NONO

Chr XX-linked

non-POU domain containing octamer binding

Also known as: MRXS34, NMT55, NRB54, P54, P54NRB, PPP1R114

NCBI Gene: 4841ENSG00000147140UniProt: Q15233

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. [provided by RefSeq, Feb 2009]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked syndromic 34MIM #300967
X-linked
395
ClinVar variants
0
Pathogenic / LP
0.99
pLI score· haploinsufficient
12
Active trials
Clinical Summary— NONO
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
395 total variants — no pathogenic classifications of 395 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.24LOEUF
pLI 0.993
Z-score 3.87
OE 0.05 (0.02–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.59Z-score
OE missense 0.27 (0.22–0.34)
52 obs / 191.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.02–0.24)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.27 (0.22–0.34)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 1 / 19.4Missense obs/exp: 52 / 191.9Syn Z: 0.32

ClinVar Variant Classifications

395 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

NONO · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

NONO-related syndromic intellectual disability

strong
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, X-linked syndromic 34

MIM #300967

Molecular basis of disorder known

X-linked
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Venous thrombosis.
Wolberg AS et al.·Nat Rev Dis Primers
2015Review
Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial.
Hill MD et al.·Lancet
2020
Genetic and phenotypic spectrum in the NONO-associated syndromic disorder.
Roessler F et al.·Am J Med Genet A
2023Review
NONO interacts with nuclear PKM2 and directs histone H3 phosphorylation to promote triple-negative breast cancer metastasis.
Li Q et al.·J Exp Clin Cancer Res
2025
circ-hnRNPU inhibits NONO-mediated c-Myc transactivation and mRNA stabilization essential for glycosylation and cancer progression.
Li H et al.·J Exp Clin Cancer Res
2023
NONO regulates m(5)C modification and alternative splicing of PTEN mRNAs to drive gastric cancer progression.
Zhao G et al.·J Exp Clin Cancer Res
2025
Exosomal Biglycan promotes gastric cancer progression via M2 polarization and CXCL10-mediated JAK/STAT1 activation.
Li W et al.·Cancer Lett
2025
Efficacy and safety of nerinetide in acute ischaemic stroke in patients undergoing endovascular thrombectomy without previous thrombolysis (ESCAPE-NEXT): a multicentre, double-blind, randomised controlled trial.
Hill MD et al.·Lancet
2025Cohort
Efficacy and safety of intravenous nerinetide initiated by paramedics in the field for acute cerebral ischaemia within 3 h of symptom onset (FRONTIER): a phase 2, multicentre, randomised, double-blind, placebo-controlled study.
Christenson J et al.·Lancet
2025Clinical trial
IKZF4/NONO-RAB11FIP3 axis promotes immune evasion in gastric cancer via facilitating PD-L1 endosome recycling.
Weng N et al.·Cancer Lett
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Breast Cancer

NeoadjuVAnt muLti-agENT Chemotherapy or Patritumab Deruxtecan With or Without endocrINE Therapy for High-risk HR+/HER2- Breast Cancer - VALENTINE Trial

ACTIVE NOT RECRUITING
NCT05569811Phase PHASE2SOLTI Breast Cancer Research GroupStarted 2022-11-25
Patritumab deruxtecanChemotherapyLetrozole
SARS CoV 2 InfectionSARS CoV 2 Vaccination

COVID-19 Transmission and Morbidity in Malawi

RECRUITING
NCT05973084Boston UniversityStarted 2023-01-17
Hereditary Breast and Ovarian Cancer

CONTIGO - A Narrative Intervention to Enhance Genetic Counseling and Testing

RECRUITING
NCT05130606Phase NAGeorgetown UniversityStarted 2021-06-01
Culturally Targeted Narrative Video: "Is My Cancer Hereditary? Rosa Visits a Genetic Counselor."FORCE Fact Sheet
DNMT3A Gene Mutation

Metformin Inhibits DNMT3A Clonal Hematopoiesis in Acute Leukemia

NOT YET RECRUITING
NCT07188740Phase PHASE1Institute of Hematology & Blood Diseases Hospital, ChinaStarted 2025-10-30
Metformin
Acute Lymphoblastic Leukemia

ALL SCTped FORUM - Pharmacogenomic Study (add-on Study)

RECRUITING
NCT02670564Phase PHASE4Swiss Pediatric Oncology GroupStarted 2013-04
PharmacogenomicsBusulfan plasma level measurements
Neoplasms

Study of TSR-042, an Anti-programmed Cell Death-1 Receptor (PD-1) Monoclonal Antibody, in Participants With Advanced Solid Tumors

ACTIVE NOT RECRUITING
NCT02715284Phase PHASE1Tesaro, Inc.Started 2016-03-07
Dostarlimab
Infiltrating Bladder Urothelial CarcinomaStage II Bladder Urothelial CarcinomaStage III Bladder Urothelial Carcinoma

Gemcitabine and Cisplatin Without Cystectomy for Patients With Muscle Invasive Bladder Urothelial Cancer and Select Genetic Alterations

RECRUITING
NCT03609216Phase PHASE2Alliance for Clinical Trials in OncologyStarted 2018-12-10
Gemcitabine HydrochlorideCisplatinPegfilgrastim
Parkinson DiseaseGBA Gene MutationGaucher Disease

The GBA Multimodal Study in Parkinson's Disease

RECRUITING
NCT04101968Pacific Parkinson's Research CentreStarted 2019-05-01
PET scanneuroQWERTY
Lysosomal Storage DiseaseMetachromatic Leukodystrophy

A Safety and Efficacy Study of Cryopreserved OTL-200 for Treatment of Metachromatic Leukodystrophy (MLD)

ACTIVE NOT RECRUITING
NCT03392987Phase PHASE2Orchard TherapeuticsStarted 2018-01-25
OTL-200
Rectum Cancer, Adenocarcinoma

ADAR1 Expression Level in Rectal Cancer

RECRUITING
NCT07108348Necmettin Erbakan UniversityStarted 2025-06-01
Adenosine deaminase acting on RNA1
Endometrial Cancer

A Study of Targeted Agents for Patients With Recurrent or Persistent Endometrial Cancer

RECRUITING
NCT04486352Phase PHASE1, PHASE2Alliance Foundation Trials, LLC.Started 2021-10-20
Atezolizumab - 28 Day CycleBevacizumabIpatasertib
Invasive PreNatal Diagnosis in a Context of Family History of Single-gene Disorders, IncludingSickle Cell DiseaseCystic Fibrosis

Development of Non-Invasive Prenatal Diagnosis for Single Gene Disorders

RECRUITING
NCT06147414Assistance Publique - Hôpitaux de ParisStarted 2024-10-23
Blood sample

External Resources

Links to major genomics databases and tools