMCHEMBL1334116
7.20Potency63.1nMCHEMBL3195346
7.20Potency63.1nMCHEMBL56393
7.15Potency70.8nMCHEMBL1490125
7.15Potency70.8nMCHEMBL3195250
7.10Potency79.4nMCHEMBL1329268
7.10Potency79.4nMCHEMBL1514546
7.10Potency79.4nMCHEMBL1436700
7.10Potency79.4nMCHEMBL1494689
7.10Potency79.4nMCHEMBL1444978
7.05Potency89.1nMCHEMBL1361558
7.05Potency89.1nMCHEMBL3196556
7.05Potency89.1nMCHEMBL1316953
7.05Potency89.1nMCHEMBL1409626
7.05Potency89.1nMCHEMBL2000202
7.05Potency89.1nMCHEMBL1468933
7.05Potency89.1nMCHEMBL1446452
7.05Potency89.1nMCHEMBL1424074
7.05Potency89.1nMCHEMBL1407370
7.05Potency89.1nMCHEMBL1496953
7.00Potency100nMCHEMBL1500886
7.00Potency100nMCHEMBL460518
7.00Potency100nMCHEMBL1354805
7.00Potency100nMCHEMBL1516808
7.00Potency100nMCHEMBL1477564
7.00Potency100nMCHEMBL1458407
7.00Potency100nMCHEMBL1449056
7.00Potency100nMCHEMBL1340515
7.00Potency100nMCHEMBL1300861
7.00Potency100nMCHEMBL1359927
7.00Potency100nMCHEMBL1528373
7.00Potency100nMCHEMBL1459623
7.00Potency100nMCHEMBL1460488
7.00Potency100nMCHEMBL1526395
7.00Potency100nMCHEMBL1486484
7.00Potency100nMCHEMBL220869
7.00Potency100nMCHEMBL3209829
7.00Potency100nMCHEMBL1299713
7.00Potency100nMCHEMBL1339797
7.00Potency100nMCHEMBL3211365
7.00Potency100nMCHEMBL1594479
7.00Potency100nMCHEMBL1399230
7.00Potency100nMCHEMBL1320223

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.

CompoundAssayTypeValueUnit
[(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 phosphate2076427: Inhibition of DNA polymerase beta (unknown origin) measured after 30 minsic500.2040uM
3,4-dihydroxy-5-(3,4,5-trihydroxybenzoyl)oxybenzoic acid397114: Inhibition of DNA polymerase beta from human KB3 cellski0.3900uM
[(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 phosphate1993592: Inhibition of DNA polymerase beta (unknown origin)ic500.4000uM
[hydroxy-[[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphoryl]methyl-phosphonooxyphosphinic acid391154: Inhibition of human DNA polymerase betaki0.6000uM
[(2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy-[[hydroxy(phosphonooxy)phosphoryl]methyl]phosphinic acid391154: Inhibition of human DNA polymerase betaki0.9000uM
[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-[[hydroxy(phosphonooxy)phosphoryl]methyl]phosphinic acid391154: Inhibition of human DNA polymerase betaki1.0000uM
[[(2S,3R,5S)-5-(4-amino-2-oxopyrimidin-1-yl)-3-fluorooxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate53486: Compound was evaluated for the inhibition of cellular DNA polymerase (beta)ic501.0000uM
[[(2S,3R,5S)-5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-fluorooxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate53486: Compound was evaluated for the inhibition of cellular DNA polymerase (beta)ic501.0000uM
sodium [(2S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [hydroxy(phosphonooxy)phosphoryl] phosphate402635: Inhibition of human recombinant DNA polymerase beta assessed as fluorescein-12-dCTP incorporation by fluorimetryic501.3000uM
[hydroxy-[[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphoryl] phosphono hydrogen phosphate1443139: Inhibition of human DNA polymerase-betaic501.4000uM
2-(2-amino-6-oxo-1H-purin-9-yl)ethoxymethyl-[hydroxy(phosphonooxy)phosphoryl]oxyphosphinic acid560429: Inhibition of human DNA polymerase beta by microplate reader analysisic501.6000uM
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-tricarboxylate265077: Inhibition of DNA polymerase betaic501.9000uM
(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 acid398466: Inhibition of DNA polymerase betaic502.2000uM
[[(2S,3R,5S)-3-fluoro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate53486: Compound was evaluated for the inhibition of cellular DNA polymerase (beta)ic502.2000uM
(3aS,4S,7R,7aR)-1,6-didodecyl-2,7-bis(methoxycarbonyl)-3-oxo-3a,4,7,7a-tetrahydroindene-4-carboxylic acid265077: Inhibition of DNA polymerase betaic502.3000uM
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-tricarboxylate265077: Inhibition of DNA polymerase betaic502.4000uM
(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 acid697027: Inhibition of DNA polymerase betaic503.0000uM
[[(2S,3R,5S)-5-(2,4-dioxopyrimidin-1-yl)-3-fluorooxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate53486: Compound was evaluated for the inhibition of cellular DNA polymerase (beta)ic503.0000uM
(3aS,4S,7R,7aR)-1,6-dihexadecyl-2,7-bis(methoxycarbonyl)-3-oxo-3a,4,7,7a-tetrahydroindene-4-carboxylic acid265077: Inhibition of DNA polymerase betaic503.2000uM
(3aS,4S,7R,7aR)-1,6-dihexadecyl-3-oxo-2,7-bis(propan-2-yloxycarbonyl)-3a,4,7,7a-tetrahydroindene-4-carboxylic acid265077: Inhibition of DNA polymerase betaic504.4000uM
[(2R,3S,5R)-5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-[[hydroxy(phosphonooxy)phosphoryl]methyl]phosphinic acid391154: Inhibition of human DNA polymerase betaki5.0000uM
2,4,5-trimethyl-N-[5-(4-methylanilino)-1H-1,2,4-triazol-3-yl]benzenesulfonamide1923837: Inhibition of human DNA polymerase beta by fluorescence anisotropyic505.0000uM
4-chloro-N-[5-(4-chloroanilino)-1H-1,2,4-triazol-3-yl]-5-methyl-2-sulfanylbenzenesulfonamide1993590: Inhibition of human DNA polymerase beta incubated for 30 mins in presence of dNTP by PAGE based assayic505.0000uM
4-chloro-5-methyl-N-[5-(naphthalen-2-ylamino)-1H-1,2,4-triazol-3-yl]-2-sulfanylbenzenesulfonamide1993590: Inhibition of human DNA polymerase beta incubated for 30 mins in presence of dNTP by PAGE based assayic505.0000uM
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-triol1959329: Inhibition of DNA polymerase beta (unknown origin)ic505.1600uM
(2S,3R)-4-methylidene-5-oxo-2-tridecyloxolane-3-carboxylic acid398466: Inhibition of DNA polymerase betaic507.4000uM
[[(2S,5R)-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate1614343: 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 analysisic508.4000uM
methyl (2S,3S,4R,5E)-2-ethyl-4-hydroxy-5-(2-oxononadecylidene)-1-(2-phenylethyl)pyrrolidine-3-carboxylate265077: Inhibition of DNA polymerase betaic508.7000uM
dimethyl (3aR,4R,7S,7aS)-3,5-dihexadecyl-1-oxo-7-(2-phenylethylcarbamoyl)-3a,4,7,7a-tetrahydroindene-2,4-dicarboxylate265077: Inhibition of DNA polymerase betaic508.7000uM
methyl (2R,3S,4R,5E)-4-hydroxy-5-(2-oxononadecylidene)-2-phenyl-1-(2-phenylethyl)pyrrolidine-3-carboxylate265077: Inhibition of DNA polymerase betaic508.8000uM
methyl (E)-3,6-dioxodocos-4-enoate265077: Inhibition of DNA polymerase betaic508.8000uM
4-[(3-carboxy-2-hydroxynaphthalen-1-yl)methyl]-3-hydroxynaphthalene-2-carboxylic acid754124: Inhibition of DNA polymerase beta (unknown origin)ic509.0000uM
methyl (2R,3S,4R,5E)-4-hydroxy-1-[2-(1H-indol-3-yl)ethyl]-5-(2-oxotetradecylidene)-2-phenylpyrrolidine-3-carboxylate265077: Inhibition of DNA polymerase betaic5010.0000uM
[[(R)-[(2S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]-fluoromethoxy]-hydroxyphosphoryl] phosphono hydrogen phosphate547084: 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 assayic5010.0000uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects expression, decreases expression, increases expression4
arseniteincreases reaction, increases expression, affects expression, affects binding3
sodium arseniteincreases activity, affects expression, affects response to substance, affects cotreatment, increases abundance (+2 more)3
bisphenol Adecreases expression, decreases reaction2
Temozolomidedecreases reaction, increases reaction, increases response to substance, decreases response to substance2
Arsenicincreases expression, decreases expression, decreases reaction, affects cotreatment, increases abundance2
Curcumindecreases reaction, decreases expression2
Methyl Methanesulfonateincreases expression2
N6-(2-hydroxy-3-buten-1-yl)-2’-deoxyadenosinedecreases activity1
bisphenol Fincreases expression1
6-thio-2’-deoxyguanosine-5’-triphosphateaffects binding, increases metabolic processing1
5-formyldeoxycytosine-5’-triphosphateaffects binding, increases metabolic processing1
dicrotophosdecreases expression1
methoxyaminedecreases reaction, increases reaction, increases response to substance1
triphenyl phosphateaffects expression1
honokioldecreases activity1
1,12-benzoperyleneincreases expression1
diepoxybutaneaffects binding, decreases activity1
5-chlorouracilaffects metabolic processing1
trichostatin Aaffects expression1
mono-(2-ethylhexyl)phthalateincreases expression1
4-hydroxy-2-nonenaldecreases expression1
methyl tert-butyl etheraffects response to substance1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamineincreases expression1
beta-methylcholineaffects expression1
2’-deoxyadenosineaffects binding, decreases activity1
di-n-butylphosphoric acidaffects expression1
perfluorooctane sulfonic acidincreases expression1
azoxystrobinincreases expression1
cylindrospermopsindecreases expression1

ChEMBL screening assays

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

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1000069BindingInhibition of human DNA polymerase betaAnti-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
CHEMBL1614079FunctionalPUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of DNA Polymerase Beta. (Class of assay: confirmatory)PubChem BioAssay data set
CHEMBL4008261ADMETInhibition 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 assayDiscovery 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

8 cell lines: 7 cancer cell line, 1 transformed cell line

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

CellosaurusNameCategorySex
CVCL_A4IJNALM-6 POLB (-/-)Cancer cell lineMale
CVCL_B2BDAbcam HeLa POLB KOCancer cell lineFemale
CVCL_D9NXUbigene HEK293 POLB KOTransformed cell lineFemale
CVCL_E2H4HAP1 POLB (-) 3Cancer cell lineMale
CVCL_E2H5HAP1 POLB (-) 4Cancer cell lineMale
CVCL_E2H6HAP1 POLB (-) 5Cancer cell lineMale
CVCL_TE88HAP1 POLB (-) 1Cancer cell lineMale
CVCL_TE89HAP1 POLB (-) 2Cancer cell lineMale

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 80

This page pulls from 80 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot