Abstract
Review on NOL4L, with data on DNA, on the protein encoded, and where the gene is implicated.
DNA/RNA
Description
11 exons
Transcription
8 potential splice forms coding for potential proteins with 76 amino acids (aa) to 680 aa.
Proteins
Note
Nothing is known concerning the domains of the protein, nor its function.
Description
Two coding proteins: NOL4L-010, from: 11 exons; transcript length: 6,577 bps translation: 680 amino acids; and NOL4L-001, from: 8 exons; transcript length: 5,991 bps translation: 436 amino acids. A Poly-Asp is found at aa 161 to 169 according to Vega (http://vega.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=OTTHUMG00000032219;r=20:32443059-32585074) and UniProt (https://www.uniprot.org/uniprot/Q96MY1#expression).
Expression
Expressed in all tissues; High expression in the testis, and, to a lesser extend, in the small intestine, other digestive organs, brain and bone marrow. NOL4L orthologs are present in most vertebrates and are well conserved. In zebrafish embryos, Znol4lb (the zebrafish nol4l with the highest identity with human NOL4L) mRNA is localized to the intermediate mesoderm. It is expressed in the central nervous system, pronephros, the gut and, at low levels, in the hematopoietic cells (Borah et al. 2016).
Localisation
Mainly localized to the nucleoplasm.
Function
Acccording to BioGRID (https://thebiogrid.org/12665), interacts with:
CTBP1 (C-terminal binding protein 1), corepressor targeting various transcription regulators.
TEX9 (testis expressed 9).
SRPK1 (SRSF protein kinase 1), involved in the regulation of splicing via phosphorylation of splicing factors.
CTBP2 (C-terminal binding protein 2), corepressor targeting various transcription regulators.
SKA3 (spindle and kinetochore associated complex subunit 3), component of a microtubule-binding complex essential for chromosome segregation.
TRIM25 (tripartite motif containing 25), ubiquitin E3 ligase.
MIR206 (microRNA 206).
CTBP1 (C-terminal binding protein 1), corepressor targeting various transcription regulators.
TEX9 (testis expressed 9).
SRPK1 (SRSF protein kinase 1), involved in the regulation of splicing via phosphorylation of splicing factors.
CTBP2 (C-terminal binding protein 2), corepressor targeting various transcription regulators.
SKA3 (spindle and kinetochore associated complex subunit 3), component of a microtubule-binding complex essential for chromosome segregation.
TRIM25 (tripartite motif containing 25), ubiquitin E3 ligase.
MIR206 (microRNA 206).
Implicated in
Top note
Expression level according to Entrez (https://www.ncbi.nlm.nih.gov/gene/140688) and The Human Protein Atlas (http://www.proteinatlas.org/ENSG00000197183-NOL4L/pathology):
High expression of NOL4L is an unfavourable prognostic factor in endometrial cancer.
- fusion 20q11-20q11 NOL4L/ COMMD7 in breast adenocarcinoma (Yoshihara et al. 2015).
Expression level of NOL4L has no prognostic significance in: Glioma, Thyroid cancer, Lung cancer, Liver cancer, Pancreatic cancer, Head and neck cancer, Stomach cancer, Colorectal cancer, Renal cancer, Prostate cancer, Testis cancer, Breast cancer, Cervical cancer, Ovarian cancer, Melanoma .
Main translocations: (detailed herein below)
- t(20;21)(q11;q22) RUNX1/NOL4L.
Other fusion transcripts: (data extracted from the Atlas http://atlasgeneticsoncology.org//Bands/20q11.html)
- fusion/translocation t(7;20)(p22;q11) ACTB/NOL4L in triple-negative (TN) adenocarcinoma. The triple-negative breast cancer subtype is the most aggressive form of invasive breast adenocarcinoma (Asmann et al. 2012).
- fusion/translocation t(17;20)(q22;q11) MMD/NOL4L in breast adenocarcinoma (Yoshihara et al. 2015).
- fusion 20q11-20q11 NOL4L/ EFCAB8 in malignant melanoma of the skin (Hu et al., 2018).
- fusion 20q11-20q11 PDRG1/NOL4L in malignant epithelial tumor of the uterus corpus (Hu et al., 2018).
High expression of NOL4L is an unfavourable prognostic factor in endometrial cancer.
- fusion 20q11-20q11 NOL4L/ COMMD7 in breast adenocarcinoma (Yoshihara et al. 2015).
Expression level of NOL4L has no prognostic significance in: Glioma, Thyroid cancer, Lung cancer, Liver cancer, Pancreatic cancer, Head and neck cancer, Stomach cancer, Colorectal cancer, Renal cancer, Prostate cancer, Testis cancer, Breast cancer, Cervical cancer, Ovarian cancer, Melanoma .
Main translocations: (detailed herein below)
- t(20;21)(q11;q22) RUNX1/NOL4L.
Other fusion transcripts: (data extracted from the Atlas http://atlasgeneticsoncology.org//Bands/20q11.html)
- fusion/translocation t(7;20)(p22;q11) ACTB/NOL4L in triple-negative (TN) adenocarcinoma. The triple-negative breast cancer subtype is the most aggressive form of invasive breast adenocarcinoma (Asmann et al. 2012).
- fusion/translocation t(17;20)(q22;q11) MMD/NOL4L in breast adenocarcinoma (Yoshihara et al. 2015).
- fusion 20q11-20q11 NOL4L/ EFCAB8 in malignant melanoma of the skin (Hu et al., 2018).
- fusion 20q11-20q11 PDRG1/NOL4L in malignant epithelial tumor of the uterus corpus (Hu et al., 2018).
Entity name
Pediatric acute lymphoblastic leukemia (ALL)
Note
5 cases of dic(9;20) (p13;q11) PAX5/NOL4L available to date (Nebral et al., 2007; An et al., 2008; Kawamata et al., 2008; Kawamata et al. 2012).
Hybrid gene
In one case, exon 5 of PAX5 was fused to exon 8 of NOL4L, and in four cases, exon 8 of PAX5 was fused to exon 3 of NOL4L, producing two proteins, a short (PAX5/C20ORF112S) and long (PAX5/C20ORF112L) form, localizing in the nucleus, and/or in the cytoplasm and the nucleus (Kawamata et al., 2008).
Oncogenesis
Entity name
Acute myeloid leukemia (AML)
Note
A 62-year-old man was diagnosed with AML with maturation (M2- AML), and presented with a t(20;21)(q11.2;q22.1) RUNX1/NOL4L accompanied with monosomy 7 (Guastadisegni et al. 2010).
Hybrid gene
RUNX1 exon 6 was fused to NOL4L exon 8.
Oncogenesis
Wild-type NOL4L was expressed at low levels in AML and normal bone marrow, whereas the RUNX1/NOL4L was expressed at high levels (Guastadisegni et al. 2010).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 18957548 | 2008 | Variable breakpoints target PAX5 in patients with dicentric chromosomes: a model for the basis of unbalanced translocations in cancer. | An Q et al |
| 22496456 | 2012 | Detection of redundant fusion transcripts as biomarkers or disease-specific therapeutic targets in breast cancer. | Asmann YW et al |
| 26934290 | 2016 | Nucleolar protein 4-like has a complex expression pattern in zebrafish embryos. | Borah S et al |
| 20520637 | 2010 | CBFA2T2 and C20orf112: two novel fusion partners of RUNX1 in acute myeloid leukemia. | Guastadisegni MC et al |
| 29099951 | 2018 | TumorFusions: an integrative resource for cancer-associated transcript fusions. | Hu X et al |
| 18697940 | 2008 | Cloning of genes involved in chromosomal translocations by high-resolution single nucleotide polymorphism genomic microarray. | Kawamata N et al |
| 17897302 | 2007 | Identification of PML as novel PAX5 fusion partner in childhood acute lymphoblastic leukaemia. | Nebral K et al |
| 25500544 | 2015 | The landscape and therapeutic relevance of cancer-associated transcript fusions. | Yoshihara K et al |
Other Information
Locus ID:
NCBI: 140688
MIM: 618893
HGNC: 16106
Ensembl: ENSG00000197183
Variants:
dbSNP: 140688
ClinVar: 140688
TCGA: ENSG00000197183
COSMIC: NOL4L
RNA/Proteins
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 33940382 | 2021 | NOL4L, a novel nuclear protein, promotes cell proliferation and metastasis by enhancing the PI3K/AKT pathway in ovarian cancer. | 1 |
| 33940382 | 2021 | NOL4L, a novel nuclear protein, promotes cell proliferation and metastasis by enhancing the PI3K/AKT pathway in ovarian cancer. | 1 |
| 32522628 | 2020 | LncRNA double homeobox A pseudogene 8 (DUXAP8) facilitates the progression of neuroblastoma and activates Wnt/β-catenin pathway via microRNA-29/nucleolar protein 4 like (NOL4L) axis. | 14 |
| 32522628 | 2020 | LncRNA double homeobox A pseudogene 8 (DUXAP8) facilitates the progression of neuroblastoma and activates Wnt/β-catenin pathway via microRNA-29/nucleolar protein 4 like (NOL4L) axis. | 14 |
| 21765475 | 2012 | Dominant-negative mechanism of leukemogenic PAX5 fusions. | 15 |
| 21765475 | 2012 | Dominant-negative mechanism of leukemogenic PAX5 fusions. | 15 |
| 20520637 | 2010 | CBFA2T2 and C20orf112: two novel fusion partners of RUNX1 in acute myeloid leukemia. | 16 |
| 20520637 | 2010 | CBFA2T2 and C20orf112: two novel fusion partners of RUNX1 in acute myeloid leukemia. | 16 |
Citation
Jean Loup Huret
NOL4L (nucleolar protein 4 like)
Atlas Genet Cytogenet Oncol Haematol. 2018-10-01
Online version: http://atlasgeneticsoncology.org/gene/51676/submit-meetings/tumors-explorer/
