POLR1B

Summary

POLR1B (RNA polymerase I subunit B, HGNC:20454) is a protein-coding gene on chromosome 2q14.1, encoding DNA-directed RNA polymerase I subunit RPA2 (Q9H9Y6). 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 99.8% of cancer cell lines).

Eukaryotic RNA polymerase I (pol I) is responsible for the transcription of ribosomal RNA (rRNA) genes and production of rRNA, the primary component of ribosomes. Pol I is a multisubunit enzyme composed of 6 to 14 polypeptides, depending on the species. Most of the mass of the pol I complex derives from the 2 largest subunits, Rpa1 and Rpa2 in yeast. POLR1B is homologous to Rpa2 (Seither and Grummt, 1996 [PubMed 8921381]).

Source: NCBI Gene 84172 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Treacher Collins syndrome 4 (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 183 total — 3 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 75
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_019014

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20454
Approved symbol	POLR1B
Name	RNA polymerase I subunit B
Location	2q14.1
Locus type	gene with protein product
Status	Approved
Aliases	Rpo1-2, FLJ21921, FLJ10816, RPA2, RPA135
Ensembl gene	ENSG00000125630
Ensembl biotype	protein_coding
OMIM	602000
Entrez	84172

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 8 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000263331, ENST00000333990, ENST00000409894, ENST00000417433, ENST00000424062, ENST00000430293, ENST00000430769, ENST00000438748, ENST00000448770, ENST00000458012, ENST00000468475, ENST00000475318, ENST00000484574, ENST00000496238, ENST00000498054, ENST00000537335, ENST00000541869

RefSeq mRNA: 10 — MANE Select: NM_019014 NM_001137604, NM_001282772, NM_001282774, NM_001282776, NM_001282777, NM_001282779, NM_001371969, NM_001371970, NM_001371971, NM_019014

CCDS: CCDS2097, CCDS46395, CCDS62988, CCDS62989, CCDS62990

Canonical transcript exons

ENST00000263331 — 15 exons

Exon	Start	End
ENSE00001470780	112542465	112542671
ENSE00003492707	112573562	112573815
ENSE00003492903	112564366	112564499
ENSE00003514645	112572562	112572758
ENSE00003542828	112557910	112558081
ENSE00003582574	112549267	112549399
ENSE00003583681	112552645	112552816
ENSE00003587438	112547012	112547179
ENSE00003590871	112551775	112551998
ENSE00003596612	112574847	112579818
ENSE00003654166	112568746	112568902
ENSE00003656450	112550866	112551002
ENSE00003670508	112559293	112559574
ENSE00003688645	112567967	112568137
ENSE00003692207	112547421	112547567

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 97.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.7832 / max 145.9400, expressed in 1740 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21985	11.7550	1740
21986	0.0281	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.14	gold quality
sperm	CL:0000019	94.34	gold quality
male germ cell	CL:0000015	93.42	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.09	gold quality
endothelial cell	CL:0000115	92.92	gold quality
superficial temporal artery	UBERON:0001614	92.82	gold quality
nipple	UBERON:0002030	92.41	gold quality
ventral tegmental area	UBERON:0002691	92.33	gold quality
renal medulla	UBERON:0000362	92.25	gold quality
cardia of stomach	UBERON:0001162	92.08	gold quality
superior surface of tongue	UBERON:0007371	91.90	gold quality
pylorus	UBERON:0001166	91.64	gold quality
inferior vagus X ganglion	UBERON:0005363	91.21	gold quality
subthalamic nucleus	UBERON:0001906	90.52	gold quality
pericardium	UBERON:0002407	90.36	gold quality
trachea	UBERON:0003126	90.22	gold quality
substantia nigra pars reticulata	UBERON:0001966	90.08	gold quality
lateral globus pallidus	UBERON:0002476	90.04	gold quality
olfactory bulb	UBERON:0002264	89.93	silver quality
trigeminal ganglion	UBERON:0001675	89.89	gold quality
medulla oblongata	UBERON:0001896	89.87	gold quality
dorsal plus ventral thalamus	UBERON:0001897	89.57	gold quality
superior vestibular nucleus	UBERON:0007227	89.12	gold quality
periodontal ligament	UBERON:0008266	88.76	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.48	gold quality
dorsal root ganglion	UBERON:0000044	88.45	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	88.20	gold quality
thymus	UBERON:0002370	88.07	gold quality
pharyngeal mucosa	UBERON:0000355	87.71	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.68	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.92

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting POLR1B, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-2116-5P	99.32	69.34	1273

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 6)

• PTEN represses RNA Pol I transcription through a novel mechanism that involves disruption of the SL1 complex (PMID:16055704)
• CK2 has the potential to regulate Pol I transcription at multiple levels, in preinitiation complex (PIC) formation, activation, and reinitiation of transcription. (PMID:16880508)
• Human Maf1 protein negatively regulates transcription by all three nuclear Pols. Changes in Maf1 expression affect Pol I-dependent transcription in human glioblastoma lines. (PMID:17499043)
• The average FIX expression level of the rDNA recombinants was additionally enhanced to that from a strong Pol II promoter as a result of elimination of position effects. (PMID:18194663)
• POLR1B and neural crest cell anomalies in Treacher Collins syndrome type 4. (PMID:31649276)
• Expression of RNA polymerase I catalytic core is influenced by RPA12. (PMID:37167337)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	polr1b	ENSDARG00000077469
mus_musculus	Polr1b	ENSMUSG00000027395
rattus_norvegicus	Polr1b	ENSRNOG00000018349
drosophila_melanogaster	Polr1B	FBGN0003278
caenorhabditis_elegans	rpoa-2	WBGENE00008781

Paralogs (2): POLR3B (ENSG00000013503), POLR2B (ENSG00000047315)

Protein

Protein identifiers

DNA-directed RNA polymerase I subunit RPA2 — Q9H9Y6 (reviewed: Q9H9Y6)

Alternative names: DNA-directed RNA polymerase I 135 kDa polypeptide

All UniProt accessions (8): Q9H9Y6, C9JJG2, C9JS83, F8WAK7, F8WBB9, F8WCS3, F8WDS4, H7C0D9

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 largest subunit POLR1A/RPA1. 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.

Subcellular location. Nucleus. Nucleolus. Chromosome.

Disease relevance. Treacher Collins syndrome 4 (TCS4) [MIM:618939] A form of Treacher Collins syndrome, a disorder of craniofacial development. Treacher Collins syndrome is characterized by a combination of bilateral downward slanting of the palpebral fissures, colobomas of the lower eyelids with a paucity of eyelashes medial to the defect, hypoplasia of the facial bones, cleft palate, malformation of the external ears, atresia of the external auditory canals, and bilateral conductive hearing loss. TCS4 inheritance pattern is autosomal dominant. The disease is 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 active site comprises the fork loops, the loops and the rudder that stabilize the transcription bubble and assist polymerase translocation.

Similarity. Belongs to the RNA polymerase beta chain family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9H9Y6-1	1	yes
Q9H9Y6-2	2
Q9H9Y6-3	3
Q9H9Y6-4	4
Q9H9Y6-5	5

RefSeq proteins (10): NP_001131076, NP_001269701, NP_001269703, NP_001269705, NP_001269706, NP_001269708, NP_001358898, NP_001358899, NP_001358900, NP_061887* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007120	DNA-dir_RNAP_su2_dom	Domain
IPR007121	RNA_pol_bsu_CS	Conserved_site
IPR007641	RNA_pol_Rpb2_7	Domain
IPR007642	RNA_pol_Rpb2_2	Domain
IPR007644	RNA_pol_bsu_protrusion	Domain
IPR007645	RNA_pol_Rpb2_3	Domain
IPR009674	Rpa2_dom_4	Domain
IPR014724	RNA_pol_RPB2_OB-fold	Homologous_superfamily
IPR015712	DNA-dir_RNA_pol_su2	Family
IPR037033	DNA-dir_RNAP_su2_hyb_sf	Homologous_superfamily
IPR037034	RNA_pol_Rpb2_2_sf	Homologous_superfamily

Pfam: PF00562, PF04560, PF04561, PF04563, PF04565, PF06883

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (163 total): strand 66, helix 39, turn 23, binding site 10, sequence conflict 7, region of interest 5, sequence variant 5, splice variant 4, chain 1, zinc finger region 1, site 1, modified residue 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-Q9H9Y6-F1	92.29	0.79

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): 687 (active site gating; blocks backward movement of nascent rna)

Ligand- & substrate-binding residues (10): 890; 1020; 1036; 1070; 1073; 1098; 1101; 180; 367; 755

Post-translational modifications (1): 1051

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: 736 (showing top): PID_FANCONI_PATHWAY, GSE45365_NK_CELL_VS_CD11B_DC_DN, REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, REACTOME_MEIOTIC_RECOMBINATION, GOBP_CHROMOSOME_ORGANIZATION, KALMA_E2F1_TARGETS, REACTOME_DNA_REPLICATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, PAL_PRMT5_TARGETS_UP, FISCHER_G1_S_CELL_CYCLE

GO Biological Process (5): embryo implantation (GO:0007566), rRNA transcription (GO:0009303), neural crest formation (GO:0014029), nucleologenesis (GO:0017126), DNA-templated transcription (GO:0006351)

GO Molecular Function (10): DNA binding (GO:0003677), DNA-directed RNA polymerase activity (GO:0003899), zinc ion binding (GO:0008270), ribonucleoside binding (GO:0032549), 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 (8): fibrillar center (GO:0001650), nucleoplasm (GO:0005654), chromosome (GO:0005694), RNA polymerase I complex (GO:0005736), cytosol (GO:0005829), 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
cellular anatomical structure	3
RNA biosynthetic process	2
nucleic acid binding	2
nucleolus	2
nuclear lumen	2
intracellular membraneless organelle	2
multicellular organism development	1
female pregnancy	1
reproductive process	1
DNA-templated transcription	1
rRNA metabolic process	1
epithelial to mesenchymal transition	1
chordate embryonic development	1
anatomical structure formation involved in morphogenesis	1
nucleolus organization	1
cellular component biogenesis	1
gene expression	1
5’-3’ RNA polymerase activity	1
transition metal ion binding	1
nucleoside binding	1
binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
RNA polymerase activity	1
cation binding	1
DNA-directed RNA polymerase complex	1
nuclear protein-containing complex	1
cytoplasm	1
RNA polymerase complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

5108 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLR1B	POLI	Q9UNA4	931
POLR1B	POLR1A	O95602	888
POLR1B	POLR1H	Q9P1U0	847
POLR1B	RRN3	Q9NYV6	831
POLR1B	POLR1F	Q3B726	818
POLR1B	POLR2L	P52436	773
POLR1B	SUPT5H	O00267	762
POLR1B	POLR1D	P0DPB6	728
POLR1B	POLR2K	P53803	704
POLR1B	POLR2H	P52434	699
POLR1B	UBTF	P17480	691
POLR1B	POLR1C	O15160	690
POLR1B	POLR2A	P24928	675
POLR1B	POLR1E	Q9GZS1	667
POLR1B	POLR2E	P19388	646

IntAct

89 interactions, top by confidence:

A	B	Type	Score
POLR2E	POLR3A	psi-mi:“MI:0914”(association)	0.870
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
KPNA1	TCERG1	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
POLR1B	POLR1C	psi-mi:“MI:0914”(association)	0.530
GPN3	POLR3A	psi-mi:“MI:0914”(association)	0.530
POLR1C	POLR3A	psi-mi:“MI:0914”(association)	0.530
MAD2L1BP	KIF20A	psi-mi:“MI:0914”(association)	0.530
POLR1D	POLR3A	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
POLR1B	HDAC6	psi-mi:“MI:0915”(physical association)	0.490
HDAC6	POLR1B	psi-mi:“MI:0915”(physical association)	0.490
GRB2	POLR1B	psi-mi:“MI:0915”(physical association)	0.400
NCK1	POLR1B	psi-mi:“MI:0915”(physical association)	0.400
POLR1B	PIK3R1	psi-mi:“MI:0915”(physical association)	0.400
POLR1B	BCAP31	psi-mi:“MI:0915”(physical association)	0.400
LZTR1	POLR1B	psi-mi:“MI:0915”(physical association)	0.370
CCND1	POLR1B	psi-mi:“MI:0915”(physical association)	0.370
RPL37	POLR1B	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (256): POLR1B (Affinity Capture-MS), POLR1B (Affinity Capture-MS), POLR1B (Affinity Capture-MS), POLR1B (Affinity Capture-MS), POLR1B (Affinity Capture-MS), POLR1B (Affinity Capture-MS), EEFSEC (Co-fractionation), EIF2S3 (Co-fractionation), POLR1A (Co-fractionation), POLR1B (Co-fractionation), POLR1B (Co-fractionation), POLR1B (Co-fractionation), POLR1B (Co-fractionation), POLR1C (Co-fractionation), POLR1D (Co-fractionation)

ESM2 similar proteins: A2BYL1, A2C6S8, A5DHT2, A5FRK5, A5PJW8, A6LPQ4, B8JKD7, C0ZIH0, F4I366, F4KD38, O54888, O74633, O83269, P08266, P08518, P20028, P22138, P22276, P25167, P28365, P30876, P38420, P41558, P59470, P70700, Q02061, Q10233, Q10578, Q110H1, Q197F1, Q27493, Q3Z8V4, Q3ZX01, Q42877, Q54BM1, Q54J75, Q5REE8, Q6FLD5, Q753Q4, Q75DS1

Diamond homologs: A0R8H2, A2RML9, A4IJI1, A4VSK2, A4VYU3, A5DHT2, A5PJW8, A5VLL4, A7Z0M9, A8AZI3, A8F976, B0R8D5, B1HMZ6, B1I8R4, B1MVW8, B5E2F3, B7HJ40, B7HQT6, B7IT11, B8JKD7, B8YB55, B8ZNW7, B9DKV0, B9E8Q5, B9IZI6, C1CA06, C1CGP4, C1CMQ8, C1CTL4, C1ET31, C3LJ74, C3P9P7, C4KZQ4, F4I366, F4KD38, O27124, O28392, O54888, O74633, P08266

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
POLR1B	“form complex”	“RNA Polymerase I”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 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
Positive epigenetic regulation of rRNA expression	15	81.1×	2e-23
RNA Polymerase III Chain Elongation	8	79.3×	1e-12
RNA Polymerase I Transcription Termination	14	71.4×	2e-21
RNA Polymerase I Promoter Clearance	15	68.6×	2e-22
RNA Polymerase I Transcription	15	66.9×	2e-22
RNA Polymerase III Transcription Termination	8	62.1×	9e-12
Negative epigenetic regulation of rRNA expression	15	60.8×	8e-22
RNA Polymerase III Transcription Initiation From Type 2 Promoter	9	59.5×	6e-13

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase II	11	8.8×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	112
Likely benign	10
Benign	40

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
932311	NM_019014.6(POLR1B):c.2046T>A (p.Ser682Arg)	Pathogenic
932312	NM_019014.6(POLR1B):c.3007C>T (p.Arg1003Cys)	Pathogenic
932313	NM_019014.6(POLR1B):c.3007C>A (p.Arg1003Ser)	Pathogenic
3250396	NM_019014.6(POLR1B):c.490G>T (p.Glu164Ter)	Likely pathogenic
3344482	NM_019014.6(POLR1B):c.2063A>G (p.Gln688Arg)	Likely pathogenic

SpliceAI

2941 predictions. Top by Δscore:

Variant	Effect	Δscore
2:112547067:T:TA	acceptor_gain	1.0000
2:112547068:G:A	acceptor_gain	1.0000
2:112547170:G:T	donor_gain	1.0000
2:112547180:G:GG	donor_gain	1.0000
2:112547416:TTTA:T	acceptor_loss	1.0000
2:112547417:TTA:T	acceptor_loss	1.0000
2:112547418:TAGGC:T	acceptor_loss	1.0000
2:112547419:A:AG	acceptor_gain	1.0000
2:112547419:AG:A	acceptor_gain	1.0000
2:112547419:AGGCT:A	acceptor_gain	1.0000
2:112547420:G:GA	acceptor_gain	1.0000
2:112547420:GG:G	acceptor_gain	1.0000
2:112547420:GGC:G	acceptor_gain	1.0000
2:112547420:GGCT:G	acceptor_gain	1.0000
2:112547420:GGCTG:G	acceptor_gain	1.0000
2:112549266:GGAA:G	acceptor_gain	1.0000
2:112549395:GTATG:G	donor_gain	1.0000
2:112549400:G:GG	donor_gain	1.0000
2:112549400:GTAA:G	donor_loss	1.0000
2:112549401:TAA:T	donor_loss	1.0000
2:112550851:T:A	acceptor_gain	1.0000
2:112550855:T:A	acceptor_gain	1.0000
2:112550856:G:A	acceptor_gain	1.0000
2:112550861:A:AG	acceptor_gain	1.0000
2:112550861:AATAG:A	acceptor_gain	1.0000
2:112550863:TAGG:T	acceptor_gain	1.0000
2:112550864:A:AG	acceptor_gain	1.0000
2:112550864:AG:A	acceptor_gain	1.0000
2:112550864:AGG:A	acceptor_loss	1.0000
2:112550864:AGGA:A	acceptor_gain	1.0000

AlphaMissense

7540 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:112559345:C:A	N461K	1.000
2:112559345:C:G	N461K	1.000
2:112572569:A:C	Q694H	1.000
2:112572569:A:T	Q694H	1.000
2:112572750:G:C	D755H	1.000
2:112572751:A:C	D755A	1.000
2:112572751:A:T	D755V	1.000
2:112572752:T:A	D755E	1.000
2:112572752:T:G	D755E	1.000
2:112574962:G:C	D881H	1.000
2:112574963:A:T	D881V	1.000
2:112574965:A:C	K882Q	1.000
2:112574965:A:G	K882E	1.000
2:112574966:A:T	K882I	1.000
2:112574967:A:C	K882N	1.000
2:112574967:A:T	K882N	1.000
2:112574974:A:C	S885R	1.000
2:112574976:T:A	S885R	1.000
2:112574976:T:G	S885R	1.000
2:112574983:G:T	G888W	1.000
2:112574984:G:A	G888E	1.000
2:112574988:G:C	Q889H	1.000
2:112574988:G:T	Q889H	1.000
2:112574991:G:C	K890N	1.000
2:112574991:G:T	K890N	1.000
2:112574992:G:C	G891R	1.000
2:112575069:T:A	N916K	1.000
2:112575069:T:G	N916K	1.000
2:112575322:C:A	R1001S	1.000
2:112575326:T:C	L1002S	1.000

dbSNP variants (sampled 300 via entrez): RS1000019390 (2:112578584 A>C,G), RS1000037345 (2:112562883 G>A), RS1000045991 (2:112566765 C>A,T), RS1000197293 (2:112566567 T>C,G), RS1000321390 (2:112560129 A>G,T), RS1000395770 (2:112566204 G>A), RS1000462494 (2:112553665 GTGTT>G), RS1000481831 (2:112554093 G>A), RS1000535330 (2:112561669 A>G), RS1000546030 (2:112566203 C>T), RS1000690804 (2:112561707 G>A), RS1000760475 (2:112555353 A>C,G), RS1000813493 (2:112553387 G>A), RS1000834416 (2:112553805 C>A), RS1000850094 (2:112548222 T>C)

Disease associations

OMIM: gene MIM:602000 | disease phenotypes: MIM:618939, MIM:154500

GenCC curated gene-disease

Disease	Classification	Inheritance
Treacher Collins syndrome 4	Strong	Autosomal dominant
Treacher-Collins syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Treacher Collins syndrome 4	Moderate	AD

Mondo (2): Treacher Collins syndrome 4 (MONDO:0030067), Treacher-Collins syndrome (MONDO:0002457)

Orphanet (1): Treacher-Collins syndrome (Orphanet:861)

HPO phenotypes

75 total (30 of 75 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000046	Small scrotum
HP:0000143	Rectovaginal fistula
HP:0000154	Wide mouth
HP:0000160	Narrow mouth
HP:0000162	Glossoptosis
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000204	Cleft upper lip
HP:0000218	High palate
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000278	Retrognathia
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000327	Hypoplasia of the maxilla
HP:0000347	Micrognathia
HP:0000356	Abnormality of the outer ear
HP:0000358	Posteriorly rotated ears
HP:0000370	Abnormality of the middle ear
HP:0000384	Preauricular skin tag
HP:0000405	Conductive hearing impairment
HP:0000413	Atresia of the external auditory canal
HP:0000431	Wide nasal bridge
HP:0000452	Choanal stenosis
HP:0000453	Choanal atresia
HP:0000486	Strabismus

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
Estradiol	increases expression	2
Hydrogen Peroxide	affects cotreatment, increases expression, affects expression	2
Tretinoin	decreases expression	2
Valproic Acid	increases expression	2
Cadmium Chloride	decreases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
methylmercuric chloride	increases expression	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	decreases expression	1
hydroquinone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation, decreases methylation	1
Coumestrol	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dimethyl Sulfoxide	affects expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Lead	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04931056	Not specified	COMPLETED	A Post Market Clinical Follow-up Study on Biomet Microfixation HTR PEKK (Midface), Facial & Mandibular Plates.