POLR2K

Summary

POLR2K (RNA polymerase II, I and III subunit K, HGNC:9198) is a protein-coding gene on chromosome 8q22.2, encoding DNA-directed RNA polymerases I, II, and III subunit RPABC4 (P53803). 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 99.8% of cancer cell lines).

This gene encodes one of the smallest subunits of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This subunit is shared by the other two DNA-directed RNA polymerases.

Source: NCBI Gene 5440 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 11 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_005034

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9198
Approved symbol	POLR2K
Name	RNA polymerase II, I and III subunit K
Location	8q22.2
Locus type	gene with protein product
Status	Approved
Aliases	RPB10alpha, RPB12
Ensembl gene	ENSG00000147669
Ensembl biotype	protein_coding
OMIM	606033
Entrez	5440

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000353107, ENST00000519765, ENST00000522439, ENST00000900937, ENST00000900938, ENST00000900939, ENST00000900940, ENST00000900941, ENST00000900942, ENST00000900943, ENST00000923583, ENST00000923584, ENST00000923585, ENST00000923586

RefSeq mRNA: 1 — MANE Select: NM_005034 NM_005034

CCDS: CCDS6285

Canonical transcript exons

ENST00000353107 — 4 exons

Exon	Start	End
ENSE00000981280	100151824	100151916
ENSE00001252225	100153294	100154003
ENSE00001396559	100151347	100151416
ENSE00002095378	100150636	100150709

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 97.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 86.7015 / max 1750.6239, expressed in 1819 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89962	86.0578	1819
89963	0.6437	327

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	97.38	gold quality
calcaneal tendon	UBERON:0003701	97.04	gold quality
popliteal artery	UBERON:0002250	96.57	gold quality
tibial artery	UBERON:0007610	96.57	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.54	gold quality
aorta	UBERON:0000947	96.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.32	gold quality
left adrenal gland	UBERON:0001234	96.28	gold quality
right adrenal gland	UBERON:0001233	96.26	gold quality
rectum	UBERON:0001052	96.25	gold quality
ganglionic eminence	UBERON:0004023	96.23	gold quality
right adrenal gland cortex	UBERON:0035827	96.22	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.18	gold quality
left adrenal gland cortex	UBERON:0035825	96.16	gold quality
left coronary artery	UBERON:0001626	96.11	gold quality
thoracic aorta	UBERON:0001515	96.09	gold quality
amygdala	UBERON:0001876	96.07	gold quality
ascending aorta	UBERON:0001496	96.06	gold quality
descending thoracic aorta	UBERON:0002345	96.04	gold quality
seminal vesicle	UBERON:0000998	96.03	gold quality
right frontal lobe	UBERON:0002810	96.01	gold quality
oocyte	CL:0000023	95.98	gold quality
pons	UBERON:0000988	95.98	gold quality
adenohypophysis	UBERON:0002196	95.87	gold quality
right coronary artery	UBERON:0001625	95.84	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.81	gold quality
corpus epididymis	UBERON:0004359	95.80	gold quality
adult organism	UBERON:0007023	95.80	gold quality
adrenal cortex	UBERON:0001235	95.79	gold quality
monocyte	CL:0000576	95.72	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-125970	no	3.42
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF1

miRNA regulators (miRDB)

43 targeting POLR2K, 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-98-3P	100.00	74.08	3907
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 1)

• results suggest that NS5A may partly modulate host cell transcription by the down-regulation of hRPB10alpha (PMID:17714821)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	polr2k	ENSDARG00000075616
mus_musculus	Polr2k	ENSMUSG00000045996
rattus_norvegicus	Polr2k	ENSRNOG00000072843
drosophila_melanogaster	Polr2K	FBGN0262954
caenorhabditis_elegans		WBGENE00009078

Protein

Protein identifiers

DNA-directed RNA polymerases I, II, and III subunit RPABC4 — P53803 (reviewed: P53803)

Alternative names: ABC10-alpha, DNA-directed RNA polymerase II subunit K, RNA polymerase II 7.0 kDa subunit, RPB10alpha

All UniProt accessions (2): P53803, E5RGX2

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 Rpo12/eukaryotic RPC10 RNA polymerase subunit family.

RefSeq proteins (1): NP_005025* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006591	RNAP_P/RPABC4	Family
IPR029040	RPABC4/Spt4	Homologous_superfamily
IPR039747	RPABC4	Family

Pfam: PF03604

UniProt features (12 total): strand 5, binding site 4, chain 1, zinc finger region 1, turn 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-P53803-F1	85.92	0.66

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): 19; 22; 36; 39

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: 264 (showing top): REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_INITIATION_FROM_TYPE_3_PROMOTER, REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_TERMINATION, REACTOME_INNATE_IMMUNE_SYSTEM, MORF_MSH3, REACTOME_RNA_POLYMERASE_III_CHAIN_ELONGATION, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, REACTOME_SIGNALING_BY_FGFR, MORF_BRCA1, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, MORF_ATRX, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, MORF_ESR1, MODULE_308, GOBP_RRNA_TRANSCRIPTION

GO Biological Process (4): regulation of transcription by RNA polymerase I (GO:0006356), transcription by RNA polymerase II (GO:0006366), transcription by RNA polymerase III (GO:0006383), 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
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

2607 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLR2K	POLR2A	P24928	999
POLR2K	POLR2L	P52436	998
POLR2K	POLR2H	P52434	995
POLR2K	POLR2F	P41584	980
POLR2K	POLR2E	P19388	979
POLR2K	POLR2J	P52435	976
POLR2K	POLR2B	P30876	939
POLR2K	POLR2C	P19387	927
POLR2K	POLR2D	O15514	922
POLR2K	POLR2I	P36954	918
POLR2K	POLR2G	P52433	901
POLR2K	POLR1C	O15160	889
POLR2K	POLR1D	P0DPB6	840
POLR2K	POLR1H	Q9P1U0	782
POLR2K	POLR3K	Q9Y2Y1	717

IntAct

78 interactions, top by confidence:

A	B	Type	Score
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
POLR2E	POLR3A	psi-mi:“MI:0915”(physical association)	0.870
POLR2J	POLR1C	psi-mi:“MI:0914”(association)	0.830
POLR2E	POLR2D	psi-mi:“MI:0915”(physical association)	0.790
MED14	MED19	psi-mi:“MI:0914”(association)	0.790
MED9	MED19	psi-mi:“MI:0914”(association)	0.790
POLR2D	MED19	psi-mi:“MI:0914”(association)	0.730
POLR2E	MED19	psi-mi:“MI:0914”(association)	0.730
MED21	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2A	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2C	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2D	POLR2C	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
POLR1E	POLR1C	psi-mi:“MI:0914”(association)	0.670
POLR2K	SH3KBP1	psi-mi:“MI:0915”(physical association)	0.560
MED29	POLR2D	psi-mi:“MI:0914”(association)	0.530
POLR1B	POLR1C	psi-mi:“MI:0914”(association)	0.530
POLR2I	SUPT5H	psi-mi:“MI:0914”(association)	0.530
POLR2J	SUPT5H	psi-mi:“MI:0914”(association)	0.530
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
POLR2M	BIN1	psi-mi:“MI:0914”(association)	0.530
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
POLR3E	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR1A	POLR2H	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
ORF24	POLR2D	psi-mi:“MI:0914”(association)	0.350

BioGRID (265): POLR2K (Co-localization), POLR2K (Co-localization), POLR2K (Co-localization), ESR1 (Co-localization), SRC (Co-localization), PSMB9 (Co-localization), POLR2K (Co-localization), TCEB3 (Co-localization), POLR2K (Affinity Capture-RNA), POLR1C (Co-fractionation), POLR2A (Co-fractionation), POLR2H (Co-fractionation), POLR2K (Co-fractionation), POLR2K (Co-fractionation), POLR2K (Co-fractionation)

ESM2 similar proteins: A2XIP9, A4IFR3, O13868, O13896, O24473, O74635, P10711, P23193, P27999, P37164, P37165, P38861, P48598, P53803, P60002, P60003, Q08DS5, Q09817, Q0VA16, Q148K0, Q15560, Q21230, Q29RL9, Q2M2S7, Q32LB0, Q3TWF6, Q3ZBC0, Q4KLL0, Q54KR5, Q5EB92, Q5RC82, Q63871, Q6FS48, Q6GPP0, Q6MFY5, Q755B3, Q75LU5, Q791N7, Q8LEF3, Q8LHP0

Diamond homologs: P40422, P48011, P53803, Q3IMF0, Q3ZBC0, Q54R66, Q63871, Q9FLM8, Q9C8M4

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
POLR2K	“form complex”	“RNA Polymerase III”	binding
POLR2K	“form complex”	“RNA Polymerase II”	binding
POLR2K	“form complex”	“RNA Polymerase I”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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	14	138.8×	2e-27
RNA Polymerase III Transcription Termination	14	108.6×	3e-25
FGFR2 mutant receptor activation	9	107.1×	1e-16
RNA Polymerase III Transcription Initiation From Type 2 Promoter	16	105.7×	3e-28
RNA Polymerase III Transcription Initiation From Type 1 Promoter	16	102.0×	4e-28
RNA Polymerase III Transcription Initiation From Type 3 Promoter	16	102.0×	4e-28
Signaling by FGFR2 IIIa TM	10	93.9×	1e-17
Abortive elongation of HIV-1 transcript in the absence of Tat	12	93.1×	7e-21

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase III	6	63.8×	1e-08
positive regulation of transcription elongation by RNA polymerase II	11	46.0×	1e-13
RNA polymerase II preinitiation complex assembly	10	37.8×	8e-12
positive regulation of transcription initiation by RNA polymerase II	10	37.8×	8e-12
positive regulation of innate immune response	5	36.6×	5e-06
transcription initiation at RNA polymerase II promoter	7	36.4×	3e-08
positive regulation of interferon-beta production	6	32.7×	8e-07
transcription by RNA polymerase II	13	12.7×	1e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
88681	NC_000008.11:g.100151617_100163589del	Pathogenic

SpliceAI

373 predictions. Top by Δscore:

Variant	Effect	Δscore
8:100150682:GCGGA:G	donor_gain	0.9900
8:100150687:G:GG	donor_gain	0.9900
8:100150706:GTAG:G	donor_gain	0.9900
8:100150707:TAG:T	donor_loss	0.9900
8:100150708:AGGTA:A	donor_loss	0.9900
8:100150709:GG:G	donor_loss	0.9900
8:100150711:TAAG:T	donor_loss	0.9900
8:100151822:A:AG	acceptor_gain	0.9900
8:100151823:G:GG	acceptor_gain	0.9900
8:100151823:GA:G	acceptor_gain	0.9900
8:100150668:T:TA	donor_gain	0.9800
8:100151823:GAGT:G	acceptor_gain	0.9800
8:100150684:GGA:G	donor_gain	0.9700
8:100150685:GA:G	donor_gain	0.9700
8:100150685:GAG:G	donor_gain	0.9700
8:100150704:GT:G	donor_gain	0.9600
8:100150710:G:GG	donor_gain	0.9600
8:100151906:GAC:G	donor_gain	0.9600
8:100151914:G:GT	donor_gain	0.9500
8:100150669:T:TA	donor_gain	0.9200
8:100150701:GCTGT:G	donor_gain	0.9000
8:100151914:GAT:G	donor_gain	0.9000
8:100150686:A:AG	donor_gain	0.8900
8:100150709:GGTAA:G	donor_gain	0.8900
8:100150710:GTAAG:G	donor_gain	0.8900
8:100151818:TTCTA:T	acceptor_loss	0.8900
8:100151819:TCTA:T	acceptor_loss	0.8900
8:100151822:A:C	acceptor_loss	0.8900
8:100150707:TAGG:T	donor_gain	0.8800
8:100150708:AGGT:A	donor_gain	0.8800

AlphaMissense

383 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:100151404:T:C	Y17H	1.000
8:100151410:T:A	C19S	1.000
8:100151410:T:C	C19R	1.000
8:100151411:G:A	C19Y	1.000
8:100151411:G:C	C19S	1.000
8:100151411:G:T	C19F	1.000
8:100151412:T:G	C19W	1.000
8:100151414:G:A	G20E	1.000
8:100151826:T:C	C22R	1.000
8:100151828:T:G	C22W	1.000
8:100151863:T:A	I34N	1.000
8:100151863:T:G	I34S	1.000
8:100151868:T:A	C36S	1.000
8:100151868:T:C	C36R	1.000
8:100151869:G:A	C36Y	1.000
8:100151869:G:C	C36S	1.000
8:100151869:G:T	C36F	1.000
8:100151870:C:G	C36W	1.000
8:100151877:T:A	C39S	1.000
8:100151877:T:C	C39R	1.000
8:100151878:G:A	C39Y	1.000
8:100151878:G:C	C39S	1.000
8:100151878:G:T	C39F	1.000
8:100151879:T:G	C39W	1.000
8:100151881:G:A	G40E	1.000
8:100151887:G:C	R42T	1.000
8:100151887:G:T	R42I	1.000
8:100151888:A:C	R42S	1.000
8:100151888:A:T	R42S	1.000
8:100151890:T:A	I43K	1.000

dbSNP variants (sampled 300 via entrez): RS1000663325 (8:100149412 G>A,C), RS1000995077 (8:100150767 C>G), RS1001914076 (8:100149342 C>G), RS1002240647 (8:100151121 A>T), RS1002438404 (8:100151429 C>T), RS1003168257 (8:100154026 T>G), RS1004287760 (8:100153688 A>C), RS1005137526 (8:100151934 C>G), RS1005259267 (8:100149837 A>T), RS1005292920 (8:100152321 A>G), RS1005456901 (8:100150088 A>T), RS1006151916 (8:100150554 G>A,C), RS1006297694 (8:100150796 G>T), RS1006577181 (8:100150538 T>C), RS1007037902 (8:100151433 C>A,T)

Disease associations

OMIM: gene MIM:606033 | disease phenotypes: MIM:244400, MIM:615505

GenCC curated gene-disease

Mondo (2): primary ciliary dyskinesia 1 (MONDO:0009484), primary ciliary dyskinesia 28 (MONDO:0014216)

Orphanet (2): Primary ciliary dyskinesia (Orphanet:244), Primary ciliary dyskinesia, Kartagener type (Orphanet:98861)

HPO phenotypes

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

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

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
Particulate Matter	decreases expression, increases abundance	2
bisphenol A	decreases expression	1
arsenite	increases reaction, affects binding	1
cobaltous chloride	decreases expression	1
zinc chromate	increases expression, increases abundance	1
versicolorin A	increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
corosolic acid	decreases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Diethylhexyl Phthalate	increases expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Gold	decreases expression	1
Rotenone	increases expression	1
Selenium	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Aflatoxin B1	decreases methylation	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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