NOL4L (nucleolar protein 4 like)

2018-10-01 Jean Loup Huret Affiliation

jean-loup.huret@atlasgeneticsoncology.org

Identity

HGNC

NOL4L

LOCATION

20q11.2

IMAGE

ALIAS

LOC140688

FUSION GENES

Show Gene Fusions

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).

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).

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

Four downstream target genes of PAX5 ( ATP1B1, BLK, SEPT2 and TCF7L2) were down-regulated by induction of PAX5/NOL4L. Loss of the C-terminal end of PAX5 may play role in generation of a dominant negative form of mutated PAX5 (Kawamata et al., 2008).

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).

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

Gene ID	Transcript ID	Uniprot
ENSG00000197183	ENST00000201961	Q5W149
ENSG00000197183	ENST00000326071	Q5JYB6
ENSG00000197183	ENST00000359676	Q96MY1
ENSG00000197183	ENST00000375677	Q5JYC2
ENSG00000197183	ENST00000375678	Q5JYC0
ENSG00000197183	ENST00000419612	H0Y778
ENSG00000197183	ENST00000475781	A0A1W2PQU1
ENSG00000197183	ENST00000616976	A0A087WTU5
ENSG00000197183	ENST00000621426	A0A087X0N3

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
20520637	2010	CBFA2T2 and C20orf112: two novel fusion partners of RUNX1 in acute myeloid leukemia.	13
21765475	2012	Dominant-negative mechanism of leukemogenic PAX5 fusions.	10

Citation

Jean Loup Huret

NOL4L (nucleolar protein 4 like)

Atlas Genet Cytogenet Oncol Haematol. 2018-10-01

Online version: http://atlasgeneticsoncology.org/gene/51676/nol4l