POLRMT

Summary

POLRMT (RNA polymerase mitochondrial, HGNC:9200) is a protein-coding gene on chromosome 19p13.3, encoding DNA-directed RNA polymerase, mitochondrial (O00411). DNA-dependent RNA polymerase catalyzes the transcription of mitochondrial DNA into RNA using the four ribonucleoside triphosphates as substrates. It is a selective cancer dependency (DepMap: 59.4% of cell lines).

This gene encodes a mitochondrial DNA-directed RNA polymerase. The gene product is responsible for mitochondrial gene expression as well as for providing RNA primers for initiation of replication of the mitochondrial genome. Although this polypeptide has the same function as the three nuclear DNA-directed RNA polymerases, it is more closely related to RNA polymerases of phage and mitochondrial polymerases of lower eukaryotes.

Source: NCBI Gene 5442 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined oxidative phosphorylation deficiency 55 (Strong, GenCC)
• Clinical variants (ClinVar): 464 total — 9 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 54
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 59.4% of screened cell lines
• MANE Select transcript: NM_005035

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9200
Approved symbol	POLRMT
Name	RNA polymerase mitochondrial
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	h-mtRPOL, APOLMT, MTRNAP, MTRPOL
Ensembl gene	ENSG00000099821
Ensembl biotype	protein_coding
OMIM	601778
Entrez	5442

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 37 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000587057, ENST00000588649, ENST00000589961, ENST00000590336, ENST00000590573, ENST00000590709, ENST00000592633, ENST00000592863, ENST00000878776, ENST00000878777, ENST00000878778, ENST00000878779, ENST00000878780, ENST00000878781, ENST00000878782, ENST00000878783, ENST00000878784, ENST00000878785, ENST00000878786, ENST00000878787, ENST00000878788, ENST00000878789, ENST00000878790, ENST00000927047, ENST00000927048, ENST00000927049, ENST00000927050, ENST00000927051, ENST00000927052, ENST00000927053, ENST00000927054, ENST00000927055, ENST00000927056, ENST00000927057, ENST00000927058, ENST00000927059, ENST00000927060, ENST00000958661, ENST00000958662, ENST00000958663, ENST00000958664, ENST00000958665

RefSeq mRNA: 21 — MANE Select: NM_005035 NM_001407805, NM_001407806, NM_001407807, NM_001407808, NM_001407809, NM_001407810, NM_001407811, NM_001407812, NM_001407813, NM_001407814, NM_001407815, NM_001407816, NM_001407829, NM_001407830, NM_001407831, NM_001407832, NM_001407833, NM_001407834, NM_001407835, NM_001407836, NM_005035

CCDS: CCDS12036

Canonical transcript exons

ENST00000588649 — 21 exons

Exon	Start	End
ENSE00000655271	629540	630168
ENSE00000655279	621058	621846
ENSE00000655281	620365	620487
ENSE00000655282	619958	620080
ENSE00000655283	619586	619765
ENSE00000655284	619210	619296
ENSE00000655286	618997	619110
ENSE00000655289	618705	618760
ENSE00000655290	618488	618586
ENSE00000655291	617777	617849
ENSE00000892315	633425	633537
ENSE00001365093	617221	617323
ENSE00003469219	632834	632938
ENSE00003480125	617570	617655
ENSE00003493611	622149	622373
ENSE00003511131	622821	622985
ENSE00003565651	623454	623603
ENSE00003576012	624719	624905
ENSE00003593025	622582	622752
ENSE00003630656	625124	625254
ENSE00003694502	617419	617480

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 97.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.5471 / max 142.0891, expressed in 1777 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177906	10.6204	1773
177907	0.7084	360
177908	0.2183	71

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.07	gold quality
right testis	UBERON:0004534	96.99	gold quality
apex of heart	UBERON:0002098	96.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.88	gold quality
testis	UBERON:0000473	95.64	gold quality
mucosa of transverse colon	UBERON:0004991	95.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.37	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.36	gold quality
lower esophagus mucosa	UBERON:0035834	95.20	gold quality
right lobe of liver	UBERON:0001114	94.63	gold quality
gastrocnemius	UBERON:0001388	94.19	gold quality
adenohypophysis	UBERON:0002196	93.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.58	gold quality
right frontal lobe	UBERON:0002810	93.31	gold quality
granulocyte	CL:0000094	93.23	gold quality
muscle of leg	UBERON:0001383	93.09	gold quality
metanephros cortex	UBERON:0010533	93.02	gold quality
anterior cingulate cortex	UBERON:0009835	92.95	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.93	gold quality
cingulate cortex	UBERON:0003027	92.77	gold quality
cerebellar hemisphere	UBERON:0002245	92.73	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.66	gold quality
cerebellar cortex	UBERON:0002129	92.65	gold quality
right lobe of thyroid gland	UBERON:0001119	92.58	gold quality
skin of leg	UBERON:0001511	92.44	gold quality
pituitary gland	UBERON:0000007	92.32	gold quality
prefrontal cortex	UBERON:0000451	92.22	gold quality
tibial nerve	UBERON:0001323	92.18	gold quality
left lobe of thyroid gland	UBERON:0001120	92.15	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	28.08
E-ANND-3	yes	3.21

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 59.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 21)

• human mitochondrial DNA polymerase has a role in autosomal dominant progressive external ophthalmoplegia (PMID:15258572)
• POLRMT recognizes promoter elements in a sequence specific manner; TFAM induces a structural change of the promoter that is required for POLRMT-dependent promoter recognition (PMID:15526033)
• transcription of some mRNAs in humans and rodents is mediated by a previously unknown single-polypeptide nuclear RNA polymerase (spRNAP-IV), expressed from an alternative transcript of the mitochondrial RNA polymerase gene POLRMT (PMID:16079853)
• the MRPL12 interaction with POLRMT is likely part of a novel regulatory mechanism that coordinates mitochondrial transcription with translation (PMID:17337445)
• Promoter-independent DNA conformation-dependent transcription required TFB2M and was suppressed by TFAM, while promoter-dependent transcription was inhibited to a lesser extent BY TFAM. (PMID:19624753)
• POLRMT can function as an origin-specific primase in mammalian mitochondria. (PMID:20129056)
• Human mitochondrial RNA polymerase: evaluation of the single-nucleotide-addition cycle on synthetic RNA/DNA scaffolds (PMID:21548588)
• muscle actin genes are transcribed by nuclear isoform of mitochondrial RNA polymerase (spRNAP-IV) whereas the non-muscle actin genes are transcribed by the conventional RNA polymerase II (PolII) (PMID:21799907)
• X-ray structure of human mtRNAP at 2.5 A resolution, which reveals a T7-like catalytic carboxy-terminal domain, an amino-terminal domain resembling the T7 promoter-binding domain, a novel pentatricopeptide repeat domain, and flexible N-terminal extension (PMID:21947009)
• Authors propose that POLRMT interacts directly with h-mtTFB1 in 28S mitochondrial ribosomes to augment its 12S rRNA methyltransferase activity. (PMID:23303773)
• Newly synthesized RNA exits toward the pentatricopeptide repeat (PPR) domain, a unique feature of mtRNAP with conserved RNA-recognition motifs. (PMID:24096365)
• The results demonstrate that human TFAM binds to the N-terminal domain of mtRNAP, which results in bending of the promoter DNA around mtRNAP. (PMID:24393772)
• The results reveal the organization of TFAM, POLRMT and TFB2M around the light-strand promoter and represent the first structural characterization of the entire mitochondrial transcriptional initiation complex. (PMID:24413562)
• Results show that polymorphisms at POLG2 and POLRMT increased risk of oral cancer and leukoplakia, respectively, probably modulating synthesis and activity of the enzymes. (PMID:26403317)
• Suggest targeting POLRMT as strategy for treating acute myeloid leukemia. (PMID:26484416)
• knock-down of MRPL12 by RNA interference results in instability of POLRMT. (PMID:26586915)
• the frequency of variation in sequence identity and length at conserved sequence block 2 amongst human mitochondrial genomes and used in vitro transcription to assess the effects of this length heterogeneity on the activity of the mitochondrial RNA polymerase, POLRMT, was examined. (PMID:27436287)
• POLRMT mutations impair mitochondrial transcription causing neurological disease. (PMID:33602924)
• The requirement of mitochondrial RNA polymerase for non-small cell lung cancer cell growth. (PMID:34326320)
• TFB2M and POLRMT are essential for mammalian mitochondrial DNA replication. (PMID:34744028)
• SUCLG1 restricts POLRMT succinylation to enhance mitochondrial biogenesis and leukemia progression. (PMID:38649537)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	polrmt	ENSDARG00000101220
mus_musculus	Polrmt	ENSMUSG00000020329
rattus_norvegicus	Polrmt	ENSRNOG00000024879
drosophila_melanogaster	PolrMT	FBGN0261938
caenorhabditis_elegans	rpom-1	WBGENE00013680

Protein

Protein identifiers

DNA-directed RNA polymerase, mitochondrial — O00411 (reviewed: O00411)

All UniProt accessions (4): O00411, K7EMH3, K7ESD1, R4GN79

UniProt curated annotations — full annotation on UniProt →

Function. DNA-dependent RNA polymerase catalyzes the transcription of mitochondrial DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT that is required for basal transcription of mitochondrial DNA. In this complex, TFAM recruits POLRMT to a specific promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand. Has DNA primase activity. Catalyzes the synthesis of short RNA primers that are necessary for the initiation of lagging-strand DNA synthesis from the origin of light-strand DNA replication (OriL).

Subunit / interactions. Homodimer. Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT. In this complex TFAM recruits POLRMT to the promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand. Upon metabolic stress, forms a complex composed of FOXO3, SIRT3 and mitochondrial RNA polymerase POLRMT; the complex is recruited to mtDNA in a SIRT3-dependent manner. Also forms a complex composed of FOXO3, SIRT3, TFAM and POLRMT. Interacts with TFB1M and TFB2M, leading to the stimulation of transcription. Interacts with TEFM. Interacts with MTRES1.

Subcellular location. Mitochondrion.

Disease relevance. Combined oxidative phosphorylation deficiency 55 (COXPD55) [MIM:619743] A mitochondrial disease characterized by global developmental delay, hypotonia, short stature, and impaired intellectual development with speech disabilities in childhood. Indolent progressive external ophthalmoplegia may be present in some patients. COXPD55 transmission pattern is consistent with autosomal dominant inheritance in some families, and with autosomal recessive inheritance in others. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the phage and mitochondrial RNA polymerase family.

RefSeq proteins (21): NP_001394734, NP_001394735, NP_001394736, NP_001394737, NP_001394738, NP_001394739, NP_001394740, NP_001394741, NP_001394742, NP_001394743, NP_001394744, NP_001394745, NP_001394758, NP_001394759, NP_001394760, NP_001394761, NP_001394762, NP_001394763, NP_001394764, NP_001394765, NP_005026* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002092	DNA-dir_Rpol_phage-type	Family
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR029262	RPOL_N	Domain
IPR037159	RNA_POL_N_sf	Homologous_superfamily
IPR043502	DNA/RNA_pol_sf	Homologous_superfamily
IPR046950	DNA-dir_Rpol_C_phage-type	Domain

Pfam: PF00940, PF14700

Enzyme classification (BRENDA):

• EC 2.7.7.6 — DNA-directed RNA polymerase (BRENDA: 114 organisms, 118 substrates, 121 inhibitors, 44 Km, 21 kcat entries)

Substrate kinetics (BRENDA)

16 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DGTP	0.015–1.4	8
RGTP	0.0103–0.32	8
ATP	0.0095–0.384	7
DUTP	1.2–1.7	2
GTP	0.1–0.234	2
RUTP	0.036–0.041	2
A10G2A2C2C	0.018	1
A9G3A2C2C	0.041	1
D(AP4T)	0.0021	1
D(TP4C)	0.0022	1
D(TP4G)	0.0017	1
D(TP4T)	0.0007	1
DTTP	0.0004	1
G2CAC2C	0.043	1
PROMOTER COMPLEX	—	1

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (118 total): helix 51, strand 34, sequence variant 12, turn 9, region of interest 4, active site 3, sequence conflict 2, transit peptide 1, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
3SPA	X-RAY DIFFRACTION	2.5
9BDC	ELECTRON MICROSCOPY	2.54
4BOC	X-RAY DIFFRACTION	2.65
9MN7	ELECTRON MICROSCOPY	2.65
9MN8	ELECTRON MICROSCOPY	2.69
9MN6	ELECTRON MICROSCOPY	2.71
8U8V	ELECTRON MICROSCOPY	2.74
9MN9	ELECTRON MICROSCOPY	2.74
9BDD	ELECTRON MICROSCOPY	2.86
8U8U	ELECTRON MICROSCOPY	2.9
7PZR	ELECTRON MICROSCOPY	3
9MN5	ELECTRON MICROSCOPY	3.04
9MN4	ELECTRON MICROSCOPY	3.05
9R96	ELECTRON MICROSCOPY	3.1
9GZO	ELECTRON MICROSCOPY	3.15
9R95	ELECTRON MICROSCOPY	3.2
7ZC4	ELECTRON MICROSCOPY	3.24
9GZM	ELECTRON MICROSCOPY	3.4
7A8P	ELECTRON MICROSCOPY	3.5
7PZP	ELECTRON MICROSCOPY	3.5
9GZN	ELECTRON MICROSCOPY	3.5
9MNA	ELECTRON MICROSCOPY	3.77
5OLA	X-RAY DIFFRACTION	3.9
6ERQ	X-RAY DIFFRACTION	4.5
6ERP	X-RAY DIFFRACTION	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00411-F1	83.99	0.64

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 (3): 922; 991; 1151

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-163282	Mitochondrial transcription initiation
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-9913635	Strand-asynchronous mitochondrial DNA replication
R-HSA-1592230	Mitochondrial biogenesis
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-69306	DNA Replication
R-HSA-74160	Gene expression (Transcription)
R-HSA-75944	Transcription from mitochondrial promoters

MSigDB gene sets: 219 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, REACTOME_DNA_REPLICATION, GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOBP_MITOCHONDRIAL_DNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_MITOCHONDRIAL_RNA_METABOLIC_PROCESS, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, GOCC_RNA_POLYMERASE_COMPLEX, GOMF_EXONUCLEASE_ACTIVITY, GOBP_DNA_REPLICATION

GO Biological Process (4): mitochondrial DNA replication (GO:0006264), mitochondrial transcription (GO:0006390), transcription initiation at mitochondrial promoter (GO:0006391), DNA-templated transcription (GO:0006351)

GO Molecular Function (10): 3’-5’-RNA exonuclease activity (GO:0000175), mitochondrial promoter sequence-specific DNA binding (GO:0001018), RNA binding (GO:0003723), DNA-directed RNA polymerase activity (GO:0003899), sequence-specific DNA binding (GO:0043565), DNA binding (GO:0003677), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), 5’-3’ RNA polymerase activity (GO:0034062)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), protein-containing complex (GO:0032991), mitochondrial DNA-directed RNA polymerase complex (GO:0034245), mitochondrial nucleoid (GO:0042645), DNA-directed RNA polymerase complex (GO:0000428)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Transcription from mitochondrial promoters	1
Mitochondrial biogenesis	1
DNA Replication	1
Organelle biogenesis and maintenance	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	5
mitochondrial RNA metabolic process	2
RNA biosynthetic process	2
nucleic acid binding	2
DNA-templated DNA replication	1
mitochondrial DNA metabolic process	1
DNA-templated transcription	1
mitochondrial gene expression	1
DNA-templated transcription initiation	1
mitochondrial transcription	1
gene expression	1
3’-5’ exonuclease activity	1
RNA exonuclease activity, producing 5’-phosphomonoesters	1
transcription cis-regulatory region binding	1
5’-3’ RNA polymerase activity	1
DNA binding	1
binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
RNA polymerase activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular organelle lumen	1
cellular_component	1
DNA-directed RNA polymerase complex	1
mitochondrial protein-containing complex	1
mitochondrial matrix	1
nucleoid	1
intracellular membraneless organelle	1
RNA polymerase complex	1

Protein interactions and networks

STRING

2154 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLRMT	TFB2M	Q9H5Q4	999
POLRMT	TFB1M	Q8WVM0	999
POLRMT	TFAM	Q00059	999
POLRMT	TEFM	Q96QE5	952
POLRMT	MRPL12	P52815	924
POLRMT	SSBP1	Q04837	866
POLRMT	TWNK	Q96RR1	853
POLRMT	MTERF1	Q99551	830
POLRMT	POLG	P54098	823
POLRMT	PTCD3	Q96EY7	793
POLRMT	DHX30	Q7L2E3	775
POLRMT	POLG2	Q9UHN1	759
POLRMT	MTERF3	Q96E29	743
POLRMT	MTERF4	Q7Z6M4	731
POLRMT	MGME1	Q9BQP7	711

IntAct

216 interactions, top by confidence:

A	B	Type	Score
MRPL12	POLRMT	psi-mi:“MI:0915”(physical association)	0.800
POLRMT	MRPL12	psi-mi:“MI:0914”(association)	0.800
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NFKBIA	POLRMT	psi-mi:“MI:0914”(association)	0.670
KLHL22	METTL15	psi-mi:“MI:0914”(association)	0.640
POLRMT	TFAM	psi-mi:“MI:0915”(physical association)	0.560
TEFM	POLRMT	psi-mi:“MI:0914”(association)	0.560
POLRMT	TFAM	psi-mi:“MI:0914”(association)	0.560
POLRMT	TEFM	psi-mi:“MI:0915”(physical association)	0.560
VWCE	ZNF316	psi-mi:“MI:0914”(association)	0.530
CACNG5	ZNF316	psi-mi:“MI:0914”(association)	0.530
LTBR	ZNF724	psi-mi:“MI:0914”(association)	0.530
DHX32	POLRMT	psi-mi:“MI:0914”(association)	0.530
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
KCTD17	CBX4	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530

BioGRID (260): POLRMT (Affinity Capture-MS), POLRMT (Affinity Capture-MS), POLRMT (Affinity Capture-MS), POLRMT (Affinity Capture-MS), POLRMT (Affinity Capture-MS), POLRMT (Affinity Capture-MS), POLRMT (Affinity Capture-MS), POLRMT (Affinity Capture-MS), POLRMT (Affinity Capture-MS), POLRMT (Affinity Capture-MS), POLRMT (Affinity Capture-MS), POLRMT (Affinity Capture-MS), POLRMT (Affinity Capture-MS), POLRMT (Affinity Capture-MS), POLRMT (Affinity Capture-MS)

ESM2 similar proteins: A0PJW6, A5PJW2, B3DI94, B5DFG1, O00411, O95382, P49753, Q059A4, Q0V9C9, Q3SX05, Q4KLZ1, Q4KM93, Q4R5Q4, Q4VAE3, Q53S58, Q5EA71, Q5T1A1, Q5XIC2, Q643R3, Q66LN0, Q6DC58, Q6NVG1, Q76MJ5, Q7YS91, Q80YU0, Q863F8, Q8BPE4, Q8BWM0, Q8N159, Q8NFF5, Q8VCA6, Q8VD26, Q921N7, Q96AN5, Q96KR6, Q99MQ3, Q9BQ95, Q9BUB7, Q9BYK8, Q9CQE2

Diamond homologs: O00411, O13993, O24600, P13433, P38671, P69242, P69243, P92969, Q8BKF1, Q8L6J1, Q8L6J2, Q8L6J3, Q8L6J4, Q8L6J5, Q8VWF8, Q93Y94, Q9LFV6, P07659, Q7Y2D9, P00573, P18147, P33540, P06221

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 171 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
Mitochondrial ribosome-associated quality control	10	11.3×	1e-05
Signaling by ALK fusions and activated point mutants	7	9.7×	8e-04
Mitochondrial translation initiation	8	9.3×	3e-04
Mitochondrial translation elongation	8	9.3×	3e-04
Mitochondrial translation	7	8.8×	1e-03
Mitochondrial translation termination	8	8.1×	8e-04
rRNA processing	6	8.1×	6e-03
Formation of a pool of free 40S subunits	7	7.2×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	9	10.2×	3e-04
cytoplasmic translation	8	9.6×	9e-04
ribosomal small subunit biogenesis	6	8.9×	8e-03
translation	10	6.7×	9e-04
protein phosphorylation	11	4.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	7
Uncertain significance	342
Likely benign	54
Benign	10

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
1341473	NM_005035.4(POLRMT):c.2641-1G>C	Pathogenic
1341474	NM_005035.4(POLRMT):c.1832C>T (p.Ser611Phe)	Pathogenic
1341475	NM_005035.4(POLRMT):c.1923C>G (p.Phe641Leu)	Pathogenic
1341476	NM_005035.4(POLRMT):c.2775C>A (p.Cys925Ter)	Pathogenic
1341478	NM_005035.4(POLRMT):c.3037C>T (p.Arg1013Cys)	Pathogenic
1341479	NM_005035.4(POLRMT):c.445C>T (p.Gln149Ter)	Pathogenic
3376607	NM_005035.4(POLRMT):c.2424del (p.Cys809fs)	Pathogenic
4528323	NM_005035.4(POLRMT):c.1940C>T (p.Pro647Leu)	Pathogenic
4528326	NM_005035.4(POLRMT):c.2438T>C (p.Phe813Ser)	Pathogenic
1341472	NM_005035.4(POLRMT):c.748C>G (p.His250Asp)	Likely pathogenic
2671936	NM_005035.4(POLRMT):c.954-1G>C	Likely pathogenic
3237469	NM_005035.4(POLRMT):c.2041C>T (p.Gln681Ter)	Likely pathogenic
3367088	NM_005035.4(POLRMT):c.1753C>T (p.Gln585Ter)	Likely pathogenic
4277451	NM_005035.4(POLRMT):c.2732_2733delinsT (p.Ala911fs)	Likely pathogenic
4796499	NM_005035.4(POLRMT):c.2351C>T (p.Ser784Leu)	Likely pathogenic
4814169	NM_005035.4(POLRMT):c.983dup (p.Lys329fs)	Likely pathogenic

SpliceAI

3372 predictions. Top by Δscore:

Variant	Effect	Δscore
19:617480:CCTGG:C	acceptor_loss	1.0000
19:617481:C:CA	acceptor_loss	1.0000
19:617481:C:CC	acceptor_gain	1.0000
19:617482:T:G	acceptor_loss	1.0000
19:617563:GCCTT:G	donor_loss	1.0000
19:617564:CCTTA:C	donor_loss	1.0000
19:617565:CTT:C	donor_loss	1.0000
19:617566:TTA:T	donor_loss	1.0000
19:617567:TA:T	donor_loss	1.0000
19:617568:A:AC	donor_gain	1.0000
19:617568:ACTC:A	donor_loss	1.0000
19:617569:C:CC	donor_gain	1.0000
19:617569:CT:C	donor_gain	1.0000
19:617569:CTCA:C	donor_gain	1.0000
19:617572:A:AC	donor_gain	1.0000
19:617572:AGAG:A	donor_gain	1.0000
19:618485:CA:C	donor_loss	1.0000
19:618486:ACC:A	donor_loss	1.0000
19:618487:C:A	donor_loss	1.0000
19:618585:TTCTG:T	acceptor_loss	1.0000
19:618587:C:CC	acceptor_gain	1.0000
19:618704:CCGG:C	donor_gain	1.0000
19:618756:ATTTG:A	acceptor_gain	1.0000
19:618757:TTTG:T	acceptor_gain	1.0000
19:618758:TTG:T	acceptor_gain	1.0000
19:618759:TG:T	acceptor_gain	1.0000
19:618761:C:CC	acceptor_gain	1.0000
19:618992:CTGA:C	donor_loss	1.0000
19:618993:TGACC:T	donor_loss	1.0000
19:618994:GACC:G	donor_loss	1.0000

AlphaMissense

7951 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:617820:T:A	D1151V	1.000
19:617819:G:C	D1151E	0.999
19:617819:G:T	D1151E	0.999
19:617820:T:G	D1151A	0.999
19:617821:C:G	D1151H	0.999
19:617824:G:C	H1150D	0.999
19:618527:T:A	D1128V	0.999
19:618527:T:G	D1128A	0.999
19:618537:G:C	H1125D	0.999
19:618544:G:C	N1122K	0.999
19:618544:G:T	N1122K	0.999
19:619056:A:G	W1070R	0.999
19:619056:A:T	W1070R	0.999
19:619667:C:A	M995I	0.999
19:619667:C:G	M995I	0.999
19:619667:C:T	M995I	0.999
19:620066:G:C	N926K	0.999
19:620066:G:T	N926K	0.999
19:621285:G:T	R805S	0.999
19:621292:G:C	F802L	0.999
19:621292:G:T	F802L	0.999
19:621294:A:G	F802L	0.999
19:621295:G:C	D801E	0.999
19:621295:G:T	D801E	0.999
19:621296:T:A	D801V	0.999
19:621296:T:G	D801A	0.999
19:621297:C:G	D801H	0.999
19:617280:G:C	F1229L	0.998
19:617280:G:T	F1229L	0.998
19:617282:A:G	F1229L	0.998

dbSNP variants (sampled 300 via entrez): RS1000012164 (19:630508 C>G,T), RS1000061307 (19:626752 T>C), RS1000082900 (19:633667 C>A,G,T), RS1000308483 (19:618111 C>T), RS1000324973 (19:616816 C>G,T), RS1000337274 (19:618897 G>A,C), RS1000487548 (19:630382 C>A), RS1000678728 (19:618034 G>A,C,T), RS1000759469 (19:616722 G>A), RS1001052891 (19:634482 T>G), RS1001135229 (19:623748 G>A,C), RS1001184970 (19:626959 T>C), RS1001381060 (19:627129 G>A,C), RS1001445724 (19:626776 C>G), RS1001656290 (19:630623 C>T)

Disease associations

OMIM: gene MIM:601778 | disease phenotypes: MIM:619743, MIM:203700

GenCC curated gene-disease

Disease	Classification	Inheritance
combined oxidative phosphorylation deficiency 55	Strong	Autosomal recessive

Mondo (5): combined oxidative phosphorylation deficiency 55 (MONDO:0859228), long QT syndrome (MONDO:0002442), autosomal dominant progressive external ophthalmoplegia (MONDO:0008003), mitochondrial DNA depletion syndrome 4a (MONDO:0008758), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Autosomal dominant progressive external ophthalmoplegia (Orphanet:254892), Alpers-Huttenlocher syndrome (Orphanet:726)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000114	Proximal tubulopathy
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000577	Exotropia
HP:0000590	Progressive external ophthalmoplegia
HP:0000592	Blue sclerae
HP:0000601	Hypotelorism
HP:0000750	Delayed speech and language development
HP:0000805	Enuresis
HP:0000954	Single transverse palmar crease
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001324	Muscle weakness
HP:0001344	Absent speech
HP:0001488	Bilateral ptosis
HP:0001762	Talipes equinovarus
HP:0001873	Thrombocytopenia
HP:0001903	Anemia
HP:0001992	Organic aciduria
HP:0001994	Renal Fanconi syndrome
HP:0002019	Constipation
HP:0002119	Ventriculomegaly
HP:0002148	Hypophosphatemia

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D065886	Neurodevelopmental Disorders	F03.625
C563575	Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions, Autosomal Dominant, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3120041 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

327 measured of 370 human assays (370 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-((R)-1-((R)-2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidin-3-yl)acetamide	IC50	9 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
isopropyl N-methyl-N-(2-oxo-4-(o-tolyl)-2H-chromen-7-yl)glycinate	IC50	20 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
ethyl N-methyl-N-(2-oxo-4-(o-tolyl)-2H-chromen-7-yl)glycinate	IC50	20 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
1-(1-((R)-2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidin-3-yl)cyclopropane-1-carboxamide	IC50	20 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
2-methyl-2-(1-((R)-2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidin-3-yl)propanoic acid	IC50	20 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
3-ethyl-1-((R)-2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidine-3-carboxylic acid	IC50	20 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
(R)-4-(2-((4-(3-fluoro-2-methylphenyl)-1-oxo-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperazine-1-carboxamide	IC50	20 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
(S)-1-(N-methyl-N-(2-oxo-4-(o-tolyl)-2H-chromen-7-yl)-D-alanyl)piperidine-3-carboxylic acid	IC50	30 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
2,2-dimethyl-3-(methyl(2-oxo-4-(o-tolyl)-2H-chromen-7-yl)amino)propanoic acid	IC50	30 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
methyl N-methyl-N-(2-oxo-4-(o-tolyl)-2H-chromen-7-yl)glycinate	IC50	30 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
7-((isoxazol-3-ylmethyl)(methyl)amino)-4-(o-tolyl)-2H-chromen-2-one	IC50	30 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
1-(1-((R)-2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidin-3-yl)cyclopropane-1-carboxylic acid	IC50	30 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
2-methyl-2-(1-((R)-2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidin-3-yl)propanamide	IC50	30 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
(R)-4-(2-((4-(4-fluoro-2-methylphenyl)-1-oxo-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperazine-1-carboxamide	IC50	30 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
tert-butyl N-methyl-N-(2-oxo-4-(o-tolyl)-2H-chromen-7-yl)glycinate	IC50	40 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
N-methyl-N-(2-oxo-4-(o-tolyl)-2H-chromen-7-yl)-D-alanine	IC50	40 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
2-((S)-1-((R)-2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidin-3-yl)acetamide	IC50	40 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
1-(1-((R)-2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidin-3-yl)cyclopropane-1-carboxamide	IC50	40 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
2-methyl-2-(1-((R)-2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidin-3-yl)propanamide	IC50	40 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
3-ethyl-1-((R)-2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidine-3-carboxylic acid	IC50	40 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
1-((R)-2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)-3-propylpiperidine-3-carboxylic acid	IC50	40 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
Synthesis of (R)-4-(2-chloro-4-fluorophenyl)-7-(methyl(1-oxo-1-(piperidin-1-yl)propan-2-yl)amino)-2H-chromen-2-one, (R)-2-((4-(2-chloro-4-fluorophenyl)-2-oxo-2H-chromen-7-yl)(methyl)amino)-N,N-dimethylpropanamide	IC50	50 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
7-(benzylamino)-4-(o-tolyl)-2H-chromen-2-one	IC50	50 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
N-methyl-2-(methyl(2-oxo-4-(o-tolyl)-2H-chromen-7-yl)amino)acetamide	IC50	50 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
7-(((1H-pyrazol-5-yl)methyl)(methyl)amino)-4-(o-tolyl)-2H-chromen-2-one	IC50	50 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
2-(methyl(2-oxo-4-(o-tolyl)-2H-chromen-7-yl)amino)propanamide	IC50	50 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
5,5-difluoro-1-((R)-2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidine-3-carboxylic acid	IC50	50 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
1-(1-((R)-2-((4-(2-chloro-4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidin-3-yl)cyclopropane-1-carboxylic acid	IC50	50 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
(S)-1-(2-methyl-3-(2-oxo-4-(o-tolyl)-2H-chromen-7-yl)propanoyl)piperidine-3-carbonitrile	IC50	60 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
5,5-difluoro-1-((R)-2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidine-3-carboxylic acid	IC50	60 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
methyl 2-(1-((R)-2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidin-3-yl)acetate	IC50	60 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
(R)-4-methyl-1-(2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidine-4-carboxylic acid	IC50	60 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
2-methyl-2-(1-((R)-2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidin-3-yl)propanoic acid	IC50	60 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
2-(1-((R)-2-((4-(2-chloro-4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidin-3-yl)-2-methylpropanoic acid	IC50	60 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
(R)-4-(2-chloro-4-fluorophenyl)-7-(methyl(1-morpholino-1-oxopropan-2-yl)amino)-2H-chromen-2-one	IC50	70 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
methyl 2-(1-((R)-2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidin-3-yl)acetate	IC50	70 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
(R)-1-(1-(2-((1-oxo-4-(o-tolyl)-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidin-4-yl)urea	IC50	70 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
7-(2-methyl-3-oxo-3-(piperidin-1-yl)propyl)-4-(o-tolyl)-2H-chromen-2-one	IC50	80 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
7-(methyl(oxazol-2-ylmethyl)amino)-4-(o-tolyl)-2H-chromen-2-one	IC50	80 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
1-(1-((R)-2-((4-(2-chloro-4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperidin-3-yl)cyclopropane-1-carboxylic acid	IC50	80 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
4-(2-(hydroxymethyl)-6-methylphenyl)-7-(2,2,2-trifluoroethoxy)isoquinolin-1(2H)-one	IC50	80 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
(R)-4-(2-((4-(2-(methyl-d3)phenyl)-1-oxo-1,2-dihydroisoquinolin-7-yl)oxy)propanoyl)piperazine-1-carboxamide	IC50	80 nM	US-20250340516: Isoquinolinones as Modulators of POLRMT
ethyl (S)-1-(2-methyl-3-(2-oxo-4-(o-tolyl)-2H-chromen-7-yl)propanoyl)piperidine-3-carboxylate	IC50	90 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
7-(methyl(pyridin-2-ylmethyl)amino)-4-(o-tolyl)-2H-chromen-2-one	IC50	90 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
1-((methyl(2-oxo-4-(o-tolyl)-2H-chromen-7-yl)amino)methyl)cyclopropane-1-carboxylic acid	IC50	90 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
(R)-4-(2-chloro-4-fluorophenyl)-7-((1-oxo-1-(piperidin-1-yl)propan-2-yl)amino)-2H-chromen-2-one	IC50	100 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
(S)-1-((2-oxo-4-(o-tolyl)-2H-chromen-7-yl)-D-alanyl)piperidine-3-carboxylic acid	IC50	100 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT
(S)-1-(2-methyl-3-(2-oxo-4-(o-tolyl)-2H-chromen-7-yl)propanoyl)piperidine-3-carboxamide	IC50	100 nM	US-20250326732: CHROMEN-2-ONE MODULATORS OF POLRMT

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.00	IC50	1000	nM	CHEMBL5575683

PubChem BioAssay actives

1 with measured affinity, of 99 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
[[(2R,3S,4R,5S)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2-azido-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate	2110144: Inhibition of recombinant human POLRMT by Phosphor imaging analysis	ic50	1.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	2
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
quercitrin	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
cupric chloride	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
theonyltrifluoroacetone	decreases response to substance	1
ICG 001	decreases expression	1
abrine	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
BMS-986094	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Thimerosal	decreases expression	1
Thiram	increases expression	1
Valproic Acid	increases methylation	1
Genistein	increases expression	1

ChEMBL screening assays

20 unique, capped per target: 12 binding, 7 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3124277	Binding	Inhibition of mitochondrial RNA polymerase (unknown origin) assessed as inhibition of single nucleotide incorporation	Discovery of the first C-nucleoside HCV polymerase inhibitor (GS-6620) with demonstrated antiviral response in HCV infected patients. — J Med Chem
CHEMBL4008258	ADMET	Inhibition of human mitochondrial RNA polymerase after 30 mins in presence of [33P]GTP	Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses. — J Med Chem
CHEMBL6194224	Functional	Inhibition of human POLRMT using Mitochondrial RNA polymerase-DdRp activity	Data for DCP probe JNJ-8003

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry