GAS5 (growth arrest-specific 5 (non-protein coding))

2009-10-01   Mirna Mourtada-Maarabouni 

Institute for Science, Technology in Medicine, Huxley Building, Keele University, Keele, Staffordshire ST5 5BG, UK




Atlas Image
Representation of five of GAS5 splice variants. Boxes numbered 2 to12 represent exons. U79, U80, U47, U81 and U74 represent the box C/D small nucleolar RNAs (snoRNAs). Horizontal lines represent the intronic sequences. Exons, introns and snoRNAs are not drawn to scale (IMAGE clone 6194071, 1249 bp; IMAGE clone 2598129, 1270 bp; IMAGE clone 3585621, 1396 bp; Gas5 3A, 1802 bp; IMAGE clone 5739605, 1802 bp; IMAGE clone 2761825, 1802 bp).


The gene spans about 4.98 Kb. Orientation minus strand. Number of exons: 12. GenBank: AF141346.1. GAS5 gene hosts multiple small nucleolar RNA (snoRNA) host gene similar to UHG (U22 host gene) which encode, within the 11 introns of the human GAS5 gene, ten box C/D snoRNAs predicted to play a role in the 2-O-methylation of rRNA. Its 5 end sequence contains an oligopyrimidine tract characteristic of the 5-TOP class of genes.


The length of GAS5 transcript is 651bp (NR_002578 in GenBank). The 5 end sequence of the GAS5 transcript contains an oligopyrimidine tract characteristic of the 5-TOP class of genes. GAS5 transcripts display several patterns of alternate splicing. The initial GAS5 transcript is subject to complex post-transcriptional processing resulting in several splice variants. However its putative open reading frame is small and poorly conserved during even relatively short periods of evolution, as demonstrated by a number of disruptions caused by frameshift mutations in several mouse strains, and by an interruption by a stop codon after the first 13 amino acids in rat GAS5. The diagram above shows some of GAS5 splice variants which are reported to affect cell fate in different ways.



GAS5 exons do not encode a polypeptide product.

Implicated in

Entity name
Regulation of cell growth
The GAS5 gene was isolated from NIH 3T3 cells using subtraction hybridisation, in a screen intended to isolate potential tumor suppressor genes. GAS5 is reported to be ubiquitously expressed during mouse development and adult life, and also to be expressed only at low levels in actively growing Friend leukemia and NIH 3T3 cells, with substantially increased abundance in cells grown to saturation density. The RNA levels of GAS5 appear to be regulated primarily through changes in its rate of degradation rather than through changes in its transcription rate. GAS5 RNA abundance was also found to be increased by amino acid deprivation. Studies also have shown that GAS5 is necessary and sufficient for growth arrest in both untransformed and leukaemic lymphocytes.
Entity name
Systemic lupus erythematosus
The GAS5 gene is located in the disease susceptibility locus in mouse BXSB strain, which develops glomerulonephritis associated with systemic lupus erythematosus (SLE). Subsequent studies involving genetic analysis of a mouse model of SLE have indicated that GAS5 may well be involved in its pathology. Besides, the human chromosomal locus 1q25 at which the GAS5 gene is encoded has been associated with SLE in genetic studies in humans.
Entity name
Apoptosis/cell cycle regulation
A fragment of GAS5 cDNA has been isolated from a retroviral cDNA expression library by using an unbiased functional screen for genes that control apoptosis in lymphocytes. Further studies have shown that GAS5 plays an essential role in normal growth arrest in both T-cell lines and non-transformed lymphocytes. Overexpression of GAS5 causes both an enhancement in apoptosis and a decrease in the rate of progression through the cell cycle in leukeamic T cell lines and primary lymphocytes. Consistent with this, downregulation of endogenous GAS5 inhibits apoptosis and maintains a more rapid cell cycle, indicating that GAS5 expression is both essential and sufficient for normal growth arrest in T-cell lines as well as human peripheral blood T-cells. Overexpression of certain GAS5 transcripts is reported to induce growth arrest and apoptosis in several mammalian cell lines.
Entity name
GAS5 is encoded at 1q25, a locus displaying abnormalities in a number of cancers, e.g. melanoma, prostate, breast, and several types of leukaemia and lymphoma. Gene expression analysis has shown that GAS5 is up-regulated 3.3-fold (the greatest up-regulation for any gene in the whole-genome array) by oncogenic kinases associated with myeloproliferative disorders. Chromosomal rearrangements involving GAS5 have also been identified in a human B-cell lymphoma. GAS5 expression levels are reported to regulate both the induction of apoptosis and cell cycle arrest in T-cell lines and non-transformed lymphocytes, suggesting that it may be very significant in the development of leukaemia and lymphoma. Overexpression of certain GAS5 transcripts is reported to induce growth arrest and apoptosis in several human cell lines, including human breast cancer cell lines. GAS5 expression is significantly downregulated in breast cancer tissue compared with those found in untransformed breast epithelial tissue from the same patients, a clear reduction of more than 65% was observed in this study, suggesting that the reduction in GAS5 expression is an early event in oncogenesis.


Pubmed IDLast YearTitleAuthors
16304591992Regulation and expression of a growth arrest-specific gene (gas5) during growth, differentiation, and development.Coccia EM et al
94615581998Effects of nutrient deprivation and differentiation on the expression of growth-arrest genes (gas and gadd) in F9 embryonal carcinoma cells.Fleming JV et al
121636522002Amino acid deficiency up-regulates specific mRNAs in murine embryonic cells.Fontanier-Razzaq N et al
165410992006Overlapping BXSB congenic intervals, in combination with microarray gene expression, reveal novel lupus candidate genes.Haywood ME et al
123736472002A major susceptibility locus for systemic lupus erythemathosus maps to chromosome 1q31.Johanneson B et al
169002072006Oncogenic kinases of myeloproliferative disorders induce both protein synthesis and G1 activators.Lelièvre H et al
188364842009GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer.Mourtada-Maarabouni M et al
97166661998The gas5 gene is disrupted by a frameshift mutation within its longest open reading frame in several inbred mouse strains and maps to murine chromosome 1.Muller AJ et al
184068792008The GAS5 (growth arrest-specific transcript 5) gene fuses to BCL6 as a result of t(1;3)(q25;q27) in a patient with B-cell lymphoma.Nakamura Y et al
110545302000The gas 5 gene shows four alternative splicing patterns without coding for a protein.Raho G et al
34093191988Genes specifically expressed at growth arrest of mammalian cells.Schneider C et al
107383102000Characterization of chromosome 1 abnormalities in malignant melanomas.Smedley D et al
98193781998Classification of gas5 as a multi-small-nucleolar-RNA (snoRNA) host gene and a member of the 5'-terminal oligopyrimidine gene family reveals common features of snoRNA host genes.Smith CM et al
164284712006High-resolution genomic profiling reveals association of chromosomal aberrations on 1q and 16p with histologic and genetic subgroups of invasive breast cancer.Stange DE et al
153144872004Update on human systemic lupus erythematosus genetics.Tsao BP et al
128077182003Radiation-induced deletions in the 5' end region of Notch1 lead to the formation of truncated proteins and are involved in the development of mouse thymic lymphomas.Tsuji H et al
93975371997Identification of a growth arrest specific (gas 5) gene by differential display as a candidate gene for determining susceptibility to hyperthermia-induced exencephaly in mice.Vacha SJ et al
173726192006Isolation of genes controlling apoptosis through their effects on cell survival.Williams GT et al

Other Information

Locus ID:

NCBI: 60674
MIM: 608280
HGNC: 16355
Ensembl: ENSG00000234741


dbSNP: 60674
ClinVar: 60674
TCGA: ENSG00000234741


Expression (GTEx)



Pubmed IDYearTitleCitations
201245512010Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor.422
188364842009GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer.307
239338122013Negative regulation of lncRNA GAS5 by miR-21.143
243571612015A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer.116
236766822013Long non-coding RNA GAS5 regulates apoptosis in prostate cancer cell lines.115
248844172014Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer.112
236211902013Long non-coding RNA GAS5 functions as a tumor suppressor in renal cell carcinoma.92
251208132014Down-regulation of long non-coding RNA GAS5 is associated with the prognosis of hepatocellular carcinoma.71
259594982015lncRNA GAS5 enhances G1 cell cycle arrest via binding to YBX1 to regulate p21 expression in stomach cancer.71
253260542014Long noncoding RNA GAS5 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer.63


Mirna Mourtada-Maarabouni

GAS5 (growth arrest-specific 5 (non-protein coding))

Atlas Genet Cytogenet Oncol Haematol. 2009-10-01

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