NSUN6

Summary

NSUN6 (NOP2/Sun RNA methyltransferase 6, HGNC:23529) is a protein-coding gene on chromosome 10p12.31, encoding tRNA (cytosine(72)-C(5))-methyltransferase NSUN6 (Q8TEA1). S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the C5 position of cytosine 72 in tRNA(Thr)(TGT) and tRNA(Cys)(GCA).

Enables tRNA (cytidine-5-)-methyltransferase activity and tRNA binding activity. Involved in tRNA C5-cytosine methylation. Located in cytoplasm. Implicated in autosomal recessive intellectual developmental disorder 82.

Source: NCBI Gene 221078 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder, autosomal recessive 82 (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 111 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 16
• Druggable target: yes
• MANE Select transcript: NM_182543

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23529
Approved symbol	NSUN6
Name	NOP2/Sun RNA methyltransferase 6
Location	10p12.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23743
Ensembl gene	ENSG00000241058
Ensembl biotype	protein_coding
OMIM	617199
Entrez	221078

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 3 retained_intron, 2 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000377304, ENST00000414939, ENST00000444660, ENST00000449529, ENST00000456217, ENST00000493816, ENST00000606425, ENST00000607346

RefSeq mRNA: 5 — MANE Select: NM_182543 NM_001351115, NM_001351116, NM_001351117, NM_001351118, NM_182543

CCDS: CCDS7130

Canonical transcript exons

ENST00000377304 — 11 exons

Exon	Start	End
ENSE00001005473	18585949	18586093
ENSE00001098810	18609845	18609926
ENSE00001163342	18551823	18551971
ENSE00001163352	18596208	18596327
ENSE00001163363	18614460	18614613
ENSE00001163411	18616184	18616293
ENSE00001473492	18545561	18546145
ENSE00001473507	18651129	18651587
ENSE00003530258	18548112	18548237
ENSE00003765404	18648490	18648645
ENSE00003770086	18642476	18642555

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 98.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.1205 / max 162.8225, expressed in 1732 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108560	6.5947	1579
108565	2.6245	989
108559	0.7064	265
108558	0.4138	218
108566	0.3623	193
108567	0.3440	173
108557	0.0647	27
108556	0.0101	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oviduct epithelium	UBERON:0004804	98.05	gold quality
sperm	CL:0000019	95.05	gold quality
right lobe of liver	UBERON:0001114	94.64	gold quality
buccal mucosa cell	CL:0002336	94.15	gold quality
oocyte	CL:0000023	91.49	gold quality
left testis	UBERON:0004533	91.20	gold quality
right testis	UBERON:0004534	91.19	gold quality
liver	UBERON:0002107	90.89	gold quality
seminal vesicle	UBERON:0000998	90.48	gold quality
right uterine tube	UBERON:0001302	89.91	gold quality
adenohypophysis	UBERON:0002196	89.90	gold quality
testis	UBERON:0000473	89.82	gold quality
pituitary gland	UBERON:0000007	89.60	gold quality
calcaneal tendon	UBERON:0003701	88.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.46	gold quality
left ovary	UBERON:0002119	87.94	gold quality
adrenal tissue	UBERON:0018303	87.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.57	gold quality
body of pancreas	UBERON:0001150	87.57	gold quality
right adrenal gland cortex	UBERON:0035827	87.53	gold quality
cerebellar hemisphere	UBERON:0002245	87.36	gold quality
left lobe of thyroid gland	UBERON:0001120	87.26	gold quality
cerebellar cortex	UBERON:0002129	87.23	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.18	gold quality
left adrenal gland cortex	UBERON:0035825	87.16	gold quality
thyroid gland	UBERON:0002046	87.09	gold quality
adrenal cortex	UBERON:0001235	87.00	gold quality
right lobe of thyroid gland	UBERON:0001119	86.95	gold quality
right adrenal gland	UBERON:0001233	86.92	gold quality
right ovary	UBERON:0002118	86.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	19.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting NSUN6, 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-9-5P	100.00	72.28	2361
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-7702	99.06	65.95	698
HSA-MIR-140-3P	99.04	67.69	1324

Literature-anchored findings (GeneRIF, showing 8)

• Findings identified NSUN6 as a novel mammalian m5C tRNA methyltransferase and suggest that methylation of tRNAs by NSUN6 occurs during a late step of tRNA biogenesis, after the addition of the CCA tail and export of the tRNA from the nucleus. (PMID:26160102)
• findings suggest that human NSun6 relies on a delicate network for RNA recognition, which involves both the primary sequence and tertiary structure of tRNA substrates. (PMID:27703015)
• The structures of NSun6, a human tRNA:m5C methyltransferase, in the apo form and in complex with a full-length tRNA substrate. (PMID:28531330)
• Sequence- and structure-specific cytosine-5 mRNA methylation by NSUN6. (PMID:33330931)
• The RNA methyltransferase NSUN6 suppresses pancreatic cancer development by regulating cell proliferation. (PMID:33418496)
• NSUN6, an RNA methyltransferase of 5-mC controls glioblastoma response to temozolomide (TMZ) via NELFB and RPS6KB2 interaction. (PMID:34705606)
• Biallelic variants in NSUN6 cause an autosomal recessive neurodevelopmental disorder. (PMID:37226891)
• NSUN6 Regulates NM23-H1 Expression in an m5C Manner to Affect Epithelial-Mesenchymal Transition in Lung Cancer. (PMID:38029727)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nsun6	ENSDARG00000103478
mus_musculus	Nsun6	ENSMUSG00000026707
rattus_norvegicus	Nsun6	ENSRNOG00000018520
drosophila_melanogaster	CG11109	FBGN0037200

Paralogs (2): NOP2 (ENSG00000111641), NSUN5 (ENSG00000130305)

Protein

Protein identifiers

tRNA (cytosine(72)-C(5))-methyltransferase NSUN6 — Q8TEA1 (reviewed: Q8TEA1)

Alternative names: NOL1/NOP2/Sun and PUA domain-containing protein 1, NOL1/NOP2/Sun domain family member 6

All UniProt accessions (3): A0A0D9SF14, Q8TEA1, U3KQU2

UniProt curated annotations — full annotation on UniProt →

Function. S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the C5 position of cytosine 72 in tRNA(Thr)(TGT) and tRNA(Cys)(GCA). In vitro also methylates tRNA(Thr)(AGT). Methylation requires, in the acceptor stem region, the presence of the 3’-CCA terminus, the target site C72, the discriminator base U73, and the second and third base pairs (2:71 and 3:70) in the tRNA substrates.

Subcellular location. Cytoplasm.

Disease relevance. Intellectual developmental disorder, autosomal recessive 82 (MRT82) [MIM:620779] An autosomal recessive disorder characterized by developmental delay, motor and speech delay, intellectual disability, and behavioral anomalies. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. The PUA domain plays a role in tRNA recognition through precisely recognizing the CCA end and the D-stem region of tRNA.

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

RefSeq proteins (5): NP_001338044, NP_001338045, NP_001338046, NP_001338047, NP_872349* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001678	MeTrfase_RsmB-F_NOP2_dom	Domain
IPR015947	PUA-like_sf	Homologous_superfamily
IPR018314	RsmB/NOL1/NOP2-like_CS	Conserved_site
IPR023267	RCMT	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR036974	PUA_sf	Homologous_superfamily
IPR049560	MeTrfase_RsmB-F_NOP2_cat	Domain

Pfam: PF01189

Enzyme classification (BRENDA):

• EC 2.1.1.202 — multisite-specific tRNA:(cytosine-C5)-methyltransferase (BRENDA: 12 organisms, 133 substrates, 4 inhibitors, 1 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 2 shown:

• cytidine(72) in tRNA(Thr) + S-adenosyl-L-methionine = 5-methylcytidine(72) in tRNA(Thr) + S-adenosyl-L-homocysteine + H(+) (RHEA:21124)
• cytidine(72) in tRNA(Cys) + S-adenosyl-L-methionine = 5-methylcytidine(72) in tRNA(Cys) + S-adenosyl-L-homocysteine + H(+) (RHEA:61584)

UniProt features (69 total): strand 22, helix 17, mutagenesis site 15, turn 6, binding site 4, chain 1, domain 1, active site 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
5WWQ	X-RAY DIFFRACTION	2.81
9IMB	X-RAY DIFFRACTION	2.9
5WWR	X-RAY DIFFRACTION	3.1
5WWT	X-RAY DIFFRACTION	3.2
5WWS	X-RAY DIFFRACTION	3.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TEA1-F1	94.23	0.88

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): 373 (nucleophile)

Ligand- & substrate-binding residues (4): 242–248; 266; 293; 323

Post-translational modifications (1): 419

Mutagenesis-validated functional residues (15):

Position	Phenotype
131	abolishes methylation of trna (cys).
159	decreases trna methyltransferase activity. abolishes trna methyltransferase activity; when associated with a-181.
160	decreases trna methyltransferase activity. abolishes trna methyltransferase activity; when associated with a-181.
181	substantially decreases trna methyltransferase activity.
218	decreases substantially trna methyltransferase activity.
220	decreases substantially trna methyltransferase activity.
223	does not affect trna methyltransferase activity.
248	abolishes trna methyltransferase activity. does not affect s-adenosylmethionine binding.
266	loss of s-adenosylmethionine binding. loss of trna methyltransferase activity.
271	loss of s-adenosylmethionine binding. loss of trna methyltransferase activity.
293	loss of s-adenosylmethionine binding. loss of trna methyltransferase activity.
323	abolishes trna methyltransferase activity. abolishes s-adenosylmethionine binding.
373	does not impair target rna binding. abolishes trna (cytosine-5-)-methyltransferase activity.
458	abolishes trna methyltransferase activity.
126	decreases substantially trna methyltransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6782315	tRNA modification in the nucleus and cytosol

MSigDB gene sets: 123 (showing top): GOBP_TRNA_METABOLIC_PROCESS, GOBP_RNA_METHYLATION, GOBP_RNA_MODIFICATION, GOBP_TRNA_METHYLATION, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GOBP_METHYLATION, GOBP_TRNA_PROCESSING, REACTOME_METABOLISM_OF_RNA, GOBP_TRNA_MODIFICATION, chr10p12, TGGAAA_NFAT_Q4_01, MARSON_BOUND_BY_FOXP3_STIMULATED, GOMF_RNA_METHYLTRANSFERASE_ACTIVITY, GOMF_TRNA_BINDING, CCGNMNNTNACG_UNKNOWN

GO Biological Process (6): RNA methylation (GO:0001510), tRNA C5-cytosine methylation (GO:0002946), tRNA modification (GO:0006400), tRNA methylation (GO:0030488), RNA processing (GO:0006396), methylation (GO:0032259)

GO Molecular Function (7): tRNA binding (GO:0000049), tRNA (cytidine-N5)-methyltransferase activity (GO:0016428), RNA binding (GO:0003723), methyltransferase activity (GO:0008168), RNA methyltransferase activity (GO:0008173), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), transferase activity (GO:0016740)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
tRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA modification	2
methyltransferase activity	2
cellular anatomical structure	2
macromolecule methylation	1
tRNA methylation	1
tRNA processing	1
RNA methylation	1
tRNA modification	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
metabolic process	1
RNA binding	1
tRNA (cytidine) methyltransferase activity	1
nucleic acid binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity, acting on RNA	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1952 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NSUN6	NSUN7	Q8NE18	827
NSUN6	TRDMT1	O14717	794
NSUN6	LLGL2	Q6P1M3	700
NSUN6	ALYREF	Q86V81	673
NSUN6	NSUN5	Q96P11	646
NSUN6	ALKBH1	Q13686	569
NSUN6	RRP8	O43159	540
NSUN6	NSUN2	Q08J23	529
NSUN6	MTERF4	Q7Z6M4	525
NSUN6	NSUN4	Q96CB9	520
NSUN6	TRMT6	Q9UJA5	519
NSUN6	YBX1	P16990	510
NSUN6	METTL16	Q86W50	471
NSUN6	BUD23	O43709	462
NSUN6	TRMT61A	Q96FX7	460

IntAct

2 interactions, top by confidence:

A	B	Type	Score
NSUN6	BCKDHA	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (23): NSUN6 (Co-fractionation), RPE (Co-fractionation), NSUN6 (Affinity Capture-MS), NSUN6 (Proximity Label-MS), NSUN6 (Reconstituted Complex), NSUN6 (Co-fractionation), NSUN6 (Co-fractionation), NSUN6 (Co-fractionation), C9orf142 (Co-fractionation), WDR13 (Co-fractionation), NSUN6 (Affinity Capture-MS), NSUN6 (Affinity Capture-MS), NSUN6 (Affinity Capture-MS), TMED10 (Cross-Linking-MS (XL-MS)), NSUN6 (Affinity Capture-RNA)

ESM2 similar proteins: A0JMS7, A2AKK5, A5PJN5, B3MF31, O55137, O55171, O88267, P08587, P10937, P21980, P21981, P34913, P40935, P40936, P49753, P51176, P70683, Q01841, Q14032, Q32Q92, Q3I5F7, Q4V8A1, Q5BJ91, Q5FVR5, Q5R8R3, Q5XHI4, Q60963, Q63276, Q6NTR1, Q6P6V7, Q6Q2C2, Q6Q2Z6, Q6QR59, Q7TS68, Q86TX2, Q8BGG9, Q8BNE1, Q8BWN8, Q8C7R4, Q8N9L9

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

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	80
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3068712	NM_182543.5(NSUN6):c.967G>A (p.Asp323Asn)	Pathogenic
3068713	NM_182543.5(NSUN6):c.1320_1323del (p.Glu441fs)	Pathogenic
4813795	NM_182543.5(NSUN6):c.839del (p.Leu280fs)	Likely pathogenic

SpliceAI

3616 predictions. Top by Δscore:

Variant	Effect	Δscore
10:18547677:A:AC	donor_gain	1.0000
10:18547678:C:CC	donor_gain	1.0000
10:18547685:C:A	donor_gain	1.0000
10:18548106:TCCTA:T	donor_loss	1.0000
10:18548107:CCTA:C	donor_loss	1.0000
10:18548108:CTACC:C	donor_loss	1.0000
10:18548109:TA:T	donor_loss	1.0000
10:18548110:A:AG	donor_loss	1.0000
10:18548111:CC:C	donor_loss	1.0000
10:18551821:A:AC	donor_gain	1.0000
10:18551822:C:CC	donor_gain	1.0000
10:18551822:CTG:C	donor_gain	1.0000
10:18551866:T:TA	donor_gain	1.0000
10:18585943:GCTCA:G	donor_loss	1.0000
10:18585944:CTCA:C	donor_loss	1.0000
10:18585945:TCAC:T	donor_loss	1.0000
10:18585946:CACCT:C	donor_loss	1.0000
10:18585948:C:CA	donor_loss	1.0000
10:18585948:CCTT:C	donor_gain	1.0000
10:18586091:TCCC:T	acceptor_loss	1.0000
10:18586092:CCCT:C	acceptor_loss	1.0000
10:18586093:CCTAA:C	acceptor_loss	1.0000
10:18586094:C:CA	acceptor_loss	1.0000
10:18586095:T:A	acceptor_loss	1.0000
10:18596202:TCTCA:T	donor_loss	1.0000
10:18596203:CTCAC:C	donor_loss	1.0000
10:18596206:A:T	donor_loss	1.0000
10:18596207:C:A	donor_loss	1.0000
10:18596324:AATT:A	acceptor_gain	1.0000
10:18596326:TT:T	acceptor_gain	1.0000

AlphaMissense

3051 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:18548196:G:C	S371R	0.998
10:18548196:G:T	S371R	0.998
10:18548198:T:G	S371R	0.998
10:18545969:A:C	F458L	0.997
10:18545969:A:T	F458L	0.997
10:18545971:A:G	F458L	0.997
10:18551913:A:C	S327R	0.996
10:18551913:A:T	S327R	0.996
10:18551915:T:G	S327R	0.996
10:18548173:T:A	E379V	0.995
10:18548188:G:A	T374I	0.995
10:18548203:A:T	V369D	0.995
10:18596242:T:A	K248I	0.995
10:18616234:A:T	V124D	0.995
10:18616258:A:T	V116D	0.995
10:18548169:A:C	N380K	0.994
10:18548169:A:T	N380K	0.994
10:18551898:T:A	R332S	0.994
10:18551898:T:G	R332S	0.994
10:18551916:A:C	C326W	0.994
10:18551918:A:G	C326R	0.994
10:18586080:G:T	A264E	0.994
10:18596257:G:T	A243E	0.994
10:18616216:A:T	V130D	0.994
10:18548172:T:A	E379D	0.993
10:18548172:T:G	E379D	0.993
10:18548201:A:C	Y370D	0.993
10:18551839:C:G	R352P	0.993
10:18551841:C:A	Q351H	0.993
10:18551841:C:G	Q351H	0.993

dbSNP variants (sampled 300 via entrez): RS1000026184 (10:18595081 G>A), RS1000051482 (10:18646063 C>A,G,T), RS1000087200 (10:18589770 G>C), RS1000091469 (10:18552524 A>T), RS1000094064 (10:18551545 A>G), RS1000137423 (10:18568896 T>A), RS1000144978 (10:18609633 A>C), RS1000147003 (10:18619080 C>G,T), RS1000157739 (10:18629140 T>C), RS1000188861 (10:18568623 CTCCATTCCAT>C,CTCCAT,CTCCATTCCATTCCAT), RS1000202428 (10:18613662 G>T), RS1000250403 (10:18610215 G>A), RS1000257420 (10:18604595 G>A), RS1000265889 (10:18634228 A>C,G), RS1000268026 (10:18651533 G>A,T)

Disease associations

OMIM: gene MIM:617199 | disease phenotypes: MIM:620779, MIM:618744

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder, autosomal recessive 82	Strong	Autosomal recessive

Mondo (2): intellectual developmental disorder, autosomal recessive 82 (MONDO:0968944), developmental and epileptic encephalopathy, 83 (MONDO:0032895)

Orphanet (0):

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000369	Low-set ears
HP:0000717	Autism
HP:0000718	Aggressive behavior
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001320	Cerebellar vermis hypoplasia
HP:0001510	Growth delay
HP:0002360	Sleep disturbance
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0007018	Attention deficit hyperactivity disorder

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002149_6	Schizophrenia	1.000000e-10
GCST004521_192	Autism spectrum disorder or schizophrenia	3.000000e-10
GCST007201_423	Schizophrenia	3.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169179 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
trichostatin A	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Cadmium	increases abundance, increases expression	1
Calcitriol	increases expression	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5136937	Binding	Inhibition of full length human NSUN6 expressed in Escherichia coli Rosetta2(DE3)pLysS at 100 uM measured at 20 mins by liquid scintillation counting analysis	Discovery of Inhibitors of DNA Methyltransferase 2, an Epitranscriptomic Modulator and Potential Target for Cancer Treatment. — J Med Chem

Clinical trials (associated diseases)

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