POLI

Summary

POLI (DNA polymerase iota, HGNC:9182) is a protein-coding gene on chromosome 18q21.2, encoding DNA polymerase iota (Q9UNA4). Error-prone DNA polymerase specifically involved in DNA repair.

The protein encoded by this gene is an error-prone DNA polymerase involved in DNA repair. The encoded protein promotes DNA synthesis across lesions in the template DNA, which other polymerases cannot do. The encoded polymerase inserts deoxynucleotides across lesions and then relies on DNA polymerase zeta to extend the nascent DNA strand to bypass the lesion.

Source: NCBI Gene 11201 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 117 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_007195

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9182
Approved symbol	POLI
Name	DNA polymerase iota
Location	18q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000101751
Ensembl biotype	protein_coding
OMIM	605252
Entrez	11201

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 12 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000217800, ENST00000406285, ENST00000577361, ENST00000577612, ENST00000577727, ENST00000577971, ENST00000579434, ENST00000579534, ENST00000579823, ENST00000580880, ENST00000580905, ENST00000581950, ENST00000582366, ENST00000583136, ENST00000583576, ENST00000585023, ENST00000854649, ENST00000854650, ENST00000930897, ENST00000941394

RefSeq mRNA: 14 — MANE Select: NM_007195 NM_001351610, NM_001351611, NM_001351612, NM_001351613, NM_001351614, NM_001351615, NM_001351616, NM_001351617, NM_001351618, NM_001351619, NM_001351620, NM_001351621, NM_001351632, NM_007195

CCDS: CCDS11954, CCDS86669, CCDS86670

Canonical transcript exons

ENST00000579534 — 10 exons

Exon	Start	End
ENSE00000669405	54282837	54283015
ENSE00002700803	54293649	54298234
ENSE00002726927	54269517	54269661
ENSE00003493684	54271360	54271485
ENSE00003497541	54287281	54287411
ENSE00003554248	54277703	54277855
ENSE00003578281	54291833	54292038
ENSE00003638856	54283922	54284013
ENSE00003647565	54273926	54274090
ENSE00003686373	54280667	54280903

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 96.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.0996 / max 107.3570, expressed in 1708 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170296	7.4361	1677
170297	0.6635	288

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.65	gold quality
left lobe of thyroid gland	UBERON:0001120	94.67	gold quality
right testis	UBERON:0004534	94.48	gold quality
left testis	UBERON:0004533	94.42	gold quality
right lobe of thyroid gland	UBERON:0001119	94.32	gold quality
thyroid gland	UBERON:0002046	94.26	gold quality
right uterine tube	UBERON:0001302	93.75	gold quality
testis	UBERON:0000473	93.43	gold quality
body of pancreas	UBERON:0001150	93.39	gold quality
left ovary	UBERON:0002119	93.14	gold quality
right ovary	UBERON:0002118	93.12	gold quality
tibial nerve	UBERON:0001323	92.31	gold quality
ventricular zone	UBERON:0003053	92.07	gold quality
ovary	UBERON:0000992	91.64	gold quality
endocervix	UBERON:0000458	91.52	gold quality
body of uterus	UBERON:0009853	91.52	gold quality
adenohypophysis	UBERON:0002196	91.46	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.35	gold quality
metanephros cortex	UBERON:0010533	91.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.09	gold quality
pituitary gland	UBERON:0000007	90.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.49	gold quality
adipose tissue	UBERON:0001013	90.48	gold quality
mucosa of stomach	UBERON:0001199	90.47	gold quality
ectocervix	UBERON:0012249	90.05	gold quality
adrenal tissue	UBERON:0018303	89.99	gold quality
connective tissue	UBERON:0002384	89.89	gold quality
omental fat pad	UBERON:0010414	89.81	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.80	gold quality
peritoneum	UBERON:0002358	89.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A, JDP2, POU2F1, SP1, TAF1, TBP, TBPL1, TBPL2, TP53, TP63, UBTF, USF1

miRNA regulators (miRDB)

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

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753

Literature-anchored findings (GeneRIF, showing 40)

• By performing gene inactivation in a Burkitt’s lymphoma cell line inducible for hypermutation, we show here that somatic hypermutation is dependent on DNA polymerase iota (PMID:12410315)
• DNA polymerase iota associates with the replication machinery & accumulates at stalled replication forks following DNA-damaging treatment. Its the C-terminal 224 AAs are sufficient for both the interaction with poleta & accumulation in replication foci. (PMID:12426396)
• Translesion replication of benzo[a]pyrene and benzo[c]phenanthrene diol epoxide adducts of deoxyadenosine and deoxyguanosine by DNA polymerase iota. (PMID:12466554)
• pol iota can complement the in vitro single-nucleotide BER deficiency of a DNA polymerase beta null cell extract (PMID:12777390)
• propose that the incipient base pair is accommodated differently in the active site of Poliota dependent upon the template base and that when T is the templating base, Poliota accommodates the wobble base pair better than the Watson-Crick base pair (PMID:14701763)
• crystal structure bound to a template primer and an incoming nucleotide; structure reveals a polymerase that is ‘specialized’ for Hoogsteen base-pairing, whereby the templating base is driven to the syn conformation (PMID:15254543)
• Data strongly suggest that pol iota may be involved in the generation of both increased spontaneous and translesion mutations during DNA replication in breast cancer cells, thereby contributing to the accumulation of genetic damage. (PMID:15313897)
• Data show that an interaction between human DNA polymerase iota (poliota) and the proliferating cell nuclear antigen (PCNA) stimulates the processivity of poliota in a template-dependent manner in vitro. (PMID:15342632)
• Poliota interacts with PCNA via only one of its conserved PCNA binding motifs, regardless of whether PCNA is bound to DNA or not. (PMID:15657443)
• DNA polymerase iota promotes replication through a ring-closed minor-groove adduct that adopts a syn conformation in DNA (PMID:16166652)
• The sequential action of Poliota and Polkappa promotes efficient and error-free synthesis through the HNE-dG adducts. (PMID:16354708)
• identification of two previously unknown ubiquitin-binding domains in the Y-family translesion synthesis polymerases that enable them to interact with monoubiquitinated targets and undergo monoubiquitination in vivo (PMID:16357261)
• results show that Pol iota has no significant role in UV lesion bypass and mutagenesis in vivo and provides some initial data suggesting that this polymerase may be involved in replication of extrachromosomal DNA (PMID:16472831)
• polymerization by pol iota is severely inhibited by a bulky group at G N2 despite an advantageous mode of Hoogsteen base pairing (PMID:16527824)
• DNA polymerases iota and eta interact noncovalently with free polyUb chains, as well as mono-ubiquitinated proliferating cell nuclear antigen (Ub-PCNA). (PMID:16763556)
• For proficient T incorporation opposite template A, only the N7 hydrogen bonding is required, but for proficient C incorporation opposite template G, hydrogen bonding at both the N7 and O(6) is an imperative. (PMID:16914729)
• These results suggest that HIF-1-mediated pol iota gene expression may be involved in the generation of translesion mutations during DNA replication after hypoxia followed by reoxygenation. (PMID:17056006)
• the cation utilized by pol iota in vivo may actually be Mn(2+) rather than Mg(2+), as tacitly assumed (PMID:17609217)
• Data suggest that DNA polymerases eta and iota transiently probe DNA/chromatin; when DNA is exposed at replication forks, the polymerase residence times increase, and this is further facilitated by the ubiquitination of PCNA. (PMID:18799611)
• These data reveal a novel role of human DNA pol iota in protecting cells from oxidative damage. (PMID:18923427)
• Lesion bypass of N2-ethylguanine by human DNA polymerase iota. (PMID:18984581)
• enzyme plays important functions in protecting humans from the deleterious consequences of exposure to both oxidative- and ultraviolet light-induced DNA damage (PMID:19162565)
• DNA synthesis across an absaic lesion by human POLI is reported. (PMID:19368886)
• Structural and domain-swapping experiments indicate that the finger domain is responsible for DNA polymerase iota’s high error rates on pyrimidines and determines the incorporation specificity. (PMID:19440206)
• Replication across template T/U by human DNA POLI is reported. (PMID:19604477)
• DNA polymerase iota’s versatility implies that this enzyme can adjust to local structural conditions in order to bypass bulky lesions by strategies that utilize Watson-Crick, Hoogsteen and perhaps other base pairing possibilities. (PMID:19767609)
• Variants in POLI is associated with predisposition for TMPRSS2-ERG fusion in prostate cancer. (PMID:19861517)
• The solution structures of the C-terminal UBM of human pol iota and its complex with ubiquitin are reported. (PMID:20159559)
• In the presence of Mn2+, the Pol iota activity in carcinoma was 2.5-fold higher than the control cells. (PMID:20673215)
• Structural basis for proficient incorporation of dTTP opposite O6-methylguanine by human DNA polymerase iota. (PMID:20961860)
• structural mechanism of high-fidelity 8-oxo-G replication by a human DNA polymerase (PMID:21300901)
• in mammalian cells, both polymerases kappa and iota are necessary for the error-free bypass of N(2)-CEdG and N(2)-CMdG. (PMID:21454642)
• this review briefly discusses the main structural features and possible functional mechanisms of the active center of Pol iota. [review] (PMID:22817454)
• Results show that the physical and functional interaction between pols eta and iota occurs between ubiquitinated forms of either polymerase via their respective ubiquitin-binding domains. (PMID:23248005)
• POLI and MC4R nearby single nucleotide polymorphisms in human chromosome 18 are associated with a moderate risk of type 2 diabetes. (PMID:23727064)
• Dysregulation of pol iota by JNK/c-Jun is involved in carcinogenesis and offer a novel understanding of the role of pol iota or c-Jun in mutagenesis. (PMID:23922701)
• Human Pol iota and yeast Pol zeta complex could function efficiently in the insertion and extension steps, respectively, of ranslesion synthesis and human Pol kappa and Pol eta could also extend past these lesions, albeit much less efficiently. (PMID:23965998)
• a single residue in pol iota is able to discriminate between NTPs and dNTPs during DNA synthesis. (PMID:24532793)
• Germline genetic variations in human POLI gene may either hinder or promote the translesion synthesis (TLS) capability of pol iota with various DNA lesions in vitro, emphasizing the potential translational importance of these pol iota genetic variations, e.g., individual differences in TLS, mutation, and cancer susceptibility to genotoxic carcinogens. (PMID:25162224)
• Mass spectrometry analysis of monoubiquitinated poliota revealed that it is ubiquitinated at over 27 unique sites. Many of these sites are localized in different functional domains of the protein. (PMID:26370087)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	poli	ENSDARG00000029250
mus_musculus	Poli	ENSMUSG00000038425
rattus_norvegicus	Poli	ENSRNOG00000012111
drosophila_melanogaster	PolI	FBGN0037554

Paralogs (5): POLK (ENSG00000122008), REV1 (ENSG00000135945), ESCO1 (ENSG00000141446), POLH (ENSG00000170734), ESCO2 (ENSG00000171320)

Protein

Protein identifiers

DNA polymerase iota — Q9UNA4 (reviewed: Q9UNA4)

Alternative names: Eta2, RAD30 homolog B

All UniProt accessions (10): Q9UNA4, J3KQ09, J3KRG0, J3KRS8, J3KSW2, J3KTM8, J3KTN3, J3QQZ8, J3QR36, X6R2I3

UniProt curated annotations — full annotation on UniProt →

Function. Error-prone DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Favors Hoogsteen base-pairing in the active site. Inserts the correct base with high-fidelity opposite an adenosine template. Exhibits low fidelity and efficiency opposite a thymidine template, where it will preferentially insert guanosine. May play a role in hypermutation of immunoglobulin genes. Forms a Schiff base with 5’-deoxyribose phosphate at abasic sites, but may not have lyase activity.

Subunit / interactions. Interacts with POLH. Interacts with REV1. Interacts with ubiquitin.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous. Highly expressed in testis.

Post-translational modifications. Monoubiquitinated. Protein monoubiquitination prevents POLI binding to ubiquitin via the ubiquitin-binding motif 1 and ubiquitin-binding motif 2.

Cofactor. Binds nucleotide much more tightly and catalyzes nucleotide insertion much more efficiently in the presence of Mg(2+) than in the presence of Mn(2+).

Domain organisation. The catalytic core consists of fingers, palm and thumb subdomains, but the fingers and thumb subdomains are much smaller than in high-fidelity polymerases; residues from five sequence motifs of the Y-family cluster around an active site cleft that can accommodate DNA and nucleotide substrates with relaxed geometric constraints, with consequently higher rates of misincorporation and low processivity. Ubiquitin-binding motif 1 and ubiquitin-binding motif 2 regulate POLI protein monoubiquitination and localization to nuclear foci after UV-induced DNA damage.

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

RefSeq proteins (14): NP_001338539, NP_001338540, NP_001338541, NP_001338542, NP_001338543, NP_001338544, NP_001338545, NP_001338546, NP_001338547, NP_001338548, NP_001338549, NP_001338550, NP_001338561, NP_009126* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001126	UmuC	Domain
IPR017961	DNA_pol_Y-fam_little_finger	Domain
IPR025527	HUWE1/Rev1_UBM	Conserved_site
IPR036775	DNA_pol_Y-fam_lit_finger_sf	Homologous_superfamily
IPR043128	Rev_trsase/Diguanyl_cyclase	Homologous_superfamily
IPR043502	DNA/RNA_pol_sf	Homologous_superfamily
IPR053848	IMS_HHH_1	Domain

Pfam: PF00817, PF11799, PF14377, PF21999

Enzyme classification (BRENDA):

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

Substrate kinetics (BRENDA)

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

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

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (86 total): helix 23, strand 22, binding site 8, sequence variant 7, turn 6, region of interest 5, sequence conflict 4, domain 3, compositionally biased region 3, short sequence motif 2, chain 1, active site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

54 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3OSN	X-RAY DIFFRACTION	1.9
3Q8P	X-RAY DIFFRACTION	1.95
5ULX	X-RAY DIFFRACTION	1.96
3GV5	X-RAY DIFFRACTION	2
3GV8	X-RAY DIFFRACTION	2
3Q8Q	X-RAY DIFFRACTION	2.03
4FS2	X-RAY DIFFRACTION	2.05
3G6X	X-RAY DIFFRACTION	2.08
3Q8S	X-RAY DIFFRACTION	2.09
3G6Y	X-RAY DIFFRACTION	2.1
4EBE	X-RAY DIFFRACTION	2.1
9DDR	X-RAY DIFFRACTION	2.15
3G6V	X-RAY DIFFRACTION	2.2
3GV7	X-RAY DIFFRACTION	2.2
3H4D	X-RAY DIFFRACTION	2.2
9DQU	X-RAY DIFFRACTION	2.2
9DR9	X-RAY DIFFRACTION	2.21
9NJH	X-RAY DIFFRACTION	2.29
1T3N	X-RAY DIFFRACTION	2.3
1ZET	X-RAY DIFFRACTION	2.3
2DPI	X-RAY DIFFRACTION	2.3
2DPJ	X-RAY DIFFRACTION	2.3
3H40	X-RAY DIFFRACTION	2.3
9DRB	X-RAY DIFFRACTION	2.36
2FLP	X-RAY DIFFRACTION	2.4
3Q8R	X-RAY DIFFRACTION	2.45
9DR7	X-RAY DIFFRACTION	2.45
9DRC	X-RAY DIFFRACTION	2.45
5KT2	X-RAY DIFFRACTION	2.49
2ALZ	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UNA4-F1	70.73	0.51

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): 152 (proton acceptor)

Ligand- & substrate-binding residues (8): 59; 59; 60; 60; 64; 96; 151; 151

Mutagenesis-validated functional residues (1):

Position	Phenotype
1–25	small decrease in catalytic activity efficiency which is partially rescued by the presence of mn(2+) instead mg(2+).

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5656121	Translesion synthesis by POLI
R-HSA-5656169	Termination of translesion DNA synthesis

MSigDB gene sets: 138 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, TGCGCANK_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, DITTMER_PTHLH_TARGETS_UP, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, GOBP_DNA_DAMAGE_TOLERANCE, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, KAUFFMANN_DNA_REPAIR_GENES, MCLACHLAN_DENTAL_CARIES_DN, GOMF_DNA_POLYMERASE_ACTIVITY, GOBP_DNA_DAMAGE_RESPONSE

GO Biological Process (7): DNA replication (GO:0006260), DNA repair (GO:0006281), translesion synthesis (GO:0019985), error-prone translesion synthesis (GO:0042276), DNA metabolic process (GO:0006259), DNA damage response (GO:0006974), DNA biosynthetic process (GO:0071897)

GO Molecular Function (8): damaged DNA binding (GO:0003684), DNA-directed DNA polymerase activity (GO:0003887), metal ion binding (GO:0046872), DNA binding (GO:0003677), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), DNA polymerase activity (GO:0034061)

GO Cellular Component (4): nucleoplasm (GO:0005654), nuclear speck (GO:0016607), cytoplasmic ribonucleoprotein granule (GO:0036464), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	3
DNA biosynthetic process	2
DNA damage response	1
DNA damage tolerance	1
DNA synthesis involved in DNA replication	1
translesion synthesis	1
nucleic acid metabolic process	1
cellular response to stress	1
nucleic acid biosynthetic process	1
DNA binding	1
DNA polymerase activity	1
cation binding	1
nucleic acid binding	1
binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
nucleotidyltransferase activity	1
catalytic activity, acting on DNA	1
nuclear lumen	1
cellular anatomical structure	1
nuclear ribonucleoprotein granule	1
cytoplasm	1
ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3014 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLI	RRN3	Q9NYV6	997
POLI	UBTF	P17480	962
POLI	SIRT7	Q9NRC8	955
POLI	POLR1B	Q9H9Y6	931
POLI	TAF1A	Q15573	898
POLI	POLM	Q9NP87	879
POLI	TP53	P04637	855
POLI	MAF1	Q9H063	846
POLI	POLR3K	Q9Y2Y1	831
POLI	POLR1D	P0DPB6	822
POLI	TBP	P20226	819
POLI	BDP1	A6H8Y1	818
POLI	POLR1E	Q9GZS1	817
POLI	TCEA1	P23193	817
POLI	POLR1A	O95602	810
POLI	POLR1H	Q9P1U0	810

IntAct

57 interactions, top by confidence:

A	B	Type	Score
POLI	TRIM39	psi-mi:“MI:0915”(physical association)	0.670
TRIM39	POLI	psi-mi:“MI:0915”(physical association)	0.670
POLI	DAZAP2	psi-mi:“MI:0915”(physical association)	0.620
DAZAP2	POLI	psi-mi:“MI:0915”(physical association)	0.620
POLI	ZBTB44	psi-mi:“MI:0915”(physical association)	0.560
POLI	TMEM239	psi-mi:“MI:0915”(physical association)	0.560
POLI	TRAF6	psi-mi:“MI:0915”(physical association)	0.560
ZBTB44	POLI	psi-mi:“MI:0915”(physical association)	0.560
TMEM239	POLI	psi-mi:“MI:0915”(physical association)	0.560
TRAF6	POLI	psi-mi:“MI:0915”(physical association)	0.560
HOMER3	POLI	psi-mi:“MI:0915”(physical association)	0.560
POLI	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
POLI	YWHAG	psi-mi:“MI:0915”(physical association)	0.560
POLI	SETDB1	psi-mi:“MI:0915”(physical association)	0.560
POLI	KAT5	psi-mi:“MI:0915”(physical association)	0.560
POLI	LMO3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (78): UBC (Co-crystal Structure), POLI (Two-hybrid), ZBTB44 (Two-hybrid), TRIM39 (Two-hybrid), TMEM239 (Two-hybrid), UBC (Reconstituted Complex), POLI (Far Western), POLI (Two-hybrid), POLI (Two-hybrid), POLI (Two-hybrid), TRIM39 (Two-hybrid), PCNA (Reconstituted Complex), POLI (Affinity Capture-Western), POLI (Co-localization), POLI (Two-hybrid)

ESM2 similar proteins: A1L3L1, A2RT67, A3KPW7, A4IIA7, A8C750, A8C752, D2HNY3, E1BGQ2, E1C3P4, Q08CL8, Q08DZ8, Q0IHB3, Q149N8, Q1RMU2, Q1RMZ1, Q3MJ13, Q3T1H6, Q5F3F2, Q5RED8, Q5VVJ2, Q5ZJ87, Q66J91, Q69Z66, Q6AYF5, Q6DE97, Q6GR37, Q6P1E7, Q6PNC0, Q6YHU6, Q7TPQ3, Q8BKW4, Q8BXK4, Q8IWR0, Q8IYF3, Q8IZE3, Q8K2I9, Q8NA31, Q8NEN0, Q8NFZ0, Q96EW2

Diamond homologs: A0KHD5, A0KTR5, A0Q6K9, A1A7U2, A1JNY3, A1KUQ3, A1RMZ5, A1S8M3, A1U339, A3D147, A3N148, A3QGY9, A4TPK8, A4W6W8, A4XT24, A5IH02, A5VZT3, A6VA50, A6W1V6, A6WRW5, A7FLI9, A7MEN4, A7NC07, A7ZHZ2, A7ZWJ6, A8AKQ2, A8FYV3, A8GAC8, A8H771, A9L0T3, A9MNS1, A9MY13, B0BPX9, B0KTK6, B0TQD1, B0TZS5, B1J100, B1KD33, B1YK83, B2SH34

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	100
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2210 predictions. Top by Δscore:

Variant	Effect	Δscore
18:54269601:G:GT	donor_gain	1.0000
18:54269634:G:GT	donor_gain	1.0000
18:54269660:GG:G	donor_gain	1.0000
18:54269661:GG:G	donor_gain	1.0000
18:54269679:G:GT	donor_gain	1.0000
18:54269696:GGGT:G	donor_gain	1.0000
18:54269697:GGTG:G	donor_gain	1.0000
18:54271349:A:AG	acceptor_gain	1.0000
18:54271350:T:G	acceptor_gain	1.0000
18:54271359:GGA:G	acceptor_gain	1.0000
18:54271481:TTTAG:T	donor_loss	1.0000
18:54271482:TTAGG:T	donor_loss	1.0000
18:54271483:TAGGT:T	donor_loss	1.0000
18:54271484:AGG:A	donor_loss	1.0000
18:54271485:GG:G	donor_loss	1.0000
18:54271486:GT:G	donor_loss	1.0000
18:54271487:T:G	donor_loss	1.0000
18:54273924:A:AG	acceptor_gain	1.0000
18:54273924:AG:A	acceptor_gain	1.0000
18:54273924:AGG:A	acceptor_gain	1.0000
18:54273925:G:GG	acceptor_gain	1.0000
18:54273925:GG:G	acceptor_gain	1.0000
18:54273925:GGG:G	acceptor_gain	1.0000
18:54274086:TACAG:T	donor_loss	1.0000
18:54274087:ACAGG:A	donor_loss	1.0000
18:54274088:CAG:C	donor_loss	1.0000
18:54274089:AG:A	donor_loss	1.0000
18:54274090:GGT:G	donor_loss	1.0000
18:54274091:GTAC:G	donor_loss	1.0000
18:54274092:T:A	donor_loss	1.0000

AlphaMissense

4890 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:54273929:T:A	V82D	0.997
18:54273968:C:A	A95D	0.996
18:54273983:T:A	V100D	0.996
18:54273960:C:A	N92K	0.995
18:54273960:C:G	N92K	0.995
18:54280733:G:C	R209P	0.995
18:54273972:G:C	R96S	0.994
18:54273972:G:T	R96S	0.994
18:54277748:A:T	D151V	0.994
18:54280824:A:C	K239N	0.994
18:54280824:A:T	K239N	0.994
18:54271431:T:C	F63L	0.993
18:54271433:T:A	F63L	0.993
18:54271433:T:G	F63L	0.993
18:54273971:G:C	R96T	0.993
18:54280772:C:A	A222D	0.993
18:54277751:A:T	E152V	0.992
18:54282968:A:C	S310R	0.992
18:54282970:T:A	S310R	0.992
18:54282970:T:G	S310R	0.992
18:54273926:G:A	G81E	0.991
18:54274009:G:C	A109P	0.991
18:54271425:G:C	D61H	0.990
18:54273967:G:C	A95P	0.990
18:54277730:T:A	V145D	0.990
18:54280775:G:A	G223E	0.990
18:54282897:T:C	L286P	0.990
18:54271420:A:C	D59A	0.989
18:54271421:T:A	D59E	0.989
18:54271421:T:G	D59E	0.989

dbSNP variants (sampled 300 via entrez): RS1000021545 (18:54288259 G>C), RS1000077967 (18:54294524 G>A,T), RS1000272373 (18:54311852 C>T), RS1000275025 (18:54269484 C>G,T), RS1000306180 (18:54269610 G>C,T), RS1000329366 (18:54318022 G>A), RS1000449654 (18:54313031 C>G,T), RS1000477893 (18:54288567 C>T), RS1000593212 (18:54269001 A>AG), RS1000610625 (18:54270478 T>A), RS1000646591 (18:54270793 A>G), RS1000677490 (18:54277012 A>G), RS1000743718 (18:54275651 A>G), RS1000780641 (18:54319366 A>G), RS1000819201 (18:54302744 A>G)

Disease associations

OMIM: gene MIM:605252 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002740_60	Inflammatory skin disease	6.000000e-11
GCST007798_106	Asthma	1.000000e-08
GCST007800_56	Asthma (childhood onset)	4.000000e-11
GCST009720_70	Asthma	1.000000e-08
GCST010042_32	Asthma	2.000000e-10
GCST010043_40	Asthma	4.000000e-11
GCST010984_42	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	3.000000e-10
GCST010985_47	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	2.000000e-10
GCST90002382_488	Eosinophil percentage of white cells	6.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5391 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 34,342 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL6246	ELLAGIC ACID	2	23,148

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.21	IC50	62	nM	ELLAGIC ACID
7.12	IC50	75	nM	AURINTRICARBOXYLIC ACID
5.21	IC50	6200	nM	CANDESARTAN CILEXETIL

PubChem BioAssay actives

3 with measured affinity, of 7 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
6,7,13,14-tetrahydroxy-2,9-dioxatetracyclo[6.6.2.04,16.011,15]hexadeca-1(15),4,6,8(16),11,13-hexaene-3,10-dione	1315753: Inhibition of human recombinant DNA polymerase iota expressed in Baculovirus expression system using TAMRA/BHQ-2-labeled primer/template measured at 2 to 6 mins by reporter-strand displacement assay	ic50	0.0620	uM
5-[(3-carboxy-4-hydroxyphenyl)-(3-carboxy-4-oxocyclohexa-2,5-dien-1-ylidene)methyl]-2-hydroxybenzoic acid	1315753: Inhibition of human recombinant DNA polymerase iota expressed in Baculovirus expression system using TAMRA/BHQ-2-labeled primer/template measured at 2 to 6 mins by reporter-strand displacement assay	ic50	0.0750	uM
Candesartan Cilexetil	1315759: Inhibition of human DNA polymerase iota preincubated for 15 mins followed by replicating non-damaged DNA substrate addition measured after 30 mins in presence of dCTP and dGTP by radioactive gel-based primer extension assay	ic50	6.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
N6-(2-hydroxy-3-buten-1-yl)-2’-deoxyadenosine	decreases activity	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
diepoxybutane	affects binding, decreases activity, decreases reaction	1
methylparaben	increases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
cupric oxide	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2’-deoxyadenosine	affects binding, decreases activity, decreases reaction	1
MK-886	decreases activity	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
3-(2’-deoxy-beta-D-erythro-pentofuranosyl)pyrimido(1,2-alpha)purin-10(3H)-one	decreases activity	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Benzo(a)pyrene	increases expression	1
Caffeine	decreases phosphorylation	1
Coumestrol	affects cotreatment, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Guanine	decreases activity	1
Plant Extracts	increases expression, affects cotreatment	1

ChEMBL screening assays

7 unique, capped per target: 5 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1794483	Functional	PUBCHEM_BIOASSAY: qHTS for Inhibitors of Polymerase Iota. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID588623]	PubChem BioAssay data set
CHEMBL2339793	Binding	Inhibition of human DNA polymerase iota using poly(dA)/oligo(dT)18 (A/T, 2/1)/dTTP DNA template-primer substrate measured at 37 degC for 60 mins	Inhibitory effect of novel somatostatin peptide analogues on human cancer cell growth based on the selective inhibition of DNA polymerase β. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TE98	HAP1 POLI (-) 1	Cancer cell line	Male
CVCL_TE99	HAP1 POLI (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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