POLR2H

Summary

POLR2H (RNA polymerase II, I and III subunit H, HGNC:9195) is a protein-coding gene on chromosome 3q27.1, encoding DNA-directed RNA polymerases I, II, and III subunit RPABC3 (P52434). 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 99.6% of cancer cell lines).

The three eukaryotic RNA polymerases are complex multisubunit enzymes that play a central role in the transcription of nuclear genes. This gene encodes an essential and highly conserved subunit of RNA polymerase II that is shared by the other two eukaryotic DNA-directed RNA polymerases, I and III. Alternative splicing results in multiple transcript variants of this gene.

Source: NCBI Gene 5437 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 18 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_006232

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9195
Approved symbol	POLR2H
Name	RNA polymerase II, I and III subunit H
Location	3q27.1
Locus type	gene with protein product
Status	Approved
Aliases	RPB8
Ensembl gene	ENSG00000163882
Ensembl biotype	protein_coding
OMIM	606023
Entrez	5437

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 19 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000412877, ENST00000429568, ENST00000430783, ENST00000438240, ENST00000443489, ENST00000452961, ENST00000455712, ENST00000456318, ENST00000460083, ENST00000476003, ENST00000488213, ENST00000489043, ENST00000490958, ENST00000883699, ENST00000883700, ENST00000883701, ENST00000883702, ENST00000883703, ENST00000883704, ENST00000883705, ENST00000883706, ENST00000938180, ENST00000962493, ENST00000962494

RefSeq mRNA: 18 — MANE Select: NM_006232 NM_001278698, NM_001278699, NM_001278700, NM_001278714, NM_001278715, NM_001346879, NM_001389576, NM_001389578, NM_001389579, NM_001389581, NM_001389582, NM_001389583, NM_001389584, NM_001389585, NM_001389586, NM_001389587, NM_001389588, NM_006232

CCDS: CCDS3264, CCDS63859, CCDS63860, CCDS63861, CCDS63862

Canonical transcript exons

ENST00000456318 — 6 exons

Exon	Start	End
ENSE00001731472	184368177	184368591
ENSE00001777980	184361710	184362146
ENSE00001787687	184362873	184363565
ENSE00003602820	184364966	184365049
ENSE00003651970	184365133	184365226
ENSE00003692713	184366717	184366800

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 98.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.1945 / max 576.1547, expressed in 1815 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40201	23.6909	1780
40199	14.8613	1756
40192	4.3378	1557
40200	1.4457	992
40202	1.3720	824
40203	1.1773	700
40193	0.5220	322
40195	0.3005	139
40196	0.2870	105
40197	0.1688	65

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.49	gold quality
lower esophagus mucosa	UBERON:0035834	98.25	gold quality
pancreatic ductal cell	CL:0002079	98.09	gold quality
metanephros cortex	UBERON:0010533	98.02	gold quality
right lobe of thyroid gland	UBERON:0001119	97.82	gold quality
right uterine tube	UBERON:0001302	97.63	gold quality
transverse colon	UBERON:0001157	97.55	gold quality
left lobe of thyroid gland	UBERON:0001120	97.46	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.43	gold quality
right adrenal gland	UBERON:0001233	97.28	gold quality
left adrenal gland cortex	UBERON:0035825	97.14	gold quality
right adrenal gland cortex	UBERON:0035827	97.14	gold quality
rectum	UBERON:0001052	97.13	gold quality
endocervix	UBERON:0000458	97.06	gold quality
left adrenal gland	UBERON:0001234	97.03	gold quality
body of stomach	UBERON:0001161	96.99	gold quality
body of uterus	UBERON:0009853	96.97	gold quality
right ovary	UBERON:0002118	96.88	gold quality
thyroid gland	UBERON:0002046	96.85	gold quality
adenohypophysis	UBERON:0002196	96.84	gold quality
body of pancreas	UBERON:0001150	96.83	gold quality
adrenal cortex	UBERON:0001235	96.83	gold quality
left ovary	UBERON:0002119	96.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.66	gold quality
small intestine	UBERON:0002108	96.62	gold quality
esophagus mucosa	UBERON:0002469	96.62	gold quality
minor salivary gland	UBERON:0001830	96.51	gold quality
ectocervix	UBERON:0012249	96.49	gold quality
right lobe of liver	UBERON:0001114	96.46	gold quality
left uterine tube	UBERON:0001303	96.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.22

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
STAT3	Activation

Upstream regulators (CollecTRI, top): STAT3

miRNA regulators (miRDB)

36 targeting POLR2H, 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-513A-5P	100.00	69.77	2465
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-486-3P	99.51	66.82	1901

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 2)

• hRPB8 interacts with single-stranded DNA nonspecifically and adopts significant conformational changes, and the hRPB8/single-stranded DNA complex is a fast exchanging system (PMID:16632472)
• We also show that endogenous microDNA associate with RNA polymerases subunits, POLR2H and POLR3F. Together, these results suggest that microDNA may modulate gene expression through the production of both known and novel regulatory small RNA. (PMID:30828735)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	polr2h	ENSDARG00000038505
mus_musculus	Polr2h	ENSMUSG00000021018
rattus_norvegicus	Polr2h	ENSRNOG00000001748
drosophila_melanogaster	Polr2H	FBGN0037121
caenorhabditis_elegans		WBGENE00017830

Protein

Protein identifiers

DNA-directed RNA polymerases I, II, and III subunit RPABC3 — P52434 (reviewed: P52434)

Alternative names: DNA-directed RNA polymerase II subunit H, DNA-directed RNA polymerases I, II, and III 17.1 kDa polypeptide, RPB17, RPB8 homolog

All UniProt accessions (3): C9JJJ9, C9JLU1, P52434

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 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. Directly interacts with POLR2A. 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 eukaryotic RPB8 RNA polymerase subunit family.

Isoforms (5)

UniProt ID	Names	Canonical?
P52434-1	1	yes
P52434-2	2
P52434-3	3
P52434-4	4
P52434-5	5

RefSeq proteins (18): NP_001265627, NP_001265628, NP_001265629, NP_001265643, NP_001265644, NP_001333808, NP_001376505, NP_001376507, NP_001376508, NP_001376510, NP_001376511, NP_001376512, NP_001376513, NP_001376514, NP_001376515, NP_001376516, NP_001376517, NP_006223* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005570	RPABC3	Family
IPR012340	NA-bd_OB-fold	Homologous_superfamily

Pfam: PF03870

UniProt features (24 total): strand 12, turn 3, splice variant 3, initiator methionine 1, chain 1, helix 1, region of interest 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

58 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-P52434-F1	84.74	0.47

Functional residue map

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

Post-translational modifications (1): 2

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: 293 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_INITIATION_FROM_TYPE_3_PROMOTER, REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_TERMINATION, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_RNA_POLYMERASE_III_CHAIN_ELONGATION, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, BASSO_B_LYMPHOCYTE_NETWORK, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, REACTOME_SIGNALING_BY_FGFR, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, BROWNE_HCMV_INFECTION_16HR_UP, USF_C, GOBP_RRNA_TRANSCRIPTION, PUJANA_CHEK2_PCC_NETWORK

GO Biological Process (2): transcription by RNA polymerase II (GO:0006366), DNA-templated transcription (GO:0006351)

GO Molecular Function (3): single-stranded DNA binding (GO:0003697), DNA-directed RNA polymerase activity (GO:0003899), DNA binding (GO:0003677)

GO Cellular Component (9): 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), protein-DNA complex (GO:0032993), 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
RNA biosynthetic process	2
nuclear lumen	2
cellular anatomical structure	2
DNA-directed RNA polymerase complex	2
nuclear protein-containing complex	2
DNA-templated transcription	1
gene expression	1
DNA binding	1
5’-3’ RNA polymerase activity	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
RNA polymerase II, holoenzyme	1
nuclear DNA-directed RNA polymerase complex	1
nucleolus	1
cytoplasm	1
protein-containing complex	1
RNA polymerase complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

3015 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLR2H	POLR2L	P52436	999
POLR2H	POLR2E	P19388	996
POLR2H	POLR2K	P53803	995
POLR2H	POLR2F	P41584	994
POLR2H	POLR2A	P24928	972
POLR2H	POLR2J	P52435	928
POLR2H	POLR2C	P19387	880
POLR2H	POLR2I	P36954	873
POLR2H	POLR1C	O15160	854
POLR2H	POLR2G	P52433	852
POLR2H	POLR2B	P30876	850
POLR2H	POLR2D	O15514	845
POLR2H	POLR1D	P0DPB6	818
POLR2H	POLR3K	Q9Y2Y1	810
POLR2H	POLR1H	Q9P1U0	773

IntAct

123 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:0915”(physical association)	0.870
MED18	MED19	psi-mi:“MI:0914”(association)	0.840
MED31	MED19	psi-mi:“MI:0914”(association)	0.840
MED7	MED19	psi-mi:“MI:0914”(association)	0.840
POLR2G	POLR2D	psi-mi:“MI:0914”(association)	0.840
POLR2J	POLR1C	psi-mi:“MI:0914”(association)	0.830
POLR2E	POLR2D	psi-mi:“MI:0915”(physical association)	0.790
POLR2G	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
RPRD1B	POLR2D	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
POLR3GL	POLR3A	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
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
POLR1E	POLR1C	psi-mi:“MI:0914”(association)	0.670
POLR2C	SUPT5H	psi-mi:“MI:0914”(association)	0.640
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
POLR3K	POLR3A	psi-mi:“MI:0914”(association)	0.640

BioGRID (400): POLR2H (Co-localization), POLR2H (Co-localization), POLR2H (Co-localization), ESR1 (Co-localization), SRC (Co-localization), PSMB9 (Co-localization), POLR2H (Co-localization), TCEB3 (Co-localization), POLR2H (Affinity Capture-MS), POLR2H (Biochemical Activity), POLR2H (Biochemical Activity), POLR2H (Co-crystal Structure), POLR2H (Affinity Capture-RNA), CRCP (Co-fractionation), POLR1A (Co-fractionation)

ESM2 similar proteins: A1CUK5, A1DP85, A4FUD3, A4RJH4, A5AB13, A8XT81, E9Q4Z2, F2Z4H3, O00763, O08810, O49074, O64981, O81097, O98997, P10871, P10896, P50408, P52434, P93431, Q01587, Q15029, Q16864, Q19826, Q1E3N5, Q28029, Q28EX9, Q2H334, Q2KJD7, Q2TYB1, Q40073, Q40460, Q40565, Q42450, Q4WLG1, Q5F3X4, Q5FWT7, Q5R4C4, Q5R6E0, Q5ZJJ8, Q641F1

Diamond homologs: A8XT81, F2Z4H3, O81097, P20436, P52434, Q19826, Q54YW8, Q92399, Q923G2, Q9M1A8

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
POLR2H	“form complex”	“RNA Polymerase III”	binding
POLR2H	“form complex”	“RNA Polymerase II”	binding
POLR2H	“form complex”	“RNA Polymerase I”	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	110.0×	5e-23
FGFR2 mutant receptor activation	9	91.4×	2e-15
RNA Polymerase III Transcription Termination	13	86.1×	1e-21
RNA Polymerase III Transcription Initiation From Type 2 Promoter	14	79.0×	2e-22
RNA Polymerase III Transcription Initiation From Type 1 Promoter	14	76.1×	2e-22
RNA Polymerase III Transcription Initiation From Type 3 Promoter	14	76.1×	2e-22
Signaling by FGFR2 IIIa TM	9	72.1×	2e-14
Abortive elongation of HIV-1 transcript in the absence of Tat	10	66.2×	2e-15

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase III	6	54.1×	2e-07
positive regulation of transcription elongation by RNA polymerase II	9	31.9×	6e-09
transcription initiation at RNA polymerase II promoter	6	26.4×	1e-05
RNA polymerase II preinitiation complex assembly	8	25.6×	2e-07
positive regulation of transcription initiation by RNA polymerase II	7	22.4×	4e-06
transcription by RNA polymerase II	10	8.3×	2e-05
defense response to virus	9	7.3×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1024 predictions. Top by Δscore:

Variant	Effect	Δscore
3:184361413:TTACC:T	donor_loss	1.0000
3:184361414:TACC:T	donor_loss	1.0000
3:184361416:C:A	donor_loss	1.0000
3:184364964:A:AG	acceptor_gain	1.0000
3:184364965:G:GG	acceptor_gain	1.0000
3:184364965:GT:G	acceptor_gain	1.0000
3:184365125:A:AG	acceptor_gain	1.0000
3:184365127:TTTCA:T	acceptor_loss	1.0000
3:184365128:TTCA:T	acceptor_loss	1.0000
3:184365129:TCAG:T	acceptor_loss	1.0000
3:184365131:A:C	acceptor_loss	1.0000
3:184365132:G:GC	acceptor_loss	1.0000
3:184366796:CGCCT:C	donor_gain	1.0000
3:184366797:GCCT:G	donor_gain	1.0000
3:184366797:GCCTG:G	donor_gain	1.0000
3:184366801:G:GG	donor_gain	1.0000
3:184361415:A:AC	donor_gain	0.9900
3:184361416:C:CT	donor_gain	0.9900
3:184361416:CCA:C	donor_gain	0.9900
3:184361416:CCAG:C	donor_gain	0.9900
3:184361416:CCAGG:C	donor_gain	0.9900
3:184363289:GAAGT:G	donor_gain	0.9900
3:184363293:T:G	donor_gain	0.9900
3:184363408:C:CA	acceptor_gain	0.9900
3:184363480:T:TA	acceptor_gain	0.9900
3:184363563:GAG:G	donor_gain	0.9900
3:184363566:G:GG	donor_gain	0.9900
3:184364953:T:A	acceptor_gain	0.9900
3:184364962:CCAG:C	acceptor_loss	0.9900
3:184364963:CAGTG:C	acceptor_loss	0.9900

AlphaMissense

991 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:184363514:G:C	D8H	1.000
3:184363514:G:T	D8Y	1.000
3:184363515:A:C	D8A	1.000
3:184363515:A:T	D8V	1.000
3:184363520:T:C	F10L	1.000
3:184363521:T:C	F10S	1.000
3:184363522:C:A	F10L	1.000
3:184363522:C:G	F10L	1.000
3:184363556:T:C	F22L	1.000
3:184363558:T:A	F22L	1.000
3:184363558:T:G	F22L	1.000
3:184364980:T:C	C30R	1.000
3:184364981:G:A	C30Y	1.000
3:184364982:T:G	C30W	1.000
3:184364986:A:C	S32R	1.000
3:184364987:G:T	S32I	1.000
3:184364988:T:A	S32R	1.000
3:184364988:T:G	S32R	1.000
3:184364992:T:C	S34P	1.000
3:184364995:T:A	F35I	1.000
3:184364995:T:C	F35L	1.000
3:184364996:T:C	F35S	1.000
3:184364997:C:A	F35L	1.000
3:184364997:C:G	F35L	1.000
3:184365002:T:G	M37R	1.000
3:184365008:T:C	L39P	1.000
3:184365016:G:C	D42H	1.000
3:184365017:A:T	D42V	1.000
3:184365142:T:C	F56S	1.000
3:184365154:T:A	I60K	1.000

dbSNP variants (sampled 300 via entrez): RS1000196001 (3:184361647 G>A,C), RS1000238210 (3:184364140 A>G), RS1000955646 (3:184368019 G>A), RS1001141188 (3:184361539 C>G,T), RS1001762184 (3:184364316 G>A), RS1002063100 (3:184362649 G>C), RS1002095768 (3:184363089 A>G), RS1002725648 (3:184366332 G>A), RS1002765000 (3:184366479 A>C,G), RS1003472461 (3:184360094 G>A,C), RS1003508181 (3:184365702 G>A,C), RS1003661056 (3:184359733 A>C), RS1004180373 (3:184366275 T>C), RS1004466198 (3:184363952 A>G), RS1005104995 (3:184363617 A>C,G,T)

Disease associations

OMIM: gene MIM:606023 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002875_76	Diisocyanate-induced asthma	3.000000e-06
GCST004607_262	Plateletcrit	9.000000e-42
GCST005312_9	Menopause (age at onset)	3.000000e-09
GCST90002400_411	Plateletcrit	4.000000e-13
GCST90002402_662	Platelet count	4.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0007985	platelet crit
EFO:0004704	age at menopause
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066400 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.39	Kd	407.5	nM	CHEMBL5653589
6.39	ED50	407.5	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149035: Binding affinity to human POLR2H incubated for 45 mins by Kinobead based pull down assay	kd	0.4075	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylselenic acid	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
versicolorin A	increases expression	1
di-n-butylphosphoric acid	affects expression	1
deguelin	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
pyrimidifen	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
abrine	decreases expression	1
pyrachlostrobin	increases expression	1
jinfukang	affects cotreatment, increases expression	1
LDN 193189	decreases expression, affects cotreatment	1
picoxystrobin	increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Antimycin A	increases expression	1
Arsenic	affects methylation	1
Cisplatin	increases expression, affects cotreatment	1
Coumestrol	increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Ivermectin	increases expression	1
Phenobarbital	affects expression	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652077	Binding	Binding affinity to human POLR2H incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_GZ93	K562 eGFP-POLR2H	Cancer cell line	Female

Clinical trials (associated diseases)

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