NONO Gene (Non-POU Domain Containing Octamer Binding)
A multifunctional RNA-binding protein involved in nuclear processes, splicing, and transcriptional regulation, with implications in cancer and neurological disorders.
Gene Information Card
| Symbol | NONO |
|---|---|
| Full Name | Non-POU Domain Containing Octamer Binding |
| Gene Type | Protein coding |
| Chromosomal Location | Xq13.1 |
| NCBI Gene ID | 4841 ncbi.nlm.nih.gov/gene/4841 |
| Ensembl ID | ENSG00000147140 |
| UniProt ID | Q15233 |
| OMIM ID | 300084 |
| HGNC ID | 7871 |
| Aliases | NMT55, p54nrb, MRG, NOP56 |
Description
The NONO gene encodes a member of the Drosophila behavior/human splicing (DBHS) family of RNA-binding proteins. The protein is involved in multiple nuclear processes including pre-mRNA splicing, transcriptional regulation, DNA repair, and nuclear retention of defective RNAs. It forms heterodimers with other DBHS family members such as SFPQ and PSPC1. NONO is ubiquitously expressed and plays a role in circadian rhythm regulation, cell cycle control, and viral infection response.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual Developmental Disorder, X-linked 109 (MRX109) | Loss-of-function mutations in NONO impair neuronal RNA processing and nuclear functions, leading to cognitive deficits. | ClinVar, OMIM |
| Prostate Cancer | NONO overexpression and fusion with TFE3 (NONO-TFE3) drive oncogenic transcriptional programs. | COSMIC, PubMed |
| Breast Cancer | NONO is overexpressed and promotes cell proliferation via alternative splicing of oncogenes. | COSMIC, PubMed |
| Melanoma | NONO fusions (e.g., NONO-TFE3) reported in rare cases, contributing to tumorigenesis. | COSMIC |
| Alveolar Soft Part Sarcoma (ASPS) | NONO-TFE3 fusion is a recurrent driver in ASPS, leading to aberrant TFE3 activation. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 28.5 | High |
| Heart | 22.1 | High |
| Lung | 18.3 | Medium |
| Liver | 15.7 | Medium |
| Kidney | 20.4 | High |
| Testis | 25.9 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 32.1 | Cervical cancer cell line |
| HEK293 | 29.8 | Embryonic kidney cell line |
| K562 | 27.4 | Leukemia cell line |
| MCF7 | 30.2 | Breast cancer cell line |
| A549 | 26.5 | Lung cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, likely loss of function |
| c.145C>T (p.Arg49*) | Nonsense | Rare | Premature stop, loss of function |
| c.502_503del (p.Leu168fs) | Frameshift | Rare | Frameshift, loss of function |
| NONO-TFE3 fusion | Gene fusion | Rare | Oncogenic fusion in ASPS and prostate cancer |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and missense mutations that disrupt RNA-binding or nuclear localization lead to loss of function, associated with X-linked intellectual disability.
Gain of Function (GOF)
NONO-TFE3 fusions result in constitutive activation of TFE3 transcriptional targets, acting as gain-of-function oncoproteins.
Dominant Negative (DN)
Not well documented; however, altered splicing due to mutant NONO may exert dominant-negative effects on DBHS complex function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Spliceosome (Reactome: R-HSA-72163)
• Processing of Capped Intron-Containing Pre-mRNA (Reactome: R-HSA-72203)
• Circadian Clock (Reactome: R-HSA-400253)
• DNA Double-Strand Break Repair (Reactome: R-HSA-5693532)
Protein Summary
NONO (p54nrb) is a 471-amino acid RNA-binding protein belonging to the DBHS family. It contains two RNA recognition motifs (RRMs), a coiled-coil domain, and a C-terminal domain. The protein localizes to nuclear speckles and is involved in pre-mRNA splicing, transcriptional regulation, DNA repair, and nuclear retention of defective RNAs. NONO forms heterodimers with SFPQ and PSPC1, and its expression is ubiquitous. Post-translational modifications include phosphorylation and sumoylation, which modulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NONO Knockout HEK293T Cell Line | EDJ-KQ181 | Human | 4841 | Details Get a Quote |
| NONO Knockout HEK293 Cell Line | EDJ-KQ50484 | Human | 4841 | Details Get a Quote |
| NONO Knockout HeLa Cell Line | EDJ-KQ54003 | Human | 4841 | Details Get a Quote |
| NONO Knockout A-549 Cell Line | EDJ-KQ62496 | Human | 4841 | Details Get a Quote |
| NONO Knockout HCT 116 Cell Line | EDJ-KQ70963 | Human | 4841 | Details Get a Quote |
