NONO

Summary

NONO (non-POU domain containing octamer binding, HGNC:7871) is a protein-coding gene on chromosome Xq13.1, encoding Non-POU domain-containing octamer-binding protein (Q15233). DNA- and RNA binding protein, involved in several nuclear processes. It is a selective cancer dependency (DepMap: 12.5% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene encodes an RNA-binding protein which plays various roles in the nucleus, including transcriptional regulation and RNA splicing. A rearrangement between this gene and the transcription factor E3 gene has been observed in papillary renal cell carcinoma. Alternatively spliced transcript variants have been described. Pseudogenes exist on Chromosomes 2 and 16.

Source: NCBI Gene 4841 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked syndromic intellectual disability (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 258 total — 23 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 104
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 12.5% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 22 downstream targets (CollecTRI)
• MANE Select transcript: NM_007363

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7871
Approved symbol	NONO
Name	non-POU domain containing octamer binding
Location	Xq13.1
Locus type	gene with protein product
Status	Approved
Aliases	p54(NRB), NRB54, NMT55, P54NRB, P54, PPP1R114
Ensembl gene	ENSG00000147140
Ensembl biotype	protein_coding
OMIM	300084
Entrez	4841

Gene structure

Transcript identifiers

Ensembl transcripts: 61 — 39 protein_coding, 12 retained_intron, 6 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay

ENST00000276079, ENST00000373841, ENST00000373856, ENST00000413858, ENST00000418921, ENST00000420903, ENST00000450092, ENST00000454976, ENST00000471419, ENST00000472185, ENST00000473525, ENST00000474431, ENST00000486613, ENST00000490044, ENST00000535149, ENST00000676495, ENST00000676499, ENST00000676797, ENST00000677014, ENST00000677218, ENST00000677245, ENST00000677274, ENST00000677446, ENST00000677612, ENST00000677766, ENST00000677826, ENST00000677879, ENST00000677977, ENST00000678231, ENST00000678323, ENST00000678335, ENST00000678414, ENST00000678437, ENST00000678660, ENST00000678830, ENST00000678852, ENST00000679029, ENST00000679062, ENST00000679254, ENST00000679267, ENST00000861754, ENST00000861755, ENST00000861756, ENST00000861757, ENST00000861758, ENST00000936524, ENST00000936525, ENST00000936526, ENST00000936527, ENST00000936528, ENST00000936529, ENST00000936530, ENST00000936531, ENST00000936532, ENST00000936533, ENST00000936534, ENST00000936535, ENST00000936536, ENST00000959799, ENST00000959800, ENST00000959801

RefSeq mRNA: 4 — MANE Select: NM_007363 NM_001145408, NM_001145409, NM_001145410, NM_007363

CCDS: CCDS14410, CCDS55445

Canonical transcript exons

ENST00000276079 — 12 exons

Exon	Start	End
ENSE00001209504	71284397	71284453
ENSE00001814876	71283635	71283721
ENSE00003464857	71298707	71298816
ENSE00003480304	71291779	71291972
ENSE00003483535	71294227	71294528
ENSE00003490510	71299942	71301168
ENSE00003526418	71290629	71290791
ENSE00003538254	71297377	71297461
ENSE00003586506	71296851	71297047
ENSE00003649071	71298469	71298508
ENSE00003656065	71297836	71297938
ENSE00003667938	71296565	71296660

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 99.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 117.1734 / max 1506.8661, expressed in 1823 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196672	87.8371	1823
196677	15.2800	1759
196673	7.9947	1742
196679	1.4822	768
196678	1.2861	767
196675	1.0478	671
196676	0.8176	486
196671	0.8056	516
196670	0.5843	300
196674	0.0382	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	99.62	gold quality
embryo	UBERON:0000922	99.60	gold quality
ganglionic eminence	UBERON:0004023	99.60	gold quality
ventricular zone	UBERON:0003053	99.54	gold quality
cortical plate	UBERON:0005343	99.46	gold quality
thymus	UBERON:0002370	99.35	gold quality
trachea	UBERON:0003126	99.20	gold quality
cerebellar vermis	UBERON:0004720	99.13	gold quality
epithelium of bronchus	UBERON:0002031	99.09	gold quality
paraflocculus	UBERON:0005351	99.09	gold quality
stromal cell of endometrium	CL:0002255	99.06	gold quality
ovary	UBERON:0000992	99.02	gold quality
left ovary	UBERON:0002119	99.00	gold quality
calcaneal tendon	UBERON:0003701	98.99	gold quality
right ovary	UBERON:0002118	98.96	gold quality
islet of Langerhans	UBERON:0000006	98.91	gold quality
body of pancreas	UBERON:0001150	98.85	gold quality
pancreas	UBERON:0001264	98.80	gold quality
left adrenal gland	UBERON:0001234	98.78	gold quality
left adrenal gland cortex	UBERON:0035825	98.77	gold quality
adenohypophysis	UBERON:0002196	98.76	gold quality
right adrenal gland cortex	UBERON:0035827	98.76	gold quality
right adrenal gland	UBERON:0001233	98.72	gold quality
pituitary gland	UBERON:0000007	98.70	gold quality
cerebellum	UBERON:0002037	98.69	gold quality
cerebellar cortex	UBERON:0002129	98.67	gold quality
adrenal tissue	UBERON:0018303	98.67	gold quality
cerebellar hemisphere	UBERON:0002245	98.66	gold quality
body of uterus	UBERON:0009853	98.64	gold quality
cortex of kidney	UBERON:0001225	98.63	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	44.44
E-CURD-114	yes	7.52
E-HCAD-5	no	21.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

22 targets.

Target	Regulation
AR
BANF1
BIRC5	Unknown
COL2A1	Activation
CYP17A1
GJA1
HTT
IL27
IRF6
KLK3
MIA	Unknown
NONO
NOS3
OCLN
PGR	Repression
POU5F1	Unknown
PRL
PSIP1
RBP4
RHO
SNCA
TOP2B

Upstream regulators (CollecTRI, top): ESR1, IRF6, NONO

miRNA regulators (miRDB)

58 targeting NONO, 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-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-501-3P	99.33	66.12	651
HSA-MIR-502-3P	99.33	66.12	651
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-3145-5P	98.57	67.83	900
HSA-MIR-4731-3P	98.56	68.60	1860

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 12.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• The nmt55/p54nrb protein is post-transcriptionally regulated in human breast tumors leading to reduced expression in ER- tumors and the expression of an amino terminal altered isoform in a subset of ER+ tumors. (PMID:11710964)
• PSF and p54nrb bind U5 snRNA with both the sequence and structure of stem 1b contributing to binding specificity.PSF interacts with p54nrb (PMID:12403470)
• Review article of p54 as a multi-functional nuclear protein. (PMID:12417296)
• nmt55 expression is related to hormone-dependency or -independence associated with the androgen receptor (PMID:12672026)
• Results suggest that p54(nrb) functions as a coactivator of androgen receptors that potentiates transcription and possibly splicing. (PMID:12810069)
• p54nrb and PSF have properties of key factors mediating INS function and likely define a novel mRNA regulatory pathway that is hijacked by HIV-1. (PMID:12944487)
• p54(nrb), which binds the C-terminal domain of the largest subunit of RNAPII, can interact directly with the 5’ SS indicates that these factors may mediate contacts between RNA polymerase II (PMID:15057275)
• The PSF.p54(nrb) complex cooperates with Ku protein to form a functional preligation complex with substrate DNA (PMID:15590677)
• Thus paraspeckles are the sites where a subset of the total cellular pool of p54nrb is targeted in a RNA Polymerase II-dependent manner. (PMID:16148043)
• These data demonstrated that PSF and p54nrb complex with AR and play a key role in modulating AR-mediated gene transcription. (PMID:17452459)
• Identification of PSF, p54(nrb), PTB, and U1A as proteins specifically bound to the COX-2 polyadenylation signal upstream sequence elements . (PMID:17507659)
• p54 is present along the length of genes, and small interfering RNA (siRNA)-mediated knockdown leads to defects in XRN2 recruitment and termination. (PMID:17639083)
• Findings suggest that the PSF.p54nrb complex is a novel MAP kinase signal-integrating kinases substrate that binds the mRNA for tumor necrosis factor alpha. (PMID:17965020)
• at the TERT gene locus in human tumour cells containing a functional SWI/SNF complex, Brm, and possibly BRG1, in concert with p54(nrb), would initiate efficient transcription and could be involved in the subsequent splicing of TERT transcripts (PMID:18042045)
• NONO is a TORC-interacting protein that is necessary for cAMP-dependent activation of CREB target genes in vivo. TORC2 and NONO complex on cAMP-responsive promoters, and NONO acts as a bridge between the CREB/TORC complex and RNA polymerase II. (PMID:18077367)
• TORC2 and NONO complex on cAMP-responsive promoters, and NONO acts as a bridge between the CREB/TORC complex and RNA polymerase II. (PMID:18077367)
• Co-expression with polypyrimidine tract-binding protein-associated splicing factor (PSF) relocates oncogenic RING finger protein 43 (RNF43) from the nuclear periphery to the nucleoplasm. (PMID:18655028)
• p54nrb plays an important role in the regulation of Sox9 function and the formation of paraspeckle bodies during chondrogenesis (PMID:18677406)
• SOCS3 regulates the action of NonO to suppress MUC8 transcriptional activation. (PMID:18952062)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• p54nrb is a transcriptional corepressor of the progesterone receptor that modulates transcription of the labor-associated gene, connexin 43 (Gja1) (PMID:19423654)
• confirm the interactions of eEF1A1, p54(nrb), hnRNP-L, GAPDH and ASF/SF2 with the right terminal stem-loop domain of HDV genomic RNA in vitro (PMID:19464723)
• PSF (polypyrimidine tract-binding protein-associated splicing factor) and p54(nrb), two highly related proteins involved in transcription and RNA processing, are identified as new binding partners of hnRNP M. (PMID:19874820)
• NONO/SFPQ heterodimer is involved in the early stage of the DSB response. (PMID:20421735)
• RVxF motifs play an important role in controlling the multifunctional properties of p54nrb and PSF in the regulation of gene transcription (PMID:21566083)
• High p54nrb is associated with malignant melanoma. (PMID:21642354)
• p54(nrb) interaction with RNA could be selectively modulated by phosphorylation during mitosis (PMID:21819346)
• Study showed that Rasd1 and NonO interact at the CRE-site of specific target genes. (PMID:21915321)
• crystal of PSPC1-NONO contained one heterodimer in the asymmetric unit and diffracted to 1.9 A resolution using synchrotron radiation (PMID:22102035)
• Localisation of TopBP1 at DNA damage sites was noticed as early as 5 s following damage induction, whereas p54(nrb) and PSF localised there after 20 s. (PMID:22213094)
• The crystal structure of the heterodimer of the multidomain conserved region of the Drosophila behavior/human splicing proteins, PSPC1 and NONO, is described. (PMID:22416126)
• p54 is essential for GC-mediated expression of occludin, claudin-5, and barrier induction, and the p54/PSF heterodimer may contribute to normal blood-retinal barrier (BRB) induction in vivo. (PMID:23640037)
• Patients with aortic dissection (AD)exhibited significantly decreased expression of P54(nrb) /NonO. The significant correlation between P54(nrb) /NonO and collagen may point to novel thinking about collagen metabolism research in AD aorta. (PMID:24720418)
• silencing p54(nrb)/NONO expression in H295R human adrenocortical cells decreases the ability of the cells to increase intracellular cAMP production and subsequent cortisol biosynthesis in response to adrenocorticotropin hormone (ACTH) stimulation. (PMID:25605330)
• The ability of the SFPQ/NONO complex to form varying protein assemblies, in conjunction with the effect of post-translational modifications of SFPQ modulating mRNA binding, suggests key roles affecting mRNP dynamics within the cell. (PMID:25605962)
• These data suggest that NonO negatively regulates HIV-1 infection in CD4(+) T cells, highlighting the importance of host proteins associated with HIV-1 preintegration complexes in regulating viral replication. (PMID:25769457)
• Data uncover a new role for NONO in mediating the cellular response to UV-induced DNA damage. (PMID:25893301)
• suggest that SFPQ.NONO promotes end joining by binding to internal DNA sequences and cooperating with other repair proteins to stabilize a synaptic pre-ligation complex (PMID:25998385)
• Subnuclear re-localization of SOX10 and p54NRB correlates with a unique neurological phenotype associated with SOX10 missense mutations (PMID:26060192)
• p54(nrb) is a novel regulator of SREBP-1a in the nucleus, and the data suggest that p54(nrb) regulation of SREBP-1a supports the increased cellular demand of lipids for breast cancer growth. (PMID:26148231)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	nono	ENSDARG00000020482
mus_musculus	Nono	ENSMUSG00000031311
rattus_norvegicus	Nono	ENSRNOG00000003689
drosophila_melanogaster	nonA	FBGN0004227
drosophila_melanogaster	nonA-l	FBGN0015520
drosophila_melanogaster	nito	FBGN0027548

Paralogs (7): SPEN (ENSG00000065526), SFPQ (ENSG00000116560), PSPC1 (ENSG00000121390), RAVER1 (ENSG00000161847), RAVER2 (ENSG00000162437), RBM15 (ENSG00000162775), RBM15B (ENSG00000259956)

Protein

Protein identifiers

Non-POU domain-containing octamer-binding protein — Q15233 (reviewed: Q15233)

Alternative names: 54 kDa nuclear RNA- and DNA-binding protein, 55 kDa nuclear protein, DNA-binding p52/p100 complex, 52 kDa subunit

All UniProt accessions (16): Q15233, A0A0S2Z4Z9, A0A7I2V447, A0A7I2V464, A0A7I2V4J2, A0A7I2V4K9, A0A7I2V4N2, A0A7I2V535, A0A7I2V5Y7, A0A7I2YQK8, A0A7P0MRW0, C9IZL7, C9J4X2, C9JJ13, C9JYS8, H7C367

UniProt curated annotations — full annotation on UniProt →

Function. DNA- and RNA binding protein, involved in several nuclear processes. Binds the conventional octamer sequence in double-stranded DNA. Also binds single-stranded DNA and RNA at a site independent of the duplex site. Involved in pre-mRNA splicing, probably as a heterodimer with SFPQ. Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3’ side of U5 snRNA stem 1b. Together with PSPC1, required for the formation of nuclear paraspeckles. The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs. The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1. The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends. In vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex. NONO is involved in transcriptional regulation. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity. NONO binds to an enhancer element in long terminal repeats of endogenous intracisternal A particles (IAPs) and activates transcription. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Important for the functional organization of GABAergic synapses. Plays a specific and important role in the regulation of synaptic RNAs and GPHN/gephyrin scaffold structure, through the regulation of GABRA2 transcript. Plays a key role during neuronal differentiation by recruiting TET1 to genomic loci and thereby regulating 5-hydroxymethylcytosine levels. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway. Promotes activation of the cGAS-STING pathway in response to HIV-2 infection: acts by interacting with HIV-2 Capsid protein p24, thereby promoting detection of viral DNA by CGAS, leading to CGAS-mediated inmmune activation. In contrast, the weak interaction with HIV-1 Capsid protein p24 does not allow activation of the cGAS-STING pathway.

Subunit / interactions. Monomer and component of the SFPQ-NONO complex, which is probably a heterotetramer of two 52 kDa (NONO) and two 100 kDa (SFPQ) subunits. NONO is a component of spliceosome and U5.4/6 snRNP complexes. Interacts with CPNE4 (via VWFA domain). Forms heterodimers with PSPC1; this involves formation of a coiled coil domain by helices from both proteins. Part of complex consisting of SFPQ, NONO and MATR3. Part of a complex consisting of SFPQ, NONO and NR5A1. Part of a complex consisting of SFPQ, NONO and TOP1. Interacts with SPI1 and SPIB. Interacts with RNF43. Interacts with PER1 and PER2. Part of the HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 RNA. Interacts (via second RRM domain) with WASL; the interaction is direct. Component of a multiprotein complex with WASL and SFPQ. Interacts with ERCC6. Interacts (via DNA-binding domain) with TET1. (Microbial infection) Interacts with HIV-2 Capsid protein p24; interacts with high affinity. Interacts with HIV-1 Capsid protein p24; interacts with low affinity.

Subcellular location. Nucleus. Nucleolus. Nucleus speckle. Chromosome.

Tissue specificity. Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Also found in a number of breast tumor cell lines.

Post-translational modifications. The N-terminus is blocked.

Disease relevance. A chromosomal aberration involving NONO may be a cause of papillary renal cell carcinoma (PRCC). Translocation t(X;X)(p11.2;q13.1) with TFE3. Intellectual developmental disorder, X-linked, syndromic 34 (MRXS34) [MIM:300967] A syndrome characterized by intellectual deficit, delayed psychomotor development, poor speech, and dysmorphic features. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15233-1	1	yes
Q15233-2	2

RefSeq proteins (4): NP_001138880, NP_001138881, NP_001138882, NP_031389* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR012975	NOPS	Domain
IPR034552	p54nrb_RRM1	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076, PF08075

UniProt features (65 total): modified residue 13, strand 12, cross-link 11, helix 11, sequence conflict 4, region of interest 3, domain 2, mutagenesis site 2, compositionally biased region 2, chain 1, splice variant 1, turn 1, coiled-coil region 1, site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
7LRU	X-RAY DIFFRACTION	1.6
3SDE	X-RAY DIFFRACTION	1.9
7LRQ	X-RAY DIFFRACTION	2.3
9QXZ	X-RAY DIFFRACTION	2.5
9NZI	X-RAY DIFFRACTION	2.52
5IFM	X-RAY DIFFRACTION	2.6
6WMZ	X-RAY DIFFRACTION	2.85
9QZL	X-RAY DIFFRACTION	2.9
7PU5	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15233-F1	77.76	0.55

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): 377–378 (breakpoint for translocation to form nono-tfe3)

Post-translational modifications (24): 1, 5, 6, 11, 147, 198, 262, 295, 371, 428, 440, 450, 456, 5, 60, 96, 99, 126, 190, 198 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
267	abolishes interaction with pspc1 and localization in nuclear paraspeckles; when associated with a-271.
271	abolishes interaction with pspc1 and localization in nuclear paraspeckles; when associated with a-267.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 550 (showing top): GOBP_CIRCADIAN_RHYTHM, MORF_MTA1, RNGTGGGC_UNKNOWN, FXR_IR1_Q6, MORF_DNMT1, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, MORF_SMC1L1, TGCGCANK_UNKNOWN, PAL_PRMT5_TARGETS_UP, GCM_NPM1, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_UBE2I, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_RESPONSE_TO_ANGIOTENSIN

GO Biological Process (17): activation of innate immune response (GO:0002218), DNA repair (GO:0006281), DNA recombination (GO:0006310), regulation of DNA-templated transcription (GO:0006355), mRNA processing (GO:0006397), circadian rhythm (GO:0007623), RNA splicing (GO:0008380), regulation of circadian rhythm (GO:0042752), innate immune response (GO:0045087), negative regulation of DNA-templated transcription (GO:0045892), cellular response to hypoxia (GO:0071456), negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway (GO:1903377), cellular response to angiotensin (GO:1904385), immune system process (GO:0002376), DNA damage response (GO:0006974), negative regulation of apoptotic process (GO:0043066), rhythmic process (GO:0048511)

GO Molecular Function (7): DNA binding (GO:0003677), chromatin binding (GO:0003682), RNA binding (GO:0003723), identical protein binding (GO:0042802), lncRNA binding (GO:0106222), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (10): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), membrane (GO:0016020), nuclear matrix (GO:0016363), nuclear speck (GO:0016607), paraspeckles (GO:0042382), RNA polymerase II transcription regulator complex (GO:0090575), nucleolus (GO:0005730)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
binding	3
nuclear lumen	3
DNA metabolic process	2
DNA-templated transcription	2
RNA processing	2
cellular response to stress	2
biological_process	2
nucleic acid binding	2
intracellular membraneless organelle	2
nuclear ribonucleoprotein granule	2
activation of immune response	1
positive regulation of innate immune response	1
DNA damage response	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
mRNA metabolic process	1
rhythmic process	1
circadian rhythm	1
regulation of biological process	1
immune response	1
defense response to symbiont	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
response to hypoxia	1
cellular response to decreased oxygen levels	1
neuron intrinsic apoptotic signaling pathway in response to oxidative stress	1
negative regulation of neuron apoptotic process	1
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	1
regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	1
cellular response to peptide hormone stimulus	1
response to angiotensin	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
protein binding	1
RNA binding	1
nucleolus	1
intracellular membrane-bounded organelle	1
transcription regulator complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

293 interactions, top by confidence:

A	B	Type	Score
PSPC1	NONO	psi-mi:“MI:0915”(physical association)	0.940
NONO	PSPC1	psi-mi:“MI:0915”(physical association)	0.940
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
NONO	SFPQ	psi-mi:“MI:0915”(physical association)	0.900
SFPQ	NONO	psi-mi:“MI:2364”(proximity)	0.900
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
NONO	NONO	psi-mi:“MI:0915”(physical association)	0.860
NONO	NONO	psi-mi:“MI:0407”(direct interaction)	0.860
H2AX	PARP1	psi-mi:“MI:0914”(association)	0.840
MED9	MED19	psi-mi:“MI:0914”(association)	0.790
YBX1	HNRNPR	psi-mi:“MI:0914”(association)	0.770
EZH2	EPOP	psi-mi:“MI:0914”(association)	0.730
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PSPC1	NONO	psi-mi:“MI:0915”(physical association)	0.690

BioGRID (1256): PTBP1 (Reconstituted Complex), SFPQ (Affinity Capture-Western), NONO (Affinity Capture-MS), NONO (Affinity Capture-MS), NONO (Two-hybrid), NONO (Two-hybrid), PIN1 (Two-hybrid), PRKAA2 (Two-hybrid), LMO4 (Two-hybrid), PSPC1 (Two-hybrid), C11orf68 (Two-hybrid), NONO (Two-hybrid), NONO (Protein-peptide), NONO (Affinity Capture-MS), NONO (Affinity Capture-MS)

ESM2 similar proteins: A0A8M1NHK4, A0AV96, B3M3R5, B4KX02, O22173, O43347, P86049, Q05196, Q15233, Q1LZD9, Q32NN2, Q3UEB3, Q4KLH4, Q5R469, Q5R5P4, Q5R9H4, Q5RFL9, Q5W9D5, Q5W9D6, Q5W9D7, Q5YD48, Q61474, Q66H68, Q6DEY7, Q6GR16, Q6IRN2, Q6P0D0, Q7JJZ8, Q8GZ26, Q8K3P4, Q8MSV2, Q8R326, Q8TBY0, Q8WXF1, Q91WT8, Q91XU1, Q920Q6, Q923K9, Q96DH6, Q96PU8

Diamond homologs: A0A0R4IEW8, A0JM51, A3LXL0, A4QNI8, A5DM21, A5DW14, A8WLV5, B3M3R5, B3NGA1, B4HUE4, B4IX08, B4KX02, B4LFQ9, B4MM23, B4PIS2, B4QRJ0, B5DF91, F1QB54, O01671, O09032, O17310, O22173, O57406, O61374, O95319, O97018, P04147, P11940, P16914, P19339, P20965, P23241, P26378, P28659, P29341, P29558, P61286, P70372, P82277, Q08E07

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NONO	“form complex”	NONO/SFPQ	binding
NONO	up-regulates	TOP1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 193 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
Processing of Capped Intron-Containing Pre-mRNA	11	6.7×	6e-04
mRNA Polyadenylation	9	5.9×	4e-03
mRNA Splicing - Major Pathway	12	4.9×	2e-03
Viral Infection Pathways	15	3.5×	5e-03
Infectious disease	18	3.3×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
stress granule assembly	5	18.5×	2e-03
activation of innate immune response	5	14.8×	3e-03
positive regulation of transcription elongation by RNA polymerase II	7	12.9×	4e-04
positive regulation of translation	7	9.8×	2e-03
regulation of alternative mRNA splicing, via spliceosome	6	9.0×	7e-03
mRNA splicing, via spliceosome	12	6.7×	1e-04
mRNA processing	11	5.3×	2e-03
chromatin remodeling	10	4.5×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	23
Likely pathogenic	10
Uncertain significance	98
Likely benign	44
Benign	16

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1098343	NM_007363.5(NONO):c.1131+1G>A	Pathogenic
1700145	NM_007363.5(NONO):c.710del (p.Pro237fs)	Pathogenic
1700214	NM_007363.5(NONO):c.279_282del (p.Phe94fs)	Pathogenic
1700215	NM_007363.5(NONO):c.201_202dup (p.Lys68fs)	Pathogenic
1704653	NM_007363.5(NONO):c.154+1GT[2]	Pathogenic
1805981	NM_007363.5(NONO):c.298_307del (p.Ala100fs)	Pathogenic
222081	NM_007363.5(NONO):c.1131G>A (p.Ala377=)	Pathogenic
222082	NM_007363.5(NONO):c.1394dup (p.Asn466fs)	Pathogenic
222083	NM_007363.5(NONO):c.1093C>T (p.Arg365Ter)	Pathogenic
235099	NM_007363.5(NONO):c.1171+1G>T	Pathogenic
2429456	NM_007363.5(NONO):c.348+2_348+15del	Pathogenic
3655631	NM_007363.5(NONO):c.1071dup (p.Gln358fs)	Pathogenic
373550	NM_007363.5(NONO):c.230_231del (p.Phe77fs)	Pathogenic
392246	NM_007363.5(NONO):c.103C>T (p.Gln35Ter)	Pathogenic
424120	NM_007363.5(NONO):c.1289del (p.Pro430fs)	Pathogenic
426955	NM_007363.5(NONO):c.1009C>T (p.Arg337Ter)	Pathogenic
427778	NM_007363.5(NONO):c.1171G>T (p.Gly391Cys)	Pathogenic
432295	NM_007363.5(NONO):c.217C>T (p.Arg73Ter)	Pathogenic
438778	NM_007363.5(NONO):c.731dup (p.Asn244fs)	Pathogenic
647910	NM_007363.5(NONO):c.245del (p.Pro82fs)	Pathogenic
691621	NM_007363.5(NONO):c.550C>T (p.Arg184Ter)	Pathogenic
807452	NM_007363.5(NONO):c.107del (p.Pro36fs)	Pathogenic
833999	NM_007363.5(NONO):c.457C>T (p.Arg153Ter)	Pathogenic
1217289	NM_007363.5(NONO):c.322_348+280del	Likely pathogenic
1526229	NM_007363.5(NONO):c.315_318del (p.His106fs)	Likely pathogenic
1679353	NM_007363.5(NONO):c.1242del (p.Gly415fs)	Likely pathogenic
2429175	NM_007363.5(NONO):c.276_288del (p.Lys92fs)	Likely pathogenic
3068943	NM_007363.5(NONO):c.332_348+280del	Likely pathogenic
3254829	NM_007363.5(NONO):c.1132-1G>A	Likely pathogenic
3764771	NC_000023.11:g.71298467AG[3]	Likely pathogenic

SpliceAI

1797 predictions. Top by Δscore:

Variant	Effect	Δscore
X:71283718:GAGG:G	donor_gain	1.0000
X:71283720:GG:G	donor_gain	1.0000
X:71283720:GGGTG:G	donor_loss	1.0000
X:71283721:GG:G	donor_gain	1.0000
X:71283722:G:GG	donor_gain	1.0000
X:71283723:T:G	donor_loss	1.0000
X:71290626:TAGGG:T	acceptor_loss	1.0000
X:71290627:AG:A	acceptor_gain	1.0000
X:71290628:GG:G	acceptor_gain	1.0000
X:71290792:G:GG	donor_gain	1.0000
X:71290803:C:G	donor_gain	1.0000
X:71291777:A:AG	acceptor_gain	1.0000
X:71291778:G:GA	acceptor_gain	1.0000
X:71291778:GA:G	acceptor_gain	1.0000
X:71291778:GAT:G	acceptor_gain	1.0000
X:71291886:G:GT	donor_gain	1.0000
X:71291898:A:T	donor_gain	1.0000
X:71291918:A:T	donor_gain	1.0000
X:71291923:C:T	donor_gain	1.0000
X:71291946:GA:G	donor_gain	1.0000
X:71291953:G:GT	donor_gain	1.0000
X:71291968:GCTTG:G	donor_gain	1.0000
X:71291973:GT:G	donor_loss	1.0000
X:71291974:TGAG:T	donor_loss	1.0000
X:71291975:GA:G	donor_loss	1.0000
X:71294217:T:TA	acceptor_gain	1.0000
X:71294223:CTA:C	acceptor_loss	1.0000
X:71294224:TAGGA:T	acceptor_loss	1.0000
X:71294225:A:AG	acceptor_gain	1.0000
X:71294225:AG:A	acceptor_gain	1.0000

AlphaMissense

3122 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:71291832:T:C	F70L	1.000
X:71291834:C:A	F70L	1.000
X:71291834:C:G	F70L	1.000
X:71291842:G:C	R73P	1.000
X:71291844:A:C	S74R	1.000
X:71291846:C:A	S74R	1.000
X:71291846:C:G	S74R	1.000
X:71291847:C:A	R75S	1.000
X:71291847:C:G	R75G	1.000
X:71291848:G:C	R75P	1.000
X:71291850:C:T	L76F	1.000
X:71291851:T:A	L76H	1.000
X:71291851:T:C	L76P	1.000
X:71291851:T:G	L76R	1.000
X:71291853:T:A	F77I	1.000
X:71291853:T:C	F77L	1.000
X:71291853:T:G	F77V	1.000
X:71291854:T:C	F77S	1.000
X:71291854:T:G	F77C	1.000
X:71291855:T:A	F77L	1.000
X:71291855:T:G	F77L	1.000
X:71291857:T:A	V78E	1.000
X:71291859:G:A	G79R	1.000
X:71291859:G:C	G79R	1.000
X:71291860:G:A	G79E	1.000
X:71291860:G:T	G79V	1.000
X:71291864:T:A	N80K	1.000
X:71291864:T:G	N80K	1.000
X:71291866:T:A	L81H	1.000
X:71291866:T:C	L81P	1.000

dbSNP variants (sampled 300 via entrez): RS1000131078 (X:71300228 G>A,T), RS1000182270 (X:71300659 G>A), RS1000387161 (X:71291345 C>T), RS1000736990 (X:71290869 G>A), RS1000872402 (X:71284260 C>T), RS1000984946 (X:71283806 G>A), RS1001165671 (X:71286372 C>T), RS1001491023 (X:71286754 T>C), RS1001519087 (X:71296391 C>T), RS1001609325 (X:71301609 C>A,G), RS1001776878 (X:71282235 C>G,T), RS1002093664 (X:71284545 A>G), RS1002178005 (X:71292436 G>A), RS1002464378 (X:71285035 A>G,T), RS1002502617 (X:71293524 A>C,G)

Disease associations

OMIM: gene MIM:300084 | disease phenotypes: MIM:300967, MIM:155255

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Definitive	X-linked
syndromic X-linked intellectual disability 34	Strong	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
X-linked syndromic intellectual disability	Definitive	XL

Mondo (4): syndromic X-linked intellectual disability 34 (MONDO:0010501), intellectual disability (MONDO:0001071), medulloblastoma (MONDO:0007959), neurodevelopmental disorder (MONDO:0700092)

Orphanet (3): Macrocephaly-intellectual disability-left ventricular non compaction syndrome (Orphanet:466791), Medulloblastoma (Orphanet:616), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

104 total (30 of 104 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000154	Wide mouth
HP:0000160	Narrow mouth
HP:0000194	Open mouth
HP:0000219	Thin upper lip vermilion
HP:0000256	Macrocephaly
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000426	Prominent nasal bridge
HP:0000446	Narrow nasal bridge
HP:0000448	Prominent nose
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000545	Myopia
HP:0000582	Upslanted palpebral fissure
HP:0000678	Dental crowding
HP:0000687	Widely spaced teeth
HP:0000717	Autism
HP:0000718	Aggressive behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000823	Delayed puberty
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008527	Medulloblastoma	C04.557.465.625.600.380.515; C04.557.465.625.600.590.500; C04.557.470.670.380.515; C04.557.470.670.590.500; C04.557.580.625.600.380.515; C04.557.580.625.600.590.500
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724613 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.29	Kd	51.73	nM	CHEMBL5653589
7.29	ED50	51.73	nM	CHEMBL5653589
5.50	Kd	3169	nM	CHEMBL3752910
5.50	ED50	3169	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 10 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	2148880: Binding affinity to human NONO incubated for 45 mins by Kinobead based pull down assay	kd	0.0517	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148880: Binding affinity to human NONO incubated for 45 mins by Kinobead based pull down assay	kd	3.1692	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
Doxorubicin	decreases expression, decreases response to substance	2
tert-Butylhydroperoxide	decreases expression, decreases reaction, increases reaction	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression, affects cotreatment	1
biochanin A	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	affects expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects binding, increases reaction, increases activity	1
16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione	decreases expression	1
tetrabromobisphenol A	decreases expression	1
cupric oxide	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
salvianolic acid B	decreases expression, decreases reaction, increases reaction	1
CPG-oligonucleotide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bromovanin	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651922	Binding	Binding affinity to human NONO 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

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 2 transformed cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B087	UOK109	Cancer cell line	Male
CVCL_B3CK	Abcam HEK293T NONO KO	Transformed cell line	Female
CVCL_D7H1	Ubigene HEK293T NONO KO	Transformed cell line	Female
CVCL_E2E9	HAP1 NONO (-) 1	Cancer cell line	Male
CVCL_E2EA	HAP1 NONO (-) 2	Cancer cell line	Male
CVCL_E2EB	HAP1 NONO (-) 3	Cancer cell line	Male
CVCL_ZX41	CMUi002-A-1	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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
NCT02875314	PHASE4	ACTIVE_NOT_RECRUITING	HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors
NCT04081701	PHASE4	RECRUITING	68-Ga DOTATATE PET/MRI in the Diagnosis and Management of Somatostatin Receptor Positive CNS Tumors.
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
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
NCT00085735	PHASE3	COMPLETED	Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma
NCT00336024	PHASE3	COMPLETED	Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma
NCT00392327	PHASE3	ACTIVE_NOT_RECRUITING	Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Previously Untreated, High-Risk Medulloblastoma/PNET
NCT01351870	PHASE3	COMPLETED	Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma (PNET4)
NCT07291102	PHASE3	NOT_YET_RECRUITING	Comparison of Neurocognitive Outcome in Two Standard Regimen for Treatment of Low-risk Medulloblastoma
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
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
NCT00031590	PHASE2	TERMINATED	Low-Dose Radiation and Combination Chemotherapy Following Surgery in Children With Newly Diagnosed Medulloblastoma
NCT00180791	PHASE2	UNKNOWN	High Risk Primitive Neuroectodermal (PNET) Brain Tumors in Childhood
NCT00180947	PHASE2	UNKNOWN	Study of Vinorelbine and Cyclofosfamide Among Patients With Refractory Tumours or in Relapse
NCT00404495	PHASE2	COMPLETED	Combination of Irinotecan and Temozolomide in Children With Brain Tumors.
NCT00407433	PHASE2	COMPLETED	Clinical Studies of Gemcitabine-Oxaliplatin
NCT00520936	PHASE2	COMPLETED	A Study of Pemetrexed in Children With Recurrent Cancer
NCT00601003	PHASE2	COMPLETED	Study of Nifurtimox to Treat Refractory or Relapsed Neuroblastoma or Medulloblastoma
NCT00840047	PHASE2	ACTIVE_NOT_RECRUITING	Methionine PET/CT Studies In Patients With Cancer
NCT01217437	PHASE2	COMPLETED	Temozolomide and Irinotecan Hydrochloride With or Without Bevacizumab in Treating Young Patients With Recurrent or Refractory Medulloblastoma or CNS Primitive Neuroectodermal Tumors
NCT01326104	PHASE2	COMPLETED	Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor
NCT01356290	PHASE2	RECRUITING	Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors
NCT01542736	PHASE2	COMPLETED	Concurrent Carboplatin and Reduced Dose Craniospinal Radiation for Medulloblastoma and Primitive Neuroectodermal Tumor (PNET)
NCT01708174	PHASE2	COMPLETED	A Phase II Study of Oral LDE225 in Patients With Hedge-Hog (Hh)-Pathway Activated Relapsed Medulloblastoma (MB)
NCT01857453	PHASE2	UNKNOWN	Interest of a Dose Decrease for Radiotherapy Associated With Chemotherapy for Treatment of Standard Risk Adult Medulloblastomas
NCT01878617	PHASE2	ACTIVE_NOT_RECRUITING	A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma