NONO

non-POU domain containing octamer binding, the group of RNA binding motif containing|Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): X:71254814-71301522

Links

ENSG00000147140 ∙ NCBI:4841 ∙ OMIM:300084 ∙ HGNC:7871 ∙ Uniprot:Q15233 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism, susceptibility to, 15 (Strong), mode of inheritance: XLR
• syndromic X-linked intellectual disability 34 (Supportive), mode of inheritance: XL
• syndromic X-linked intellectual disability 34 (Strong), mode of inheritance: XL
• autism, susceptibility to, 15 (Strong), mode of inheritance: XL
• X-linked syndromic intellectual disability (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked, syndrome 34	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	26571461

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NONO gene.

• Syndromic X-linked intellectual disability 34 (9 variants)
• not provided (7 variants)
• Inborn genetic diseases (2 variants)
• Medulloblastoma (1 variants)
• Non-ossifying fibromas with pathologic factures and X-linked intellectual disability (1 variants)
• Neurodevelopmental delay (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NONO gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				21	4	25
missense			41	2		43
nonsense	5		1			6
start loss						0
frameshift	10	5	1			16
inframe indel			8			8
splice donor/acceptor (+/-2bp)	2	3		1	1	7
splice region	1		3	3	3	10
non coding				7	8	15
Total	17	8	51	31	13

Variants in NONO

This is a list of pathogenic ClinVar variants found in the NONO region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-71290651-A-T			Uncertain significance (Sep 05, 2021)
X-71290697-T-C			Likely benign (Dec 31, 2019)
X-71290701-C-T			Uncertain significance (Jul 24, 2019)
X-71290703-TCACCACCAGCAGCAG-T		Syndromic X-linked intellectual disability 34	Uncertain significance (Apr 04, 2024)
X-71290706-C-CCACCAGCAGCAG			Uncertain significance (Feb 13, 2022)
X-71290709-C-CCAG			Uncertain significance (Oct 13, 2022)
X-71290712-GCAGCAGCACCAC-G			Uncertain significance (Jul 13, 2022)
X-71290712-G-GCAGCAGCACCAC		Inborn genetic diseases	Uncertain significance (Mar 02, 2022)
X-71290724-CCAGCAGCAACAG-GCAGCAGCACCAC			Uncertain significance (Oct 30, 2019)
X-71290740-C-T			Pathogenic (Jan 19, 2017)
X-71290741-A-C			Uncertain significance (Sep 01, 2021)
X-71290742-G-T			Uncertain significance (Apr 17, 2021)
X-71290742-GC-G		Syndromic X-linked intellectual disability 34	Pathogenic (May 16, 2018)
X-71290744-C-T		Syndromic X-linked intellectual disability 34	Uncertain significance (Jan 22, 2021)
X-71290753-C-T		not specified • See cases	Uncertain significance (Dec 14, 2023)
X-71290755-C-T		NONO-related disorder	Uncertain significance (May 25, 2024)
X-71290756-C-G			Uncertain significance (May 05, 2022)
X-71290758-A-G			Uncertain significance (Aug 27, 2023)
X-71290763-T-C			Likely benign (Nov 15, 2022)
X-71290779-G-T			Uncertain significance (Jul 25, 2018)
X-71290790-A-G		not specified	Uncertain significance (Mar 01, 2024)
X-71290791-AGT-A		Syndromic X-linked intellectual disability 34	Pathogenic (Sep 12, 2022)
X-71290802-G-C		Syndromic X-linked intellectual disability 34	Benign/Likely benign (Jan 25, 2024)
X-71290941-G-C			Benign (May 13, 2021)
X-71291820-G-A			Uncertain significance (Dec 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NONO	protein_coding	protein_coding	ENST00000276079	10	17977

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.994	0.00650	116649	0	1	116650	0.00000429

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.59	52	192	0.271	0.0000164	3101
Missense in Polyphen		3	22.101	0.13574		493
Synonymous	0.321	54	57.1	0.946	0.00000412	879
Loss of Function	3.87	1	19.4	0.0515	0.00000179	281

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000377	0.0000377
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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-ARNTL/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 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 (PubMed:28712728). {ECO:0000250|UniProtKB:Q99K48, ECO:0000269|PubMed:10858305, ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:11897684, ECO:0000269|PubMed:15590677, ECO:0000269|PubMed:22416126, ECO:0000269|PubMed:26571461, ECO:0000269|PubMed:28712728}.
• Disease: DISEASE: Note=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. {ECO:0000269|PubMed:9393982}.; DISEASE: Mental retardation, X-linked, syndromic, 34 (MRXS34) [MIM:300967]: A mental retardation syndrome characterized by intellectual deficit, delayed psychomotor development, poor speech, and dysmorphic features. Mental retardation is defined by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:26571461}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: mRNA Processing;antisense pathway;AndrogenReceptor;Circadian rhythm pathway (Consensus)

Recessive Scores

• pRec: 0.546

Intolerance Scores

• loftool: 0.624
• rvis_EVS: 0.1
• rvis_percentile_EVS: 61.28

Haploinsufficiency Scores

• pHI: 0.893
• hipred: Y
• hipred_score: 0.825
• ghis: 0.649

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.914

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nono
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; normal phenotype

Gene ontology

• Biological process: activation of innate immune response;DNA repair;DNA recombination;regulation of transcription by RNA polymerase II;mRNA processing;circadian rhythm;RNA splicing;regulation of circadian rhythm;innate immune response;negative regulation of transcription, DNA-templated;negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
• Cellular component: nucleus;nucleoplasm;nucleolus;membrane;nuclear matrix;nuclear speck;paraspeckles;RNA polymerase II transcription factor complex
• Molecular function: transcription regulatory region sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;chromatin binding;RNA binding;protein binding;identical protein binding;E-box binding