POLN
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Summary
POLN (DNA polymerase nu, HGNC:18870) is a protein-coding gene on chromosome 4p16.3, encoding DNA polymerase nu (Q7Z5Q5). DNA polymerase with very low fidelity that catalyzes considerable misincorporation by inserting dTTP opposite a G template, and dGTP opposite a T template.
This gene encodes a DNA polymerase type-A family member. The encoded protein plays a role in DNA repair and homologous recombination. This gene shares its 5’ exons with some transcripts from overlapping GeneID: 79441, which encodes an augmentin-like protein complex subunit.
Source: NCBI Gene 353497 — RefSeq curated summary.
At a glance
- GWAS associations: 4
- Clinical variants (ClinVar): 158 total — 1 pathogenic
- Druggable target: yes
- MANE Select transcript:
NM_181808
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:18870 |
| Approved symbol | POLN |
| Name | DNA polymerase nu |
| Location | 4p16.3 |
| Locus type | gene with protein product |
| Status | Approved |
| Ensembl gene | ENSG00000130997 |
| Ensembl biotype | protein_coding |
| OMIM | 610887 |
| Entrez | 353497 |
Gene structure
Transcript identifiers
Ensembl transcripts: 13 — 6 protein_coding_CDS_not_defined, 4 retained_intron, 3 protein_coding
ENST00000382865, ENST00000503371, ENST00000503601, ENST00000506518, ENST00000508568, ENST00000509623, ENST00000510344, ENST00000511098, ENST00000511777, ENST00000511885, ENST00000514521, ENST00000514858, ENST00000515357
RefSeq mRNA: 1 — MANE Select: NM_181808
NM_181808
CCDS: CCDS3360
Canonical transcript exons
ENST00000511885 — 26 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000897203 | 2080958 | 2081036 |
| ENSE00001288463 | 2071918 | 2072299 |
| ENSE00003471895 | 2072968 | 2073029 |
| ENSE00003473151 | 2131233 | 2131290 |
| ENSE00003488950 | 2193204 | 2193316 |
| ENSE00003494595 | 2229099 | 2229243 |
| ENSE00003506470 | 2081633 | 2081743 |
| ENSE00003513003 | 2242051 | 2242121 |
| ENSE00003534336 | 2213047 | 2213126 |
| ENSE00003540612 | 2207987 | 2208487 |
| ENSE00003553786 | 2159155 | 2159211 |
| ENSE00003567330 | 2129179 | 2129256 |
| ENSE00003568696 | 2156788 | 2156853 |
| ENSE00003578899 | 2174691 | 2174751 |
| ENSE00003601529 | 2198524 | 2198717 |
| ENSE00003603469 | 2075452 | 2075519 |
| ENSE00003606593 | 2176266 | 2176334 |
| ENSE00003612680 | 2085613 | 2085744 |
| ENSE00003613523 | 2173955 | 2174019 |
| ENSE00003618280 | 2128113 | 2128227 |
| ENSE00003629677 | 2171098 | 2171181 |
| ENSE00003630966 | 2170679 | 2170774 |
| ENSE00003633935 | 2095851 | 2095933 |
| ENSE00003663304 | 2179308 | 2179465 |
| ENSE00003680492 | 2241520 | 2241790 |
| ENSE00003689912 | 2157858 | 2157911 |
Expression profiles
Bgee: expression breadth ubiquitous, 160 present calls, max score 86.25.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.0187 / max 44.9892, expressed in 1482 samples.
FANTOM5 promoters (5 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 51109 | 4.0187 | 1482 |
| 51107 | 2.4718 | 874 |
| 51108 | 1.5590 | 922 |
| 51106 | 0.5361 | 216 |
| 51105 | 0.1876 | 48 |
Top tissues by expression
236 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| caudate nucleus | UBERON:0001873 | 86.25 | gold quality |
| putamen | UBERON:0001874 | 84.13 | gold quality |
| nucleus accumbens | UBERON:0001882 | 82.13 | gold quality |
| right frontal lobe | UBERON:0002810 | 82.10 | gold quality |
| Brodmann (1909) area 9 | UBERON:0013540 | 80.45 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 80.41 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 79.80 | gold quality |
| left testis | UBERON:0004533 | 79.60 | gold quality |
| right testis | UBERON:0004534 | 79.39 | gold quality |
| cerebellar hemisphere | UBERON:0002245 | 78.45 | gold quality |
| cerebellar cortex | UBERON:0002129 | 78.35 | gold quality |
| right hemisphere of cerebellum | UBERON:0014890 | 78.27 | gold quality |
| omental fat pad | UBERON:0010414 | 77.74 | gold quality |
| peritoneum | UBERON:0002358 | 77.72 | gold quality |
| amygdala | UBERON:0001876 | 77.61 | gold quality |
| right uterine tube | UBERON:0001302 | 77.55 | gold quality |
| cerebellum | UBERON:0002037 | 77.52 | gold quality |
| dorsolateral prefrontal cortex | UBERON:0009834 | 77.15 | gold quality |
| hypothalamus | UBERON:0001898 | 77.11 | gold quality |
| testis | UBERON:0000473 | 77.01 | gold quality |
| adipose tissue of abdominal region | UBERON:0007808 | 76.72 | gold quality |
| vena cava | UBERON:0004087 | 75.23 | gold quality |
| forebrain | UBERON:0001890 | 75.16 | gold quality |
| brain | UBERON:0000955 | 75.01 | gold quality |
| C1 segment of cervical spinal cord | UBERON:0006469 | 74.79 | gold quality |
| spinal cord | UBERON:0002240 | 74.33 | gold quality |
| parotid gland | UBERON:0001831 | 73.65 | gold quality |
| neocortex | UBERON:0001950 | 73.61 | gold quality |
| substantia nigra | UBERON:0002038 | 73.42 | gold quality |
| right adrenal gland cortex | UBERON:0035827 | 73.40 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 0.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | no | 4.88 |
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
5 targeting POLN, 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-6749-3P | 99.00 | 65.73 | 1443 |
| HSA-MIR-4717-5P | 98.19 | 67.97 | 894 |
| HSA-MIR-5699-5P | 97.36 | 67.03 | 1014 |
| HSA-MIR-1288-3P | 96.86 | 66.95 | 536 |
| HSA-MIR-3189-3P | 96.80 | 66.34 | 896 |
Literature-anchored findings (GeneRIF, showing 25)
- identification as homolog to Mus308 (PMID:12794064)
- pol nu error rates for all 12 single base-base mismatches and for insertion and deletion errors (PMID:17118716)
- The DNA cross-linking agent mitomycin C hypersensitivity of PolN knockdown cells is rescued by overexpression of DNA polymerase-proficient PolN but not by DNA polymerase-deficient PolN. (PMID:19908865)
- The recently discovered polymerase POLN identified here is involved in repair of DNA cross-links. (PMID:19995904)
- Described is a novel translesion DNA synthesis substrate specificity of pol nu, demonstrating that it is able to bypass exceptionally large DNA lesions whose linkages are through the DNA major groove. (PMID:20102227)
- Our finding suggests that polymorphisms in DNA repair genes, POLN and PRKDC, were associated with increased melanoma risk in melanoma families with and without CDKN2A mutations. (PMID:21671477)
- The lower fidelity of POLN compared to that of Klenow fragment of Escherichia coli can be attributed to a much lower catalytic efficiency for correct dNTP incorporation, whereas both enzymes have similar kinetic parameters for G-dTTP misinsertion. (PMID:22008035)
- both yeast and human pol eta synthesize past the 3’-(m)C CPD in a >99% error-free manner, consistent with the highly water-exposed nature of the active site. (PMID:22262850)
- Epstein-Barr virus BPLF1 deubiquitinates PCNA and attenuates polymerase eta recruitment to DNA damage sites (PMID:22623772)
- WRN improves the efficiency and fidelity of hpol eta to promote more effective replication of DNA. (PMID:23045531)
- Pol nu catalyzes both correct and mispair formation with high catalytic efficiency. (PMID:25963146)
- This is the first crystal structure of a DNA polymerase with an incoming rNTP opposite a DNA lesion. (PMID:26740629)
- The Proliferating Cell Nuclear Antigen (PCNA)-interacting Protein (PIP) Motif of DNA Polymerase eta Mediates Its Interaction with the C-terminal Domain of Rev1. (PMID:26903512)
- Five x-ray crystal structures of hpol eta ternary complexes were determined, three at the insertion and two at the extension stage. (PMID:27226627)
- The structural data are consistent with the observed tendency of hpol eta to insert both dC and dT opposite the O(6)-MeG lesion with similar efficiencies. (PMID:27694439)
- Data suggest that translesion DNA synthesis mediated by (1) POLI-dependent pathway (2) REV1- and POLN-dependent pathway, or (3) POLtheta-dependent pathway occur in predominantly error-free manner in human cells. (POLI = DNA polymerase iota; REV1 = DNA repair protein-REV1; POLN = DNA polymerase nu; POLtheta = DNA polymerase theta) (PMID:29330301)
- Crystallographic evidence for two-metal-ion catalysis in human pol eta. (PMID:30368948)
- the Poleta-oxaliplatin-GpG structure provides a structural basis for TLS-mediated bypass of the major oxaliplatin-DNA adducts and insights into resistance to platinum-based chemotherapy in humans. (PMID:30709915)
- These results suggest that hpol eta is one of the major reverse transcriptases involved in physiological processes in human cells. (PMID:30842261)
- The roles of polymerases nu and theta in replicative bypass of O (6)- and N (2)-alkyl-2’-deoxyguanosine lesions in human cells. (PMID:32098870)
- Translesion synthesis of the major nitrogen mustard-induced DNA lesion by human DNA polymerase eta. (PMID:33175093)
- Multiple deprotonation paths of the nucleophile 3’-OH in the DNA synthesis reaction. (PMID:34088846)
- DNA polymerases eta and kappa bypass N(2)-guanine-O(6)-alkylguanine DNA alkyltransferase cross-linked DNA-peptides. (PMID:34461101)
- Next-Generation Sequencing-Based Analysis of the Roles of DNA Polymerases nu and theta in the Replicative Bypass of 8-Oxo-7,8-dihydroguanine in Human Cells. (PMID:35815634)
- Rare POLN mutations confer risk for familial nasopharyngeal carcinoma through weakened Epstein-Barr virus lytic replication. (PMID:36116213)
Cross-species orthologs
3 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | poln | ENSDARG00000103961 |
| mus_musculus | Poln | ENSMUSG00000045102 |
| rattus_norvegicus | Haus3 | ENSRNOG00000069005 |
Protein
Protein identifiers
DNA polymerase nu — Q7Z5Q5 (reviewed: Q7Z5Q5)
All UniProt accessions (2): Q7Z5Q5, H0YA88
UniProt curated annotations — full annotation on UniProt →
Function. DNA polymerase with very low fidelity that catalyzes considerable misincorporation by inserting dTTP opposite a G template, and dGTP opposite a T template. Is the least accurate of the DNA polymerase A family (i.e. POLG, POLN and POLQ). Can perform accurate translesion DNA synthesis (TLS) past a 5S-thymine glycol. Can perform efficient strand displacement past a nick or a gap and gives rise to an amount of product similar to that on non-damaged template. Has no exonuclease activity. Error-prone DNA polymerase that preferentially misincorporates dT regardless of template sequence. May play a role in TLS during interstrand cross-link (ICL) repair. May be involved in TLS when genomic replication is blocked by extremely large major groove DNA lesions. May function in the bypass of some DNA-protein and DNA-DNA cross-links. May have a role in cellular tolerance to DNA cross-linking agents. Involved in the repair of DNA cross-links and double-strand break (DSB) resistance. Participates in FANCD2-mediated repair. Forms a complex with HELQ helicase that participates in homologous recombination (HR) repair and is essential for cellular protection against DNA cross-links.
Subunit / interactions. Interacts with FANCD2, FANCI, PCNA, RAD51 and HELQ.
Subcellular location. Nucleus.
Tissue specificity. Highly expressed in testis and heart. Weakly expressed in skeletal muscle.
Activity regulation. Inhibited by ddTTP.
Similarity. Belongs to the DNA polymerase type-A family.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q7Z5Q5-1 | 1 | yes |
| Q7Z5Q5-3 | 2 |
RefSeq proteins (1): NP_861524* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR001098 | DNA-dir_DNA_pol_A_palm_dom | Domain |
| IPR002298 | DNA_polymerase_A | Family |
| IPR036397 | RNaseH_sf | Homologous_superfamily |
| IPR040940 | DNA_pol_P_Exo | Domain |
| IPR043502 | DNA/RNA_pol_sf | Homologous_superfamily |
Pfam: PF00476, PF18049
Catalyzed reactions (Rhea), 1 shown:
- DNA(n) + a 2’-deoxyribonucleoside 5’-triphosphate = DNA(n+1) + diphosphate (RHEA:22508)
UniProt features (78 total): helix 31, strand 23, sequence variant 8, turn 5, mutagenesis site 3, region of interest 2, compositionally biased region 2, splice variant 2, chain 1, sequence conflict 1
Structure
Experimental structures (PDB)
4 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 4XVK | X-RAY DIFFRACTION | 2.95 |
| 4XVI | X-RAY DIFFRACTION | 3.1 |
| 4XVM | X-RAY DIFFRACTION | 3.2 |
| 4XVL | X-RAY DIFFRACTION | 3.3 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q7Z5Q5-F1 | 75.70 | 0.56 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Mutagenesis-validated functional residues (3):
| Position | Phenotype |
|---|---|
| 623 | abolishes catalytic activity. |
| 675 | reduces polymerase activity. no effect on accuracy. |
| 679 | no effect on polymerase activity. increases accuracy by ten-fold. |
Function
Pathways and Gene Ontology
Reactome pathways
1 pathways
| ID | Pathway |
|---|---|
| R-HSA-6783310 | Fanconi Anemia Pathway |
MSigDB gene sets: 59 (showing top):
GOBP_DNA_DAMAGE_TOLERANCE, KAUFFMANN_DNA_REPAIR_GENES, GOMF_DNA_POLYMERASE_ACTIVITY, GOBP_DNA_DAMAGE_RESPONSE, chr4p16, GOBP_DNA_BIOSYNTHETIC_PROCESS, GOBP_INTERSTRAND_CROSS_LINK_REPAIR, REACTOME_FANCONI_ANEMIA_PATHWAY, REACTOME_DNA_REPAIR, GOBP_RECOMBINATIONAL_REPAIR, BURTON_ADIPOGENESIS_12, GOBP_DNA_REPLICATION, BURTON_ADIPOGENESIS_6, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, MARSON_BOUND_BY_E2F4_UNSTIMULATED
GO Biological Process (9): double-strand break repair via homologous recombination (GO:0000724), DNA synthesis involved in DNA repair (GO:0000731), DNA-templated DNA replication (GO:0006261), double-strand break repair (GO:0006302), translesion synthesis (GO:0019985), interstrand cross-link repair (GO:0036297), DNA replication (GO:0006260), DNA repair (GO:0006281), DNA damage response (GO:0006974)
GO Molecular Function (8): DNA binding (GO:0003677), DNA-directed DNA polymerase activity (GO:0003887), cyclin binding (GO:0030332), nucleic acid binding (GO:0003676), 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 Repair | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| DNA repair | 3 |
| DNA biosynthetic process | 3 |
| DNA metabolic process | 2 |
| binding | 2 |
| recombinational repair | 1 |
| double-strand break repair | 1 |
| DNA replication | 1 |
| DNA damage tolerance | 1 |
| DNA synthesis involved in DNA replication | 1 |
| DNA damage response | 1 |
| cellular response to stress | 1 |
| nucleic acid binding | 1 |
| DNA polymerase activity | 1 |
| protein binding | 1 |
| catalytic activity | 1 |
| transferase activity, transferring phosphorus-containing groups | 1 |
| nucleotidyltransferase activity | 1 |
| catalytic activity, acting on DNA | 1 |
| intracellular membrane-bounded organelle | 1 |
| nuclear lumen | 1 |
| cellular anatomical structure | 1 |
Protein interactions and networks
STRING
1577 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| POLN | HELQ | Q8TDG4 | 989 |
| POLN | POLA1 | P09884 | 933 |
| POLN | POLM | Q9NP87 | 758 |
| POLN | FANCD2 | Q9BXW9 | 678 |
| POLN | REV3L | O60673 | 658 |
| POLN | POLG | P54098 | 655 |
| POLN | POLD1 | P28340 | 642 |
| POLN | REV1 | Q9UBZ9 | 636 |
| POLN | POLL | Q9UGP5 | 621 |
| POLN | POLE | Q07864 | 605 |
| POLN | POLK | Q9UBT6 | 559 |
| POLN | MAD2L2 | Q9UI95 | 540 |
| POLN | FANCM | Q8IYD8 | 527 |
| POLN | RAD18 | Q9NS91 | 526 |
| POLN | POLQ | O75417 | 512 |
IntAct
0 interactions, top by confidence:
BioGRID (44): BRCA1 (Affinity Capture-MS), BARD1 (Affinity Capture-MS), PALB2 (Affinity Capture-MS), BRCA2 (Affinity Capture-MS), BRIP1 (Affinity Capture-MS), RBBP8 (Affinity Capture-MS), BRCA1 (Affinity Capture-Western), POLN (Affinity Capture-Western), POLN (Affinity Capture-Western), POLN (Negative Genetic), POLN (Negative Genetic), POLN (Negative Genetic), POLN (Negative Genetic), POLN (Negative Genetic), POLN (Positive Genetic)
ESM2 similar proteins: A4D126, A7MCT6, C3VPR6, D3ZSK5, E1C5V0, E9PYK3, P50747, P58467, Q14CH1, Q1JP61, Q3TYX3, Q497B8, Q5BKC6, Q5F3V0, Q5I0C5, Q5ND52, Q5R5X9, Q5ZIZ2, Q5ZK17, Q6E804, Q6GMV2, Q6GQ33, Q7TQ07, Q7TQC5, Q7YRZ2, Q7Z2E3, Q7Z5Q5, Q80WC9, Q8BK58, Q8BTK5, Q8IYR2, Q8K3Z0, Q8K4H4, Q8N371, Q8NFZ0, Q8R5A0, Q8TBK2, Q920N2, Q96DP5, Q96EN8
Diamond homologs: A0KHE3, A0KZ94, A1JP96, A1RLT6, A1S8B8, A1SYB8, A3D2C6, A3QGM4, A4SQK3, A4Y4Y4, A6WL18, A7MR03, A7MYB8, A8FYJ2, A8GIF8, A8H6V6, A9KTM9, A9R2J1, B0TPG7, B1KQX1, B7LVW5, B8CS65, B8EAT2, C5BHA5, C6DAH2, F4I6M1, O05949, O08307, O32801, O34996, O51498, O52225, O67550, P00582, P0A551, P19821, P30313, P30314, P43741, P46835
SIGNOR signaling
0 interactions.
Disease & clinical
Clinical variants and AI predictions
ClinVar
158 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 1 |
| Likely pathogenic | 0 |
| Uncertain significance | 113 |
| Likely benign | 15 |
| Benign | 3 |
Top pathogenic / likely-pathogenic (1)
| Variant ID | HGVS | Classification |
|---|---|---|
| 57873 | GRCh38/hg38 4p16.3(chr4:56878-3870653)x1 | Pathogenic |
SpliceAI
6509 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 4:2167233:C:CA | donor_gain | 1.0000 |
| 4:2170678:CCA:C | donor_gain | 1.0000 |
| 4:2170775:C:CC | acceptor_gain | 1.0000 |
| 4:2170779:A:T | acceptor_gain | 1.0000 |
| 4:2171092:CTTTA:C | donor_loss | 1.0000 |
| 4:2171093:TTTAC:T | donor_loss | 1.0000 |
| 4:2171094:TTA:T | donor_loss | 1.0000 |
| 4:2171095:TAC:T | donor_loss | 1.0000 |
| 4:2171096:A:AC | donor_gain | 1.0000 |
| 4:2171096:A:C | donor_loss | 1.0000 |
| 4:2171097:C:CA | donor_loss | 1.0000 |
| 4:2171097:C:CC | donor_gain | 1.0000 |
| 4:2171097:CCT:C | donor_gain | 1.0000 |
| 4:2171177:CGAGC:C | acceptor_gain | 1.0000 |
| 4:2171178:GAGC:G | acceptor_gain | 1.0000 |
| 4:2171179:AGC:A | acceptor_gain | 1.0000 |
| 4:2171180:GC:G | acceptor_gain | 1.0000 |
| 4:2171181:CC:C | acceptor_gain | 1.0000 |
| 4:2171181:CCT:C | acceptor_loss | 1.0000 |
| 4:2171182:C:CC | acceptor_gain | 1.0000 |
| 4:2171182:C:CG | acceptor_loss | 1.0000 |
| 4:2171182:C:T | acceptor_gain | 1.0000 |
| 4:2171188:A:AC | acceptor_gain | 1.0000 |
| 4:2171188:A:C | acceptor_gain | 1.0000 |
| 4:2174028:C:CT | acceptor_gain | 1.0000 |
| 4:2174035:C:T | acceptor_gain | 1.0000 |
| 4:2198522:A:AC | donor_gain | 1.0000 |
| 4:2198523:C:CC | donor_gain | 1.0000 |
| 4:2198713:GGGGT:G | acceptor_gain | 1.0000 |
| 4:2198716:GTCT:G | acceptor_loss | 1.0000 |
AlphaMissense
5907 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 4:2095882:C:A | K678N | 0.992 |
| 4:2095882:C:G | K678N | 0.992 |
| 4:2156835:A:G | W562R | 0.992 |
| 4:2156835:A:T | W562R | 0.992 |
| 4:2128133:A:C | F654L | 0.988 |
| 4:2128133:A:T | F654L | 0.988 |
| 4:2128135:A:G | F654L | 0.988 |
| 4:2072263:A:G | W852R | 0.987 |
| 4:2072263:A:T | W852R | 0.987 |
| 4:2128114:A:G | W661R | 0.986 |
| 4:2128114:A:T | W661R | 0.986 |
| 4:2075499:T:A | D803V | 0.985 |
| 4:2075493:A:G | L805P | 0.981 |
| 4:2171128:A:C | F476L | 0.981 |
| 4:2171128:A:T | F476L | 0.981 |
| 4:2171130:A:G | F476L | 0.981 |
| 4:2081014:C:A | K777N | 0.979 |
| 4:2081014:C:G | K777N | 0.979 |
| 4:2171154:C:G | A468P | 0.979 |
| 4:2171129:A:G | F476S | 0.977 |
| 4:2075511:G:T | A799D | 0.975 |
| 4:2075512:C:G | A799P | 0.975 |
| 4:2179423:A:G | L355P | 0.975 |
| 4:2193273:A:G | C318R | 0.975 |
| 4:2081718:T:A | R741S | 0.974 |
| 4:2081718:T:G | R741S | 0.974 |
| 4:2095894:T:A | R674S | 0.974 |
| 4:2095894:T:G | R674S | 0.974 |
| 4:2073023:A:T | V821D | 0.973 |
| 4:2075490:A:G | L806P | 0.971 |
dbSNP variants (sampled 300 via entrez): RS1000016383 (4:2149542 C>G), RS1000028922 (4:2189696 A>G), RS1000033942 (4:2091120 C>G), RS1000036190 (4:2154900 T>C), RS1000037462 (4:2175051 T>C,G), RS1000040089 (4:2190233 T>C), RS1000083363 (4:2224509 A>T), RS10000953 (4:2182592 T>A,C), RS1000121252 (4:2172646 C>A,G,T), RS1000123561 (4:2232670 TAC>T), RS1000140004 (4:2074457 C>T), RS1000145629 (4:2080191 G>A,T), RS1000152275 (4:2227038 C>T), RS1000159202 (4:2148844 A>G), RS1000190709 (4:2108164 G>A,T)
Disease associations
OMIM: gene MIM:610887 | disease phenotypes:
GenCC curated gene-disease
Mondo (1): prostate cancer (MONDO:0008315)
Orphanet (1): Familial prostate cancer (Orphanet:1331)
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
4 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST001342_6 | Alzheimer’s disease | 6.000000e-06 |
| GCST006630_59 | Diastolic blood pressure | 6.000000e-13 |
| GCST007637_34 | Diffusing capacity of carbon monoxide | 8.000000e-06 |
| GCST008839_598 | Height | 7.000000e-09 |
EFO canonical traits (2, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0006336 | diastolic blood pressure |
| EFO:0009369 | diffusing capacity of the lung for carbon monoxide |
MeSH disease descriptors (1)
| Descriptor | Name | Tree numbers |
|---|---|---|
| D011471 | Prostatic Neoplasms | C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750 |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL2010628 (SINGLE PROTEIN)
PharmGKB: 1 entry (VIP=true, CPIC=false)
CTD chemical–gene interactions
19 total (human), top 19 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Benzo(a)pyrene | affects methylation | 2 |
| aristolochic acid I | increases expression | 1 |
| N6-(2-hydroxy-3-buten-1-yl)-2’-deoxyadenosine | decreases activity | 1 |
| bisphenol A | decreases methylation, affects cotreatment | 1 |
| diepoxybutane | decreases activity, decreases reaction, affects binding | 1 |
| ferrous chloride | decreases expression | 1 |
| 2’-deoxyadenosine | affects binding, decreases activity, decreases reaction | 1 |
| CGP 52608 | affects binding, increases reaction | 1 |
| abrine | decreases expression | 1 |
| (+)-JQ1 compound | increases expression | 1 |
| Fulvestrant | affects cotreatment, decreases methylation | 1 |
| Arsenic | affects methylation | 1 |
| Silicon Dioxide | decreases expression | 1 |
| Smoke | increases expression | 1 |
| Tobacco Smoke Pollution | decreases expression | 1 |
| Aflatoxin B1 | decreases methylation | 1 |
| Antirheumatic Agents | decreases expression | 1 |
| Acrylamide | increases expression | 1 |
| Particulate Matter | increases expression | 1 |
ChEMBL screening assays
2 unique, capped per target: 2 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL2013672 | Binding | Inhibition of C-terminal-His6-tagged human pol nu expressed in Escherichia coli assessed as inhibition of incorporation of dTTP into poly(dA)/oligo(dT)18 after 60 mins | Pinophilins A and B, inhibitors of mammalian A-, B-, and Y-family DNA polymerases and human cancer cell proliferation. — J Nat Prod |
Cellosaurus cell lines
3 cell lines: 3 cancer cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_TF09 | HAP1 POLN (-) 1 | Cancer cell line | Male |
| CVCL_TF10 | HAP1 POLN (-) 2 | Cancer cell line | Male |
| CVCL_TF11 | HAP1 POLN (-) 3 | Cancer cell line | Male |
Clinical trials (associated diseases)
300 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT00029224 | PHASE4 | COMPLETED | Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions |
| NCT00035997 | PHASE4 | COMPLETED | Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis |
| NCT00063609 | PHASE4 | COMPLETED | The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy |
| NCT00103623 | PHASE4 | SUSPENDED | The Plenaxis® Experience Study |
| NCT00106392 | PHASE4 | COMPLETED | A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy |
| NCT00185029 | PHASE4 | UNKNOWN | MR-Lymphography and Lymph Node Staging in Prostate Cancer |
| NCT00199485 | PHASE4 | COMPLETED | Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer |
| NCT00219219 | PHASE4 | COMPLETED | Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases |
| NCT00219271 | PHASE4 | COMPLETED | Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer |
| NCT00237146 | PHASE4 | COMPLETED | Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy |
| NCT00242554 | PHASE4 | COMPLETED | Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases |
| NCT00280098 | PHASE4 | COMPLETED | Docetaxel in the Treatment of Hormone Refractory Prostate Cancer |
| NCT00293696 | PHASE4 | COMPLETED | Casodex/Zoladex Biomarkers in Localised Prostate Cancer |
| NCT00334139 | PHASE4 | COMPLETED | Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer |
| NCT00375765 | PHASE4 | COMPLETED | Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer |
| NCT00391690 | PHASE4 | COMPLETED | Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer |
| NCT00422708 | PHASE4 | COMPLETED | Local Anesthesia for Prostate Biopsy |
| NCT00526331 | PHASE4 | COMPLETED | Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy |
| NCT00590213 | PHASE4 | COMPLETED | Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX |
| NCT00629330 | PHASE4 | TERMINATED | Dissemination of Prostate Cancer Screening to PCP’s in African American Communities |
| NCT00771966 | PHASE4 | COMPLETED | Radical Prostatectomy and Perioperative Fluid Therapy |
| NCT00805701 | PHASE4 | COMPLETED | Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation |
| NCT00859027 | PHASE4 | COMPLETED | Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer |
| NCT00906269 | PHASE4 | UNKNOWN | Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer |
| NCT00953277 | PHASE4 | COMPLETED | Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer |
| NCT00982800 | PHASE4 | COMPLETED | Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy? |
| NCT01083199 | PHASE4 | COMPLETED | Global Performance Evaluation of the AMS CONTINUUM™ Device |
| NCT01136226 | PHASE4 | COMPLETED | Evaluate Recovery of Testosterone for Patients Using Eligard |
| NCT01161563 | PHASE4 | COMPLETED | Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration |
| NCT01230905 | PHASE4 | COMPLETED | Study to Monitor the Effects of Androgen Suppression Treatment on the Heart |
| NCT01296672 | PHASE4 | COMPLETED | 3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer |
| NCT01365143 | PHASE4 | TERMINATED | Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy |
| NCT01379742 | PHASE4 | UNKNOWN | Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy |
| NCT01486563 | PHASE4 | COMPLETED | Hydroxyethyl Starch and Renal Function After Radical Prostatectomy |
| NCT01511874 | PHASE4 | COMPLETED | Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer |
| NCT01512472 | PHASE4 | TERMINATED | Firmagon (Degarelix) Intermittent Therapy |
| NCT01547416 | PHASE4 | COMPLETED | The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function |
| NCT01571544 | PHASE4 | COMPLETED | The Use of Thermal Suits as Preventing Hypothermia During Surgery |
| NCT01581749 | PHASE4 | UNKNOWN | Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer |
| NCT01649635 | PHASE4 | COMPLETED | Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer |
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.