RNMT

Summary

RNMT (RNA guanine-7 methyltransferase, HGNC:10075) is a protein-coding gene on chromosome 18p11.21, encoding mRNA cap guanine-N(7) methyltransferase (O43148). Catalytic subunit of the mRNA-capping methyltransferase RNMT:RAMAC complex that methylates the N7 position of the added guanosine to the 5’-cap structure of mRNAs. It is a common-essential gene (DepMap: required in 96.3% of cancer cell lines).

Enables RNA binding activity and mRNA 5’-cap (guanine-N7-)-methyltransferase activity. Involved in 7-methylguanosine mRNA capping. Located in fibrillar center and nucleoplasm. Part of mRNA cap methyltransferase RNMT:RAMAC complex; mRNA capping enzyme complex; and receptor complex.

Source: NCBI Gene 8731 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 71 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 96.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_003799

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10075
Approved symbol	RNMT
Name	RNA guanine-7 methyltransferase
Location	18p11.21
Locus type	gene with protein product
Status	Approved
Aliases	RG7MT1, N7-MTase
Ensembl gene	ENSG00000101654
Ensembl biotype	protein_coding
OMIM	603514
Entrez	8731

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000262173, ENST00000383314, ENST00000543302, ENST00000588417, ENST00000588457, ENST00000589866, ENST00000591746, ENST00000591922, ENST00000592764, ENST00000593007, ENST00000907443, ENST00000907444, ENST00000907445, ENST00000916360, ENST00000916361

RefSeq mRNA: 5 — MANE Select: NM_003799 NM_001308263, NM_001378132, NM_001378134, NM_001378135, NM_003799

CCDS: CCDS11867, CCDS77156, CCDS92440

Canonical transcript exons

ENST00000383314 — 12 exons

Exon	Start	End
ENSE00000666436	13741510	13741691
ENSE00000666437	13742488	13742652
ENSE00000666438	13746220	13746337
ENSE00000883621	13752326	13752427
ENSE00000883622	13754114	13754147
ENSE00001120461	13731476	13731934
ENSE00001313973	13726673	13726729
ENSE00001496033	13759942	13764556
ENSE00001540359	13730627	13730755
ENSE00003478439	13740167	13740279
ENSE00003568967	13734464	13734599
ENSE00003689017	13737010	13737135

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 96.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.9302 / max 803.8024, expressed in 1768 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169581	19.9302	1768

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.39	gold quality
amniotic fluid	UBERON:0000173	94.26	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.07	gold quality
middle temporal gyrus	UBERON:0002771	92.47	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.28	gold quality
cortical plate	UBERON:0005343	92.20	gold quality
substantia nigra pars compacta	UBERON:0001965	92.00	gold quality
tendon	UBERON:0000043	91.36	gold quality
calcaneal tendon	UBERON:0003701	91.34	gold quality
adrenal tissue	UBERON:0018303	90.76	gold quality
cartilage tissue	UBERON:0002418	90.67	gold quality
medial globus pallidus	UBERON:0002477	90.59	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.51	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.24	gold quality
substantia nigra pars reticulata	UBERON:0001966	90.16	gold quality
ventricular zone	UBERON:0003053	89.98	gold quality
primary visual cortex	UBERON:0002436	89.89	gold quality
cingulate cortex	UBERON:0003027	89.89	gold quality
anterior cingulate cortex	UBERON:0009835	89.78	gold quality
prefrontal cortex	UBERON:0000451	89.53	gold quality
hypothalamus	UBERON:0001898	89.48	gold quality
globus pallidus	UBERON:0001875	89.42	gold quality
ganglionic eminence	UBERON:0004023	89.23	gold quality
lateral globus pallidus	UBERON:0002476	89.02	gold quality
occipital lobe	UBERON:0002021	88.70	gold quality
cerebral cortex	UBERON:0000956	88.64	gold quality
neocortex	UBERON:0001950	88.62	gold quality
tendon of biceps brachii	UBERON:0008188	88.54	gold quality
amygdala	UBERON:0001876	88.48	gold quality
putamen	UBERON:0001874	88.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

194 targeting RNMT, 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-4262	100.00	73.26	3931
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
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-98-3P	100.00	74.08	3907
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-12136	99.98	72.81	5713

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 13)

• Nuclear localization of cap methyltransferase is mediated by alternative nuclear localization signal motifs (PMID:15767670)
• The RNMT N-terminal domain is required for transcript expression, translation and cell proliferation. (PMID:23863084)
• Data suggest the C-terminal nuclear localization domain (QYP) is critical for RAM (RNMT-activating mini protein) to enter the cell nucleus where RAM activates RNMT resulting in mRNA cap methylation. TNPO1/TNPO2 mediate RAM nuclear entry. (PMID:24200467)
• High RNMT expression is associated with liver cancer. (PMID:24763612)
• CDK1-Cyclin B1 activates RNMT, coordinating mRNA cap methylation with G1 phase transcription. (PMID:26942677)
• MYC promotes mRNA cap methylation and protein production of Wnt/beta-catenin signaling transcripts through recruitment of cyclin-dependent kinase 7 (CDK7) and consequently RNMT to gene promoters. (PMID:27899423)
• RNMT-RAM complex coordinates mRNA processing with ribosome production. (PMID:27934633)
• Results identify a cytoplasmic pool of RNMT which is a component of the cytoplasmic capping complex, and demonstrate its function as the methyltransferase that catalyzes the final maturation step in cap homeostasis. (PMID:28981715)
• These findings suggest that multiple interactions among RNMT-RAM, RNA Pol II factors, and RNA along the transcription unit stimulate transcription. (PMID:29719263)
• Data show that most of the cell lines which exhibited enhanced dependency on RNA guanine-7 methyltransferase (RNMT) harboured oncogenic mutations in phosphatidylinositol 3-kinase catalytic 110-KD alpha (PI3Kalpha). (PMID:30991934)
• Mechanism of allosteric activation of human RNMT by RAM has been reported. (PMID:31329932)
• Identification and Characterization of the Interaction Between the Methyl-7-Guanosine Cap Maturation Enzyme RNMT and the Cap-Binding Protein eIF4E. (PMID:35026230)
• Kinetic characterization of human mRNA guanine-N7 methyltransferase. (PMID:38402266)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnmt	ENSDARG00000070553
mus_musculus	Rnmt	ENSMUSG00000009535
rattus_norvegicus	Rnmt	ENSRNOG00000016698
drosophila_melanogaster	Rnmt	FBGN0286027
caenorhabditis_elegans	tag-72	WBGENE00006447

Protein

Protein identifiers

mRNA cap guanine-N(7) methyltransferase — O43148 (reviewed: O43148)

Alternative names: RG7MT1, mRNA (guanine-N(7))-methyltransferase, mRNA cap methyltransferase

All UniProt accessions (4): O43148, K7EP06, K7EPP5, K7ERH6

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic subunit of the mRNA-capping methyltransferase RNMT:RAMAC complex that methylates the N7 position of the added guanosine to the 5’-cap structure of mRNAs. Binds RNA containing 5’-terminal GpppC.

Subunit / interactions. Interacts with importin alpha, leading to stimulate both RNA-binding and methyltransferase activity. Interaction with importin alpha and beta is required for its nuclear localization, importin beta dissociating in response to RanGTP, allowing RNMT-importin alpha to bind RNA substrates. Interacts with elongating form of polymerase II and RNGTT. Interacts with RAMAC, this interaction significantly enhances RNA-binding and cap methyltransferase activity (PubMed:22099306, Ref.14).

Subcellular location. Nucleus.

Tissue specificity. Widely expressed.

Activity regulation. Methyltransferase activity is activated by RAMAC.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. mRNA cap 0 methyltransferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43148-1	1, hCMT1a	yes
O43148-2	2, hCMT1b

RefSeq proteins (5): NP_001295192, NP_001365061, NP_001365063, NP_001365064, NP_003790* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004971	mRNA_G-N7_MeTrfase_dom	Domain
IPR016899	mRNA_G-N7_MeTrfase_euk	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR039753	RG7MT1	Family

Pfam: PF03291

Enzyme classification (BRENDA):

• EC 2.1.1.56 — mRNA (guanine-N7)-methyltransferase (BRENDA: 24 organisms, 64 substrates, 252 inhibitors, 33 Km, 24 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
G(5’)PPPR-RNA	0.023–1.8	14
S-ADENOSYL-L-METHIONINE	0.0002–0.18	9
GTP	0.0075–1	4
G(5’)PPPG	0.085–0.101	2
GPPPA	0.1–0.24	2
5’-(5’-TRIPHOSPHOGUANOSINE)-[MRNA]	0.0002	1
GDP	2.4	1

Catalyzed reactions (Rhea), 1 shown:

• a 5’-end (5’-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-methionine = a 5’-end (N(7)-methyl 5’-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-homocysteine (RHEA:67008)

UniProt features (78 total): mutagenesis site 16, strand 16, helix 12, binding site 7, site 6, turn 6, compositionally biased region 5, modified residue 4, chain 1, domain 1, region of interest 1, splice variant 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
8Q69	X-RAY DIFFRACTION	1.96
5E9W	X-RAY DIFFRACTION	2.28
3BGV	X-RAY DIFFRACTION	2.3
5E8J	X-RAY DIFFRACTION	2.35
8Q8G	X-RAY DIFFRACTION	2.4
3EPP	X-RAY DIFFRACTION	2.41
8Q9W	X-RAY DIFFRACTION	2.5
5E9J	X-RAY DIFFRACTION	3.47

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43148-F1	78.27	0.61

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 (6): 208 (mrna cap binding); 214 (mrna cap binding); 239 (mrna cap binding); 288 (mrna cap binding); 370 (mrna cap binding); 467 (mrna cap binding)

Ligand- & substrate-binding residues (7): 180; 205; 227; 261; 284; 289; 176–177

Post-translational modifications (4): 24, 28, 29, 118

Mutagenesis-validated functional residues (16):

Position	Phenotype
80–83	does not abolish nuclear localization. abolishes nuclear localization; when associated with 103-aaaaa-107 and i-127.
103–107	does not abolish nuclear localization. abolishes nuclear localization; when associated with 80-aaaa-83 and i-127.
127	does not abolish nuclear localization. abolishes nuclear localization; when associated with 80-aaaa-83 and 103-aaaaa-107
178	loss of methyltransferase activity in presence or absence of ramac; when associated with c-417. complete restored ramac-
203	loss of activity.
239	loss of activity.
289	loss of activity.
291	strongly impairs enzyme activity.
354	loss of activity.
393	loss of methyltransferase activity in presence or absence of ramac; when associated with c-178; c-398 and c-417. partial
398	loss of methyltransferase activity in presence or absence of ramac; when associated with c-178; c-393 and c-417. partial
409	decreased s-adenosyl-l-methionine binding and methyltransferase activity in absence of ramac; when associated with e-413
413	decreased s-adenosyl-l-methionine binding and methyltransferase activity in absence of ramac; when associated with e-409
417	loss of methyltransferase activity in presence or absence of ramac; when associated with c-178. complete restored ramac-
450	increased s-adenosyl-l-methionine binding and methyltransferase activity in absence of ramac; when associated with e-452
452	increased s-adenosyl-l-methionine binding and methyltransferase activity in absence of ramac; when associated with e-450

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-167160	RNA Pol II CTD phosphorylation and interaction with CE during HIV infection
R-HSA-72086	mRNA Capping
R-HSA-77075	RNA Pol II CTD phosphorylation and interaction with CE
R-HSA-162587	HIV Life Cycle
R-HSA-162599	Late Phase of HIV Life Cycle
R-HSA-162906	HIV Infection
R-HSA-1643685	Disease
R-HSA-167172	Transcription of the HIV genome
R-HSA-5663205	Infectious disease
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953854	Metabolism of RNA
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 182 (showing top): GOBP_RESPONSE_TO_PEPTIDE, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_RNA_METHYLATION, REACTOME_HIV_INFECTION, GOBP_RNA_MODIFICATION, GOBP_RNA_CAPPING, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, MODULE_98, BASAKI_YBX1_TARGETS_UP, ZHANG_BREAST_CANCER_PROGENITORS_UP, GOBP_METHYLATION, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, REACTOME_METABOLISM_OF_RNA, GOCC_TRANSFERASE_COMPLEX

GO Biological Process (5): 7-methylguanosine mRNA capping (GO:0006370), cellular response to leukemia inhibitory factor (GO:1990830), mRNA processing (GO:0006397), methylation (GO:0032259), RNA 5’-cap (guanine-N7)-methylation (GO:0106005)

GO Molecular Function (5): RNA binding (GO:0003723), mRNA 5’-cap (guanine-N7-)-methyltransferase activity (GO:0004482), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (6): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), mRNA capping enzyme complex (GO:0031533), signaling receptor complex (GO:0043235), mRNA cap methyltransferase RNMT:RAMAC complex (GO:0160130)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Transcription of the HIV genome	1
Metabolism of RNA	1
RNA Polymerase II Transcription	1
HIV Infection	1
HIV Life Cycle	1
Viral Infection Pathways	1
Late Phase of HIV Life Cycle	1
Disease	1
Gene expression (Transcription)	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
7-methylguanosine RNA capping	2
cellular anatomical structure	2
mRNA processing	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
RNA processing	1
mRNA metabolic process	1
metabolic process	1
RNA (guanine-N7)-methylation	1
nucleic acid binding	1
7-methylguanosine mRNA capping	1
N-methyltransferase activity	1
mRNA methyltransferase activity	1
RNA 5’-cap (guanine-N7)-methylation	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
nucleolus	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
protein-containing complex	1
methyltransferase complex	1

Protein interactions and networks

STRING

1398 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNMT	RNGTT	O60942	981
RNMT	PMP22	Q01453	971
RNMT	RAMAC	Q9BTL3	950
RNMT	GJB1	P08034	946
RNMT	MPZL1	O95297	901
RNMT	GDAP1	Q8TB36	880
RNMT	LITAF	Q99732	870
RNMT	EGR2	P11161	838
RNMT	CLEC14A	Q86T13	813
RNMT	MFN2	O95140	787
RNMT	SNX25	Q9H3E2	766
RNMT	PMP2	P02689	748
RNMT	NEFL	P07196	748
RNMT	CMTR2	Q8IYT2	725
RNMT	SH3TC2	Q8TF17	718

IntAct

82 interactions, top by confidence:

A	B	Type	Score
RNMT	RAMAC	psi-mi:“MI:0915”(physical association)	0.810
RAMAC	RNMT	psi-mi:“MI:0914”(association)	0.810
RNMT	KPNA6	psi-mi:“MI:0915”(physical association)	0.800
KPNA6	RNMT	psi-mi:“MI:0914”(association)	0.800
RNMT	KPNA2	psi-mi:“MI:0915”(physical association)	0.670
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
RNMT	EIF4E	psi-mi:“MI:0915”(physical association)	0.630
EIF4E	RNMT	psi-mi:“MI:0403”(colocalization)	0.630
EIF4E	RNMT	psi-mi:“MI:0407”(direct interaction)	0.630
RNMT	GMCL1	psi-mi:“MI:0915”(physical association)	0.560
RNMT	PLEKHA3	psi-mi:“MI:0915”(physical association)	0.560
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
TRPC4AP	SMCHD1	psi-mi:“MI:0914”(association)	0.530
RNMT	KPNA5	psi-mi:“MI:0914”(association)	0.530
	RNMT	psi-mi:“MI:0407”(direct interaction)	0.440
KPNA1	MTA3	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
ORF10	NUP42	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350

BioGRID (119): KIF23 (Co-fractionation), NFATC2IP (Co-fractionation), RNMT (Affinity Capture-MS), RNMT (Affinity Capture-MS), RNMT (Affinity Capture-MS), FAM103A1 (Affinity Capture-MS), KPNA6 (Affinity Capture-MS), HSP90AB4P (Affinity Capture-MS), RNMT (Affinity Capture-MS), KPNA1 (Affinity Capture-MS), KPNA5 (Affinity Capture-MS), RNMT (Affinity Capture-MS), RNMT (Affinity Capture-MS), RNMT (Affinity Capture-MS), RNMT (Affinity Capture-MS)

ESM2 similar proteins: A1A4L5, A2VE39, A4QP75, A9T6G5, B8A5G9, C5XX79, D2HRF1, F6H2F8, F6HH45, F6VSS6, F7GSQ4, O43148, O82387, P97770, Q08BM0, Q14527, Q28E61, Q2T9V5, Q32P41, Q3MHN8, Q3MIT2, Q4KLT3, Q4R3W5, Q4R7K1, Q5R981, Q5T8I9, Q5U2U7, Q5U2Z5, Q5W9E7, Q5ZLV4, Q6DDT5, Q6NS23, Q6P1Q9, Q6PCN7, Q7T287, Q8BYH3, Q8CE96, Q8N1G2, Q8NE18, Q93YU6

Diamond homologs: A1CT57, A1DMG9, A2QVS9, A3GEV2, A4R8D7, A5DDJ4, A5E032, O43148, O74880, P0CO64, P0CO65, P32783, Q1MTD3, Q2UM19, Q4R7K1, Q4WN42, Q5ADX5, Q5U2U7, Q6BMH4, Q6CC11, Q6CKI0, Q6FML4, Q6K833, Q754U7, Q9D0L8, Q9XVS1, Q6Z9U7, Q9I8S2, Q28FT4, Q61E36, Q9LHQ7, Q9VJQ4, Q8SR66, Q5HZ60, Q5UQX1, P44074

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CDK1	“up-regulates activity”	RNMT	phosphorylation
KPNA2	“down-regulates activity”	RNMT	binding
RNMT	up-regulates	mRNA_capping
RNMT	“up-regulates quantity”	“messenger RNA”	“chemical modification”
RAMAC	“up-regulates activity”	RNMT	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 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
NS1 Mediated Effects on Host Pathways	7	55.5×	1e-08
ISG15 antiviral mechanism	8	33.4×	1e-08
Maturation of DENV proteins	5	29.4×	6e-05
Antimicrobial mechanism of IFN-stimulated genes	5	27.4×	7e-05
Influenza Infection	5	24.4×	1e-04
Interferon Signaling	5	16.7×	5e-04
Neddylation	8	10.5×	6e-05
Cytokine Signaling in Immune system	6	6.8×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
NLS-bearing protein import into nucleus	6	102.4×	7e-09
intrinsic apoptotic signaling pathway	5	38.1×	2e-05
protein import into nucleus	7	21.4×	6e-06
G1/S transition of mitotic cell cycle	5	21.3×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2137 predictions. Top by Δscore:

Variant	Effect	Δscore
18:13730626:GGAT:G	acceptor_gain	1.0000
18:13731474:A:AG	acceptor_gain	1.0000
18:13731475:G:GG	acceptor_gain	1.0000
18:13731475:GT:G	acceptor_gain	1.0000
18:13731475:GTGTT:G	acceptor_gain	1.0000
18:13731914:G:GT	donor_gain	1.0000
18:13731931:GAAA:G	donor_gain	1.0000
18:13731932:A:T	donor_gain	1.0000
18:13731934:AG:A	donor_loss	1.0000
18:13731935:G:GG	donor_gain	1.0000
18:13731935:GT:G	donor_loss	1.0000
18:13731936:T:G	donor_loss	1.0000
18:13734456:A:AG	acceptor_gain	1.0000
18:13734457:T:G	acceptor_gain	1.0000
18:13734461:CA:C	acceptor_loss	1.0000
18:13734462:A:AG	acceptor_gain	1.0000
18:13734463:G:GT	acceptor_gain	1.0000
18:13734463:GA:G	acceptor_gain	1.0000
18:13734463:GAAT:G	acceptor_gain	1.0000
18:13734517:GGAA:G	donor_gain	1.0000
18:13734518:GAAG:G	donor_gain	1.0000
18:13734519:A:T	donor_gain	1.0000
18:13734532:GAAGC:G	donor_gain	1.0000
18:13734535:GC:G	donor_gain	1.0000
18:13734541:TCA:T	donor_gain	1.0000
18:13734546:GTC:G	donor_gain	1.0000
18:13734560:C:CG	donor_gain	1.0000
18:13734560:C:G	donor_gain	1.0000
18:13734617:GCTAC:G	donor_gain	1.0000
18:13734618:C:G	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000050802 (18:13756044 G>A,T), RS1000141547 (18:13754456 G>C), RS1000204455 (18:13762234 T>C), RS1000250024 (18:13742246 G>T), RS1000280335 (18:13726478 C>G,T), RS1000296261 (18:13761476 A>C,G), RS1000319489 (18:13762601 T>C,G), RS1000395901 (18:13726222 G>C), RS1000415726 (18:13726258 A>G), RS1000597889 (18:13759580 T>G), RS1000630211 (18:13759820 G>A), RS1000684458 (18:13738287 G>C), RS1000744130 (18:13745492 G>A,C), RS1000753315 (18:13725198 T>C), RS1000848569 (18:13751444 G>A)

Disease associations

OMIM: gene MIM:603514 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006423_14	Fracture	1.000000e-18

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295662 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,703 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1214186	SINEFUNGIN	2	2,165
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 7 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.26	IC50	0.55	nM	SINEFUNGIN
5.28	IC50	5300	nM	SINEFUNGIN
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

5 with measured affinity, of 70 total; 2 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
(2S,5S)-2,5-diamino-6-[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]hexanoic acid	1718108: Inhibition of human guanine-N7 methyltransferase expressed in Saccharomyces cerevisiae YBS40 (MATa leu2 ade2 trp1 his3 ura3 can1 abd1::hisGp360-ABD1)	ic50	0.0006	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179021: Inhibition of RNMT (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects cotreatment, affects expression, increases abundance	3
sodium arsenite	increases abundance, increases expression, decreases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	2
Lead	affects splicing, increases expression	2
Nickel	increases expression	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
ginger extract	increases abundance, affects cotreatment, affects expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
decabromobiphenyl ether	decreases expression	1
1,6-hexamethylene diisocyanate	increases methylation	1
tetrabromobisphenol A	decreases expression	1
nickel chloride	increases expression	1
cupric oxide	increases expression	1
nivalenol	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
tamibarotene	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1

ChEMBL screening assays

18 unique, capped per target: 13 binding, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4275457	ADMET	Inhibition of recombinant human N-terminal His-tagged RNMT (1 to 476 residues) expressed in Escherichia coli BL21 using 5’-GpppAGAACCUG-biotin-TEG-3 as substrate after 10 mins by [3H]methyl incorporation assay	Design, synthesis and in vitro anti-Zika virus evaluation of novel Sinefungin derivatives. — Eur J Med Chem
CHEMBL5362045	Binding	Inhibition of human RNMT assessed as inhibition constant	Recent advances in the development of methyltransferase (MTase) inhibitors against (re)emerging arboviruses diseases dengue and Zika. — Eur J Med Chem

Clinical trials (associated diseases)

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