MRM1

Summary

MRM1 (mitochondrial rRNA methyltransferase 1, HGNC:26202) is a protein-coding gene on chromosome 17q12, encoding rRNA methyltransferase 1, mitochondrial (Q6IN84). S-adenosyl-L-methionine-dependent 2’-O-ribose methyltransferase that catalyzes the formation of 2’-O-methylguanosine at position 1145 (Gm1145) in the 16S mitochondrial large subunit ribosomal RNA (mtLSU rRNA), a universally conserved modification in the peptidyl transferase doma….

Enables rRNA (guanosine-2’-O-)-methyltransferase activity. Involved in rRNA processing. Located in mitochondrial matrix.

Source: NCBI Gene 79922 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 65 total
• Druggable target: yes
• MANE Select transcript: NM_024864

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26202
Approved symbol	MRM1
Name	mitochondrial rRNA methyltransferase 1
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22578
Ensembl gene	ENSG00000278619
Ensembl biotype	protein_coding
OMIM	618099
Entrez	79922

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000612760, ENST00000614766, ENST00000858970, ENST00000940336

RefSeq mRNA: 1 — MANE Select: NM_024864 NM_024864

CCDS: CCDS32631

Canonical transcript exons

ENST00000611231 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 86.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.0292 / max 65.2894, expressed in 1519 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160439	4.0292	1519

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.65	gold quality
mucosa of transverse colon	UBERON:0004991	85.34	gold quality
apex of heart	UBERON:0002098	81.20	gold quality
gastrocnemius	UBERON:0001388	78.89	gold quality
granulocyte	CL:0000094	78.30	gold quality
heart left ventricle	UBERON:0002084	78.27	gold quality
muscle of leg	UBERON:0001383	77.84	gold quality
right adrenal gland	UBERON:0001233	76.63	gold quality
transverse colon	UBERON:0001157	76.24	gold quality
left adrenal gland	UBERON:0001234	76.09	gold quality
lower esophagus mucosa	UBERON:0035834	75.95	gold quality
right lobe of liver	UBERON:0001114	75.85	gold quality
right adrenal gland cortex	UBERON:0035827	75.62	gold quality
left adrenal gland cortex	UBERON:0035825	75.47	gold quality
heart	UBERON:0000948	75.37	gold quality
spleen	UBERON:0002106	75.27	gold quality
hindlimb stylopod muscle	UBERON:0004252	75.24	gold quality
skeletal muscle tissue	UBERON:0001134	75.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.76	gold quality
adrenal gland	UBERON:0002369	74.66	gold quality
muscle tissue	UBERON:0002385	74.65	gold quality
right ovary	UBERON:0002118	74.51	gold quality
lower esophagus muscularis layer	UBERON:0035833	74.43	gold quality
lower esophagus	UBERON:0013473	74.41	gold quality
colon	UBERON:0001155	74.34	gold quality
small intestine	UBERON:0002108	74.31	gold quality
lymph node	UBERON:0000029	74.28	gold quality
esophagus mucosa	UBERON:0002469	74.14	gold quality
duodenum	UBERON:0002114	74.08	gold quality
esophagus	UBERON:0001043	74.04	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting MRM1, 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-8485	100.00	77.57	4731
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-6823-3P	95.45	66.14	704
HSA-MIR-2114-3P	95.45	66.11	579
HSA-MIR-2861	95.24	65.47	1056
HSA-MIR-4765	93.11	66.17	737

Literature-anchored findings (GeneRIF, showing 1)

• Data show that 2’-O-methyltransferases MRM1, MRM2, and RNMTL1 are responsible for modification of large subunit rRNA at residues G1145, U1369, and G1370, respectively. (PMID:25074936)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrm1	ENSDARG00000059658
mus_musculus	Mrm1	ENSMUSG00000018405
rattus_norvegicus	Mrm1	ENSRNOG00000027901
caenorhabditis_elegans		WBGENE00012864

Paralogs (2): TARBP1 (ENSG00000059588), MRM3 (ENSG00000171861)

Protein

Protein identifiers

rRNA methyltransferase 1, mitochondrial — Q6IN84 (reviewed: Q6IN84)

Alternative names: 16S rRNA (guanosine(1145)-2’-O)-methyltransferase, 16S rRNA [Gm1145] 2’-O-methyltransferase

All UniProt accessions (2): A0A087WZC1, Q6IN84

UniProt curated annotations — full annotation on UniProt →

Function. S-adenosyl-L-methionine-dependent 2’-O-ribose methyltransferase that catalyzes the formation of 2’-O-methylguanosine at position 1145 (Gm1145) in the 16S mitochondrial large subunit ribosomal RNA (mtLSU rRNA), a universally conserved modification in the peptidyl transferase domain of the mtLSU rRNA.

Subcellular location. Mitochondrion matrix.

Similarity. Belongs to the class IV-like SAM-binding methyltransferase superfamily. RNA methyltransferase TrmH family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6IN84-1	1	yes
Q6IN84-2	2

RefSeq proteins (1): NP_079140* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001537	SpoU_MeTrfase	Domain
IPR004441	rRNA_MeTrfase_TrmH	Family
IPR013123	SpoU_subst-bd	Domain
IPR029026	tRNA_m1G_MTases_N	Homologous_superfamily
IPR029028	Alpha/beta_knot_MTases	Homologous_superfamily
IPR029064	Ribosomal_eL30-like_sf	Homologous_superfamily
IPR047182	MRM1	Family
IPR047261	MRM1_MeTrfase_dom	Domain

Pfam: PF00588, PF08032

Enzyme classification (BRENDA):

• EC 2.1.1.B125 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• guanosine(1145) in 16S rRNA + S-adenosyl-L-methionine = 2’-O-methylguanosine(1145) in 16S rRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:47776)

UniProt features (5 total): transit peptide 1, chain 1, region of interest 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IN84-F1	78.89	0.61

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6793080	rRNA modification in the mitochondrion
R-HSA-72312	rRNA processing
R-HSA-8868766	rRNA processing in the mitochondrion
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 108 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RIBOSOME_BIOGENESIS, PAX4_01, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_RNA_METHYLATION, GOBP_RNA_MODIFICATION, DOUGLAS_BMI1_TARGETS_UP, GOBP_RRNA_MODIFICATION, GOBP_METHYLATION, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOBP_RRNA_METHYLATION, REACTOME_METABOLISM_OF_RNA, GOCC_MITOCHONDRIAL_MATRIX, SCGGAAGY_ELK1_02, GOMF_RNA_METHYLTRANSFERASE_ACTIVITY

GO Biological Process (6): rRNA modification (GO:0000154), rRNA 2’-O-methylation (GO:0000451), rRNA processing (GO:0006364), RNA processing (GO:0006396), rRNA methylation (GO:0031167), methylation (GO:0032259)

GO Molecular Function (7): RNA binding (GO:0003723), rRNA (guanine) methyltransferase activity (GO:0016435), rRNA (guanosine-2’-O-ribose)-methyltransferase activity (GO:0070039), protein binding (GO:0005515), methyltransferase activity (GO:0008168), RNA methyltransferase activity (GO:0008173), transferase activity (GO:0016740)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
rRNA processing in the mitochondrion	1
Metabolism of RNA	1
rRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
rRNA processing	1
RNA modification	1
rRNA methylation	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
rRNA modification	1
RNA methylation	1
metabolic process	1
nucleic acid binding	1
rRNA methyltransferase activity	1
rRNA 2’-O-methylation	1
rRNA (guanine) methyltransferase activity	1
RNA 2’-O-methyltransferase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
methyltransferase activity	1
catalytic activity, acting on RNA	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2007 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRM1	MRM2	Q9UI43	916
MRM1	MTG1	Q9BT17	814
MRM1	MRM3	Q9HC36	807
MRM1	RPUSD4	Q96CM3	698
MRM1	MTG2	Q9H4K7	693
MRM1	NSUN4	Q96CB9	692
MRM1	ZNHIT3	Q15649	648
MRM1	PIGW	Q7Z7B1	645
MRM1	MTERF4	Q7Z6M4	644
MRM1	GGNBP2	Q9H3C7	643
MRM1	SYNRG	Q9UMZ2	628
MRM1	TADA2A	O75478	626
MRM1	MYO19	Q96H55	625
MRM1	DDX52	Q9Y2R4	624
MRM1	C17orf78	Q8N4C9	621

IntAct

163 interactions, top by confidence:

A	B	Type	Score
MRM1	CGGBP1	psi-mi:“MI:0915”(physical association)	0.800
MRM1	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
AGTRAP	MRM1	psi-mi:“MI:0915”(physical association)	0.560
TMEM11	MRM1	psi-mi:“MI:0915”(physical association)	0.560
TMEM42	MRM1	psi-mi:“MI:0915”(physical association)	0.560
LPAR3	MRM1	psi-mi:“MI:0915”(physical association)	0.560
TMEM97	MRM1	psi-mi:“MI:0915”(physical association)	0.560
ERG28	MRM1	psi-mi:“MI:0915”(physical association)	0.560
TUSC5	MRM1	psi-mi:“MI:0915”(physical association)	0.560
AQP1	MRM1	psi-mi:“MI:0915”(physical association)	0.560
BRICD5	MRM1	psi-mi:“MI:0915”(physical association)	0.560
AQP2	MRM1	psi-mi:“MI:0915”(physical association)	0.560
TMEM243	MRM1	psi-mi:“MI:0915”(physical association)	0.560
ADIPOQ	MRM1	psi-mi:“MI:0915”(physical association)	0.560
NRM	MRM1	psi-mi:“MI:0915”(physical association)	0.560
SELENOK	MRM1	psi-mi:“MI:0915”(physical association)	0.560
MRM1	CMTM5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (413): MRM1 (Two-hybrid), MRM1 (Affinity Capture-MS), CGGBP1 (Affinity Capture-MS), VPS35 (Affinity Capture-MS), KIAA0391 (Affinity Capture-MS), UBR1 (Affinity Capture-MS), TOP3A (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), CUL2 (Affinity Capture-MS), ZYG11B (Affinity Capture-MS), DBT (Affinity Capture-MS), HECTD3 (Affinity Capture-MS), ZER1 (Affinity Capture-MS), GLS (Affinity Capture-MS), GRPEL2 (Affinity Capture-MS)

ESM2 similar proteins: A1L134, A1L1C2, A6QP75, E1BE10, E2RD63, G5E872, O00587, P56433, P70295, Q0V8G3, Q11128, Q16512, Q28DT3, Q2TBI8, Q32M88, Q3UFB7, Q4R942, Q501J2, Q5E9V4, Q5F2F2, Q5IS64, Q5SWZ9, Q6AYG0, Q6IN84, Q6P9U1, Q8BH73, Q8BNV1, Q8BZG5, Q8IZ69, Q8N2A8, Q8N9H8, Q8NE01, Q8TD43, Q8VHS5, Q8WXI3, Q91ZT7, Q920N2, Q969S8, Q96DC7, Q96NS5

Diamond homologs: A0PV26, A0QAB6, A0R557, A1KPR5, A1TG08, A1UMF4, A3Q6V9, A4T5L0, A5U8Q4, B1MGY6, B2HJ20, B8ZUB0, O30272, P0AGJ5, P0AGJ6, P18644, P44906, P52391, P52393, P63177, P63178, P63179, P63180, P74261, P74328, P75424, P9WFY4, P9WFY5, Q06753, Q1B2P4, Q49V41, Q4L3J1, Q5HIE3, Q5HRM1, Q5SM16, Q6D127, Q6FF50, Q6GBV6, Q6GJD7, Q6IN84

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 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
Peptide chain elongation	5	15.5×	1e-03
Major pathway of rRNA processing in the nucleolus and cytosol	7	10.5×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	6	15.0×	1e-03
translation	6	8.3×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

558 predictions. Top by Δscore:

Variant	Effect	Δscore
17:36607665:TTCA:T	acceptor_loss	1.0000
17:36607666:TCA:T	acceptor_loss	1.0000
17:36607668:A:AG	acceptor_gain	1.0000
17:36607668:AGAC:A	acceptor_loss	1.0000
17:36607669:G:A	acceptor_loss	1.0000
17:36607669:G:GC	acceptor_gain	1.0000
17:36607669:GAC:G	acceptor_gain	1.0000
17:36607669:GACC:G	acceptor_gain	1.0000
17:36607669:GACCA:G	acceptor_gain	1.0000
17:36607798:GCTGG:G	donor_gain	1.0000
17:36607801:GG:G	donor_gain	1.0000
17:36607802:GG:G	donor_gain	1.0000
17:36607802:GGT:G	donor_loss	1.0000
17:36607803:G:GG	donor_gain	1.0000
17:36607803:GT:G	donor_loss	1.0000
17:36607804:T:G	donor_loss	1.0000
17:36602358:G:GT	donor_gain	0.9900
17:36607669:GA:G	acceptor_gain	0.9900
17:36607897:AG:A	acceptor_gain	0.9900
17:36607898:GG:G	acceptor_gain	0.9900
17:36608016:CAGG:C	donor_loss	0.9900
17:36608017:AGGT:A	donor_loss	0.9900
17:36608018:GGTG:G	donor_loss	0.9900
17:36608019:GTGA:G	donor_loss	0.9900
17:36608020:T:G	donor_loss	0.9900
17:36607666:TCAGA:T	acceptor_gain	0.9800
17:36607667:CAGAC:C	acceptor_gain	0.9800
17:36607893:CTGCA:C	acceptor_loss	0.9800
17:36607894:TGCAG:T	acceptor_loss	0.9800
17:36607895:GCAGG:G	acceptor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000039620 (17:36630757 G>A), RS1000098796 (17:36601508 C>A,T), RS1000165338 (17:36630150 T>C), RS1000187935 (17:36619451 T>C), RS1000205771 (17:36602331 T>TG), RS1000320009 (17:36623909 C>T), RS1000434476 (17:36612922 C>T), RS1000447848 (17:36608328 A>C,G), RS1000553167 (17:36612222 T>C), RS1000577145 (17:36613201 T>TC), RS1000788635 (17:36618110 G>A), RS1000995169 (17:36606991 T>C), RS1001020058 (17:36606639 C>G,T), RS1001081505 (17:36617848 G>A), RS1001104646 (17:36629467 A>T)

Disease associations

OMIM: gene MIM:618099 | disease phenotypes: MIM:614526

GenCC curated gene-disease

Mondo (1): chromosome 17q12 duplication syndrome (MONDO:0013796)

Orphanet (1): 17q12 microduplication syndrome (Orphanet:261272)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005951_15	Body mass index	3.000000e-13
GCST010151_27	Carotid intima media thickness x smoking interaction	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006527	smoking status measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067228 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.25	Kd	56.87	nM	CHEMBL5653589
7.25	ED50	56.87	nM	CHEMBL5653589

PubChem BioAssay actives

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

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148768: Binding affinity to human MRM1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0569	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
trichostatin A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
zinc chromate	increases abundance, decreases expression	1
ferrous chloride	decreases expression	1
nivalenol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651810	Binding	Binding affinity to human MRM1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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