NSUN3

Summary

NSUN3 (NOP2/Sun RNA methyltransferase 3, HGNC:26208) is a protein-coding gene on chromosome 3q11.2, encoding tRNA (cytosine(34)-C(5))-methyltransferase, mitochondrial (Q9H649). Mitochondrial tRNA methyltransferase that mediates methylation of cytosine to 5-methylcytosine (m5C) at position 34 of mt-tRNA(Met). mt-tRNA(Met) methylation at cytosine(34) takes place at the wobble position of the anticodon and initiates the formation of 5-formylcytosine (f(5)….

Enables tRNA (cytidine-5-)-methyltransferase activity. Involved in regulation of mitochondrial translation and tRNA wobble base cytosine methylation. Located in mitochondrial matrix. Implicated in combined oxidative phosphorylation deficiency 48.

Source: NCBI Gene 63899 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined oxidative phosphorylation deficiency 48 (Moderate, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 143 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 17
• Druggable target: yes
• MANE Select transcript: NM_022072

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26208
Approved symbol	NSUN3
Name	NOP2/Sun RNA methyltransferase 3
Location	3q11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22609
Ensembl gene	ENSG00000178694
Ensembl biotype	protein_coding
OMIM	617491
Entrez	63899

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding_CDS_not_defined, 1 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000314622, ENST00000461625, ENST00000468555, ENST00000476588, ENST00000477077, ENST00000483378, ENST00000485793, ENST00000494128

RefSeq mRNA: 1 — MANE Select: NM_022072 NM_022072

CCDS: CCDS2927

Canonical transcript exons

ENST00000314622 — 6 exons

Exon	Start	End
ENSE00001214344	94095033	94095154
ENSE00001214360	94084107	94084450
ENSE00001214376	94126211	94131832
ENSE00001933479	94063061	94063138
ENSE00003612632	94094140	94094294
ENSE00003655957	94064437	94064546

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 87.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0467 / max 264.9091, expressed in 1775 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37477	10.9997	1762
37478	0.5703	262
37481	0.5554	64
37480	0.4404	59
37479	0.2533	75
37476	0.2276	82

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	87.99	gold quality
male germ cell	CL:0000015	86.15	gold quality
calcaneal tendon	UBERON:0003701	84.17	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.13	gold quality
monocyte	CL:0000576	82.94	gold quality
mononuclear cell	CL:0000842	82.80	gold quality
leukocyte	CL:0000738	82.67	gold quality
islet of Langerhans	UBERON:0000006	82.42	gold quality
bone marrow	UBERON:0002371	81.29	gold quality
cortical plate	UBERON:0005343	81.17	gold quality
adrenal tissue	UBERON:0018303	80.80	gold quality
colonic epithelium	UBERON:0000397	80.32	gold quality
bone marrow cell	CL:0002092	80.20	gold quality
buccal mucosa cell	CL:0002336	80.16	silver quality
colonic mucosa	UBERON:0000317	80.14	gold quality
blood	UBERON:0000178	79.92	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.41	gold quality
tendon	UBERON:0000043	79.38	gold quality
tibia	UBERON:0000979	79.21	gold quality
esophagus squamous epithelium	UBERON:0006920	79.01	silver quality
visceral pleura	UBERON:0002401	78.94	gold quality
mucosa of urinary bladder	UBERON:0001259	78.87	gold quality
jejunal mucosa	UBERON:0000399	78.74	gold quality
rectum	UBERON:0001052	78.64	gold quality
hair follicle	UBERON:0002073	78.19	gold quality
stromal cell of endometrium	CL:0002255	77.81	gold quality
nephron tubule	UBERON:0001231	77.78	silver quality
pancreatic ductal cell	CL:0002079	77.67	silver quality
ventricular zone	UBERON:0003053	77.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.77
E-MTAB-6379	no	723.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting NSUN3, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-6807-3P	99.15	69.23	1275
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-5000-5P	97.40	66.11	1055
HSA-MIR-3622A-3P	97.06	66.43	1000
HSA-MIR-3622B-3P	96.82	66.36	988
HSA-MIR-3130-3P	94.98	66.97	574

Literature-anchored findings (GeneRIF, showing 5)

• The NSUN3-knockout cells showed strong reduction in mitochondrial protein synthesis and reduced oxygen consumption, leading to deficient mitochondrial activity. It reconstituted formation of 5-methylcytidine (m(5)C) at position 34 (m(5)C34) on mt-tRNA(Met) with recombinant NSUN3 in the presence of AdoMet, demonstrating that NSUN3-mediated m(5)C34 formation initiates f(5)C34 biogenesis. (PMID:27214402)
• The authors show that the RNA methyltransferase NSUN3 localises to mitochondria and interacts with mt-tRNA(M)(et) to methylate cytosine 34 (C34) at the wobble position. (PMID:27497299)
• Novel Biallelic NSUN3 Variants Cause Early-Onset Mitochondrial Encephalomyopathy and Seizures. (PMID:32488845)
• RNA 5-Methylcytosine Regulator NSUN3 promotes tumor progression through regulating immune infiltration in head and neck squamous cell carcinoma. (PMID:35997137)
• NSUN3-mediated mitochondrial tRNA 5-formylcytidine modification is essential for embryonic development and respiratory complexes in mice. (PMID:36949224)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nsun3	ENSDARG00000013023
mus_musculus	Nsun3	ENSMUSG00000050312
rattus_norvegicus	Nsun3	ENSRNOG00000070121

Paralogs (2): NSUN2 (ENSG00000037474), NSUN4 (ENSG00000117481)

Protein

Protein identifiers

tRNA (cytosine(34)-C(5))-methyltransferase, mitochondrial — Q9H649 (reviewed: Q9H649)

Alternative names: NOL1/NOP2/Sun domain family member 3

All UniProt accessions (2): Q9H649, F8WF52

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial tRNA methyltransferase that mediates methylation of cytosine to 5-methylcytosine (m5C) at position 34 of mt-tRNA(Met). mt-tRNA(Met) methylation at cytosine(34) takes place at the wobble position of the anticodon and initiates the formation of 5-formylcytosine (f(5)c) at this position. mt-tRNA(Met) containing the f(5)c modification at the wobble position enables recognition of the AUA codon in addition to the AUG codon, expanding codon recognition in mitochondrial translation.

Subcellular location. Mitochondrion matrix.

Disease relevance. Combined oxidative phosphorylation deficiency 48 (COXPD48) [MIM:619012] An autosomal recessive, mitochondrial encephalomyopathy characterized by global developmental delay, microcephaly, failure to thrive, hypotonia, muscle weakness, external ophthalmoplegia, and seizures. Laboratory studies show metabolic acidosis, increased serum lactate, and combined oxidative phosphorylation deficiency in skeletal muscle. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family.

RefSeq proteins (1): NP_071355* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001678	MeTrfase_RsmB-F_NOP2_dom	Domain
IPR023267	RCMT	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR049560	MeTrfase_RsmB-F_NOP2_cat	Domain

Pfam: PF01189

Enzyme classification (BRENDA):

• EC 2.1.1.203 — tRNA (cytosine34-C5)-methyltransferase (BRENDA: 8 organisms, 25 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• cytidine(34) in mitochondrial tRNA + S-adenosyl-L-methionine = 5-methylcytidine(34) in mitochondrial tRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:53076)

UniProt features (12 total): binding site 4, sequence variant 4, mutagenesis site 2, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H649-F1	90.97	0.78

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 (1): 265 (nucleophile)

Ligand- & substrate-binding residues (4): 139–145; 162; 193; 211

Mutagenesis-validated functional residues (2):

Position	Phenotype
214	in c2a; catalytic mutant. abolishes ability to methylate mt-trna(met).
265	catalytic mutant. abolishes ability to methylate mt-trna(met).

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 145 (showing top): GOBP_RIBOSOME_BIOGENESIS, MODULE_255, GOBP_TRNA_METABOLIC_PROCESS, GOBP_MITOCHONDRIAL_TRANSLATION, MODULE_317, MODULE_453, GOBP_RNA_METHYLATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, MODULE_205, GOBP_RNA_MODIFICATION, TGCTGAY_UNKNOWN, GOBP_TRNA_METHYLATION, GOBP_RRNA_MODIFICATION, GOBP_METHYLATION

GO Biological Process (6): tRNA wobble base cytosine methylation (GO:0002127), rRNA methylation (GO:0031167), regulation of mitochondrial translation (GO:0070129), RNA methylation (GO:0001510), RNA processing (GO:0006396), methylation (GO:0032259)

GO Molecular Function (8): tRNA binding (GO:0000049), methyltransferase activity (GO:0008168), tRNA (cytidine-N5)-methyltransferase activity (GO:0016428), RNA binding (GO:0003723), protein binding (GO:0005515), RNA methyltransferase activity (GO:0008173), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), transferase activity (GO:0016740)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), mitochondrial large ribosomal subunit (GO:0005762)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
methyltransferase activity	2
tRNA wobble cytosine modification	1
tRNA C5-cytosine methylation	1
rRNA modification	1
RNA methylation	1
regulation of translation	1
mitochondrial translation	1
regulation of mitochondrial gene expression	1
RNA modification	1
macromolecule methylation	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
metabolic process	1
RNA binding	1
transferase activity, transferring one-carbon groups	1
tRNA (cytidine) methyltransferase activity	1
nucleic acid binding	1
binding	1
catalytic activity, acting on RNA	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
organellar large ribosomal subunit	1
mitochondrial ribosome	1
mitochondrial protein-containing complex	1

Protein interactions and networks

STRING

1790 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NSUN3	NSUN5	Q96P11	920
NSUN3	HNRNPK	P61978	890
NSUN3	TRDMT1	O14717	879
NSUN3	NSUN7	Q8NE18	845
NSUN3	ALKBH1	Q13686	695
NSUN3	NSUN2	Q08J23	664
NSUN3	MTERF4	Q7Z6M4	663
NSUN3	ALYREF	Q86V81	661
NSUN3	NOP2	P46087	623
NSUN3	DNMT1	P26358	621
NSUN3	ZXDB	P98169	593
NSUN3	MTO1	Q9Y2Z2	590
NSUN3	PUS1	Q9Y606	587
NSUN3	TRMT5	Q32P41	560
NSUN3	TRMT6	Q9UJA5	554

IntAct

43 interactions, top by confidence:

A	B	Type	Score
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
NSUN3	HSPD1	psi-mi:“MI:0914”(association)	0.560
HSPD1	NSUN3	psi-mi:“MI:0915”(physical association)	0.560
TOR1AIP2	TMEM223	psi-mi:“MI:0914”(association)	0.530
LRFN4	RIMOC1	psi-mi:“MI:0914”(association)	0.530
CD79A	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC2A12	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
VSIG4	TCAF2	psi-mi:“MI:0914”(association)	0.530
LRRTM1	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
SLC31A1	PRORP	psi-mi:“MI:0914”(association)	0.530
NSUN3	PHB2	psi-mi:“MI:0915”(physical association)	0.400
NSUN3	ADAMTS4	psi-mi:“MI:0915”(physical association)	0.400
LRRTM1	TMEM223	psi-mi:“MI:0914”(association)	0.350
THUMPD3	TRMU	psi-mi:“MI:0914”(association)	0.350
BSCL2	TMEM223	psi-mi:“MI:0914”(association)	0.350
RAMP2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CTLA4	TMEM120B	psi-mi:“MI:0914”(association)	0.350
OSTM1	ILVBL	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
UQCRFS1	VWA8	psi-mi:“MI:0914”(association)	0.350
P2RY10	POTEF	psi-mi:“MI:0914”(association)	0.350
TACSTD2	RIMOC1	psi-mi:“MI:0914”(association)	0.350
MAGEA8	METTL15	psi-mi:“MI:0914”(association)	0.350
TMEM106A	RTL8C	psi-mi:“MI:0914”(association)	0.350
MPL	FAM171A2	psi-mi:“MI:0914”(association)	0.350

BioGRID (39): NSUN3 (Affinity Capture-MS), NSUN3 (Affinity Capture-MS), NSUN3 (Affinity Capture-MS), NSUN3 (Affinity Capture-MS), NSUN3 (Affinity Capture-MS), NSUN3 (Affinity Capture-MS), NSUN3 (Affinity Capture-MS), NSUN3 (Proximity Label-MS), HSPD1 (Affinity Capture-MS), NSUN3 (Affinity Capture-MS), NSUN3 (Affinity Capture-MS), NSUN3 (Affinity Capture-MS), CBWD2 (Affinity Capture-MS), NSUN3 (Affinity Capture-MS), NSUN3 (Affinity Capture-MS)

ESM2 similar proteins: A7M6E8, B0F481, F4JP46, F4KBF3, H9A1V3, M4IRL9, P18485, P23279, P23599, P27486, P31531, P37821, Q00257, Q00379, Q06402, Q07262, Q28EN2, Q2KIA9, Q2TBU5, Q37001, Q3UNX5, Q43309, Q5IH13, Q5IH14, Q5R9T5, Q5RAK7, Q5RAT4, Q5ZJU3, Q6INX4, Q6P6M7, Q6YXW6, Q6ZHE5, Q7L5Y1, Q84P17, Q8CCT7, Q8K0L3, Q8K3F7, Q8L794, Q93ZC9, Q94AH8

Diamond homologs: A0KKI5, A0KW34, A1AC00, A1RIZ0, A1S788, A1SWV0, A3D5D5, A3QDA2, A4SMI9, A4WBJ4, A4Y7J8, A6TB06, A6WP46, A7MKH5, A7N0K6, A7ZMV8, A8A133, A8AFL6, A8FWM8, A8GDM6, A8H3W2, A9L4E6, A9MNH4, A9MV57, B0TIZ6, B1J0Q3, B1KQN1, B1LD37, B1XHA3, B2U477, B2VJ83, B4SV89, B4TKI0, B4TY18, B5BHA6, B5F3P3, B5FE06, B5FTI4, B5R2S1, B5R8V2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	86
Likely benign	40
Benign	4

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
2275962	NM_022072.5(NSUN3):c.150G>A (p.Trp50Ter)	Pathogenic
978074	NM_022072.5(NSUN3):c.123-615_466+2155del	Pathogenic
978076	NM_022072.5(NSUN3):c.454T>A (p.Cys152Ser)	Pathogenic
978077	NM_022072.5(NSUN3):c.421G>C (p.Ala141Pro)	Pathogenic
809516	NM_022072.5(NSUN3):c.465dup (p.Gly156fs)	Likely pathogenic

SpliceAI

1368 predictions. Top by Δscore:

Variant	Effect	Δscore
3:94063041:G:GT	donor_gain	1.0000
3:94063139:GTGA:G	donor_loss	1.0000
3:94063140:T:G	donor_loss	1.0000
3:94064435:A:AG	acceptor_gain	1.0000
3:94064436:G:GG	acceptor_gain	1.0000
3:94064436:GCT:G	acceptor_gain	1.0000
3:94095031:A:AG	acceptor_gain	1.0000
3:94095031:A:T	acceptor_loss	1.0000
3:94095032:G:GG	acceptor_gain	1.0000
3:94095032:GGT:G	acceptor_gain	1.0000
3:94095152:AAGGT:A	donor_loss	1.0000
3:94095153:AGGT:A	donor_loss	1.0000
3:94095154:GGTAA:G	donor_loss	1.0000
3:94095155:GTAAG:G	donor_loss	1.0000
3:94095156:T:G	donor_loss	1.0000
3:94063139:G:GG	donor_gain	0.9900
3:94064436:GCTGA:G	acceptor_gain	0.9900
3:94064542:GTAAG:G	donor_gain	0.9900
3:94064544:AAGGT:A	donor_loss	0.9900
3:94064545:AGG:A	donor_loss	0.9900
3:94064546:GG:G	donor_loss	0.9900
3:94064547:G:A	donor_loss	0.9900
3:94064548:T:A	donor_loss	0.9900
3:94081660:C:G	donor_gain	0.9900
3:94095031:AG:A	acceptor_gain	0.9900
3:94095031:AGGT:A	acceptor_gain	0.9900
3:94095032:GG:G	acceptor_gain	0.9900
3:94095032:GGTG:G	acceptor_gain	0.9900
3:94095107:GA:G	donor_gain	0.9900
3:94095155:G:GG	donor_gain	0.9900

AlphaMissense

2204 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:94084418:A:T	K145I	0.991
3:94084401:T:G	C139W	0.990
3:94094173:G:C	R167T	0.990
3:94084403:C:A	A140D	0.989
3:94084406:C:A	A141D	0.989
3:94095148:T:C	L246P	0.989
3:94084419:A:C	K145N	0.987
3:94084419:A:T	K145N	0.987
3:94094185:T:C	L171P	0.987
3:94095046:C:A	A212D	0.987
3:94095053:T:G	C214W	0.987
3:94126283:T:A	N272K	0.987
3:94126283:T:G	N272K	0.987
3:94094173:G:T	R167I	0.986
3:94094174:A:C	R167S	0.986
3:94094174:A:T	R167S	0.986
3:94095044:T:A	D211E	0.986
3:94095044:T:G	D211E	0.986
3:94095051:T:C	C214R	0.986
3:94095060:G:C	D217H	0.986
3:94126280:A:C	E271D	0.985
3:94126280:A:T	E271D	0.985
3:94095061:A:C	D217A	0.984
3:94084391:T:C	L136P	0.983
3:94084400:G:A	C139Y	0.983
3:94126434:T:A	W323R	0.983
3:94126434:T:C	W323R	0.983
3:94095040:T:A	V210E	0.982
3:94095052:G:A	C214Y	0.982
3:94126251:T:G	Y262D	0.982

dbSNP variants (sampled 300 via entrez): RS1000038209 (3:94065212 C>G,T), RS1000070825 (3:94064771 C>A,G,T), RS1000074520 (3:94101771 A>G), RS1000211876 (3:94070093 A>G), RS1000277127 (3:94092026 A>G), RS1000345039 (3:94095829 G>A,C), RS1000367508 (3:94098195 A>G), RS1000469764 (3:94072442 A>G), RS1000492840 (3:94079044 A>G), RS1000535919 (3:94063407 C>T), RS1000625866 (3:94112906 C>G,T), RS1000705233 (3:94085058 T>C), RS1000752638 (3:94129540 T>C), RS1000774068 (3:94078860 A>G), RS1000786183 (3:94087696 G>A)

Disease associations

OMIM: gene MIM:617491 | disease phenotypes: MIM:619012, MIM:612291

GenCC curated gene-disease

Disease	Classification	Inheritance
combined oxidative phosphorylation deficiency 48	Moderate	Autosomal recessive

Mondo (2): combined oxidative phosphorylation deficiency 48 (MONDO:0033566), Joubert syndrome 8 (MONDO:0012855)

Orphanet (1): Isolated Joubert syndrome (Orphanet:475)

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000544	External ophthalmoplegia
HP:0000639	Nystagmus
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001324	Muscle weakness
HP:0001508	Failure to thrive
HP:0002151	Increased circulating lactate concentration
HP:0003128	Lactic acidosis
HP:0003593	Infantile onset
HP:0008347	Decreased activity of mitochondrial complex IV
HP:0011923	Decreased activity of mitochondrial complex I
HP:0011924	Decreased activity of mitochondrial complex III
HP:0012762	Cerebral white matter atrophy
HP:0030890	Hyperintensity of cerebral white matter on MRI

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002249_7	Blood pressure measurement (high sodium intervention)	4.000000e-07
GCST002249_9	Blood pressure measurement (high sodium intervention)	5.000000e-06
GCST007323_50	Risk-taking tendency (4-domain principal component model)	5.000000e-08
GCST007325_239	General risk tolerance (MTAG)	1.000000e-09
GCST007326_34	Number of sexual partners	1.000000e-10
GCST007326_45	Number of sexual partners	1.000000e-09
GCST008465_8	Anorexia nervosa	4.000000e-08
GCST008646_4	Gastric cancer	5.000000e-09
GCST010988_107	Adult body size	3.000000e-19
GCST90000047_54	Age at first sexual intercourse	2.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005401	response to high sodium diet
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0008579	risk-taking behaviour
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567358	Joubert Syndrome 8 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724616 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs144470777	NSUN3		0.00	0

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
resorcinol	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Clorgyline	increases expression	1
Doxorubicin	decreases expression	1
Methapyrilene	increases methylation	1
Methotrexate	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Urethane	increases expression	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5527514	Binding	Binding affinity to human NSUN3 assessed as signal to noise ratio incubated for 1 hr by proteasome microarray	Bipyridine Derivatives as NOP2/Sun RNA Methyltransferase 3 Inhibitors for the Treatment of Colorectal Cancer. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_F1U9	HyCyte THP-1 KO-hNSUN3	Cancer cell line	Male
CVCL_TB16	HAP1 NSUN3 (-) 1	Cancer cell line	Male
CVCL_TB17	HAP1 NSUN3 (-) 2	Cancer cell line	Male
CVCL_TB18	HAP1 NSUN3 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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