POLR1A

Summary

POLR1A (RNA polymerase I subunit A, HGNC:17264) is a protein-coding gene on chromosome 2p11.2, encoding DNA-directed RNA polymerase I subunit RPA1 (O95602). Catalytic core component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates. It is a common-essential gene (DepMap: required in 99.6% of cancer cell lines).

The protein encoded by this gene is the largest subunit of the RNA polymerase I complex. The encoded protein represents the catalytic subunit of the complex, which transcribes DNA into ribosomal RNA precursors. Defects in this gene are a cause of the Cincinnati type of acrofacial dysostosis.

Source: NCBI Gene 25885 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pulmonary fibrosis and/or bone marrow failure, telomere-related, 6 (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 1,161 total — 5 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 142
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_015425

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17264
Approved symbol	POLR1A
Name	RNA polymerase I subunit A
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP586M0122, FLJ21915, RPO1-4, RPA1, RPA190
Ensembl gene	ENSG00000068654
Ensembl biotype	protein_coding
OMIM	616404
Entrez	25885

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 6 retained_intron, 5 protein_coding_CDS_not_defined, 3 protein_coding, 2 nonsense_mediated_decay

ENST00000263857, ENST00000409024, ENST00000409681, ENST00000424089, ENST00000462078, ENST00000471427, ENST00000483538, ENST00000486964, ENST00000492034, ENST00000496892, ENST00000683266, ENST00000683470, ENST00000684026, ENST00000684177, ENST00000684556, ENST00000931492

RefSeq mRNA: 1 — MANE Select: NM_015425 NM_015425

CCDS: CCDS42706

Canonical transcript exons

ENST00000263857 — 34 exons

Exon	Start	End
ENSE00000463084	86045278	86045360
ENSE00000767636	86027885	86028049
ENSE00000767637	86028594	86028711
ENSE00000767639	86030196	86030396
ENSE00000767715	86038700	86038857
ENSE00000767717	86039327	86039462
ENSE00000767784	86040392	86040559
ENSE00000767838	86045617	86045769
ENSE00000767839	86047165	86047263
ENSE00000767842	86049160	86049242
ENSE00000902548	86042974	86043195
ENSE00000902549	86052817	86053000
ENSE00000902550	86054140	86054289
ENSE00000902551	86065274	86065465
ENSE00000902552	86070018	86070272
ENSE00000902553	86075030	86075260
ENSE00000902554	86077859	86077981
ENSE00000902555	86078114	86078284
ENSE00000963644	86048884	86049042
ENSE00000963645	86044139	86044304
ENSE00000963646	86031330	86031635
ENSE00001261436	86041889	86042103
ENSE00001622878	86105700	86105886
ENSE00002579688	86020216	86027523
ENSE00003474416	86083082	86083168
ENSE00003476334	86080816	86080978
ENSE00003477919	86088785	86088870
ENSE00003502657	86032272	86032382
ENSE00003508947	86033661	86033787
ENSE00003546058	86089822	86089929
ENSE00003546938	86098611	86098760
ENSE00003554146	86088566	86088669
ENSE00003657456	86081601	86081706
ENSE00003671244	86099968	86100172

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 92.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.5741 / max 240.7400, expressed in 1798 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29522	25.3803	1797
29523	0.1061	20
29521	0.0598	31
29518	0.0279	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	92.89	gold quality
tibialis anterior	UBERON:0001385	85.41	silver quality
stromal cell of endometrium	CL:0002255	85.14	gold quality
adrenal tissue	UBERON:0018303	84.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.73	gold quality
islet of Langerhans	UBERON:0000006	83.51	gold quality
ventricular zone	UBERON:0003053	82.96	gold quality
ileal mucosa	UBERON:0000331	82.78	silver quality
muscle of leg	UBERON:0001383	82.67	gold quality
gastrocnemius	UBERON:0001388	82.66	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.12	gold quality
body of uterus	UBERON:0009853	82.05	gold quality
cortical plate	UBERON:0005343	81.77	gold quality
smooth muscle tissue	UBERON:0001135	80.97	gold quality
embryo	UBERON:0000922	80.74	gold quality
ganglionic eminence	UBERON:0004023	80.74	gold quality
bone marrow cell	CL:0002092	80.11	gold quality
muscle organ	UBERON:0001630	80.03	gold quality
skeletal muscle organ	UBERON:0014892	80.03	gold quality
apex of heart	UBERON:0002098	79.30	gold quality
colonic epithelium	UBERON:0000397	79.10	gold quality
calcaneal tendon	UBERON:0003701	78.73	gold quality
pancreatic ductal cell	CL:0002079	78.32	silver quality
heart left ventricle	UBERON:0002084	77.90	gold quality
adrenal gland	UBERON:0002369	77.69	gold quality
left adrenal gland	UBERON:0001234	77.53	gold quality
cardiac ventricle	UBERON:0002082	77.37	gold quality
left adrenal gland cortex	UBERON:0035825	77.12	gold quality
right adrenal gland	UBERON:0001233	77.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.55

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
E2F1	Repression

Upstream regulators (CollecTRI, top): UBTF

miRNA regulators (miRDB)

39 targeting POLR1A, 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-6798-5P	100.00	65.77	699
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-1266-5P	97.71	66.92	1052

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 9)

• analyzed the kinetics of assembly and elongation of the RNA polymerase I complex on endogenous ribosomal genes in the nuclei of living cells with the use of in vivo microscopy [RPA43] (PMID:12446911)
• Interference of POLR1A inhibited the synthesis of rRNA and hindered cell cycle progression in cells with inactivated p53, as a consequence of downregulation of the transcription factor E2F-1. (PMID:21878508)
• findings demonstrate that Bloom’s syndrome helicase (BLM)interacts with RPA194; studies suggest that nucleolar BLM modulates rDNA structures in association with RNA polymerase I to facilitate RNA polymerase I-mediated rRNA transcription (PMID:22106380)
• SIRT7 knockdown leads to reduced levels of RNA Pol I protein, but not messenger RNA (PMID:22586326)
• Consistent with this observation, we discovered that polr1a mutant zebrafish exhibited cranioskeletal anomalies mimicking the human phenotype. polr1a loss of function led to perturbed ribosome biogenesis and p53-dependent cell death (PMID:25913037)
• Data show that BRCA1 interacts directly with the basal RNA polymerase I (Pol-I) transcription factors as well as interacting with RNA Pol-I itself. (PMID:27589844)
• Homozygous c.2801C>T (p.(Ser934Leu)) in POLR1A was identified in two brothers with unusual neurological disease that manifested with ataxia, psychomotor retardation, cerebellar and cerebral atrophy, and leukodystrophy. (PMID:28051070)
• POLR1A variants underlie phenotypic heterogeneity in craniofacial, neural, and cardiac anomalies. (PMID:37075751)
• Expression of RNA polymerase I catalytic core is influenced by RPA12. (PMID:37167337)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	polr1a	ENSDARG00000098375
mus_musculus	Polr1a	ENSMUSG00000049553
rattus_norvegicus	Polr1a	ENSRNOG00000009545
drosophila_melanogaster	Polr1A	FBGN0019938
caenorhabditis_elegans		WBGENE00012999

Paralogs (2): POLR3A (ENSG00000148606), POLR2A (ENSG00000181222)

Protein

Protein identifiers

DNA-directed RNA polymerase I subunit RPA1 — O95602 (reviewed: O95602)

Alternative names: A190, DNA-directed RNA polymerase I largest subunit, DNA-directed RNA polymerase I subunit A, RNA polymerase I 194 kDa subunit

All UniProt accessions (3): O95602, B9ZVN9, F2Z3I7

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic core component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates. Transcribes 47S pre-rRNAs from multicopy rRNA gene clusters, giving rise to 5.8S, 18S and 28S ribosomal RNAs. Pol I-mediated transcription cycle proceeds through transcription initiation, transcription elongation and transcription termination stages. During transcription initiation, Pol I pre-initiation complex (PIC) is recruited by the selectivity factor 1 (SL1/TIF-IB) complex bound to the core promoter that precedes an rDNA repeat unit. The PIC assembly bends the promoter favoring the formation of the transcription bubble and promoter escape. Once the polymerase has escaped from the promoter it enters the elongation phase during which RNA is actively polymerized, based on complementarity with the template DNA strand. Highly processive, assembles in structures referred to as ‘Miller trees’ where many elongating Pol I complexes queue and transcribe the same rDNA coding regions. At terminator sequences downstream of the rDNA gene, PTRF interacts with Pol I and halts Pol I transcription leading to the release of the RNA transcript and polymerase from the DNA. Forms Pol I active center together with the second largest subunit POLR1B/RPA2. Appends one nucleotide at a time to the 3’ end of the nascent RNA, with POLR1A/RPA1 contributing a Mg(2+)-coordinating DxDGD motif, and POLR1B/RPA2 participating in the coordination of a second Mg(2+) ion and providing lysine residues believed to facilitate Watson-Crick base pairing between the incoming nucleotide and the template base. Typically, Mg(2+) ions direct a 5’ nucleoside triphosphate to form a phosphodiester bond with the 3’ hydroxyl of the preceding nucleotide of the nascent RNA, with the elimination of pyrophosphate. Has proofreading activity: Pauses and backtracks to allow the cleavage of a missincorporated nucleotide via POLR1H/RPA12. High Pol I processivity is associated with decreased transcription fidelity.

Subunit / interactions. Component of the RNA polymerase I (Pol I) complex consisting of 13 subunits: a ten-subunit catalytic core composed of POLR1A/RPA1, POLR1B/RPA2, POLR1C/RPAC1, POLR1D/RPAC2, POLR1H/RPA12, POLR2E/RPABC1, POLR2F/RPABC2, POLR2H/RPABC3, POLR2K/RPABC4 and POLR2L/RPABC5; a mobile stalk subunit POLR1F/RPA43 protruding from the core and additional subunits homologous to general transcription factors POLR1E/RPA49 and POLR1G/RPA34. Part of Pol I pre-initiation complex (PIC), in which Pol I core assembles with RRN3 and promoter-bound UTBF and SL1/TIF-IB complex. Interacts (via dock II domain) with TOP2A; this interaction may assist Pol I transcription initiation by releasing supercoils occurring during DNA unwinding. Interacts with CAVIN1; this interaction induces the dissociation of Pol I complex paused at rDNA terminator sequences. Interacts with MYO1C. Interacts with ERBB2. Interacts with DDX11. Interacts with RECQL5.

Subcellular location. Nucleus. Nucleolus. Chromosome.

Disease relevance. Acrofacial dysostosis, Cincinnati type (AFDCIN) [MIM:616462] A form of acrofacial dysostosis, a group of disorders characterized by malformations of the craniofacial skeleton and, in some patients, the limbs. AFDCIN patients may also have structural cardiac defects and neurologic abnormalities including developmental delay, hypotonia, motor delay and seizures. AFDCIN inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Leukodystrophy, hypomyelinating, 27 (HLD27) [MIM:620675] A form of hypomyelinating leukodystrophy, a group of heterogeneous disorders characterized by persistent deficit of myelin observed on brain imaging. HLD27 is an autosomal recessive form characterized by global developmental delay apparent from infancy, poor or absent speech, ataxic gait or inability to sit or walk, spasticity, and abnormal eye movements. Some patients have seizures. Brain imaging shows hypomyelinating leukodystrophy, cerebellar atrophy, and thin corpus callosum. The disease may be caused by variants affecting the gene represented in this entry.

Cofactor. Two Mg(2+) ions are coordinated by both the catalytic residues and the nucleic acid substrate to enhance substrate recognition and catalytic efficiency.

Domain organisation. The clamps form the DNA-binding cleft. The bridging helix crosses the cleft near the catalytic site and is thought to promote polymerase translocation by acting as a ratchet that moves the DNA-RNA hybrid through the active site. The trigger loop allows entry of NTPs into the active site, switching between an open and closed state with each NTP addition cycle. The funnel accommodates POLR1H/RPA12 favoring mismatched RNA cleavage upon backtracking. The high mobility group-like domain (dock II; residues 1060-1155) binds TOP2A, but cannot bind DNA; may assist Pol I initiation by releasing supercoils occurring during DNA unwinding.

Similarity. Belongs to the RNA polymerase beta’ chain family.

RefSeq proteins (1): NP_056240* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000722	RNA_pol_asu	Domain
IPR006592	RNA_pol_N	Domain
IPR007066	RNA_pol_Rpb1_3	Domain
IPR007080	RNA_pol_Rpb1_1	Domain
IPR007081	RNA_pol_Rpb1_5	Domain
IPR007083	RNA_pol_Rpb1_4	Domain
IPR015699	DNA-dir_RNA_pol1_lsu_N	Domain
IPR038120	Rpb1_funnel_sf	Homologous_superfamily
IPR042102	RNA_pol_Rpb1_3_sf	Homologous_superfamily
IPR044893	RNA_pol_Rpb1_clamp_domain	Homologous_superfamily
IPR045867	DNA-dir_RpoC_beta_prime	Family
IPR047107	DNA-dir_RNA_pol1_lsu_C	Domain

Pfam: PF00623, PF04983, PF04997, PF04998, PF05000

Catalyzed reactions (Rhea), 1 shown:

• RNA(n) + a ribonucleoside 5’-triphosphate = RNA(n+1) + diphosphate (RHEA:21248)

UniProt features (224 total): helix 68, strand 64, sequence variant 21, turn 20, binding site 20, sequence conflict 12, region of interest 9, compositionally biased region 5, site 2, modified residue 2, chain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7OB9	ELECTRON MICROSCOPY	2.7
7VBB	ELECTRON MICROSCOPY	2.81
7VBA	ELECTRON MICROSCOPY	2.89
7VBC	ELECTRON MICROSCOPY	3.01
7OBA	ELECTRON MICROSCOPY	3.1
7OBB	ELECTRON MICROSCOPY	3.3
8A43	ELECTRON MICROSCOPY	4.09

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95602-F1	80.25	0.30

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 (2): 554 (ntp recognition and base pairing); 798 (ntp recognition and base pairing)

Ligand- & substrate-binding residues (20): 64; 67; 74; 77; 104; 107; 205; 208; 424; 429; 429; 436 …

Post-translational modifications (2): 240, 1386

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-427413	NoRC negatively regulates rRNA expression
R-HSA-5250924	B-WICH complex positively regulates rRNA expression
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-73772	RNA Polymerase I Promoter Escape
R-HSA-73863	RNA Polymerase I Transcription Termination
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-5250913	Positive epigenetic regulation of rRNA expression
R-HSA-5250941	Negative epigenetic regulation of rRNA expression
R-HSA-73854	RNA Polymerase I Promoter Clearance
R-HSA-73864	RNA Polymerase I Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 938 (showing top): PID_FANCONI_PATHWAY, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, MORF_MTA1, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, REACTOME_MEIOTIC_RECOMBINATION, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_DNA_REPLICATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, MODULE_451, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, KAAB_FAILED_HEART_ATRIUM_DN, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT

GO Biological Process (4): transcription by RNA polymerase I (GO:0006360), nucleolar large rRNA transcription by RNA polymerase I (GO:0042790), negative regulation of protein localization to nucleolus (GO:1904750), DNA-templated transcription (GO:0006351)

GO Molecular Function (11): magnesium ion binding (GO:0000287), DNA binding (GO:0003677), chromatin binding (GO:0003682), DNA-directed RNA polymerase activity (GO:0003899), zinc ion binding (GO:0008270), DNA/RNA hybrid binding (GO:0071667), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), 5’-3’ RNA polymerase activity (GO:0034062), metal ion binding (GO:0046872)

GO Cellular Component (7): chromatin (GO:0000785), nucleoplasm (GO:0005654), chromosome (GO:0005694), RNA polymerase I complex (GO:0005736), DNA-directed RNA polymerase complex (GO:0000428), nucleus (GO:0005634), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
RNA Polymerase I Promoter Clearance	2
RNA Polymerase I Transcription	2
Gene expression (Transcription)	2
Epigenetic regulation of gene expression	2
Negative epigenetic regulation of rRNA expression	1
Positive epigenetic regulation of rRNA expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA biosynthetic process	2
nucleic acid binding	2
binding	2
cellular anatomical structure	2
nuclear lumen	2
intracellular membraneless organelle	2
DNA-templated transcription	1
transcription by RNA polymerase I	1
rRNA transcription	1
negative regulation of protein localization to nucleus	1
protein localization to nucleolus	1
regulation of protein localization to nucleolus	1
gene expression	1
metal ion binding	1
5’-3’ RNA polymerase activity	1
transition metal ion binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
RNA polymerase activity	1
cation binding	1
chromosome	1
DNA-directed RNA polymerase complex	1
nucleolus	1
nuclear protein-containing complex	1
RNA polymerase complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

4122 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLR1A	POLR1B	Q9H9Y6	888
POLR1A	NOLC1	Q14978	863
POLR1A	UBTF	P17480	820
POLR1A	POLR1D	P0DPB6	817
POLR1A	POLI	Q9UNA4	810
POLR1A	FBL	P22087	808
POLR1A	POLR1E	Q9GZS1	808
POLR1A	NUCLEOLIN	P19338	751
POLR1A	RRN3	Q9NYV6	744
POLR1A	POLR1F	Q3B726	726
POLR1A	POLR2H	P52434	721
POLR1A	POLR1H	Q9P1U0	719
POLR1A	POLR1C	O15160	718
POLR1A	TCOF1	Q13428	698
POLR1A	GAR1	Q9NY12	692

IntAct

134 interactions, top by confidence:

A	B	Type	Score
POLR2E	POLR3A	psi-mi:“MI:0914”(association)	0.870
RARA	NCOR1	psi-mi:“MI:0914”(association)	0.800
POLR1A	POLR1B	psi-mi:“MI:0915”(physical association)	0.740
POLR2E	MED19	psi-mi:“MI:0914”(association)	0.730
POLR1A	POLR1C	psi-mi:“MI:0914”(association)	0.730
POLR1E	POLR1C	psi-mi:“MI:0914”(association)	0.670
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
POLR2F	POLR3A	psi-mi:“MI:0914”(association)	0.640
POLR1F	POLR1A	psi-mi:“MI:0914”(association)	0.640
POLR2L	POLR3A	psi-mi:“MI:0914”(association)	0.640
ERBB2	POLR1A	psi-mi:“MI:0915”(physical association)	0.570
POLR1A	ERBB2	psi-mi:“MI:0915”(physical association)	0.570
POLR1A	ERBB2	psi-mi:“MI:0403”(colocalization)	0.570
ERBB2	POLR1A	psi-mi:“MI:0403”(colocalization)	0.570
ERBB2	POLR1A	psi-mi:“MI:0914”(association)	0.570

BioGRID (364): POLR1A (Two-hybrid), POLR1A (Two-hybrid), POLR1A (Affinity Capture-RNA), POLR1A (Affinity Capture-RNA), POLR1A (Affinity Capture-RNA), POLR1A (Affinity Capture-RNA), POLR1A (Affinity Capture-Western), POLR1A (Affinity Capture-Western), KAT2B (Co-localization), POLR1A (Affinity Capture-MS), POLR1A (Affinity Capture-MS), POLR1A (Affinity Capture-MS), POLR1A (Affinity Capture-MS), POLR1A (Affinity Capture-MS), POLR1A (Affinity Capture-MS)

ESM2 similar proteins: A3N326, A4IF62, A5DCV3, A5WH34, A6TGP1, A6VKC4, A9MHE9, A9N0J5, B0BSF6, B0URZ7, B3GYV5, F4JXF9, G3MZY8, O14802, O35134, O54889, O94666, O95602, P04050, P04051, P04052, P08775, P0A2R4, P0A2R5, P10964, P11414, P15398, P16356, P17545, P17546, P24928, P28364, P35074, P35084, P36594, P41556, P91875, Q0I5B8, Q47UW0, Q57H68

Diamond homologs: A0PXT9, A2RML8, A3CKD4, A4FWF5, A4IF62, A4YCR0, A5CUC6, A5DCV3, A6UV49, A6VGV0, A8AZI2, A8F4G1, A9A9U9, A9BCH4, B0R8D3, B0RB26, B4U738, B6YT17, B8YB54, C0ZVQ7, C1AYV8, C3MRK4, C3MYA0, C3MZM9, C3N7Q1, C3NFS2, C4KIV9, C5A207, F4JXF9, G3MZY8, O14802, O27126, O28390, O35134, O54889, O93777, O94666, O95602, P04050, P04051

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
POLR1A	“form complex”	“RNA Polymerase I”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RNA Polymerase III Chain Elongation	8	74.6×	2e-12
RNA Polymerase I Transcription Termination	15	72.0×	4e-23
Positive epigenetic regulation of rRNA expression	14	71.2×	1e-21
RNA Polymerase I Promoter Clearance	16	68.9×	5e-24
RNA Polymerase I Transcription	16	67.2×	5e-24
RNA Polymerase III Transcription Termination	8	58.4×	1e-11
Negative epigenetic regulation of rRNA expression	15	57.2×	1e-21
RNA Polymerase III Transcription Initiation From Type 2 Promoter	9	56.0×	1e-12

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair	7	14.4×	1e-04
transcription by RNA polymerase II	8	5.7×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1161 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	7
Uncertain significance	620
Likely benign	369
Benign	86

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1342931	NM_002945.5(RPA1):c.718G>A (p.Glu240Lys)	Pathogenic
1342932	NM_002945.5(RPA1):c.680T>C (p.Val227Ala)	Pathogenic
203464	NM_015425.6(POLR1A):c.3649del (p.Gln1217fs)	Pathogenic
3602728	NM_015425.6(POLR1A):c.2357C>T (p.Thr786Ile)	Pathogenic
626284	NM_015425.6(POLR1A):c.2527C>T (p.Arg843Ter)	Pathogenic
2500796	NM_015425.6(POLR1A):c.190del (p.Cys64fs)	Likely pathogenic
3778758	NM_015425.6(POLR1A):c.928C>T (p.Arg310Cys)	Likely pathogenic
3905475	NM_015425.6(POLR1A):c.2267_2288del (p.Ser756fs)	Likely pathogenic
3910088	NM_015425.6(POLR1A):c.2374dup (p.Tyr792fs)	Likely pathogenic
421393	NM_015425.6(POLR1A):c.4685G>T (p.Cys1562Phe)	Likely pathogenic
4688021	NM_015425.6(POLR1A):c.2164C>T (p.Arg722Ter)	Likely pathogenic
4845757	NM_015425.6(POLR1A):c.4297G>T (p.Glu1433Ter)	Likely pathogenic

SpliceAI

5445 predictions. Top by Δscore:

Variant	Effect	Δscore
2:86028047:TGC:T	acceptor_gain	1.0000
2:86028050:C:CC	acceptor_gain	1.0000
2:86028611:T:TA	donor_gain	1.0000
2:86028707:AGGAC:A	acceptor_gain	1.0000
2:86028708:GGAC:G	acceptor_gain	1.0000
2:86028709:GAC:G	acceptor_gain	1.0000
2:86028709:GACC:G	acceptor_loss	1.0000
2:86028710:AC:A	acceptor_gain	1.0000
2:86028711:CC:C	acceptor_gain	1.0000
2:86028712:C:CC	acceptor_gain	1.0000
2:86028712:C:T	acceptor_gain	1.0000
2:86028713:T:A	acceptor_loss	1.0000
2:86030193:TA:T	donor_loss	1.0000
2:86030195:CCT:C	donor_gain	1.0000
2:86030392:GTCAC:G	acceptor_gain	1.0000
2:86030393:TCAC:T	acceptor_gain	1.0000
2:86030394:CAC:C	acceptor_gain	1.0000
2:86030394:CACC:C	acceptor_gain	1.0000
2:86030395:AC:A	acceptor_gain	1.0000
2:86030396:CC:C	acceptor_gain	1.0000
2:86030396:CCTG:C	acceptor_loss	1.0000
2:86030397:C:CC	acceptor_gain	1.0000
2:86030397:C:CG	acceptor_loss	1.0000
2:86031326:TGAC:T	donor_loss	1.0000
2:86031327:GACC:G	donor_loss	1.0000
2:86031329:C:CT	donor_loss	1.0000
2:86032267:CTCA:C	donor_loss	1.0000
2:86032269:CACCT:C	donor_loss	1.0000
2:86032270:ACCT:A	donor_gain	1.0000
2:86032271:CCTC:C	donor_gain	1.0000

AlphaMissense

11325 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:86027925:A:C	F1674L	1.000
2:86027925:A:T	F1674L	1.000
2:86027927:A:G	F1674L	1.000
2:86040401:C:T	G1244D	1.000
2:86040402:C:G	G1244R	1.000
2:86040412:G:C	N1240K	1.000
2:86040412:G:T	N1240K	1.000
2:86040438:G:C	H1232D	1.000
2:86040439:G:C	F1231L	1.000
2:86040439:G:T	F1231L	1.000
2:86040441:A:G	F1231L	1.000
2:86040445:G:C	N1229K	1.000
2:86040445:G:T	N1229K	1.000
2:86040449:A:G	L1228P	1.000
2:86040449:A:T	L1228H	1.000
2:86040455:A:C	M1226R	1.000
2:86040455:A:G	M1226T	1.000
2:86040455:A:T	M1226K	1.000
2:86044254:A:T	V1007D	1.000
2:86045278:C:A	R990M	1.000
2:86045288:A:G	Y987H	1.000
2:86045290:C:T	G986D	1.000
2:86045304:T:A	K981N	1.000
2:86045304:T:G	K981N	1.000
2:86045305:T:A	K981I	1.000
2:86045311:G:T	A979D	1.000
2:86045323:A:G	L975P	1.000
2:86045323:A:T	L975Q	1.000
2:86045327:C:G	G974R	1.000
2:86070112:C:T	G591E	1.000

dbSNP variants (sampled 300 via entrez): RS1000007219 (2:86037613 C>A,T), RS1000043245 (2:86085113 C>G), RS1000071928 (2:86078846 A>G), RS1000118984 (2:86090679 A>C,G), RS1000154595 (2:86088015 C>T), RS1000174605 (2:86054839 T>C), RS1000222697 (2:86073470 G>A), RS1000234063 (2:86069856 A>C), RS1000239002 (2:86023721 A>G), RS1000249889 (2:86043488 A>C), RS1000252640 (2:86105576 A>T), RS1000287395 (2:86031936 G>A), RS1000294624 (2:86073127 A>G), RS1000334220 (2:86027089 G>C), RS1000337103 (2:86107437 G>A)

Disease associations

OMIM: gene MIM:616404 | disease phenotypes: MIM:616462, MIM:619767, MIM:620675, MIM:609056, MIM:614255

GenCC curated gene-disease

Disease	Classification	Inheritance
acrofacial dysostosis Cincinnati type	Strong	Autosomal dominant
pulmonary fibrosis and/or bone marrow failure, telomere-related, 6	Strong	Autosomal dominant
leukodystrophy, hypomyelinating, 27	Moderate	Autosomal recessive
choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
dyskeratosis congenita and related telomere biology disorder	Limited	AD

Mondo (6): acrofacial dysostosis Cincinnati type (MONDO:0014651), pulmonary fibrosis and/or bone marrow failure, telomere-related, 6 (MONDO:0030690), leukodystrophy, hypomyelinating, 27 (MONDO:0958018), GM3 synthase deficiency (MONDO:0018274), intellectual disability, autosomal dominant 9 (MONDO:0013656), choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome (MONDO:0012064)

Orphanet (5): Burn-McKeown syndrome (Orphanet:1200), Amish infantile epilepsy syndrome (Orphanet:171714), GM3 synthase deficiency (Orphanet:370933), NESCAV syndrome (Orphanet:662367), Salt-and-pepper syndrome (Orphanet:370938)

HPO phenotypes

142 total (30 of 142 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000126	Hydronephrosis
HP:0000174	Abnormal palate morphology
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000327	Hypoplasia of the maxilla
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000403	Recurrent otitis media
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000453	Choanal atresia
HP:0000463	Anteverted nares
HP:0000478	Abnormality of the eye
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002941_2	Airway imaging phenotypes	2.000000e-06
GCST004602_288	Mean corpuscular volume	9.000000e-11
GCST004730_1	Facial emotion recognition (sad faces)	2.000000e-06
GCST008103_174	Bipolar disorder	8.000000e-06
GCST009391_1259	Metabolite levels	5.000000e-06
GCST90002390_125	Mean corpuscular hemoglobin	2.000000e-10
GCST90002392_3	Mean corpuscular volume	5.000000e-17
GCST90002396_606	Mean reticulocyte volume	6.000000e-12
GCST90002397_726	Mean spheric corpuscular volume	4.000000e-19

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007627	airway imaging measurement
EFO:0008329	facial emotion recognition measurement
EFO:0004761	uric acid measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563682	Oculootofacial Dysplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3286067 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

54 potent at pChembl≥5 of 64 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.40	IC50	40	nM	CHEMBL3289424
7.30	IC50	50	nM	CHEMBL3289398
7.05	IC50	90	nM	CHEMBL3289421
6.96	IC50	110	nM	CHEMBL3289423
6.85	IC50	140	nM	CHEMBL3289422
6.80	IC50	160	nM	CHEMBL5091256
6.75	IC50	180	nM	CHEMBL3289414
6.75	IC50	180	nM	CHEMBL3289420
6.68	IC50	210	nM	CHEMBL3289413
6.68	IC50	210	nM	CHEMBL5091818
6.48	IC50	330	nM	CHEMBL3289398
6.43	IC50	370	nM	CHEMBL3289421
6.38	IC50	420	nM	CHEMBL5093823
6.37	IC50	430	nM	CHEMBL3289410
6.33	IC50	470	nM	CHEMBL5072152
6.27	IC50	540	nM	CHEMBL5076121
6.23	IC50	590	nM	CHEMBL5088110
6.22	IC50	600	nM	CHEMBL5089364
6.22	IC50	600	nM	CHEMBL5074659
6.19	IC50	640	nM	CHEMBL5091051
6.19	IC50	650	nM	CHEMBL5094886
6.18	IC50	660	nM	CHEMBL3289409
6.14	IC50	730	nM	CHEMBL3289428
6.13	IC50	740	nM	CHEMBL5082214
6.11	IC50	780	nM	CHEMBL5090345
6.11	IC50	780	nM	CHEMBL5093028
6.04	IC50	920	nM	CHEMBL5080399
6.01	IC50	980	nM	CHEMBL3289403
6.00	IC50	990	nM	CHEMBL5080842
6.00	IC50	1000	nM	CHEMBL5071620
5.98	IC50	1040	nM	CHEMBL5077311
5.96	IC50	1090	nM	CHEMBL3289427
5.94	IC50	1160	nM	CHEMBL5084657
5.90	IC50	1250	nM	CHEMBL3289426
5.87	IC50	1350	nM	CHEMBL3289399
5.86	IC50	1390	nM	CHEMBL5094505
5.77	IC50	1700	nM	CHEMBL5091868
5.73	IC50	1860	nM	MOLIBRESIB
5.72	IC50	1900	nM	CHEMBL5089676
5.70	IC50	2010	nM	CHEMBL3289411
5.66	IC50	2170	nM	CHEMBL160057
5.52	IC50	3040	nM	CHEMBL3289425
5.41	IC50	3940	nM	CHEMBL5091418
5.38	IC50	4200	nM	CHEMBL5083095
5.28	IC50	5210	nM	CHEMBL3289408
5.26	IC50	5500	nM	CHEMBL5088652
5.24	IC50	5750	nM	CHEMBL5080196
5.22	IC50	6000	nM	CHEMBL5089657
5.16	IC50	6860	nM	CHEMBL5081206
5.02	IC50	9500	nM	CHEMBL5072213

PubChem BioAssay actives

54 with measured affinity, of 99 total; 50 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
N-[2-(dimethylamino)propyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	0.0400	uM
N-[2-(dimethylamino)ethyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	0.0500	uM
12-oxo-N-(2-pyrrolidin-1-ylethyl)-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	0.0900	uM
N-[1-(dimethylamino)propan-2-yl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	0.1100	uM
N-[2-(diethylamino)ethyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	0.1400	uM
N-[2-(dimethylamino)ethyl]-11-oxo-12,18-diazatetracyclo[8.8.0.02,7.012,17]octadeca-1(10),2,4,6,8,13,15,17-octaene-16-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	0.1600	uM
N-(1-methylpiperidin-4-yl)-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	0.1800	uM
12-oxo-N-(2-piperidin-1-ylethyl)-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	0.1800	uM
11-oxo-N-(2-pyrrolidin-1-ylethyl)-12,18-diazatetracyclo[8.8.0.02,7.012,17]octadeca-1(10),2,4,6,8,13,15,17-octaene-16-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	0.2100	uM
N-(azetidin-3-yl)-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	0.2100	uM
14,14-difluoro-9-oxo-N-(2-pyrrolidin-1-ylethyl)-13,15-dioxa-2,8-diazatetracyclo[8.7.0.03,8.012,16]heptadeca-1(17),2,4,6,10,12(16)-hexaene-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	0.4200	uM
N-[3-(dimethylamino)propyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	0.4300	uM
N-[2-(methylamino)ethyl]-11-oxo-12,18-diazatetracyclo[8.8.0.02,7.012,17]octadeca-1(10),2,4,6,8,13,15,17-octaene-16-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	0.4700	uM
9-oxo-N-(2-pyrrolidin-1-ylethyl)-13,15-dioxa-2,8-diazatetracyclo[8.7.0.03,8.012,16]heptadeca-1(17),2,4,6,10,12(16)-hexaene-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	0.5400	uM
12-oxo-N-(piperidin-2-ylmethyl)-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	0.5900	uM
N-[2-(diethylamino)ethyl]-11-oxo-12,18-diazatetracyclo[8.8.0.02,7.012,17]octadeca-1(10),2,4,6,8,13,15,17-octaene-16-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	0.6000	uM
N-[2-(4,4-dihydroxypiperidin-1-yl)ethyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	0.6000	uM
11-oxo-N-(2-piperidin-1-ylethyl)-12,18-diazatetracyclo[8.8.0.02,7.012,17]octadeca-1(10),2,4,6,8,13,15,17-octaene-16-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	0.6400	uM
N-[[6-(hydroxymethyl)piperidin-2-yl]methyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	0.6500	uM
N-[4-(dimethylamino)butyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	0.6600	uM
N-[2-[2-methoxyethyl(methyl)amino]ethyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	0.7300	uM
N-[2-(4-cyanopiperidin-1-yl)ethyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	0.7400	uM
12-oxo-N-(pyrrolidin-2-ylmethyl)-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	0.7800	uM
N-[2-(4-fluoropiperidin-1-yl)ethyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	0.7800	uM
12-oxo-N-(1-piperidin-2-ylethyl)-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	0.9200	uM
N-(2-imidazol-1-ylethyl)-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	0.9800	uM
N-[(1-ethylpiperidin-2-yl)methyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	0.9900	uM
N-[(4-methylmorpholin-3-yl)methyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	1.0000	uM
9-oxo-N-(2-pyrrolidin-1-ylethyl)-13,16-dioxa-2,8-diazatetracyclo[8.8.0.03,8.012,17]octadeca-1(18),2,4,6,10,12(17)-hexaene-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	1.0400	uM
N-[2-(4-methylpiperazin-1-yl)ethyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	1.0900	uM
2,3-dimethyl-11-oxo-N-(2-pyrrolidin-1-ylethyl)pyrido[2,1-b]quinazoline-6-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	1.1600	uM
N-(2-morpholin-4-ylethyl)-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	1.2500	uM
N-[2-(diethylamino)ethyl]-11-oxopyrido[2,1-b]quinazoline-6-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	1.3500	uM
9-oxo-N-(2-pyrrolidin-1-ylethyl)-2,8-diazatetracyclo[8.8.0.03,8.012,17]octadeca-1(10),2,4,6,11,17-hexaene-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	1.3900	uM
N-(2-pyrrolidin-1-ylethyl)-11,17-diazatetracyclo[8.7.0.03,8.011,16]heptadeca-1,3,5,7,9,12,14,16-octaene-15-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	1.7000	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178637: Inhibition of POLR1A (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	1.8600	uM
N-[2-[(3R)-3-fluoropyrrolidin-1-yl]ethyl]-11-oxo-12,18-diazatetracyclo[8.8.0.02,7.012,17]octadeca-1(10),2,4,6,8,13,15,17-octaene-16-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	1.9000	uM
N-[2-(1-methylpyrrolidin-2-yl)ethyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	2.0100	uM
N-[2-(dimethylamino)ethyl]-11-oxopyrido[2,1-b]quinazoline-6-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	2.1700	uM
N-[2-[di(propan-2-yl)amino]ethyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	3.0400	uM
N-[(1-methylpyrrolidin-2-yl)methyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	3.9400	uM
18-oxo-N-(2-pyrrolidin-1-ylethyl)-4,5,11,17-tetrazatetracyclo[8.8.0.02,7.012,17]octadeca-1(10),2,4,6,8,11,13,15-octaene-13-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	4.2000	uM
N-(2-methylsulfonylethyl)-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1153911: Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	ic50	5.2100	uM
5,9-dioxo-N-(2-pyrrolidin-1-ylethyl)-2,8-diazatetracyclo[8.8.0.03,8.012,17]octadeca-1(18),3,6,10,12,14,16-heptaene-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	5.5000	uM
N-[2-(3-fluoropyrrolidin-1-yl)ethyl]-12-oxo-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	5.7500	uM
N-(2-pyrrolidin-1-ylethyl)-9,11,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1,3,5,7,9,12,14,16-octaene-15-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	6.0000	uM
2,3-dimethoxy-11-oxo-N-(2-pyrrolidin-1-ylethyl)pyrido[2,1-b]quinazoline-6-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	6.8600	uM
N-(2-hydroxyethyl)-11-oxo-12,18-diazatetracyclo[8.8.0.02,7.012,17]octadeca-1(10),2,4,6,8,13,15,17-octaene-16-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	9.5000	uM
12-oxo-N-[(1-propan-2-ylpiperidin-2-yl)methyl]-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	10.0000	uM
12-oxo-N-(2-thiomorpholin-4-ylethyl)-12H-benzo[g]pyrido[2,1-b]quinazoline-4-carboxamide	1816026: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
Estradiol	increases expression	2
Oxygen	decreases expression	2
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
benzo(e)pyrene	decreases methylation	1
fipronil	decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	increases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Methapyrilene	decreases methylation	1
Ozone	affects expression, increases abundance	1
Ribonucleotides	affects binding	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
Cadmium Chloride	increases expression, increases abundance	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

16 unique, capped per target: 16 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3291669	Binding	Induction of RNA polymerase-1 RPA194 subunit degradation in human U2OS cells after 3 hrs by epifluorescence microscopic analysis	Design, synthesis, and structure-activity relationships of pyridoquinazolinecarboxamides as RNA polymerase I inhibitors. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02234024	Not specified	UNKNOWN	Oral Supplementation of Gangliosides to Treat a Rare Metabolic Disorder