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 signaling receptor complex.

Source: NCBI Gene 8731 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 71 total
• GTEx eGene: eQTL in 27 tissues, sQTL in 0 (q < 0.05)
• ChEMBL bioactivity: 2 clinical-phase molecules tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 96.3% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.92 (unconstrained)
• MANE Select transcript: NM_003799
• Notable: 71 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 22 — 18 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000383314

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 4, TSL 3: 1, TSL 4: 2

ENST00000383314, ENST00000262173, ENST00000543302, ENST00000588417, ENST00000588457, ENST00000589866, ENST00000591746, ENST00000591922, ENST00000592764, ENST00000593007, ENST00000907443, ENST00000907444, ENST00000907445, ENST00000916360, ENST00000916361, ENST00000998364, ENST00000998365, ENST00001110861, ENST00001110862, ENST00001110863, ENST00001123369, ENST00001132069

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.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, amniotic fluid, lateral nuclear group of thalamus, middle temporal gyrus, Brodmann (1909) area 23.

Genetic regulation across tissues (GTEx eQTL / sQTL)

RNMT is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 27 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 27 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	6.4e-38	+0.39	18:13705731:C:T
Testis	eqtl	9.2e-11	-0.22	18:13691344:C:T
Thyroid	eqtl	9.2e-10	+0.94	18:13709586:A:C
Esophagus Mucosa	eqtl	1.0e-09	+0.31	18:13708329:C:T
Brain Cerebellum	eqtl	7.8e-09	-0.42	18:13691344:C:T
Spleen	eqtl	1.5e-07	+0.39	18:13683294:C:A
Muscle Skeletal	eqtl	1.9e-06	+0.13	18:13673667:GATT:G
Nerve Tibial	eqtl	1.1e-05	+0.67	18:13709586:A:C
Brain Cerebellar Hemisphere	eqtl	1.7e-05	-0.29	18:13691344:C:T
Skin Sun Exposed Lower leg	eqtl	1.9e-05	+0.20	18:13734898:A:G
Brain Frontal Cortex BA9	eqtl	2.2e-05	+0.18	18:13772524:G:A
Pancreas	eqtl	5.6e-05	+0.91	18:13709586:A:C
Esophagus Muscularis	eqtl	5.9e-05	+0.17	18:13683294:C:A
Adipose Subcutaneous	eqtl	1.2e-04	+0.22	18:13808718:A:G
Skin Not Sun Exposed Suprapubic	eqtl	1.3e-04	+0.49	18:13709586:A:C
Brain Nucleus accumbens basal ganglia	eqtl	1.7e-04	+0.20	18:13705731:C:T
Cells EBV-transformed lymphocytes	eqtl	4.9e-04	-0.18	18:13726082:G:A
Artery Aorta	eqtl	1.0e-03	+0.67	18:13709586:A:C
Breast Mammary Tissue	eqtl	1.2e-03	+0.63	18:13709586:A:C
Adipose Visceral Omentum	eqtl	4.2e-03	+0.61	18:13709586:A:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
169581	19.9302	1768

Top tissues by expression

showing 100 of 298 tissues 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
telencephalon	UBERON:0001893	88.35	gold quality
lower esophagus mucosa	UBERON:0035834	88.23	gold quality
forebrain	UBERON:0001890	88.22	gold quality
caudate nucleus	UBERON:0001873	88.20	gold quality
frontal cortex	UBERON:0001870	88.11	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	88.02	gold quality
nucleus accumbens	UBERON:0001882	87.95	gold quality
tibia	UBERON:0000979	87.89	gold quality
brain	UBERON:0000955	87.85	gold quality
central nervous system	UBERON:0001017	87.76	gold quality
right frontal lobe	UBERON:0002810	87.74	gold quality
substantia nigra	UBERON:0002038	87.69	gold quality
inferior olivary complex	UBERON:0002127	87.66	gold quality
parietal pleura	UBERON:0002400	87.54	gold quality
pons	UBERON:0000988	87.51	gold quality
tonsil	UBERON:0002372	87.49	gold quality
midbrain	UBERON:0001891	87.46	gold quality
Ammon’s horn	UBERON:0001954	87.42	gold quality
temporal lobe	UBERON:0001871	87.39	gold quality
superior vestibular nucleus	UBERON:0007227	87.36	gold quality
Brodmann (1909) area 10	UBERON:0013541	87.33	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.14	gold quality
hair follicle	UBERON:0002073	86.90	silver quality
epithelium of nasopharynx	UBERON:0001951	86.85	gold quality
right atrium auricular region	UBERON:0006631	86.77	gold quality
pleura	UBERON:0000977	86.72	gold quality
germinal epithelium of ovary	UBERON:0001304	86.66	gold quality
superior frontal gyrus	UBERON:0002661	86.66	gold quality
gastrocnemius	UBERON:0001388	86.56	gold quality
cardiac atrium	UBERON:0002081	86.49	gold quality
ovary	UBERON:0000992	86.47	gold quality
stromal cell of endometrium	CL:0002255	86.44	gold quality
islet of Langerhans	UBERON:0000006	86.36	gold quality
adenohypophysis	UBERON:0002196	86.24	gold quality
muscle of leg	UBERON:0001383	86.23	gold quality
cerebellar cortex	UBERON:0002129	86.13	gold quality
cerebellar hemisphere	UBERON:0002245	86.12	gold quality
embryo	UBERON:0000922	86.05	gold quality
cerebellar vermis	UBERON:0004720	86.03	gold quality
Brodmann (1909) area 46	UBERON:0006483	86.02	gold quality
pituitary gland	UBERON:0000007	85.99	gold quality
colonic epithelium	UBERON:0000397	85.82	gold quality
cerebellum	UBERON:0002037	85.77	gold quality
medulla oblongata	UBERON:0001896	85.75	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.72	gold quality
corpus callosum	UBERON:0002336	85.70	gold quality
left ovary	UBERON:0002119	85.68	gold quality
heart left ventricle	UBERON:0002084	85.63	gold quality
upper leg skin	UBERON:0004262	85.63	gold quality
heart	UBERON:0000948	85.56	gold quality
CA1 field of hippocampus	UBERON:0003881	85.54	gold quality
endometrium	UBERON:0001295	85.51	gold quality
cardiac ventricle	UBERON:0002082	85.48	gold quality
visceral pleura	UBERON:0002401	85.47	gold quality
entorhinal cortex	UBERON:0002728	85.46	gold quality
gingival epithelium	UBERON:0001949	85.44	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.40	gold quality
bone marrow cell	CL:0002092	85.39	gold quality
pigmented layer of retina	UBERON:0001782	85.38	gold quality
skin of abdomen	UBERON:0001416	85.30	gold quality
eye	UBERON:0000970	85.21	gold quality
palpebral conjunctiva	UBERON:0001812	85.18	gold quality
type B pancreatic cell	CL:0000169	85.16	gold quality
spinal cord	UBERON:0002240	85.10	gold quality
right ovary	UBERON:0002118	85.06	gold quality
pancreas	UBERON:0001264	85.02	gold quality
skin of hip	UBERON:0001554	84.98	gold quality
endothelial cell	CL:0000115	84.93	gold quality
apex of heart	UBERON:0002098	84.88	gold quality
thyroid gland	UBERON:0002046	84.87	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	41.2
Bone marrow	tissue	40.8	medium
Cerebral cortex	tissue	37.4	high
Somatosensory cortex	tissue	37.4
Pons	tissue	36.9
Thalamus	tissue	36.0
Hippocampal formation	tissue	34.6
Occipital cortex	tissue	34.5
Frontal cortex	tissue	34.3
Midbrain	tissue	34.0
Cerebellum	tissue	33.6	not detected
Motor cortex	tissue	32.9
Putamen	tissue	32.6
Superior colliculi	tissue	32.1
Locus coeruleus	tissue	31.8
Caudate putamen	tissue	31.8
Prefrontal cortex	tissue	31.7
Entorhinal cortex	tissue	31.7
Retrosplenial and cingulate cortex	tissue	31.6
Postcentral gyrus	tissue	31.3
Septum	tissue	30.0
Temporal cortex	tissue	29.6
Retrosplenial cortex	tissue	29.2
Medulla oblongata	tissue	28.3
Ventral forebrain	tissue	28.1
Hypothalamus	tissue	28.0
Substantia nigra	tissue	27.8
Nucleus accumbens	tissue	26.9
Periaqueductal gray	tissue	26.3
Corpus callosum	tissue	26.1
Basal ganglia	tissue	25.9	medium
Olfactory bulb	tissue	25.8
Retina	tissue	25.4
Spinal cord	tissue	25.1
Insular cortex	tissue	24.5
Hippocampus	tissue	24.2	medium
Amygdala	tissue	24.1
Heart muscle	tissue	19.0	medium
Thyroid gland	tissue	16.4	high
Testis	tissue	15.6	high
Tongue	tissue	14.5
Breast	tissue	14.4	medium
Placenta	tissue	14.3	medium
Tonsil	tissue	14.2	medium
Ovary	tissue	13.9	not detected
Thymus	tissue	13.9
Lymph node	tissue	13.5	medium
Pituitary gland	tissue	13.2
Endometrium 1	tissue	13.1	medium
Parathyroid gland	tissue	12.3	high
Appendix	tissue	11.9	medium
Skin 1	tissue	11.6	medium
Smooth muscle	tissue	11.6	medium
Salivary gland	tissue	11.4	medium
Spleen	tissue	11.4	medium
Epididymis	tissue	10.9	medium
Prostate	tissue	10.9	high
Skeletal muscle	tissue	10.8	medium
Kidney	tissue	10.8	medium
Vagina	tissue	10.4	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Median raphe nucleus (37.1), Pontine raphe nucleus (35.8), Lateral hypothalamic area (34.9), Dorsal hippocampus (34.6), Nuclei of the trapezoid body (33.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting RNMT by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 194 miRNAs:

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

gnomAD constraint: pLI 0.000768, LOEUF 0.92, missense Z 0.826 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000383314 — one region, missense o/e 0.94. DepMap (CRISPR cell-line fitness): dependent in 96.3% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): COLO-800 (-1.942), HEL (-1.896), MJ (-1.833), PA-TU-8988T (-1.763), TC-71 (-1.742), EFE-184 (-1.735), 8-MG-BA (-1.663), T84 (-1.658), NCI-H841 (-1.652), SNU-213 (-1.651), OCI-LY-19 (-1.636), KP-N-SI9s (-1.624), TE-5 (-1.601), T24 (-1.6), DEL (-1.587).

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1915147) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
limb grasping	1
preweaning lethality, complete penetrance	1
embryonic lethality prior to organogenesis	1
embryonic lethality prior to tooth bud stage	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Cryptococcus deneoformans JEC21	P0CO64	99.0%	Diamond
Cryptococcus deneoformans B-3501A	P0CO65	99.0%	Diamond
Macaca fascicularis	Q4R7K1	95.8%	Diamond
Xenopus tropicalis	Q28FT4	89.9%	Diamond
Xenopus laevis	Q9I8S2	89.9%	Diamond
Aspergillus fischeri NRRL 181	A1DMG9	88.9%	Diamond
Aspergillus fumigatus Af293	Q4WN42	88.9%	Diamond
Aspergillus clavatus NRRL 1	A1CT57	85.5%	Diamond
Aspergillus oryzae RIB40	Q2UM19	81.3%	Diamond
Oryza sativa Japonica Group	Q6Z9U7	77.2%	Diamond
Arabidopsis thaliana	Q9LHQ7	77.2%	Diamond
Caenorhabditis briggsae	Q61E36	76.9%	Diamond
Meyerozyma guilliermondii ATCC 6260	A5DDJ4	74.7%	Diamond
Debaryomyces hansenii CBS767	Q6BMH4	74.7%	Diamond
Aspergillus niger CBS 513.88	A2QVS9	72.9%	Diamond
Saccharomyces cerevisiae S288C	P32783	72.5%	Diamond
Eremothecium gossypii ATCC 10895	Q754U7	72.5%	Diamond
Candida albicans SC5314	Q5ADX5	69.8%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CKI0	69.2%	Diamond
Lodderomyces elongisporus NRRL YB-4239	A5E032	68.6%	Diamond
Nakaseomyces glabratus CBS 138	Q6FML4	68.1%	Diamond
Scheffersomyces stipitis CBS 6054	A3GEV2	65.8%	Diamond
Pyricularia oryzae 70-15	A4R8D7	58.5%	Diamond
Schizosaccharomyces pombe 972h-	O74880	50.6%	Diamond
Yarrowia lipolytica CLIB122	Q6CC11	50.6%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SR66	36.9%	Diamond
Trypanosoma brucei brucei TREU927	Q57V03	32.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR5190	ncRNA	100847080
LDLRAD4-AS3	ncRNA	124904256
MIMS1	protein-coding	125228
LDLRAD4	protein-coding	753
MIR4526	ncRNA	100616130
MC5R	protein-coding	4161
MC2R	protein-coding	4158
LDLRAD4-AS1	ncRNA	100288122
C18orf15	ncRNA	147276

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)

• 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 by resolution:

PDB	Title	Method	Resolution (Å)
8Q69	Crystal structure of HsRNMT complexed with inhibitor DDD1060606	X-RAY DIFFRACTION	1.96
5E9W	Crystal structure of mRNA cap guanine-N7 methyltransferase obtained by limited proteolysis	X-RAY DIFFRACTION	2.28
3BGV	Crystal structure of mRNA cap guanine-N7 methyltransferase in complex with SAH	X-RAY DIFFRACTION	2.3
5E8J	Crystal structure of mRNA cap guanine-N7 methyltransferase in complex with RAM	X-RAY DIFFRACTION	2.35
8Q8G	Crystal structure of HsRNMT complexed with inhibitor DDD1870799	X-RAY DIFFRACTION	2.4
3EPP	Crystal structure of mRNA cap guanine-N7 methyltransferase (RNMT) in complex with …	X-RAY DIFFRACTION	2.41
8Q9W	Crystal structure of HsRNMT complexed with sinefungin and GMP-PnP	X-RAY DIFFRACTION	2.5
5E9J	Crystal structure of the mRNA cap guanine-N7 methyltransferase - modular lobe (416-456) …	X-RAY DIFFRACTION	3.47

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; nucleoli fibrillar center

Antibody reliability (HPA): IH approved · IF supported

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)

Position	Role
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)

Position	Role
180	S-adenosyl-L-methionine
205	S-adenosyl-L-methionine
227	S-adenosyl-L-methionine
261	S-adenosyl-L-methionine
284	S-adenosyl-L-methionine
289	S-adenosyl-L-methionine
176–177	mRNA

Post-translational modifications (4)

Type	Positions
Phosphoserine	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-mediated …
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. partially restored …
398	loss of methyltransferase activity in presence or absence of ramac; when associated with c-178; c-393 and c-417. partially restored …
409	decreased s-adenosyl-l-methionine binding and methyltransferase activity in absence of ramac; when associated with e-413. decreased …
413	decreased s-adenosyl-l-methionine binding and methyltransferase activity in absence of ramac; when associated with e-409. decreased …
417	loss of methyltransferase activity in presence or absence of ramac; when associated with c-178. complete restored ramac-mediated …
450	increased s-adenosyl-l-methionine binding and methyltransferase activity in absence of ramac; when associated with e-452. no change in …
452	increased s-adenosyl-l-methionine binding and methyltransferase activity in absence of ramac; when associated with e-450. no change in …

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 13; 8 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

13 pathways:

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

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 (4): 7-methylguanosine mRNA capping (GO:0006370), 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

10 top-level categories:

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

21 GO namespaces:

Category	Terms
7-methylguanosine RNA capping	2
cellular anatomical structure	2
mRNA processing	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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
7-methylguanosine mRNA capping	BP	direct assay
fibrillar center	CC	direct assay
mRNA cap methyltransferase RNMT:RAMAC complex	CC	direct assay
mRNA capping enzyme complex	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
signaling receptor complex	CC	direct assay
RNA binding	MF	mutant phenotype
mRNA 5’-cap (guanine-N7-)-methyltransferase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,262 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNMT	RNGTT	O60942	965
RNMT	PMP22	Q01453	961
RNMT	GJB1	P08034	937
RNMT	GDAP1	Q8TB36	921
RNMT	MPZL1	O95297	884
RNMT	LITAF	Q99732	848
RNMT	CLEC14A	Q86T13	798
RNMT	EGR2	P11161	795
RNMT	RAMAC	Q9BTL3	780
RNMT	MFN2	O95140	762
RNMT	SNX25	Q9H3E2	759
RNMT	FOXG1	P55315	734
RNMT	NEFL	P07196	700
RNMT	CMTR2	Q8IYT2	697
RNMT	FOXM1	Q08050	675

IntAct

Human interaction partners of RNMT in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

7 partners by confidence:

Partner	Interaction type	MIscore	Records
RAMAC	physical association	0.810	8
KPNA6	physical association	0.800	4
KPNA2	physical association	0.670	3
EIF4E	physical association	0.630	8
GMCL1	physical association	0.560	3
PLEKHA3	physical association	0.560	3
KPNA5	association	0.530	3

BioGRID (123 interactions; top human partners by supporting records): EIF4E (Co-fractionation; 4 records), FAM103A1 (Affinity Capture-MS; 4 records), KPNA1 (Affinity Capture-MS; 4 records), KPNA6 (Affinity Capture-MS; 4 records), HEXB (Co-fractionation; 2 records), HSP90AB4P (Affinity Capture-MS; 2 records), KPNA2 (Two-hybrid; 2 records), KPNA5 (Affinity Capture-MS; 2 records), MYC (Affinity Capture-MS; 2 records), TRPC4AP (Affinity Capture-MS; 2 records), ACE2 (Proximity Label-MS), AGO2 (Co-fractionation), APP (Co-fractionation), APPL1 (Co-fractionation), AR (Proximity Label-MS)

SIGNOR signaling

5 signaling 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

Disease & clinical

Genetic variants

Variant evidence for RNMT: 71 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 23 predictions of 1,102):

Position(s)	Effect	Δscore	Sites
18:13731932	donor_gain	1.0000
18:13731935–13731936	donor_loss	1.0000	4
18:13734457	acceptor_gain	1.0000
18:13734462–13734463	acceptor_loss	1.0000	6
18:13734519	donor_gain	1.0000
18:13734560	donor_gain	1.0000
18:13734618	donor_gain	1.0000
18:13734621	donor_gain	1.0000
18:13737008–13737009	acceptor_loss	1.0000	3
18:13740165–13740166	acceptor_loss	1.0000	4

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.00016
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000188

Disease associations

OMIM: gene MIM:603514 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST006423_14	Fracture	1e-18

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295662 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,782 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,601
CHEMBL1214186	SINEFUNGIN	2	2,181

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

10 measured of 15 human assays (23 total across all organisms); most potent 10 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4292798	IC50	3.6 nM
CHEMBL4285979	IC50	9.4 nM
CHEMBL4286154	IC50	45 nM
CARFILZOMIB	IC50	270 nM
CHEMBL4282765	IC50	900 nM
CHEMBL4293877	IC50	1430 nM
CHEMBL4290778	IC50	1560 nM
CHEMBL4778451	IC50	10900 nM
CHEMBL4794760	IC50	169000 nM
CHEMBL4798931	IC50	276000 nM

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 77 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	affects expression, increases abundance, decreases expression, increases expression, affects cotreatment	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
Air Pollutants	decreases expression, increases abundance, affects expression, affects cotreatment	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	affects cotreatment, affects expression, increases abundance	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for RNMT across ~30M SureChEMBL compounds — explore on Sugi Predict.