NONO

Chr XX-linked

non-POU domain containing octamer binding

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

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]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismX-linkedLOEUF 0.241 OMIM phenotype
Clinical SummaryNONO
🧬
Gene-Disease Validity (ClinGen)
X-linked syndromic intellectual disability · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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.
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — NONO
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint?
0.24LOEUF
pLI 0.993
Z-score 3.87
OE 0.05 (0.020.24)
Highly constrained

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

Missense Constraint?
3.59Z-score
OE missense 0.27 (0.220.34)
52 obs / 191.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.05 (0.020.24)
00.351.4
Missense OE?0.27 (0.220.34)
00.61.4
Synonymous OE?0.95
01.21.6
LoF obs/exp: 1 / 19.4Missense obs/exp: 52 / 191.9Syn Z: 0.32
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongNONO-related syndromic intellectual disabilityLOFXLR

This gene — mechanism propensity

DN
0.3196th %ile
GOF
0.3491th %ile
LOF
0.82top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.24 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NONO · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Glioblastoma (GBM)

Safety and Efficacy of NRG-103 Injection in the Treatment of Recurrent Glioblastoma Patients

RECRUITING
NCT06757153Phase EARLY_PHASE1Zhongnan HospitalStarted 2024-12-19
NRG-103
Phenylketonurias

Nutritional Impacts of Palynziq on Patients With Phenylketonuria (PKU)

RECRUITING
NCT04404530Emory UniversityStarted 2019-10-08
Palynziq
Recurrent B-Cell Non-Hodgkin LymphomaRecurrent Chronic Lymphocytic LeukemiaRecurrent Small Lymphocytic Lymphoma

CD19-Directed CAR-T Cell Therapy for the Treatment of Relapsed/Refractory B Cell Malignancies

RECRUITING
NCT04892277Phase PHASE1Mayo ClinicStarted 2022-10-03
Autologous Anti-CD19 CAR-expressing T-lymphocytes IC19/1563BendamustineBiospecimen Collection
Carcinoma, Non-Small-Cell LungNeoplasm Metastasis

A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer

RECRUITING
NCT06119581Phase PHASE3Eli Lilly and CompanyStarted 2023-12-21
LY3537982PembrolizumabPlacebo
Pancreas CancerPancreas CystPancreatic Ductal Adenocarcinoma

Pancreatic Cancer Early Detection Consortium

RECRUITING
NCT04970056Arbor Research Collaborative for HealthStarted 2020-09-18
Ovarian Cancer

Safety and Efficacy of KM1 in Subjects With Recurrent or Refractory Ovarian Cancer

RECRUITING
NCT05684731Phase PHASE1Tongji HospitalStarted 2023-02-01
KM1Chemotherapy
Leber Hereditary Optic Neuropathy (LHON)

A Phase 3, Multicenter, Randomized, Double-Masked, Sham-Controlled Clinical Trial for Leber's Hereditary Optic Neuropathy (LHON) Associated With ND4 Mutation

ACTIVE NOT RECRUITING
NCT07406854Phase PHASE3Wuhan Neurophth Biotechnology Limited CompanyStarted 2024-09-19
rAAV2-ND4Sham (No Treatment)
Rare DiseasesOphthalmology

Identification of Cellular Biomarkers of Rare Eye Diseases in Adults

RECRUITING
NCT07063719Phase NAInstitut National de la Santé Et de la Recherche Médicale, FranceStarted 2026-06-01
Ophthalmological visitQuestionnairesBlood sample collection
Locally Advanced Pancreatic CancerIrreversible Electroporation

Systemic Therapy With a Loco-regional Treatment in Patients With Locally Advanced Pancreatic Cancer

RECRUITING
NCT04276857Phase NAUniversity of SaskatchewanStarted 2025-05-01
Irreversible electroporation (NanoKnife® )
Hemophilia A

Study to Evaluate the Efficacy and Safety of PF-07055480 / Giroctocogene Fitelparvovec Gene Therapy in Moderately Severe to Severe Hemophilia A Adults

ACTIVE NOT RECRUITING
NCT04370054Phase PHASE3PfizerStarted 2020-08-18
PF-07055480 (giroctocogene fitelparovec): Recombinant AAV2/6 Human Factor VIII Gene Therapy
Acute Lymphoblastic Leukemia, PediatricALL, Infants

Combined Immuno-chemotherapy for Patients With B-linear Acute Lymphoblastic Leukemia Diagnosed From 0 to 365 Days of Life (ALL-Baby-2021)

RECRUITING
NCT05029531Phase PHASE3Federal Research Institute of Pediatric Hematology, Oncology and ImmunologyStarted 2021-09-23
the risk-adapted choice of therapy and the use of a combination of chemotherapy with immunotherapy and hematopoietic stem cell transplantation for patients with risk factors.
NSCLC

Analysis of Deoxyribonucleic Acid and Ribonucleic Acid Next-Generation Sequencing in Non-Small Cell Lung Cancer Patients Without Pathological Complete Response Following Neoadjuvant Immunotherapy

NOT YET RECRUITING
NCT07179445Tianjin Medical University Cancer Institute and HospitalStarted 2025-09-20
Not applicable- observational study