POLM

Summary

POLM (DNA polymerase mu, HGNC:9185) is a protein-coding gene on chromosome 7p13, encoding DNA-directed DNA/RNA polymerase mu (Q9NP87). Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ).

Predicted to enable DNA-directed DNA polymerase activity. Predicted to be involved in double-strand break repair via nonhomologous end joining. Predicted to act upstream of or within B cell differentiation and somatic hypermutation of immunoglobulin genes. Predicted to be located in nucleoplasm. Predicted to be active in nucleus.

Source: NCBI Gene 27434 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 91 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_013284

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9185
Approved symbol	POLM
Name	DNA polymerase mu
Location	7p13
Locus type	gene with protein product
Status	Approved
Aliases	Tdt-N
Ensembl gene	ENSG00000122678
Ensembl biotype	protein_coding
OMIM	606344
Entrez	27434

Gene structure

Transcript identifiers

Ensembl transcripts: 51 — 38 protein_coding, 6 nonsense_mediated_decay, 6 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000242248, ENST00000335195, ENST00000395831, ENST00000414235, ENST00000418926, ENST00000430942, ENST00000434229, ENST00000435068, ENST00000445616, ENST00000452049, ENST00000458246, ENST00000467607, ENST00000483644, ENST00000492312, ENST00000492321, ENST00000492605, ENST00000492971, ENST00000497300, ENST00000881064, ENST00000881065, ENST00000881066, ENST00000881067, ENST00000881068, ENST00000881069, ENST00000881070, ENST00000881071, ENST00000881072, ENST00000881073, ENST00000881074, ENST00000881075, ENST00000881076, ENST00000881077, ENST00000881078, ENST00000881079, ENST00000935513, ENST00000935514, ENST00000935515, ENST00000935516, ENST00000965029, ENST00000965030, ENST00000965031, ENST00000965032, ENST00000965033, ENST00000965034, ENST00000965035, ENST00000965036, ENST00000965037, ENST00000965038, ENST00000965039, ENST00000965040, ENST00000965041

RefSeq mRNA: 4 — MANE Select: NM_013284 NM_001284330, NM_001284331, NM_001362683, NM_013284

CCDS: CCDS34625, CCDS64635, CCDS64636

Canonical transcript exons

ENST00000242248 — 11 exons

Exon	Start	End
ENSE00000832554	44078740	44078811
ENSE00001233387	44074131	44074233
ENSE00001646543	44082251	44082530
ENSE00003477356	44079861	44079959
ENSE00003478855	44073783	44074025
ENSE00003536880	44073625	44073708
ENSE00003561565	44074398	44074530
ENSE00003573332	44076509	44076629
ENSE00003596529	44080733	44080916
ENSE00003684288	44079571	44079741
ENSE00003845509	44072062	44073377

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 93.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.6747 / max 164.1732, expressed in 1806 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83840	14.9229	1803
83837	0.4773	248
83834	0.3641	119
83839	0.2897	142
83833	0.2868	99
83836	0.2022	97
83835	0.0902	29
83838	0.0414	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	93.88	gold quality
metanephros cortex	UBERON:0010533	92.05	gold quality
right lobe of thyroid gland	UBERON:0001119	92.04	gold quality
spleen	UBERON:0002106	91.81	gold quality
left lobe of thyroid gland	UBERON:0001120	91.75	gold quality
thyroid gland	UBERON:0002046	91.51	gold quality
blood	UBERON:0000178	91.20	gold quality
right uterine tube	UBERON:0001302	89.84	gold quality
right lobe of liver	UBERON:0001114	89.79	gold quality
lower esophagus mucosa	UBERON:0035834	89.78	gold quality
lymph node	UBERON:0000029	89.64	gold quality
cortex of kidney	UBERON:0001225	89.38	gold quality
fundus of stomach	UBERON:0001160	89.14	gold quality
mucosa of stomach	UBERON:0001199	89.01	gold quality
body of stomach	UBERON:0001161	88.95	gold quality
left ovary	UBERON:0002119	88.87	gold quality
prostate gland	UBERON:0002367	88.86	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.68	gold quality
endocervix	UBERON:0000458	88.49	gold quality
vagina	UBERON:0000996	88.48	gold quality
ectocervix	UBERON:0012249	88.29	gold quality
tibial artery	UBERON:0007610	88.26	gold quality
popliteal artery	UBERON:0002250	88.24	gold quality
small intestine	UBERON:0002108	88.16	gold quality
esophagus mucosa	UBERON:0002469	88.12	gold quality
right ovary	UBERON:0002118	88.06	gold quality
ovary	UBERON:0000992	88.05	gold quality
minor salivary gland	UBERON:0001830	87.80	gold quality
right atrium auricular region	UBERON:0006631	87.75	gold quality
saliva-secreting gland	UBERON:0001044	87.58	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.06

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A

miRNA regulators (miRDB)

58 targeting POLM, 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-4283	100.00	66.42	2097
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-182-3P	99.57	67.57	825

Literature-anchored findings (GeneRIF, showing 28)

• DNA polymerase mu performs DNA synthesis at a AAF lesion (PMID:11972346)
• role in DNA repair (PMID:11974916)
• Association of DNA polymerase mu (pol mu) with Ku and ligase IV: role for pol mu in end-joining double-strand break repair. (PMID:12077346)
• DNA polymerase mu acts in response to several types of DNA damage with a lesion bypass mechanism (PMID:12228225)
• expression in B-cell non-Hodgkin’s lymphomas (PMID:12368208)
• Pol mu’s substrate specificity is similar to that of pol beta in most respects but has an approximately 1,000-fold-reduced ability to discriminate against ribonucleotides compared to pol beta (PMID:12640116)
• human DNA polymerase mu has a template-dependent, sequence-independent nucleotidyl transferase activity (PMID:14581466)
• Poliota incorporates a C opposite the gamma-HOPdG adduct with nearly the same efficiency as opposite a nonadducted G residue. The subsequent extension step is performed by Polkappa, which efficiently extends from the C incorporated opposite the adduct. (PMID:15199127)
• DNA polymerase mu has been overexpressed, purified, and its fidelity estimated for incorporation of both deoxynucleotides and ribonucleotides based on pre-steady-state kinetic data under single-turnover conditions. (PMID:15504045)
• Overexpression of DNA polymerase mu in a Burkitt’s lymphoma cell line induced an increase in somatic mutations specifically targeted to G/C residues in immunoglobulin variable genes. (PMID:15520469)
• Pol mu promotes accuracy during Ig kappa recombination. (PMID:16061182)
• When the terminal deoxynucleotidyl transferase (TdT) loop1 was deleted, human Polmu lacked TdT activity but improved DNA-binding and DNA template-dependent polymerization. (PMID:16963491)
• Studies shed light on the mechanism by which a rate-limited terminal transferase activity in Polmu could regulate the balance between accuracy and necessary efficiency, providing some variability during NHEJ. (PMID:19805281)
• Pol mu binds to DNA through its amino-terminal and pol beta-like regions. (PMID:22897684)
• The results uncovered a new DNA-binding function for the BRCT domain of Polmicro and demonstrated the importance of several residues located at the primer-binding region, for both DNA-binding and polymerization activities. (PMID:23034807)
• The study points at human Polmicro residues His(329) and Arg(387) as responsible for regulating nucleotide expansions occurring during DNA repair transactions, either promoting or blocking, respectively, iterative polymerization. (PMID:23143108)
• A physiological concentration of Mn(2+) ions did benefit Polmicro-mediated non-homologous end joining by improving the efficiency and accuracy of nucleotide insertion. (PMID:23275568)
• evidence suggests that Polmu could be regulated in vivo by phosphorylation of the BRCT domain (Ser12/Thr21) and of Ser372, affecting the function of loop1; Polmu’s most distinctive activities would be turned off at specific cell-cycle phases (S and G2), when these functions might be harmful to the cell (PMID:23933132)
• A specific N-terminal extension of the 8 kDa domain of DNA polymerase mu is potentially implicated in the maintenance of a closed conformation throughout the catalytic cycle, and this study indicated that it could be a target of Cdk phosphorylation. (PMID:23935073)
• specific loop 1 residues contribute to Pol mu’s unique ability to catalyze template-dependent NHEJ of DSBs with unpaired 3’ ends (PMID:24487959)
• A study of how Polmu fixes and/or orients the mobile Loop1 part of the protein in accordance with the substrate on which it is polymerizing. (PMID:24878922)
• analysis of template-dependent synthesis by human polymerase mu (PMID:26240373)
• Structural accommodation of ribonucleotide incorporation by the DNA repair enzyme polymerase Mu has been described. (PMID:28911097)
• Polmu point mutations affecting 2 conserved adjacent residues located in the 8 kDa domain, G174S and R175H, limit the efficiency of accurate NHEJ by Polmu in vitro and in vivo due to decreased template dependency during NHEJ, which renders the error-rate of the mutants higher due to the ability of Polmu to randomly incorporate nucleotides at DSBs. (PMID:28973441)
• pol mu-mediated deoxyguanosine triphosphate mismatch insertion opposite template base T coupled with ligation could be a feature of mutation prone nonhomologous end joining during double-strand break repair. (PMID:30310068)
• DNA polymerase mu: An inflexible scaffold for substrate flexibility. (PMID:33087269)
• DNA Polymerase and dRP-lyase activities of polymorphic variants of human Pol iota. (PMID:33600564)
• Mechanism of genome instability mediated by human DNA polymerase mu misincorporation. (PMID:34145298)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	polm	ENSDARG00000103470
mus_musculus	Polm	ENSMUSG00000020474
rattus_norvegicus	Polm	ENSRNOG00000013647

Paralogs (3): POLB (ENSG00000070501), DNTT (ENSG00000107447), POLL (ENSG00000166169)

Protein

Protein identifiers

DNA-directed DNA/RNA polymerase mu — Q9NP87 (reviewed: Q9NP87)

Alternative names: Terminal transferase

All UniProt accessions (9): A1PQG8, C9J222, C9JF34, Q9NP87, F8WB78, F8WDE4, F8WEJ1, H7C2M2, Q6PIY2

UniProt curated annotations — full annotation on UniProt →

Function. Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ). Participates in immunoglobulin (Ig) light chain gene rearrangement in V(D)J recombination.

Subcellular location. Nucleus.

Tissue specificity. Expressed in a number of tissues. Abundant in thymus.

Miscellaneous. DPOLM has a reduced ability to distinguish dNTP and rNTP as substrates, and elongates them on DNA primer strand with a similar efficiency. It is able to polymerize nucleotides on RNA primer strands.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NP87-1	1	yes
Q9NP87-2	2
Q9NP87-3	3

RefSeq proteins (4): NP_001271259, NP_001271260, NP_001349612, NP_037416* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001357	BRCT_dom	Domain
IPR001726	TdT/Mu	Family
IPR002054	DNA-dir_DNA_pol_X	Domain
IPR010996	HHH_MUS81	Domain
IPR018944	DNA_pol_lambd_fingers_domain	Domain
IPR019843	DNA_pol-X_BS	Binding_site
IPR022312	DNA_pol_X	Family
IPR027249	DNA/RNApol_mu	Family
IPR027421	DNA_pol_lamdba_lyase_dom_sf	Homologous_superfamily
IPR028207	DNA_pol_B_palm_palm	Domain
IPR029398	PolB_thumb	Domain
IPR036420	BRCT_dom_sf	Homologous_superfamily
IPR037160	DNA_Pol_thumb_sf	Homologous_superfamily
IPR043519	NT_sf	Homologous_superfamily

Pfam: PF10391, PF14716, PF14791, PF14792

Enzyme classification (BRENDA):

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

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 (58 total): helix 24, strand 13, splice variant 4, sequence variant 4, turn 4, binding site 3, region of interest 2, chain 1, domain 1, site 1, modified residue 1

Structure

Experimental structures (PDB)

129 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7KTN	X-RAY DIFFRACTION	1.33
7KT0	X-RAY DIFFRACTION	1.36
7KSZ	X-RAY DIFFRACTION	1.42
7KTK	X-RAY DIFFRACTION	1.42
7KTL	X-RAY DIFFRACTION	1.42
7KTG	X-RAY DIFFRACTION	1.45
7KTJ	X-RAY DIFFRACTION	1.45
7KT5	X-RAY DIFFRACTION	1.46
7KTH	X-RAY DIFFRACTION	1.48
7KTE	X-RAY DIFFRACTION	1.48
7KT9	X-RAY DIFFRACTION	1.48
7KTF	X-RAY DIFFRACTION	1.49
7KSW	X-RAY DIFFRACTION	1.49
7KT2	X-RAY DIFFRACTION	1.5
5VZB	X-RAY DIFFRACTION	1.5
5VZI	X-RAY DIFFRACTION	1.5
6WID	X-RAY DIFFRACTION	1.5
6WIE	X-RAY DIFFRACTION	1.5
5VZA	X-RAY DIFFRACTION	1.5
7KSS	X-RAY DIFFRACTION	1.5
5VZE	X-RAY DIFFRACTION	1.51
6VF3	X-RAY DIFFRACTION	1.52
7KTM	X-RAY DIFFRACTION	1.53
6VFB	X-RAY DIFFRACTION	1.55
6WIC	X-RAY DIFFRACTION	1.55
5VZ7	X-RAY DIFFRACTION	1.55
7KTD	X-RAY DIFFRACTION	1.55
5VZC	X-RAY DIFFRACTION	1.55
6VF9	X-RAY DIFFRACTION	1.56
7KSX	X-RAY DIFFRACTION	1.57

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NP87-F1	89.39	0.78

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): 433 (responsible for the low discrimination between dntp and rntp)

Ligand- & substrate-binding residues (3): 330; 332; 418

Post-translational modifications (1): 12

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)

MSigDB gene sets: 132 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_B_CELL_ACTIVATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, KAUFFMANN_DNA_REPAIR_GENES, GOMF_DNA_POLYMERASE_ACTIVITY, GOBP_IMMUNOGLOBULIN_PRODUCTION, GOBP_DNA_DAMAGE_RESPONSE, GOBP_SOMATIC_DIVERSIFICATION_OF_IMMUNE_RECEPTORS, GOBP_DNA_BIOSYNTHETIC_PROCESS, WINTER_HYPOXIA_METAGENE, chr7p13, GOBP_SOMATIC_DIVERSIFICATION_OF_IMMUNE_RECEPTORS_VIA_SOMATIC_MUTATION, REACTOME_DNA_REPAIR, OCT1_B, NAKAMURA_METASTASIS_MODEL_DN

GO Biological Process (8): double-strand break repair via nonhomologous end joining (GO:0006303), DNA recombination (GO:0006310), somatic hypermutation of immunoglobulin genes (GO:0016446), B cell differentiation (GO:0030183), DNA metabolic process (GO:0006259), DNA repair (GO:0006281), DNA damage response (GO:0006974), DNA biosynthetic process (GO:0071897)

GO Molecular Function (7): DNA binding (GO:0003677), DNA-directed DNA polymerase activity (GO:0003887), metal ion binding (GO:0046872), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), DNA polymerase activity (GO:0034061)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
DNA Double-Strand Break Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	3
double-strand break repair	1
somatic diversification of immune receptors via somatic mutation	1
somatic diversification of immunoglobulins	1
lymphocyte differentiation	1
B cell activation	1
nucleic acid metabolic process	1
DNA damage response	1
cellular response to stress	1
nucleic acid biosynthetic process	1
nucleic acid binding	1
DNA polymerase activity	1
cation binding	1
binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
nucleotidyltransferase activity	1
DNA biosynthetic process	1
catalytic activity, acting on DNA	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1194 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLM	REV1	Q9UBZ9	992
POLM	TENT4A	Q5XG87	947
POLM	POLH	Q9Y253	924
POLM	POLI	Q9UNA4	879
POLM	XRCC4	Q13426	839
POLM	RAD18	Q9NS91	830
POLM	REV3L	O60673	805
POLM	LIG1	P18858	797
POLM	MAD2L2	Q9UI95	788
POLM	UNG	P13051	773
POLM	POLN	Q7Z5Q5	758
POLM	PRKDC	P78527	756
POLM	WRN	Q14191	731
POLM	NHEJ1	Q9H9Q4	719
POLM	LIG4	P49917	717

IntAct

13 interactions, top by confidence:

A	B	Type	Score
POLM	tax	psi-mi:“MI:0915”(physical association)	0.560
tax	POLM	psi-mi:“MI:0915”(physical association)	0.560
rep	POLM	psi-mi:“MI:0915”(physical association)	0.490
POLM	tax	psi-mi:“MI:0915”(physical association)	0.490
POLM	MTUS1	psi-mi:“MI:0915”(physical association)	0.400
POLM	E7	psi-mi:“MI:0915”(physical association)	0.370
POLM	CEP55	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
POLM	CTU2	psi-mi:“MI:0914”(association)	0.350

BioGRID (31): POLM (Two-hybrid), POLM (Two-hybrid), CEP55 (Two-hybrid), POLM (Synthetic Growth Defect), POLM (Synthetic Growth Defect), POLM (Synthetic Lethality), CTU2 (Affinity Capture-MS), ACAD8 (Affinity Capture-MS), USHBP1 (Two-hybrid), CEP55 (Two-hybrid), CTAG1B (Two-hybrid), CTAG1A (Two-hybrid), POLM (Affinity Capture-RNA), POLM (Reconstituted Complex), ACAD8 (Affinity Capture-MS)

ESM2 similar proteins: A4FV98, A5PK51, A6NDG6, E1BE10, O00587, O35595, O95294, P60487, Q12788, Q17QS4, Q1JPJ0, Q2T9S4, Q2TBI8, Q32NY4, Q3T063, Q3ZBF9, Q501J2, Q5E9V4, Q5F4B1, Q5IS64, Q5SUV1, Q5T9C9, Q6AYG0, Q6AYR8, Q6XQN1, Q6XQN6, Q6ZMM2, Q80US4, Q8BNV1, Q8BZG5, Q8CC86, Q8IZ69, Q8N9H8, Q8NE01, Q8R2H9, Q8TCT1, Q8VCA8, Q8VD52, Q969S8, Q96AZ1

Diamond homologs: A4PCD4, O02789, O57486, P04053, P06526, P09838, P36195, P42118, Q92089, Q9JIW4, Q9NP87, Q4R380, Q09693, O57383, P06746, P06766, Q27958, Q5RKI3, Q67VC8, Q6DRD3, Q7T6Y4, Q8K409, Q9FNY4, Q9QXE2, Q9UGP5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CyclinA2/CDK2	“down-regulates activity”	POLM	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	68
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
442833	GRCh37/hg19 7p22.3-q36.3(chr7:43361-159119707)	Pathogenic

SpliceAI

2318 predictions. Top by Δscore:

Variant	Effect	Δscore
7:44073705:AAAG:A	acceptor_gain	1.0000
7:44073706:AAG:A	acceptor_gain	1.0000
7:44073707:AG:A	acceptor_gain	1.0000
7:44073709:C:CC	acceptor_gain	1.0000
7:44074392:TCTTA:T	donor_loss	1.0000
7:44074394:TTAC:T	donor_loss	1.0000
7:44074395:TACCT:T	donor_loss	1.0000
7:44074396:ACC:A	donor_loss	1.0000
7:44074397:C:G	donor_loss	1.0000
7:44076503:GCTCA:G	donor_loss	1.0000
7:44076504:CTCA:C	donor_loss	1.0000
7:44076505:TCA:T	donor_loss	1.0000
7:44076506:CA:C	donor_loss	1.0000
7:44076507:A:AC	donor_gain	1.0000
7:44076507:A:C	donor_loss	1.0000
7:44076507:AC:A	donor_gain	1.0000
7:44076508:C:CC	donor_gain	1.0000
7:44076508:C:CG	donor_loss	1.0000
7:44076508:CC:C	donor_gain	1.0000
7:44076508:CCCG:C	donor_gain	1.0000
7:44076626:AGAG:A	acceptor_gain	1.0000
7:44076627:GAG:G	acceptor_gain	1.0000
7:44076630:C:CC	acceptor_gain	1.0000
7:44080729:TCACC:T	donor_loss	1.0000
7:44080730:CA:C	donor_loss	1.0000
7:44080731:A:T	donor_loss	1.0000
7:44080846:T:TA	donor_gain	1.0000
7:44080912:CGGAG:C	acceptor_gain	1.0000
7:44080914:GAG:G	acceptor_gain	1.0000
7:44080917:C:CC	acceptor_gain	1.0000

AlphaMissense

3178 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:44082272:A:G	F56S	0.987
7:44080781:G:C	S108R	0.982
7:44080781:G:T	S108R	0.982
7:44080783:T:G	S108R	0.982
7:44080795:A:G	W104R	0.979
7:44080795:A:T	W104R	0.979
7:44073300:T:A	R492S	0.977
7:44073300:T:G	R492S	0.977
7:44082271:G:C	F56L	0.975
7:44082271:G:T	F56L	0.975
7:44082273:A:G	F56L	0.975
7:44074403:G:C	F321L	0.971
7:44074403:G:T	F321L	0.971
7:44074405:A:G	F321L	0.971
7:44082301:G:C	F46L	0.969
7:44082301:G:T	F46L	0.969
7:44082303:A:G	F46L	0.969
7:44076612:G:C	F244L	0.967
7:44076612:G:T	F244L	0.967
7:44076614:A:G	F244L	0.967
7:44080793:C:A	W104C	0.965
7:44080793:C:G	W104C	0.965
7:44073301:C:G	R492T	0.961
7:44073703:G:C	F440L	0.957
7:44073703:G:T	F440L	0.957
7:44073705:A:G	F440L	0.957
7:44074206:G:C	D332E	0.954
7:44074206:G:T	D332E	0.954
7:44076584:A:G	W254R	0.954
7:44076584:A:T	W254R	0.954

dbSNP variants (sampled 300 via entrez): RS1000219874 (7:44080356 A>C,G,T), RS1000269048 (7:44080595 G>C,T), RS1001110517 (7:44080391 A>T), RS1001439281 (7:44080020 G>A), RS1001494849 (7:44080259 C>T), RS1001566068 (7:44076176 C>T), RS1001777637 (7:44077686 CCT>C), RS1001808552 (7:44078020 G>A), RS1001959465 (7:44084380 T>C), RS1002004672 (7:44082879 G>A), RS1002265564 (7:44075512 C>T), RS1002492525 (7:44081560 C>G), RS1002639190 (7:44082461 G>A), RS1003114084 (7:44078586 G>T), RS1003241648 (7:44083945 T>C)

Disease associations

OMIM: gene MIM:606344 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1914260 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 2 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.10	IC50	7900	nM	CHEMBL1917196

PubChem BioAssay actives

1 with measured affinity, of 11 total; 1 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
(5,8-dioxonaphthalen-1-yl) dodecanoate	627960: Inhibition of His-tagged human DNA polymerase mu using poly(dA)/oligo(dT)18 (A/T = 2/1) and dTTP as the DNA template-primer and nucleotide substrate after 60 mins	ic50	7.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, increases abundance	2
Estradiol	affects expression, affects cotreatment, increases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	increases expression	1
beta-lapachone	increases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
MK-886	decreases activity	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
Bortezomib	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Amphotericin B	increases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	increases phosphorylation	1
Cisplatin	increases expression	1
Cyclophosphamide	increases expression	1
Doxorubicin	decreases expression	1
Gentamicins	increases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Smoke	decreases expression	1
Taurine	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Okadaic Acid	decreases expression	1
Raloxifene Hydrochloride	increases expression	1
Volatile Organic Compounds	affects cotreatment, decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1919787	Binding	Inhibition of His-tagged human DNA polymerase mu using poly(dA)/oligo(dT)18 (A/T = 2/1) and dTTP as the DNA template-primer and nucleotide substrate after 60 mins	Inhibitory effect of novel 5-O-acyl juglones on mammalian DNA polymerase activity, cancer cell growth and inflammatory response. — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1R07	HCT116-POLM(+/-)	Cancer cell line	Male
CVCL_B2BH	Abcam HeLa POLM KO	Cancer cell line	Female
CVCL_TF06	HAP1 POLM (-) 1	Cancer cell line	Male
CVCL_TF07	HAP1 POLM (-) 2	Cancer cell line	Male
CVCL_TF08	HAP1 POLM (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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