POLR2L

Summary

POLR2L (RNA polymerase II, I and III subunit L, HGNC:9199) is a protein-coding gene on chromosome 11p15.5, encoding DNA-directed RNA polymerases I, II, and III subunit RPABC5 (P62875). DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

This gene encodes a subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains four conserved cysteines characteristic of an atypical zinc-binding domain. Like its counterpart in yeast, this subunit may be shared by the other two DNA-directed RNA polymerases.

Source: NCBI Gene 5441 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 13 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_021128

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9199
Approved symbol	POLR2L
Name	RNA polymerase II, I and III subunit L
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	RPB10beta, RBP10, RPABC5, RPB7.6, hRPB7.6, hsRPB10b
Ensembl gene	ENSG00000177700
Ensembl biotype	protein_coding
OMIM	601189
Entrez	5441

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000322028, ENST00000534030, ENST00000894693, ENST00000934860

RefSeq mRNA: 1 — MANE Select: NM_021128 NM_021128

CCDS: CCDS7720

Canonical transcript exons

ENST00000322028 — 2 exons

Exon	Start	End
ENSE00001263170	839721	840480
ENSE00002152676	842414	842529

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 139.7815 / max 750.6931, expressed in 1827 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117841	132.9580	1826
117840	4.4129	1601
117842	1.4800	868
117843	0.9307	646

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.16	gold quality
heart right ventricle	UBERON:0002080	99.03	gold quality
cardiac ventricle	UBERON:0002082	98.82	gold quality
heart left ventricle	UBERON:0002084	98.82	gold quality
right atrium auricular region	UBERON:0006631	98.80	gold quality
cardiac atrium	UBERON:0002081	98.77	gold quality
left ventricle myocardium	UBERON:0006566	98.71	gold quality
myocardium	UBERON:0002349	98.66	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.63	gold quality
adipose tissue	UBERON:0001013	98.61	gold quality
peritoneum	UBERON:0002358	98.58	gold quality
omental fat pad	UBERON:0010414	98.58	gold quality
mucosa of transverse colon	UBERON:0004991	98.52	gold quality
biceps brachii	UBERON:0001507	98.51	gold quality
right adrenal gland	UBERON:0001233	98.50	gold quality
body of pancreas	UBERON:0001150	98.48	gold quality
left adrenal gland	UBERON:0001234	98.46	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.45	gold quality
stromal cell of endometrium	CL:0002255	98.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.42	gold quality
left adrenal gland cortex	UBERON:0035825	98.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.41	gold quality
diaphragm	UBERON:0001103	98.37	gold quality
pigmented layer of retina	UBERON:0001782	98.34	gold quality
right adrenal gland cortex	UBERON:0035827	98.31	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.30	gold quality
adrenal cortex	UBERON:0001235	98.29	gold quality
heart	UBERON:0000948	98.27	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.21	gold quality
connective tissue	UBERON:0002384	98.19	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	1951.50
E-HCAD-1	yes	88.90
E-HCAD-5	yes	36.39
E-MTAB-6701	yes	17.16
E-MTAB-8410	yes	16.96
E-CURD-46	yes	10.84
E-GEOD-130148	yes	5.14
E-MTAB-10596	no	1560.08
E-MTAB-6075	no	349.05
E-GEOD-93593	no	7.47
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting POLR2L, 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-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-140-5P	99.44	67.20	792
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-378A-3P	98.43	66.10	548
HSA-MIR-378B	98.43	65.36	573
HSA-MIR-378C	98.43	66.10	548
HSA-MIR-378D	98.43	66.10	548
HSA-MIR-378E	98.43	65.99	551
HSA-MIR-378F	98.43	65.66	554
HSA-MIR-378H	98.43	66.16	545
HSA-MIR-378I	98.43	66.10	548
HSA-MIR-3613-5P	98.40	68.91	604
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-1225-3P	97.29	64.60	876
HSA-MIR-6759-3P	96.94	68.31	823
HSA-MIR-3649	96.85	64.10	340
HSA-MIR-152-5P	96.42	66.59	960

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	polr2l	ENSDARG00000058349
mus_musculus	Polr2l	ENSMUSG00000038489
rattus_norvegicus	Polr2l	ENSRNOG00000023805
rattus_norvegicus	Polr2sl1	ENSRNOG00000042507
drosophila_melanogaster	Polr2L	FBGN0039218
caenorhabditis_elegans	rpb-10	WBGENE00021347

Paralogs (1): RPL32 (ENSG00000144713)

Protein

Protein identifiers

DNA-directed RNA polymerases I, II, and III subunit RPABC5 — P62875 (reviewed: P62875)

Alternative names: DNA-directed RNA polymerase III subunit L, RNA polymerase II 7.6 kDa subunit, RPB10 homolog

All UniProt accessions (1): P62875

UniProt curated annotations — full annotation on UniProt →

Function. DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and a small RNAs, such as 5S rRNA and tRNAs, respectively.

Subunit / interactions. Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively. Pol I complex consists of 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. Pol II complex contains a ten-subunit catalytic core composed of POLR2A/RPB1, POLR2B/RPB2, POLR2C/RPB3, POLR2I/RPB9, POLR2J/RPB11, POLR2E/RPABC1, POLR2F/RPABC2, POLR2H/RPABC3, POLR2K/RPABC4 and POLR2L/RPABC5 and a mobile stalk composed of two subunits POLR2D/RPB4 and POLR2G/RPB7. Part of Pol II(G) complex, in which Pol II core associates with an additional subunit POLR2M; unlike conventional Pol II, Pol II(G) functions as a transcriptional repressor. Part of TBP-based Pol II pre-initiation complex (PIC), in which Pol II core assembles with general transcription factors and other specific initiation factors including GTF2E1, GTF2E2, GTF2F1, GTF2F2, TCEA1, ERCC2, ERCC3, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2A1, GTF2A2, GTF2B and TBP; this large multi-subunit PIC complex mediates DNA unwinding and targets Pol II core to the transcription start site where the first phosphodiester bond forms. Pol III complex consists of a ten-subunit catalytic core composed of POLR3A/RPC1, POLR3B/RPC2, POLR1C/RPAC1, POLR1D/RPAC2, POLR3K/RPC10, POLR2E/RPABC1, POLR2F/RPABC2, POLR2H/RPABC3, POLR2K/RPABC4 and POLR2L/RPABC5; a mobile stalk composed of two subunits POLR3H/RPC8 and CRCP/RPC9, protruding from the core and functioning primarily in transcription initiation; and additional subunits homologous to general transcription factors of the RNA polymerase II machinery, POLR3C/RPC3-POLR3F/RPC6-POLR3G/RPC7 heterotrimer required for transcription initiation and POLR3D/RPC4-POLR3E/RPC5 heterodimer involved in both transcription initiation and termination.

Subcellular location. Nucleus. Nucleolus.

Similarity. Belongs to the archaeal Rpo10/eukaryotic RPB10 RNA polymerase subunit family.

RefSeq proteins (1): NP_066951* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000268	RPABC5/Rpb10	Family
IPR020789	RNA_pol_suN_Zn-BS	Binding_site
IPR023580	RNA_pol_su_RPB10	Homologous_superfamily

Pfam: PF01194

UniProt features (12 total): helix 5, binding site 4, turn 2, chain 1

Structure

Experimental structures (PDB)

57 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9EHZ	ELECTRON MICROSCOPY	2.6
7OB9	ELECTRON MICROSCOPY	2.7
8XSO	ELECTRON MICROSCOPY	2.7
7AE1	ELECTRON MICROSCOPY	2.8
9K39	ELECTRON MICROSCOPY	2.8
7VBB	ELECTRON MICROSCOPY	2.81
7VBA	ELECTRON MICROSCOPY	2.89
7D58	ELECTRON MICROSCOPY	2.9
9K36	ELECTRON MICROSCOPY	2.9
9K2G	ELECTRON MICROSCOPY	3
9K3U	ELECTRON MICROSCOPY	3
7VBC	ELECTRON MICROSCOPY	3.01
7AE3	ELECTRON MICROSCOPY	3.1
7D59	ELECTRON MICROSCOPY	3.1
7OBA	ELECTRON MICROSCOPY	3.1
9K38	ELECTRON MICROSCOPY	3.1
8XRM	ELECTRON MICROSCOPY	3.13
9EI1	ELECTRON MICROSCOPY	3.2
9EI3	ELECTRON MICROSCOPY	3.2
9FSO	ELECTRON MICROSCOPY	3.28
7A6H	ELECTRON MICROSCOPY	3.3
7OBB	ELECTRON MICROSCOPY	3.3
9LXN	ELECTRON MICROSCOPY	3.3
7DU2	ELECTRON MICROSCOPY	3.35
9FSP	ELECTRON MICROSCOPY	3.39
7AEA	ELECTRON MICROSCOPY	3.4
8IUH	ELECTRON MICROSCOPY	3.4
7DN3	ELECTRON MICROSCOPY	3.5
9K3V	ELECTRON MICROSCOPY	3.5
9LKT	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62875-F1	92.72	0.88

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 7; 10; 44; 45

Function

Pathways and Gene Ontology

Reactome pathways

97 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-113418	Formation of the Early Elongation Complex
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167158	Formation of the HIV-1 Early Elongation Complex
R-HSA-167160	RNA Pol II CTD phosphorylation and interaction with CE during HIV infection
R-HSA-167161	HIV Transcription Initiation
R-HSA-167162	RNA Polymerase II HIV Promoter Escape
R-HSA-167172	Transcription of the HIV genome
R-HSA-167200	Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167238	Pausing and recovery of Tat-mediated HIV elongation
R-HSA-167242	Abortive elongation of HIV-1 transcript in the absence of Tat
R-HSA-167243	Tat-mediated HIV elongation arrest and recovery
R-HSA-167246	Tat-mediated elongation of the HIV-1 transcript
R-HSA-167287	HIV elongation arrest and recovery
R-HSA-167290	Pausing and recovery of HIV elongation
R-HSA-168325	Viral Messenger RNA Synthesis
R-HSA-1834949	Cytosolic sensors of pathogen-associated DNA
R-HSA-203927	MicroRNA (miRNA) biogenesis
R-HSA-427413	NoRC negatively regulates rRNA expression
R-HSA-5250924	B-WICH complex positively regulates rRNA expression
R-HSA-5578749	Transcriptional regulation by small RNAs
R-HSA-5601884	PIWI-interacting RNA (piRNA) biogenesis
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6781823	Formation of TC-NER Pre-Incision Complex
R-HSA-6781827	Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-6782135	Dual incision in TC-NER
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-6803529	FGFR2 alternative splicing

MSigDB gene sets: 227 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_INITIATION_FROM_TYPE_3_PROMOTER, REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_TERMINATION, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_RNA_POLYMERASE_III_CHAIN_ELONGATION, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, REACTOME_SIGNALING_BY_FGFR, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, GOBP_TRNA_METABOLIC_PROCESS, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, HSIAO_HOUSEKEEPING_GENES

GO Biological Process (5): regulation of transcription by RNA polymerase I (GO:0006356), transcription by RNA polymerase I (GO:0006360), transcription by RNA polymerase II (GO:0006366), tRNA transcription by RNA polymerase III (GO:0042797), DNA-templated transcription (GO:0006351)

GO Molecular Function (5): DNA binding (GO:0003677), DNA-directed RNA polymerase activity (GO:0003899), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), RNA polymerase II, core complex (GO:0005665), RNA polymerase III complex (GO:0005666), RNA polymerase I complex (GO:0005736), cytosol (GO:0005829), DNA-directed RNA polymerase complex (GO:0000428), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Transcription of the HIV genome	8
HIV Transcription Elongation	3
RNA Polymerase II Transcription Elongation	2
Late Phase of HIV Life Cycle	1
Tat-mediated elongation of the HIV-1 transcript	1
Influenza Viral RNA Transcription and Replication	1
Innate Immune System	1
Gene Silencing by RNA	1
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
DNA-templated transcription	2
RNA biosynthetic process	2
nuclear lumen	2
cellular anatomical structure	2
DNA-directed RNA polymerase complex	2
nuclear protein-containing complex	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase I	1
transcription by RNA polymerase III	1
tRNA transcription	1
gene expression	1
nucleic acid binding	1
5’-3’ RNA polymerase activity	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
RNA polymerase II, holoenzyme	1
nuclear DNA-directed RNA polymerase complex	1
nucleolus	1
cytoplasm	1
RNA polymerase complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

147 interactions, top by confidence:

A	B	Type	Score
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
POLR2E	POLR3A	psi-mi:“MI:0914”(association)	0.870
POLR2E	POLR3A	psi-mi:“MI:0915”(physical association)	0.870
POLR2G	POLR2D	psi-mi:“MI:0914”(association)	0.840
POLR2L	POLR2D	psi-mi:“MI:0915”(physical association)	0.800
POLR2E	POLR2D	psi-mi:“MI:0915”(physical association)	0.790
RPAP1	POLR2L	psi-mi:“MI:0915”(physical association)	0.740
POLR2L	RPAP1	psi-mi:“MI:0915”(physical association)	0.740
POLR3GL	POLR3A	psi-mi:“MI:0914”(association)	0.730
POLR2G	RECQL5	psi-mi:“MI:0914”(association)	0.730
RPRD1B	RECQL5	psi-mi:“MI:0914”(association)	0.730
POLR2D	MED19	psi-mi:“MI:0914”(association)	0.730
POLR2E	MED19	psi-mi:“MI:0914”(association)	0.730
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
MED26	MED19	psi-mi:“MI:0914”(association)	0.730
POLR2C	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2J	POLR2D	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
POLR3D	POLR3A	psi-mi:“MI:0914”(association)	0.640
POLR2D	RECQL5	psi-mi:“MI:0914”(association)	0.640
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
POLR2F	POLR3A	psi-mi:“MI:0914”(association)	0.640
POLR2L	POLR3A	psi-mi:“MI:0914”(association)	0.640

BioGRID (310): POLR2L (Co-localization), POLR2L (Co-localization), POLR2L (Co-localization), ESR1 (Co-localization), SRC (Co-localization), PSMB9 (Co-localization), POLR2L (Co-localization), TCEB3 (Co-localization), POLR2L (Two-hybrid), REL (Two-hybrid), TP53BP2 (Two-hybrid), ZBTB14 (Two-hybrid), COIL (Two-hybrid), SPAG5 (Two-hybrid), RPAP1 (Two-hybrid)

ESM2 similar proteins: A0B6E7, A2SSV3, A3CWI3, A3DMR0, A3MXZ9, A4FWK8, A4WNA8, A4YIM8, A6UPX1, A6VGR3, A7IAH1, A8Y1E9, A9A9Y7, B0TI73, B1YC34, B6YSQ7, B8GEG1, B8YB63, B9LPW4, C3MJQ1, C3MZ09, C3N058, C3N8S2, C3NMP6, C4KJ97, O13877, O26147, O29135, P22139, P39472, P62875, P62876, Q0W8C7, Q12TI4, Q2FTN7, Q32P78, Q46CK8, Q5JJC9, Q6L292, Q6LXM4

Diamond homologs: A0B6E7, A1RSD9, A2BK83, A2SSV3, A3CWI3, A3DMR0, A3MXZ9, A4FWK8, A4WNA8, A4YIM8, A6UPX1, A6VGR3, A7IAH1, A8M9S4, A8Y1E9, A9A9Y7, B0R4Y6, B1YC34, B6YSQ7, B8GEG1, B8YB63, B9LPW4, C3MJQ1, C3MZ09, C3N058, C3N8S2, C3NMP6, C4KJ97, O13877, O26147, O29135, O55725, O59298, P22139, P29199, P39472, P60291, P60292, P62875, P62876

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
POLR2L	“form complex”	“RNA Polymerase III”	binding
POLR2L	“form complex”	“RNA Polymerase I”	binding
POLR2L	“form complex”	“RNA Polymerase II”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 102 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	13	125.0×	1e-24
FGFR2 mutant receptor activation	9	103.8×	2e-16
RNA Polymerase III Transcription Termination	13	97.8×	9e-23
RNA Polymerase III Transcription Initiation From Type 2 Promoter	15	96.1×	1e-25
RNA Polymerase III Transcription Initiation From Type 1 Promoter	15	92.7×	1e-25
RNA Polymerase III Transcription Initiation From Type 3 Promoter	15	92.7×	1e-25
Signaling by FGFR2 IIIa TM	9	82.0×	3e-15
RNA Polymerase III Transcription Initiation	15	76.3×	4e-24

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase III	6	50.0×	4e-07
transcription initiation at RNA polymerase II promoter	6	24.4×	2e-05
positive regulation of interferon-beta production	5	21.3×	3e-04
positive regulation of transcription elongation by RNA polymerase II	5	16.4×	9e-04
RNA polymerase II preinitiation complex assembly	5	14.8×	1e-03
positive regulation of transcription initiation by RNA polymerase II	5	14.8×	1e-03
DNA-templated transcription	5	12.2×	2e-03
transcription by RNA polymerase II	15	11.5×	2e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

856 predictions. Top by Δscore:

Variant	Effect	Δscore
11:837452:T:TA	acceptor_gain	1.0000
11:837458:A:AG	acceptor_gain	1.0000
11:837458:AGTTC:A	acceptor_loss	1.0000
11:837459:G:GA	acceptor_gain	1.0000
11:837459:GT:G	acceptor_gain	1.0000
11:837459:GTT:G	acceptor_gain	1.0000
11:837459:GTTC:G	acceptor_gain	1.0000
11:837459:GTTCC:G	acceptor_gain	1.0000
11:837566:T:TA	donor_gain	1.0000
11:837567:G:GA	donor_gain	1.0000
11:837617:AG:A	donor_loss	1.0000
11:837618:GG:G	donor_loss	1.0000
11:837619:G:GA	donor_loss	1.0000
11:837620:T:A	donor_loss	1.0000
11:837940:A:AG	acceptor_gain	1.0000
11:837940:AG:A	acceptor_gain	1.0000
11:837940:AGGGC:A	acceptor_gain	1.0000
11:837941:G:GA	acceptor_loss	1.0000
11:837941:G:GG	acceptor_gain	1.0000
11:837941:GG:G	acceptor_gain	1.0000
11:837941:GGGC:G	acceptor_gain	1.0000
11:837941:GGGCG:G	acceptor_gain	1.0000
11:838027:AGGTG:A	donor_loss	1.0000
11:838028:GG:G	donor_loss	1.0000
11:838029:G:A	donor_loss	1.0000
11:838030:T:G	donor_loss	1.0000
11:840476:CATCC:C	acceptor_gain	1.0000
11:840478:TCC:T	acceptor_gain	1.0000
11:840479:CC:C	acceptor_gain	1.0000
11:840479:CCC:C	acceptor_gain	1.0000

AlphaMissense

421 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:842485:G:C	F8L	0.997
11:842485:G:T	F8L	0.997
11:842487:A:G	F8L	0.997
11:842490:A:G	C7R	0.997
11:842498:G:T	P4H	0.996
11:840442:C:T	C45Y	0.995
11:840445:C:T	C44Y	0.995
11:840446:A:G	C44R	0.995
11:842466:C:G	G15R	0.995
11:842465:C:T	G15D	0.994
11:842480:C:T	C10Y	0.994
11:842481:A:G	C10R	0.994
11:840444:G:C	C44W	0.993
11:840472:A:G	L35P	0.993
11:842457:A:G	W18R	0.993
11:842457:A:T	W18R	0.993
11:840440:G:T	R46S	0.992
11:840441:G:C	C45W	0.992
11:840443:A:G	C45R	0.992
11:842477:C:A	G11V	0.992
11:842488:G:C	C7W	0.992
11:842489:C:T	C7Y	0.992
11:842493:G:T	R6S	0.992
11:842498:G:C	P4R	0.992
11:840436:C:G	R47P	0.991
11:840442:C:A	C45F	0.991
11:840445:C:G	C44S	0.991
11:840446:A:T	C44S	0.991
11:842483:G:A	T9I	0.991
11:842489:C:G	C7S	0.991

dbSNP variants (sampled 300 via entrez): RS1000293658 (11:839623 C>T), RS1000441734 (11:843285 G>T), RS1000522558 (11:840130 T>C), RS1000676155 (11:840183 T>A,C), RS1000695966 (11:844245 G>A), RS1000748085 (11:839383 C>T), RS1000959726 (11:839974 G>C), RS1000987371 (11:844421 C>G), RS1001560368 (11:840754 T>C), RS1001623783 (11:842989 G>A,C), RS1001674696 (11:842877 G>A,C,T), RS1001742981 (11:844013 A>C), RS1001853197 (11:839989 T>C), RS1001926262 (11:841018 T>A), RS1002011564 (11:843627 G>T)

Disease associations

OMIM: gene MIM:601189 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007269_193	Pulse pressure	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6195763 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	6
sodium arsenite	decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
bisphenol A	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
K 7174	decreases expression	1
abrine	decreases expression	1
MT19c compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Fulvestrant	decreases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects expression	1
Dexamethasone	increases expression	1
Diazinon	increases methylation	1
Diethylstilbestrol	decreases expression	1
Doxorubicin	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Manganese	decreases expression, increases abundance	1
Phenobarbital	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL6194225	Functional	Inhibition of human POLR2L using RNA polymerase II-DdRp activity	Data for DCP probe JNJ-8003

Clinical trials (associated diseases)

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