NSUN2

Summary

NSUN2 (NOP2/Sun RNA methyltransferase 2, HGNC:25994) is a protein-coding gene on chromosome 5p15.31, encoding RNA cytosine C(5)-methyltransferase NSUN2 (Q08J23). RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs).

This gene encodes a methyltransferase that catalyzes the methylation of cytosine to 5-methylcytosine (m5C) at position 34 of intron-containing tRNA(Leu)(CAA) precursors. This modification is necessary to stabilize the anticodon-codon pairing and correctly translate the mRNA. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.

Source: NCBI Gene 54888 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 682 total — 32 pathogenic, 18 likely-pathogenic
• Phenotypes (HPO): 140
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_017755

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25994
Approved symbol	NSUN2
Name	NOP2/Sun RNA methyltransferase 2
Location	5p15.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20303, TRM4, Misu, SAKI
Ensembl gene	ENSG00000037474
Ensembl biotype	protein_coding
OMIM	610916
Entrez	54888

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 17 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000264670, ENST00000502932, ENST00000504374, ENST00000505264, ENST00000505892, ENST00000506139, ENST00000507888, ENST00000513888, ENST00000514127, ENST00000902913, ENST00000902914, ENST00000902915, ENST00000902916, ENST00000902917, ENST00000902918, ENST00000902919, ENST00000902920, ENST00000902921, ENST00000902922, ENST00000939214, ENST00000939215, ENST00000939216, ENST00000939217, ENST00000940950

RefSeq mRNA: 2 — MANE Select: NM_017755 NM_001193455, NM_017755

CCDS: CCDS3869, CCDS54832

Canonical transcript exons

ENST00000264670 — 19 exons

Exon	Start	End
ENSE00001010775	6599239	6600232
ENSE00001353389	6622016	6622100
ENSE00003461858	6617950	6618024
ENSE00003463693	6604605	6604685
ENSE00003487595	6610955	6611085
ENSE00003491280	6620106	6620298
ENSE00003493471	6631873	6631977
ENSE00003495463	6632599	6632756
ENSE00003508124	6625564	6625669
ENSE00003511408	6609826	6609922
ENSE00003556463	6607200	6607384
ENSE00003566868	6606820	6606912
ENSE00003601940	6602461	6602500
ENSE00003623714	6623214	6623285
ENSE00003637803	6611725	6611798
ENSE00003655381	6605273	6605408
ENSE00003693690	6604138	6604276
ENSE00003694461	6616727	6616857
ENSE00003850928	6632884	6633044

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 97.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.2222 / max 411.1196, expressed in 1827 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60857	38.5024	1826
60858	2.7198	1159

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	97.47	gold quality
right uterine tube	UBERON:0001302	96.08	gold quality
secondary oocyte	CL:0000655	96.00	gold quality
right lobe of liver	UBERON:0001114	95.31	gold quality
skin of abdomen	UBERON:0001416	95.14	gold quality
vermiform appendix	UBERON:0001154	94.95	gold quality
skin of leg	UBERON:0001511	94.88	gold quality
lymph node	UBERON:0000029	94.72	gold quality
epithelial cell of pancreas	CL:0000083	94.69	gold quality
oviduct epithelium	UBERON:0004804	94.52	gold quality
spleen	UBERON:0002106	94.45	gold quality
mucosa of transverse colon	UBERON:0004991	94.44	gold quality
body of pancreas	UBERON:0001150	94.39	gold quality
esophagus mucosa	UBERON:0002469	94.21	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.20	gold quality
left ovary	UBERON:0002119	94.18	gold quality
left uterine tube	UBERON:0001303	94.13	gold quality
right ovary	UBERON:0002118	94.03	gold quality
zone of skin	UBERON:0000014	93.98	gold quality
caecum	UBERON:0001153	93.96	gold quality
body of uterus	UBERON:0009853	93.95	gold quality
vagina	UBERON:0000996	93.94	gold quality
gastrocnemius	UBERON:0001388	93.88	gold quality
transverse colon	UBERON:0001157	93.87	gold quality
ectocervix	UBERON:0012249	93.87	gold quality
monocyte	CL:0000576	93.81	gold quality
nerve	UBERON:0001021	93.81	gold quality
tibial nerve	UBERON:0001323	93.81	gold quality
granulocyte	CL:0000094	93.76	gold quality
leukocyte	CL:0000738	93.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.12
E-MTAB-7303	no	319.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting NSUN2, 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-5692A	100.00	74.40	6850
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-569	99.42	66.32	1009
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-4438	97.96	63.70	947
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-3192-5P	96.98	65.76	1926

Literature-anchored findings (GeneRIF, showing 40)

• First report showing intron-dependent methylation of human pre-tRNA Leu(CAA) and identification of human gene encoding tRNA methylase(Trm4) responsible for this reaction. (PMID:17071714)
• These results indicate that Aurora-B participates to regulate the assembly of nucleolar RNA-processing machinery and the RNA methyltransferase activity of NSUN2 via phosphorylation at Ser139 during mitosis. (PMID:17215513)
• These results suggest a novel mechanism by which c-Myc promotes proliferation by stabilizing the mitotic spindle in fast-dividing cells via Misu and NuSAP. (PMID:19596847)
• was extensive copy number gain, and increased mRNA and protein levels, of Misu in approximately one third of breast cancer cell lines and primary tumours examined, irrespective of tumour subtype (PMID:19740597)
• Increased gene copy number and high protein expression of NSUN2 is associated with cancers. (PMID:22136356)
• findings show that NSun2, a transfer RNA methyltransferase, inhibits the turnover of p16(INK4) mRNA; conclude that NSun2-mediated methylation of the p16 3’UTR is a novel mechanism to stabilize p16 mRNA (PMID:22395603)
• A deficiency in NSUN2 function causes intellectual disability in individuals homozygous for these mutations. (PMID:22541559)
• The substitution of glycine to arginine at position 679 impairs the proper cellular localization of NSUN2 to the nucleolus. This mutation causes autosomal-recessive intellectual disability. (PMID:22541562)
• Enrolled a multiplex consanguineous family from the United Arab Emirates with many key clinical features of Dubowitz syndrome. Identified a homozygous splice mutation in the NSUN2 gene, encoding a conserved RNA methyltransferase. (PMID:22577224)
• Impaired processing of vault ncRNA may contribute to the etiology of NSun2-deficiency human disorders. (PMID:23871666)
• Results show that NSun2 methylates primary (pri-miR-125b), precursor (pre-miR-125b), and mature microRNA 125b (miR-125b) in vitro and in vivo. (PMID:25047833)
• In conclusion, failure in NSun2-mediated tRNA methylation contributes to human diseases via stress-induced RNA cleavage. (PMID:25063673)
• tRNA modifying enzymes, NSUN2 and METTL1, determine sensitivity to 5-fluorouracil in HeLa cells (PMID:25233213)
• A novel homozygous variant c.1020delA in NSUN2 gene segregated in an autosomal recessive mode in the family of a child with intellectual disability. It causes a frameshift and premature stop codon, decreasing mRNA levels. (PMID:26055038)
• By methylating the CDK1 mRNA at the 3’UTR, NSun2 enhances the translation of CDK1, thereby influencing entry into and the progression of the cell division cycle. (PMID:26391950)
• Report frequencies of short tandem repeat markers linked to TUSC3 (MRT7) or NSUN2 (MRT5) genes used for homozygosity mapping of recessive intellectual disability. (PMID:26427135)
• These findings indicate that NSun2-mediated mRNA methylation regulates p27 and CDK1 levels during replicative senescence. (PMID:26687548)
• Findings indicate the critical impact of RNA methyltransferase NSUN2-mediated mRNA methylation in promoting premature senescence. (PMID:26992231)
• Our findings provide a unique insight into the roles and effects of NSUN2 overexpression in breast cancer cells (PMID:27447970)
• methylation at m6A by METTL3/METTL14 facilitates the methylation of m5C by NSUN2, and vice versa. NSUN2-mediated m5C and METTL3/METTL14-mediated m6A methylation synergistically enhance p21 expression at the translational level (PMID:28247949)
• findings point to YB-1 and NSUN2 as possible mediators of the process of transfer of specific mRNAs into exosomes, allowing us to speculate on an involvement of these proteins in the mRNA sorting via the recognition of the above motifs (PMID:28341602)
• Dysregulation of ALYREF-mediated mRNA export upon NSUN2 depletion could be restored by reconstitution of wild-type but not methyltransferase-defective NSUN2. (PMID:28418038)
• Upregulation of NSUN2 expression is associated with ovarian cancer. (PMID:28829218)
• Study identified a novel NSUN2 methylated lncRNA (NMR), which was significantly upregulated in esophageal squamous cell carcinoma (ESCC), functioned as a key regulator of ESCC tumor metastasis and drug resistance. NMR could directly bind to chromatin regulator BPTF, and potentially promote MMP3 and MMP10 expression by ERK1/2 pathway through recruiting BPTF to chromatin. (PMID:29763634)
• Patients with high NSUN2 levels had approximately 22 months shorter overall survival, and had a higher mortality risk than those with low one (p-trend = 0.020). (PMID:29775108)
• NSUN2 introduces 5-methylcytosines in mammalian mitochondrial tRNAs. (PMID:31276587)
• Mammalian NSUN2 introduces 5-methylcytosines in mammalian mitochondrial tRNAs. (PMID:31287866)
• The highly expressed NSUN2, through closely coordinating with RPL6, promoted gallbladder carcinoma cells proliferation and tumorigenesis both in vitro and in vivo. This newly discovered orchestration also helped explain the regulation of cell proliferation by NSUN2 in gallbladder carcinoma, which makes it an important marker during gallbladder carcinoma progression. (PMID:31487418)
• N(6)-methyladenosine modification of circNSUN2 modulates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis. (PMID:31619685)
• Aberrant NSUN2-mediated m(5)C modification of H19 lncRNA is associated with poor differentiation of hepatocellular carcinoma. (PMID:32978516)
• Further delineation of autosomal recessive intellectual disability syndrome caused by homozygous variant of the NSUN2 gene in a chinese pedigree. (PMID:33002343)
• Expanding the phenotype of biallelic loss-of-function variants in the NSUN2 gene: Description of four individuals with juvenile cataract, chronic nephritis, or brain anomaly as novel complications. (PMID:33084202)
• NSun2 promotes cell migration through methylating autotaxin mRNA. (PMID:33093178)
• FOXC2-AS1 stabilizes FOXC2 mRNA via association with NSUN2 in gastric cancer cells. (PMID:34324140)
• RNA methyltransferase NSUN2 promotes growth of hepatocellular carcinoma cells by regulating fizzy-related-1 in vitro and in vivo. (PMID:34370374)
• NSUN2 modified by SUMO-2/3 promotes gastric cancer progression and regulates mRNA m5C methylation. (PMID:34504059)
• Regulation and Site-Specific Covalent Labeling of NSUN2 via Genetic Encoding Expansion. (PMID:34680884)
• Reorganization of the Landscape of Translated mRNAs in NSUN2-Deficient Cells and Specific Features of NSUN2 Target mRNAs. (PMID:36077143)
• Positive epigenetic regulation loop between AR and NSUN2 promotes prostate cancer progression. (PMID:36169095)
• NSUN2-mediated mRNA m[5]C Modification Regulates the Progression of Hepatocellular Carcinoma. (PMID:36183976)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nsun2	ENSDARG00000056665
mus_musculus	Nsun2	ENSMUSG00000021595
rattus_norvegicus	Nsun2	ENSRNOG00000017254
drosophila_melanogaster	Nsun2	FBGN0026079

Paralogs (2): NSUN4 (ENSG00000117481), NSUN3 (ENSG00000178694)

Protein

Protein identifiers

RNA cytosine C(5)-methyltransferase NSUN2 — Q08J23 (reviewed: Q08J23)

Alternative names: Myc-induced SUN domain-containing protein, NOL1/NOP2/Sun domain family member 2, Substrate of AIM1/Aurora kinase B, mRNA cytosine C(5)-methyltransferase, tRNA cytosine C(5)-methyltransferase, tRNA methyltransferase 4 homolog

All UniProt accessions (3): A0A140T9Y7, A0A140T9Z1, Q08J23

UniProt curated annotations — full annotation on UniProt →

Function. RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs). Involved in various processes, such as epidermal stem cell differentiation, testis differentiation and maternal to zygotic transition during early development: acts by increasing protein synthesis; cytosine C(5)-methylation promoting tRNA stability and preventing mRNA decay. Methylates cytosine to 5-methylcytosine (m5C) at positions 34 and 48 of intron-containing tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of tRNA(Gly)(GCC) precursors. tRNA methylation is required generation of RNA fragments derived from tRNAs (tRFs). Also mediates C(5)-methylation of mitochondrial tRNAs. Catalyzes cytosine C(5)-methylation of mRNAs, leading to stabilize them and prevent mRNA decay: mRNA stabilization involves YBX1 that specifically recognizes and binds m5C-modified transcripts. Cytosine C(5)-methylation of mRNAs also regulates mRNA export: methylated transcripts are specifically recognized by THOC4/ALYREF, which mediates mRNA nucleo-cytoplasmic shuttling. Also mediates cytosine C(5)-methylation of non-coding RNAs, such as vault RNAs (vtRNAs), promoting their processing into regulatory small RNAs. Cytosine C(5)-methylation of vtRNA VTRNA1.1 promotes its processing into small-vault RNA4 (svRNA4) and regulates epidermal differentiation. May act downstream of Myc to regulate epidermal cell growth and proliferation. Required for proper spindle assembly and chromosome segregation, independently of its methyltransferase activity.

Subunit / interactions. Interacts with NPM1 and NCL during interphase; interaction is disrupted following phosphorylation at Ser-139.

Subcellular location. Nucleus. Nucleolus. Cytoplasm. Mitochondrion. Cytoskeleton. Spindle. Secreted. Extracellular exosome.

Tissue specificity. Expressed in adult and fetal brain and in lymphoblastoid cells.

Post-translational modifications. Phosphorylated at Ser-139 by AURKB during mitosis, leading to abolish methyltransferase activity and the interaction with NPM1.

Disease relevance. Intellectual developmental disorder, autosomal recessive 5 (MRT5) [MIM:611091] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by magnesium ions.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family. TRM4 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q08J23-1	1	yes
Q08J23-2	2
Q08J23-3	3

RefSeq proteins (2): NP_001180384, NP_060225* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001678	MeTrfase_RsmB-F_NOP2_dom	Domain
IPR023267	RCMT	Family
IPR023270	RCMT_NCL1	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR049560	MeTrfase_RsmB-F_NOP2_cat	Domain
IPR057285	Pre-PUA_NSUN2	Domain
IPR057286	PUA_NSUN2	Domain

Pfam: PF01189, PF25376, PF25378

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

Catalyzed reactions (Rhea), 5 shown:

• cytidine(34) in tRNA precursor + S-adenosyl-L-methionine = 5-methylcytidine(34) in tRNA precursor + S-adenosyl-L-homocysteine + H(+) (RHEA:42940)
• cytidine(48) in tRNA + S-adenosyl-L-methionine = 5-methylcytidine(48) in tRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:42948)
• cytidine(49) in tRNA + S-adenosyl-L-methionine = 5-methylcytidine(49) in tRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:42952)
• a cytidine in mRNA + S-adenosyl-L-methionine = a 5-methylcytidine in mRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:61464)
• cytidine(50) in tRNA + S-adenosyl-L-methionine = 5-methylcytidine(50) in tRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:61488)

UniProt features (44 total): modified residue 10, cross-link 9, mutagenesis site 5, sequence conflict 5, binding site 4, region of interest 3, splice variant 2, sequence variant 2, compositionally biased region 2, chain 1, active site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
9Z2N	ELECTRON MICROSCOPY	2.57
9Z2O	ELECTRON MICROSCOPY	2.66
9Z2Q	ELECTRON MICROSCOPY	2.88
9Z2P	ELECTRON MICROSCOPY	2.91
9Z3D	ELECTRON MICROSCOPY	2.96
9Z2U	ELECTRON MICROSCOPY	3
9Z2W	ELECTRON MICROSCOPY	3.1
9Z2T	ELECTRON MICROSCOPY	3.7
9Z2R	ELECTRON MICROSCOPY	3.71

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08J23-F1	79.09	0.63

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): 321 (nucleophile)

Ligand- & substrate-binding residues (4): 268; 184–190; 215; 242

Post-translational modifications (19): 139, 456, 473, 586, 586, 593, 718, 724, 743, 751, 46, 464, 470, 511, 516, 586, 640, 654, 660

Mutagenesis-validated functional residues (5):

Position	Phenotype
139	induces a constitutive association with npm1.
139	mimicks constitutive phosphorylation and abolishes methyltransferase activity.
190	loss of rna methyltransferase activity.
271	abolished mrna methyltransferase activity; when associated with a-321.
321	abolished mrna methyltransferase activity; when associated with a-271.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 529 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, MODULE_97, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, TSENG_IRS1_TARGETS_UP, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_TRNA_METABOLIC_PROCESS, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_493, LANG_MYB_FAMILY_TARGETS, MODULE_182, GOBP_MALE_GAMETE_GENERATION, GOBP_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT

GO Biological Process (16): in utero embryonic development (GO:0001701), mRNA processing (GO:0006397), tRNA modification (GO:0006400), spermatid development (GO:0007286), regulation of mRNA export from nucleus (GO:0010793), tRNA methylation (GO:0030488), meiotic cell cycle checkpoint signaling (GO:0033313), tRNA stabilization (GO:0036416), hair follicle maturation (GO:0048820), cell division (GO:0051301), regulation of stem cell differentiation (GO:2000736), RNA methylation (GO:0001510), spermatogenesis (GO:0007283), tRNA processing (GO:0008033), cell differentiation (GO:0030154), methylation (GO:0032259)

GO Molecular Function (9): tRNA binding (GO:0000049), RNA binding (GO:0003723), tRNA (cytidine-N5)-methyltransferase activity (GO:0016428), mRNA (cytidine-5-)-methyltransferase activity (GO:0062152), protein binding (GO:0005515), methyltransferase activity (GO:0008168), RNA methyltransferase activity (GO:0008173), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), transferase activity (GO:0016740)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitochondrion (GO:0005739), spindle (GO:0005819), chromatoid body (GO:0033391), extracellular exosome (GO:0070062), extracellular region (GO:0005576), cytoskeleton (GO:0005856)

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
cellular anatomical structure	3
intracellular membraneless organelle	3
RNA processing	2
RNA modification	2
methyltransferase activity	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
chordate embryonic development	1
mRNA metabolic process	1
tRNA processing	1
germ cell development	1
spermatid differentiation	1
mRNA export from nucleus	1
regulation of RNA export from nucleus	1
regulation of ribonucleoprotein complex localization	1
RNA methylation	1
tRNA modification	1
cell cycle checkpoint signaling	1
meiotic cell cycle	1
meiotic cell cycle process	1
regulation of tRNA stability	1
RNA stabilization	1
negative regulation of tRNA catabolic process	1
hair follicle development	1
hair cycle process	1
anatomical structure maturation	1
cellular process	1
regulation of cell differentiation	1
stem cell differentiation	1
macromolecule methylation	1
developmental process involved in reproduction	1
male gamete generation	1
tRNA metabolic process	1
cellular developmental process	1
metabolic process	1
RNA binding	1
nucleic acid binding	1
tRNA (cytidine) methyltransferase activity	1
mRNA methyltransferase activity	1
binding	1

Protein interactions and networks

STRING

2670 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NSUN2	TRDMT1	O14717	875
NSUN2	NSUN7	Q8NE18	816
NSUN2	ALYREF	Q86V81	795
NSUN2	AURKB	Q96GD4	769
NSUN2	METTL1	Q9UBP6	768
NSUN2	FTSJ1	Q9UET6	760
NSUN2	YTHDC1	Q96MU7	757
NSUN2	NPM1	P06748	752
NSUN2	PUS7	Q96PZ0	745
NSUN2	WDR4	P57081	717
NSUN2	TRMT1	Q9NXH9	716
NSUN2	METTL14	Q9HCE5	715
NSUN2	MYC	P01106	713
NSUN2	TRMT6	Q9UJA5	711
NSUN2	NOP2	P46087	704

IntAct

181 interactions, top by confidence:

A	B	Type	Score
NRP1	CSNK2A2	psi-mi:“MI:0914”(association)	0.790
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
Cep78	UBR5	psi-mi:“MI:0915”(physical association)	0.560
NSUN2	LIN7A	psi-mi:“MI:0914”(association)	0.530
NSUN2	UBE3A	psi-mi:“MI:0915”(physical association)	0.500
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
LTK	PIK3R2	psi-mi:“MI:0914”(association)	0.420
Dync1h1	DYNLT3	psi-mi:“MI:0915”(physical association)	0.400
Cdk1		psi-mi:“MI:0915”(physical association)	0.400
Plk1		psi-mi:“MI:0915”(physical association)	0.400
Tubg1		psi-mi:“MI:0915”(physical association)	0.400
NSUN2	CCR4	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
Eif3a	RPSA	psi-mi:“MI:0914”(association)	0.350
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
Srp72		psi-mi:“MI:0914”(association)	0.350

BioGRID (362): NSUN2 (Affinity Capture-MS), NSUN2 (Affinity Capture-MS), NSUN2 (Affinity Capture-MS), NSUN2 (Affinity Capture-MS), CSNK1E (Co-fractionation), DDX49 (Co-fractionation), NSUN2 (Co-fractionation), NSUN2 (Co-fractionation), NSUN2 (Co-fractionation), NSUN2 (Co-fractionation), PNO1 (Co-fractionation), YES1 (Co-fractionation), NSUN2 (Affinity Capture-MS), NSUN2 (Affinity Capture-MS), NSUN2 (Proximity Label-MS)

ESM2 similar proteins: A0JN95, A4IF87, A6NJ78, B5DEQ3, B7ZMP1, D3ZLY0, E9Q4Z2, F1QDI9, G1SPE9, O14717, O15228, O22268, O55055, O95453, O95671, P37287, P69341, P97770, Q05B63, Q08J23, Q0V8R7, Q0VGM9, Q10D00, Q1HFZ0, Q2T9W2, Q4G073, Q5R5T5, Q5R962, Q5R9W8, Q5RC51, Q5RJZ1, Q6GR37, Q6H1L8, Q6NYU2, Q6YJI5, Q7TNK6, Q7YS61, Q7Z4G4, Q8JZM0, Q8R2Y8

Diamond homologs: A1JRZ3, A1S788, A4SMI9, A4TH21, A4WF97, A7FNK4, A8AQI3, A8GDM6, A8GKG7, A9MN78, A9N8B3, A9R925, B1JJH6, B2K506, B2VK95, B4F1L5, B4SUR0, B4TJX9, B4TXB2, B5BGV5, B5F7R5, B5R1E5, B5RH47, B5XQ35, C0PZV1, C3LMI5, O13935, O94268, P38205, P40991, P44788, P72943, Q08J23, Q12MJ8, Q1C2X7, Q1CCX4, Q1HFZ0, Q28E61, Q2NQQ2, Q4V7N2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
AURKB	down-regulates	NSUN2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 220 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
Tie2 Signaling	5	19.1×	6e-04
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	16.5×	7e-04
Downstream signal transduction	5	12.1×	2e-03
SPOP-mediated proteasomal degradation of PD-L1(CD274)	7	10.2×	6e-04
Eukaryotic Translation Initiation	5	9.8×	3e-03
Cap-dependent Translation Initiation	5	9.8×	3e-03
SARS-CoV-1 modulates host translation machinery	5	9.8×	3e-03
Formation of the ternary complex, and subsequently, the 43S complex	7	9.6×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	8	17.4×	9e-06
cellular response to vascular endothelial growth factor stimulus	5	14.5×	2e-03
ribosomal large subunit biogenesis	6	13.7×	6e-04
cell surface receptor protein tyrosine kinase signaling pathway	14	12.5×	9e-09
vascular endothelial growth factor receptor signaling pathway	5	12.4×	4e-03
inner ear development	6	11.6×	1e-03
cytoplasmic translation	10	9.6×	3e-05
protein autophosphorylation	11	8.2×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	18
Uncertain significance	242
Likely benign	231
Benign	92

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1203838	NM_017755.6(NSUN2):c.1095+1G>A	Pathogenic
1319735	NC_000005.10:g.6611086del	Pathogenic
1722540	NM_017755.6(NSUN2):c.953A>C (p.Tyr318Ser)	Pathogenic
1722581	NM_017755.6(NSUN2):c.97-1G>C	Pathogenic
1782639	NM_017755.6(NSUN2):c.191del (p.Gly64fs)	Pathogenic
1783646	NM_017755.6(NSUN2):c.1071G>A (p.Trp357Ter)	Pathogenic
1910346	NM_017755.6(NSUN2):c.560del (p.Pro187fs)	Pathogenic
2113943	NM_017755.6(NSUN2):c.337dup (p.Glu113fs)	Pathogenic
2240674	NM_017755.6(NSUN2):c.1346_1352del (p.Thr449fs)	Pathogenic
2426349	NC_000005.9:g.(?6600039)(6845036_?)del	Pathogenic
2506872	NM_017755.6(NSUN2):c.1617_1621dup (p.Pro541fs)	Pathogenic
2699555	NM_017755.6(NSUN2):c.1868C>G (p.Ser623Ter)	Pathogenic
2784085	NM_017755.6(NSUN2):c.416C>A (p.Ser139Ter)	Pathogenic
2856351	NM_017755.6(NSUN2):c.1251_1252del (p.Asn418fs)	Pathogenic
2858490	NM_017755.6(NSUN2):c.1398_1399delinsCTTCTGTTTTTTTTTTTATCTATCATGTTCACAAAGTAAAAGTTTACTTTCTCCTTAAATTAAAAGATTGAGTAACCTCTAAAGTTTC (p.Asp467delinsPheCysPhePhePheTyrLeuSerCysSerGlnSerLysSerLeuLeuSerProTer)	Pathogenic
31675	NM_017755.6(NSUN2):c.679C>T (p.Gln227Ter)	Pathogenic
31676	NM_017755.6(NSUN2):c.1114C>T (p.Gln372Ter)	Pathogenic
31677	NM_017755.6(NSUN2):c.538-11T>G	Pathogenic
3246528	NC_000005.9:g.(?6600039)(6633092_?)del	Pathogenic
3390924	NM_017755.6(NSUN2):c.726_730del (p.Ala243fs)	Pathogenic
37005	NM_017755.6(NSUN2):c.538-1G>C	Pathogenic
4080641	NM_017755.6(NSUN2):c.1478del (p.Asn493fs)	Pathogenic
426340	NM_017755.6(NSUN2):c.1131G>A (p.Trp377Ter)	Pathogenic
426687	NM_017755.6(NSUN2):c.753_756del (p.Ile251fs)	Pathogenic
4531997	NM_017755.6(NSUN2):c.69del (p.Glu24fs)	Pathogenic
4710618	NM_017755.6(NSUN2):c.439C>T (p.Gln147Ter)	Pathogenic
4712852	NM_017755.6(NSUN2):c.250_251insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTCAGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGAATTACTGGTTACA (p.Lys84fs)	Pathogenic
4719285	NM_017755.6(NSUN2):c.1219G>T (p.Glu407Ter)	Pathogenic
664755	NM_017755.6(NSUN2):c.1305G>A (p.Trp435Ter)	Pathogenic
687967	GRCh37/hg19 5p15.31(chr5:6599369-6603435)x1	Pathogenic

SpliceAI

3360 predictions. Top by Δscore:

Variant	Effect	Δscore
5:6602460:CG:C	donor_gain	1.0000
5:6604606:T:TA	donor_gain	1.0000
5:6605254:G:C	donor_gain	1.0000
5:6606818:A:AC	donor_gain	1.0000
5:6606819:C:CC	donor_gain	1.0000
5:6606819:CT:C	donor_gain	1.0000
5:6606913:C:CC	acceptor_gain	1.0000
5:6616722:CTTA:C	donor_loss	1.0000
5:6616723:TTAC:T	donor_loss	1.0000
5:6616724:TAC:T	donor_loss	1.0000
5:6616725:A:AC	donor_gain	1.0000
5:6616725:A:AT	donor_loss	1.0000
5:6616726:C:CC	donor_gain	1.0000
5:6616726:CCTT:C	donor_gain	1.0000
5:6616858:C:CC	acceptor_gain	1.0000
5:6617948:A:AC	donor_gain	1.0000
5:6617948:AC:A	donor_gain	1.0000
5:6617949:C:CC	donor_gain	1.0000
5:6617949:CC:C	donor_gain	1.0000
5:6618020:CTCCA:C	acceptor_gain	1.0000
5:6618022:CCA:C	acceptor_gain	1.0000
5:6618023:CA:C	acceptor_gain	1.0000
5:6618023:CAC:C	acceptor_gain	1.0000
5:6618025:C:CC	acceptor_gain	1.0000
5:6619314:A:AC	donor_gain	1.0000
5:6619315:C:CC	donor_gain	1.0000
5:6620152:T:A	donor_gain	1.0000
5:6620294:TCCCT:T	acceptor_gain	1.0000
5:6620295:CCCT:C	acceptor_gain	1.0000
5:6620295:CCCTC:C	acceptor_gain	1.0000

AlphaMissense

5071 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:6600192:A:G	W680R	1.000
5:6600192:A:T	W680R	1.000
5:6604672:C:T	G584E	1.000
5:6604673:C:A	G584W	1.000
5:6617981:A:G	W287R	1.000
5:6617981:A:T	W287R	1.000
5:6617990:A:G	W284R	1.000
5:6617990:A:T	W284R	1.000
5:6618003:T:A	K279N	1.000
5:6618003:T:G	K279N	1.000
5:6618004:T:A	K279I	1.000
5:6618006:T:A	R278S	1.000
5:6618006:T:G	R278S	1.000
5:6618007:C:G	R278T	1.000
5:6618020:C:G	D274H	1.000
5:6620118:T:A	D268V	1.000
5:6620250:A:G	L224P	1.000
5:6620258:G:C	C221W	1.000
5:6620259:C:T	C221Y	1.000
5:6620279:A:C	N214K	1.000
5:6620279:A:T	N214K	1.000
5:6623256:G:C	S165R	1.000
5:6623256:G:T	S165R	1.000
5:6623258:T:G	S165R	1.000
5:6623273:G:T	R160S	1.000
5:6625618:T:A	R137S	1.000
5:6625618:T:G	R137S	1.000
5:6625619:C:G	R137T	1.000
5:6600185:C:T	G682E	0.999
5:6600190:C:A	W680C	0.999

dbSNP variants (sampled 300 via entrez): RS1000093478 (5:6602015 G>A,C), RS1000117715 (5:6633562 T>C), RS1000243373 (5:6627367 G>C), RS1000300357 (5:6606664 T>C), RS1000303865 (5:6601188 A>G), RS1000388984 (5:6632925 C>T), RS1000411784 (5:6601421 C>T), RS1000425733 (5:6611929 C>G,T), RS1000469455 (5:6627247 T>A,C), RS1000782730 (5:6631378 G>A,T), RS1000935098 (5:6617789 A>G), RS1001045988 (5:6627526 C>T), RS1001090310 (5:6602998 A>C), RS1001128316 (5:6621514 C>A,G,T), RS1001153532 (5:6602329 C>G)

Disease associations

OMIM: gene MIM:610916 | disease phenotypes: MIM:611091, MIM:249500, MIM:261600

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal recessive 5	Strong	Autosomal recessive
Dubowitz syndrome	Supportive	Autosomal recessive
autosomal recessive non-syndromic intellectual disability	Supportive	Autosomal recessive
RASopathy	Disputed Evidence	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
RASopathy	Disputed	AR
syndromic intellectual disability	Definitive	AR

Mondo (6): intellectual disability, autosomal recessive 5 (MONDO:0012613), autosomal recessive non-syndromic intellectual disability (MONDO:0019502), intellectual disability (MONDO:0001071), phenylketonuria (MONDO:0009861), RASopathy (MONDO:0021060), Dubowitz syndrome (MONDO:0009124)

Orphanet (3): Autosomal recessive non-syndromic intellectual disability (Orphanet:88616), Phenylketonuria (Orphanet:716), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

140 total (30 of 140 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000049	Shawl scrotum
HP:0000055	Abnormal female external genitalia morphology
HP:0000126	Hydronephrosis
HP:0000154	Wide mouth
HP:0000164	Abnormality of the dentition
HP:0000176	Submucous cleft hard palate
HP:0000215	Thick upper lip vermilion
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000260	Wide anterior fontanel
HP:0000270	Delayed cranial suture closure
HP:0000275	Narrow face
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000331	Short chin
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000403	Recurrent otitis media
HP:0000411	Protruding ear
HP:0000426	Prominent nasal bridge

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001525_8	Visceral fat	3.000000e-06
GCST008156_102	Hip circumference adjusted for BMI	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D010661	Phenylketonurias	C10.228.140.163.100.687; C16.320.565.100.766; C16.320.565.189.687; C18.452.132.100.687; C18.452.648.100.766; C18.452.648.189.687
C535718	Dubowitz syndrome (supp.)
C567018	Mental Retardation, Autosomal Recessive 5 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4739683 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
9.73	Kd	0.187	nM	CHEMBL5653589
9.73	ED50	0.187	nM	CHEMBL5653589
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 21 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148891: Binding affinity to human NSUN2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0002	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	2178725: Inhibition of NSUN2 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
bisphenol A	decreases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Valproic Acid	increases expression, affects expression	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
lead acetate	affects cotreatment, decreases expression	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, affects localization, decreases expression	1
decabromobiphenyl ether	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ochratoxin A	increases expression	1
potassium chromate(VI)	increases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
ICG 001	decreases 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
bisphenol S	affects expression	1
LDN 193189	affects cotreatment, decreases expression	1
Venlafaxine Hydrochloride	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4709790	Binding	Binding affinity to NSUN2 (unknown origin)	Discovery and structure-activity relationship studies of 1-aryl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione derivatives as potent dual inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1) and trytophan 2,3-dioxygenase (TDO). — Eur J Med Chem

Cellosaurus cell lines

6 cell lines: 4 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3CV	Abcam HEK293T NSUN2 KO	Transformed cell line	Female
CVCL_D9LQ	Ubigene HEK293 NSUN2 KO	Transformed cell line	Female
CVCL_E0UN	Ubigene Hep G2 NSUN2 KO	Cancer cell line	Male
CVCL_F1R7	HyCyte KYSE-150 KO-hNSUN2	Cancer cell line	Female
CVCL_TB15	HAP1 NSUN2 (-) 1	Cancer cell line	Male
CVCL_XR16	HAP1 NSUN2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT04888936	Not specified	RECRUITING	Clinical, Genetic, and Epidemiologic Study of Children and Adults With RASopathies
NCT05761314	Not specified	RECRUITING	Solid Tumors in RASopathies
NCT06331117	Not specified	UNKNOWN	Effect of RAS/MAPK Pathway Hyperactivation on Growth’ and Bone’ Profile of the RASopathies
NCT06355622	Not specified	UNKNOWN	Prevalence and Characterization of Pain in RASopathies
NCT06489067	Not specified	RECRUITING	Study of the Thyroid Function and Echostructural Morphology in Patients Affected With Rasopathies (ECORAS2023)
NCT06776380	Not specified	RECRUITING	Pubertal Development in Patients with RASopathies
NCT07005297	Not specified	NOT_YET_RECRUITING	Clinical Genetics Branch Eligibility Screening Survey
NCT07344480	Not specified	RECRUITING	Retrospective Natural History Study of RASopathy-associated Cardiomyopathy (RAS-CM)
NCT07464821	Not specified	RECRUITING	National Multicentre Study on Lipid Profile in Noonan Syndrome and Related Disorders: Trends by Age, Gender and Genotype
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)