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): 116 total
• GTEx eGene: eQTL in 50 tissues, sQTL in 46 (q < 0.05)
• ChEMBL bioactivity: 2 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.72 (unconstrained)
• MANE Select transcript: NM_007195
• Interaction hub: 2,118 STRING partners (top 6% of genes corpus-wide)
• Notable: 116 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 28 — 16 protein_coding, 6 nonsense_mediated_decay, 4 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000579534

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 6, TSL 3: 5, TSL 5: 2

ENST00000579534, ENST00000217800, ENST00000406285, ENST00000577361, ENST00000577612, ENST00000577727, ENST00000577971, ENST00000579434, ENST00000579823, ENST00000580880, ENST00000580905, ENST00000581950, ENST00000582366, ENST00000583136, ENST00000583576, ENST00000585023, ENST00000854649, ENST00000854650, ENST00000930897, ENST00000941394, ENST00000978712, ENST00000978713, ENST00000978714, ENST00001051790, ENST00001051791, ENST00001051792, ENST00001110037, ENST00001131977

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.

Highest expression (Bgee): calcaneal tendon, lobe of thyroid gland, testis, thyroid gland, uterine tube.

Genetic regulation across tissues (GTEx eQTL / sQTL)

POLI is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 50 tissues and its splicing (sQTL) in 46 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 96 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	1.7e-114	-0.56	18:54269477:G:T
Cells Cultured fibroblasts	eqtl	1.4e-103	-0.37	18:54267598:A:G
Adipose Subcutaneous	eqtl	4.1e-98	-0.54	18:54288913:A:G
Thyroid	eqtl	3.2e-92	-0.56	18:54269477:G:T
Lung	eqtl	2.1e-85	-0.50	18:54269477:G:T
Skin Not Sun Exposed Suprapubic	eqtl	2.4e-84	-0.55	18:54288913:A:G
Thyroid	sqtl	1.4e-80	+1.10	18:54257461:G:A
Esophagus Mucosa	eqtl	2.4e-77	-0.51	18:54254649:T:C
Adipose Visceral Omentum	eqtl	1.4e-76	-0.42	18:54267598:A:G
Muscle Skeletal	eqtl	2.6e-76	-0.48	18:54261622:T:A
Nerve Tibial	eqtl	1.6e-72	-0.48	18:54269477:G:T
Artery Tibial	eqtl	4.1e-66	-0.49	18:54288913:A:G
Breast Mammary Tissue	eqtl	4.6e-61	-0.50	18:54255524:T:C
Esophagus Muscularis	eqtl	5.2e-57	-0.53	18:54288913:A:G
Colon Transverse	eqtl	1.4e-55	-0.40	18:54269477:G:T
Nerve Tibial	sqtl	2.2e-52	+1.02	18:54293105:G:A
Colon Sigmoid	eqtl	5.2e-47	-0.45	18:54276338:C:A
Testis	eqtl	8.4e-45	-0.55	18:54269477:G:T
Artery Aorta	eqtl	3.0e-42	-0.45	18:54276338:C:A
Testis	sqtl	6.7e-42	+1.08	18:54253250:A:G

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 286 tissues 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
muscle layer of sigmoid colon	UBERON:0035805	89.49	gold quality
right coronary artery	UBERON:0001625	89.31	gold quality
descending thoracic aorta	UBERON:0002345	89.31	gold quality
left coronary artery	UBERON:0001626	89.30	gold quality
tibial artery	UBERON:0007610	89.01	gold quality
popliteal artery	UBERON:0002250	88.99	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.90	gold quality
thoracic aorta	UBERON:0001515	88.85	gold quality
vagina	UBERON:0000996	88.84	gold quality
right lung	UBERON:0002167	88.82	gold quality
ascending aorta	UBERON:0001496	88.81	gold quality
aorta	UBERON:0000947	88.79	gold quality
pancreas	UBERON:0001264	88.70	gold quality
left uterine tube	UBERON:0001303	88.56	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.56	gold quality
lower esophagus	UBERON:0013473	88.54	gold quality
right adrenal gland	UBERON:0001233	88.40	gold quality
tendon	UBERON:0000043	88.37	gold quality
minor salivary gland	UBERON:0001830	88.22	gold quality
rectum	UBERON:0001052	88.09	gold quality
gall bladder	UBERON:0002110	88.08	gold quality
left adrenal gland cortex	UBERON:0035825	88.03	gold quality
coronary artery	UBERON:0001621	87.98	gold quality
right adrenal gland cortex	UBERON:0035827	87.95	gold quality
prostate gland	UBERON:0002367	87.92	gold quality
seminal vesicle	UBERON:0000998	87.87	gold quality
left adrenal gland	UBERON:0001234	87.82	gold quality
body of stomach	UBERON:0001161	87.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.54	gold quality
female reproductive system	UBERON:0000474	87.49	gold quality
skin of abdomen	UBERON:0001416	87.19	gold quality
endometrium	UBERON:0001295	87.13	gold quality
tibia	UBERON:0000979	87.01	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.83	gold quality
upper lobe of left lung	UBERON:0008952	86.83	gold quality
adrenal gland	UBERON:0002369	86.77	gold quality
bronchial epithelial cell	CL:0002328	86.67	gold quality
saliva-secreting gland	UBERON:0001044	86.62	gold quality
stomach	UBERON:0000945	86.58	gold quality
adrenal cortex	UBERON:0001235	86.58	gold quality
monocyte	CL:0000576	86.39	gold quality
germinal epithelium of ovary	UBERON:0001304	86.31	gold quality
right atrium auricular region	UBERON:0006631	86.04	gold quality
ganglionic eminence	UBERON:0004023	85.94	gold quality
mononuclear cell	CL:0000842	85.91	gold quality
upper lobe of lung	UBERON:0008948	85.91	gold quality
uterus	UBERON:0000995	85.85	gold quality
endothelial cell	CL:0000115	85.67	gold quality
thoracic mammary gland	UBERON:0005200	85.56	gold quality
esophagus	UBERON:0001043	85.52	gold quality
skin of leg	UBERON:0001511	85.50	gold quality
mammary gland	UBERON:0001911	85.44	gold quality
leukocyte	CL:0000738	85.43	gold quality
spleen	UBERON:0002106	85.33	gold quality
placenta	UBERON:0001987	85.28	gold quality
corpus callosum	UBERON:0002336	85.17	gold quality
apex of heart	UBERON:0002098	85.14	gold quality
transverse colon	UBERON:0001157	85.13	gold quality
stromal cell of endometrium	CL:0002255	85.05	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.05	gold quality
spinal cord	UBERON:0002240	85.04	gold quality
fundus of stomach	UBERON:0001160	84.83	gold quality
mouth mucosa	UBERON:0003729	84.72	gold quality
right lobe of liver	UBERON:0001114	84.61	gold quality
small intestine	UBERON:0002108	84.49	gold quality
granulocyte	CL:0000094	84.35	gold quality
zone of skin	UBERON:0000014	84.23	gold quality
lymph node	UBERON:0000029	84.09	gold quality
material anatomical entity	UBERON:0000465	83.72	gold quality
multicellular organism	UBERON:0000468	83.72	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Testis	tissue	35.5	high
Thyroid gland	tissue	29.3	high
Retina	tissue	23.5
Adipose tissue	tissue	19.9
Nucleus accumbens	tissue	19.5
Breast	tissue	17.0	medium
Locus coeruleus	tissue	16.3
Parathyroid gland	tissue	14.9	high
Ovary	tissue	14.4	not detected
Hippocampus	tissue	14.4	not detected
Choroid plexus	tissue	14.3
Endometrium 1	tissue	14.1	medium
Placenta	tissue	13.9	medium
Seminal vesicle	tissue	13.7	medium
Thymus	tissue	13.6
Epididymis	tissue	13.5	medium
Kidney	tissue	13.4	medium
Prostate	tissue	13.2	low
Cervix	tissue	12.9	low
Postcentral gyrus	tissue	12.9
Pancreas	tissue	12.7	medium
Smooth muscle	tissue	10.7	not detected
Fallopian tube	tissue	10.6	medium
Pituitary gland	tissue	10.5
Heart muscle	tissue	10.0	low
Lung	tissue	9.4
Stomach 1	tissue	9.1	medium
Corpus callosum	tissue	9.1
Gallbladder	tissue	9.0	medium
Lymph node	tissue	8.9	low
Spleen	tissue	8.9	not detected
Adrenal gland	tissue	8.6	low
Vagina	tissue	8.2	low
Spinal cord	tissue	8.2
Rectum	tissue	8.0	medium
Urinary bladder	tissue	7.9	medium
Tonsil	tissue	7.9	not detected
Salivary gland	tissue	7.7	medium
Midbrain	tissue	7.7
Medulla oblongata	tissue	7.7
Periaqueductal gray	tissue	7.6
Olfactory bulb	tissue	7.5
Amygdala	tissue	7.4
Duodenum	tissue	7.4	medium
Septum	tissue	7.4
Pons	tissue	7.2
Putamen	tissue	7.1
Thalamus	tissue	7.1
Hippocampal formation	tissue	7.1
Cerebral cortex	tissue	7.0	low
Superior colliculi	tissue	7.0
Liver	tissue	7.0	not detected
Ventral forebrain	tissue	7.0
Somatosensory cortex	tissue	7.0
Occipital cortex	tissue	7.0
Hypothalamus	tissue	6.9
Substantia nigra	tissue	6.9
Entorhinal cortex	tissue	6.9
Temporal cortex	tissue	6.9
Retrosplenial cortex	tissue	6.8

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Corpus callosum, genu (white matter) (30.3), Temporal white matter (27.7), Cerebellar white matter (26.8), Globus pallidus, externus (26.0), Globus pallidus, internus (25.9).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

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

showing 30 of 123 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 7.09e-05, LOEUF 1.72, missense Z -0.877 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000579534 — one region, missense o/e 1.06.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1347081) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased incidence of tumors by chemical induction	1
prolonged RR interval	1

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Arabidopsis thaliana	Q8H2D5	41.6%	Diamond

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
STARD6	protein-coding	147323
SNORA37	snoRNA	677819
MBD2	protein-coding	8932
C18orf54	protein-coding	162681
LINC01917	ncRNA	101928167
LINC01919	ncRNA	102724651

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)

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

UniProt features (87 total): helix 25, strand 21, 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)

showing 30 of 54 structures by resolution:

PDB	Title	Method	Resolution (Å)
3OSN	Structural Basis for Proficient Incorporation of dTTP Opposite O6-Methylguanine by Human …	X-RAY DIFFRACTION	1.9
3Q8P	Human DNA polymerase iota incorporating dCTP opposite 8-oxo-guanine	X-RAY DIFFRACTION	1.95
5ULX	Structure of human DNA polymerase iota bound to template 1-methyl-deoxyadenosine …	X-RAY DIFFRACTION	1.96
3GV5	Human DNA polymerase iota in complex with T template DNA and incoming ddADP	X-RAY DIFFRACTION	2
3GV8	Human DNA polymerase iota in complex with T template DNA and incoming dGTP	X-RAY DIFFRACTION	2
3Q8Q	Human DNA polymerase iota incorporating dATP opposite 8-oxo-guanine	X-RAY DIFFRACTION	2.03
4FS2	Base pairing mechanism of N2,3-ethenoguanine with dCTP by human polymerase iota	X-RAY DIFFRACTION	2.05
3G6X	Ternary complex of DNA Polymerase iota:DNA:dGTP with an abasic site at the templating …	X-RAY DIFFRACTION	2.08
3Q8S	Human DNA polymerase iota incorporating dTTP opposite 8-oxo-guanine	X-RAY DIFFRACTION	2.09
3G6Y	Ternary complex of DNA Polymerase iota:DNA:dTTP with an abasic site at the templating …	X-RAY DIFFRACTION	2.1
4EBE	Conformationally Restrained North-methanocarba-2’-deoxyadenosine Corrects the Error-Prone …	X-RAY DIFFRACTION	2.1
9DDR	Ternary substrate complex of DNA polymerase iota with DNA (template A), Ca2+, and dTTP	X-RAY DIFFRACTION	2.15
3G6V	DNA synthesis across an abasic lesion by human DNA polymerase-iota	X-RAY DIFFRACTION	2.2
3GV7	Human DNA polymerase iota in complex with T template DNA and incoming dTTP	X-RAY DIFFRACTION	2.2
3H4D	Ternary complex of human DNA polymerase iota with template U/T and incoming dGTP	X-RAY DIFFRACTION	2.2
9DQU	Product complex of DNA polymerase iota with Pyrophosphate	X-RAY DIFFRACTION	2.2
9DR9	Binary product complex of DNA polymerase iota with DNA	X-RAY DIFFRACTION	2.21
9NJH	Translocated product complex of DNA polymerase iota with DNA (template A)	X-RAY DIFFRACTION	2.29
1T3N	Structure of the catalytic core of DNA polymerase Iota in complex with DNA and dTTP	X-RAY DIFFRACTION	2.3
1ZET	X-ray data do not support hoogsteen base-pairing during replication by human polymerase …	X-RAY DIFFRACTION	2.3
2DPI	Ternary complex of hPoli with DNA and dCTP	X-RAY DIFFRACTION	2.3
2DPJ	structure of hPoli with DNA and dTTP	X-RAY DIFFRACTION	2.3
3H40	Binary complex of human DNA polymerase iota with template U/T	X-RAY DIFFRACTION	2.3
9DRB	Binary complex of DNA polymerase iota with product DNA	X-RAY DIFFRACTION	2.36
2FLP	Binary complex of the catalytic core of human DNA polymerase iota with DNA (template G)	X-RAY DIFFRACTION	2.4
3Q8R	Human DNA polymerase iota incorporating dGTP opposite 8-oxo-guanine	X-RAY DIFFRACTION	2.45
9DR7	Product complex of DNA polymerase iota with 2 monophosphates	X-RAY DIFFRACTION	2.45
9DRC	Ternary substrate complex of DNA polymerase iota R71A mutant with DNA (template A) and …	X-RAY DIFFRACTION	2.45
5KT2	Teranry complex of human DNA polymerase iota(26-445) inserting dCMPNPP opposite template …	X-RAY DIFFRACTION	2.49
2ALZ	Ternary Complex of hPoli with DNA and dCTP	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear speckles; cytoplasmic bodies

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
152	proton acceptor

Ligand- & substrate-binding residues (8)

Position	Role
59	Mg(2+)
59	Mn(2+)
60	Mg(2+)
60	Mn(2+)
64	a 2’-deoxyribonucleoside 5’-triphosphate
96	a 2’-deoxyribonucleoside 5’-triphosphate
151	Mg(2+)
151	Mn(2+)

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

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

7 pathways:

ID	Pathway	Evidence
R-HSA-9968295	Somatic hypermutation of immunoglobulin genes by error-prone mismatch repair (MMR)	curated
R-HSA-5656169	Termination of translesion DNA synthesis	curated
R-HSA-5656121	Translesion synthesis by POLI	curated
R-HSA-73893	DNA Damage Bypass	—
R-HSA-73894	DNA Repair	—
R-HSA-9968297	Somatic hypermutation of immunoglobulin genes by error-prone base excision repair (BER)	electronic
R-HSA-110313	Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	—

MSigDB gene sets: 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 repair (GO:0006281), translesion synthesis (GO:0019985), error-prone translesion synthesis (GO:0042276), DNA metabolic process (GO:0006259), DNA replication (GO:0006260), 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 (3): nucleoplasm (GO:0005654), nuclear speck (GO:0016607), nucleus (GO:0005634)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	2
Somatic hypermutation of immunoglobulin genes	2
DNA Damage Bypass	1
DNA Repair	1

GO top-level categories

22 GO namespaces:

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
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
translesion synthesis	BP	direct assay
nuclear speck	CC	direct assay
DNA-directed DNA polymerase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,118 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLI	RRN3	Q9NYV6	962
POLI	BDP1	A6H8Y1	947
POLI	TBP	P20226	924
POLI	POLR1B	Q9H9Y6	924
POLI	UBTF	P17480	881
POLI	POLM	Q9NP87	855
POLI	TAF1A	Q15573	848
POLI	MAF1	Q9H063	830
POLI	POLR3K	Q9Y2Y1	826
POLI	POLR1D	P0DPB6	823
POLI	FBL	P22087	800
POLI	POLR1A	O95602	773
POLI	POLR3A	O14802	766
POLI	POLL	Q9UGP5	751
POLI	SIRT7	Q9NRC8	730

IntAct

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

23 partners by confidence:

Partner	Interaction type	MIscore	Records
TRIM39	physical association	0.670	4
DAZAP2	physical association	0.620	3
HOMER3	physical association	0.560	3
KAT5	physical association	0.560	3
LMO3	physical association	0.560	3
PRKCA	physical association	0.560	3
SETDB1	physical association	0.560	3
TMEM239	physical association	0.560	3
TRAF6	physical association	0.560	3
YWHAG	physical association	0.560	3
ZBTB44	physical association	0.560	3
DVL2	physical association	0.550	2
UBC	physical association	0.530	4
PCNA	physical association	0.530	2
NEDD8	physical association	0.520	2
TRIM23	physical association	0.490	2
MFHAS1	direct interaction	0.440	1
XRCC1	physical association	0.400	2
CALCOCO2	physical association	0.370	1
ENTREP1	physical association	0.370	1
MTNR1B	physical association	0.370	1
RNF11	physical association	0.370	1
UBA1	ubiquitination reaction	0.000	1

BioGRID (2,118 interactions; top human partners by supporting records in a sample of 600 records): TP53 (Affinity Capture-Western; 6 records), UBC (Co-crystal Structure; 5 records), USP7 (Reconstituted Complex; 5 records), EP300 (Affinity Capture-Western; 3 records), PCNA (Reconstituted Complex; 3 records), XIAP (Affinity Capture-MS; 3 records), DVL2 (Two-hybrid; 2 records), NEDD8 (Protein-peptide; 2 records), RAI14 (Affinity Capture-MS; 2 records), TRAF6 (Two-hybrid; 2 records), TRIM39 (Two-hybrid; 2 records), ABCF2 (Reconstituted Complex), ABHD12B (Reconstituted Complex), ABL1 (Reconstituted Complex), ACOT4 (Reconstituted Complex)

Disease & clinical

Genetic variants

Variant evidence for POLI: 116 ClinVar records (0 pathogenic / likely pathogenic); 9 GWAS associations.

ClinVar

116 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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 1,343):

Position(s)	Effect	Δscore	Sites
18:54271350	acceptor_gain	1.0000
18:54271486–54271487	donor_loss	1.0000	6
18:54274091–54274092	donor_loss	1.0000	4
18:54274100	donor_gain	1.0000
18:54277697	acceptor_gain	1.0000
18:54277701	acceptor_loss	1.0000
18:54282835–54282836	acceptor_loss	1.0000	5
18:54283016–54283017	donor_loss	1.0000	5
18:54292039–54292040	donor_loss	1.0000	5
18:54293728	donor_gain	1.0000

AlphaMissense

835 missense substitutions predicted likely pathogenic (of 4,890 scored), across 241 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
D151	8	0.979	0.994
D59	8	0.976	0.989
D61	8	0.974	0.990
H57	8	0.886	0.968
D314	8	0.872	0.969
M69	8	0.783	0.859
F63	7	0.972	0.993
N92	7	0.941	0.995
E152	7	0.938	0.992
R96	7	0.937	0.994
F426	7	0.918	0.987
F154	7	0.917	0.983
C113	7	0.903	0.983
C62	7	0.864	0.973
D156	7	0.862	0.916
Q84	7	0.857	0.981
E68	7	0.847	0.954
W728	7	0.829	0.941
F416	7	0.817	0.954
E330	7	0.777	0.866

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.09e-06
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000484

Disease associations

OMIM: gene MIM:605252 | disease phenotypes:

GWAS associations

9 associations:

Study	Trait	p-value
GCST90002382_415	Eosinophil percentage of white cells	6e-12
GCST007800_51	Asthma (childhood onset)	4e-11
GCST010043_19	Asthma	4e-11
GCST002740_47	Inflammatory skin disease	6e-11
GCST010042_140	Asthma	2e-10
GCST010985_50	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	2e-10
GCST010984_42	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	3e-10
GCST007798_1	Asthma	1e-8
GCST009720_84	Asthma	1e-8

EFO canonical traits (from GWAS)

2 canonical traits:

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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 34,679 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,240
CHEMBL6246	ELLAGIC ACID	2	23,439

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

2 measured of 3 human assays (4 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
MLS002153482	IC50	3200 nM
TCV-116	IC50	5000 nM

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	decreases expression, affects 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	decreases expression, increases abundance	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)

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

Predicted chemistry — Sugi Predict

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