STIL (SCL/TAL1 interrupting locus)

2005-10-01 Asher Castiel , Shai Izraeli Affiliation

Pediatric Hemato-Oncology, Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel 52621

Identity

HGNC

STIL

LOCATION

1p33

LOCUSID

6491

ALIAS

MCPH7,SIL

FUSION GENES

Show Gene Fusions

DNA/RNA

Genomic structure of SIL. EcoRI sites (R) are indicated. Exons are as shown; the smaller exons are not drawn to scale.

Description

18 exons distributed over 70 kb. 5 portion of the gene demonstrating alternate exon utilization.

Proteins

Expression

SIL is an immediate early gene, with ubiquitous expression in proliferating cells and during early embryonic development. SIL protein levels peak during mitosis and are degraded on transition to G1. SIL is phosphorylated in mitosis. It is expressed in multiple cancers. In lung cancer its expression correlates with the expression of mitotic checkpoint genes

Localisation

Cytosolic protein

Function

SIL knockout mouse embryos die in utero displaying holopresencephaly, randomized left/right asymmetry and marked apoptosis of the neural folds. Genetic evidence showed that SIL is required for the Sonic Hedgehog response pathway. SIL phosphorylation and interactions with PIN1 is required for maintenance of the mitotic checkpoint.

Homology

There is no homology to other known proteins.

Mutations

Note

No mutations were found in families with hereditary holoprosencephaly.

Implicated in

Entity name

SIL-TAL1(SCL) fusion.

Note

A submicroscopic deletions fuses the promoter of SIL to TAL1 to induce an abnormal expression of TAL1.

Disease

T-cell ALL. This TAL1-SIL fusion transcript is found in approximately 25% of T-ALL patients.

Cytogenetics

Normal karyotype.

Hybrid gene

the promoter region of the SCL gene, a hematopoietic transcription factor, and the coding region of the SIL gene are deleted. The molecular result of this SIL/SCL rearrangement is an interstitial deletion on chromosome 1 that juxtaposes the 5 portion of the SIL gene to the coding region of the SCL gene. A SIL/SCL fusion mRNA is produced, with SIL exon 1 splicing to SCL exon 3 in a head-to-tail fashion. Because these are both 5 untranslated region (UTR) exons, the net result is that SIL promoter and enhancer elements drive the expression of a full length SCL gene product.

Schematic representation of SIL/SCL fusion mRNA. The germ line SIL (solid boxes) and SCL (open boxes) genomic structures are shown. The deletion breakpoints are indicated with arrows. The SIL/SCL genomic rearrangement is indicated below. The SIL/SCL fusion mRNA is formed by SIL exon 1 (solid box) splicing to SCL exon 3 (open box) in a head-to-tail fashion.

Entity name

SIL overexpression in lung cancer.

Note

SIL is also overexpressed in various solid tumors (melanoma, lymphoma, ovary cancer, breast cancer colon cancer lung and prostate cancer) and leukemic cell lines (Dami-acute megakaryocytic, and K562- erythroid blast crisis of chronic myeloid leukemia).

Disease

High expression in non- small cell lung cancer (NSCLC). In addition, high expression levels in lung adenocarcinoma, lung squamous carcinoma and lung small cell carcinoma.

Prognosis

SIL expression is associated with cell proliferation. In lung cancer, SIL overexpression is correlated with high mitotic activity.

Article Bibliography

Pubmed ID	Last Year	Title	Authors
1311214	1992	Involvement of the putative hematopoietic transcription factor SCL in T-cell acute lymphoblastic leukemia.	Aplan PD et al
16024801	2005	Sil phosphorylation in a Pin1 binding domain affects the duration of the spindle checkpoint.	Campaner S et al
12438742	2002	Isolation and characterization of a human novel RAB (RAB39B) gene.	Cheng H et al
12531481	2003	Cloning and characterization of the SIL promoter.	Colaizzo-Anas T et al
15107824	2004	Sil overexpression in lung cancer characterizes tumors with increased mitotic activity.	Erez A et al
9372240	1997	Expression of the SIL gene is correlated with growth induction and cellular proliferation.	Izraeli S et al
11668681	2001	Genetic evidence that Sil is required for the Sonic Hedgehog response pathway.	Izraeli S et al

Other Information

Locus ID:

NCBI: 6491
MIM: 181590
HGNC: 10879
Ensembl: ENSG00000123473

Variants:

dbSNP: 6491
ClinVar: 6491
TCGA: ENSG00000123473
COSMIC: STIL

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000123473	ENST00000337817	A0A0A0MR87
ENSG00000123473	ENST00000360380	Q15468
ENSG00000123473	ENST00000371877	Q15468
ENSG00000123473	ENST00000396221	E9PSF2
ENSG00000123473	ENST00000413565	Q5T0C8
ENSG00000123473	ENST00000436811	H0Y702
ENSG00000123473	ENST00000447475	Q5T0C7

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

References

Pubmed ID	Year	Title	Citations
37101292	2023	STIL/AURKA axis promotes cell proliferation by influencing primary cilia formation in bladder cancer.	1
37834064	2023	Molecular Mechanism of STIL Coiled-Coil Domain Oligomerization.	0
37101292	2023	STIL/AURKA axis promotes cell proliferation by influencing primary cilia formation in bladder cancer.	1
37834064	2023	Molecular Mechanism of STIL Coiled-Coil Domain Oligomerization.	0
33725572	2021	circ0000069 promotes cervical cancer cell proliferation and migration by inhibiting miR-4426.	16
33725572	2021	circ0000069 promotes cervical cancer cell proliferation and migration by inhibiting miR-4426.	16
31607137	2020	STIL is upregulated in nasopharyngeal carcinoma tissues and promotes nasopharyngeal carcinoma proliferation, migration and invasion.	9
31754215	2020	Indispensable role of STIL in the regulation of cancer cell motility through the lamellipodial accumulation of ARHGEF7-PAK1 complex.	12
32107292	2020	Direct interaction between CEP85 and STIL mediates PLK4-driven directed cell migration.	4
33132204	2020	Novel compound heterozygous variants in the STIL gene identified in a Chinese family with presentation of foetal microcephaly.	1
31607137	2020	STIL is upregulated in nasopharyngeal carcinoma tissues and promotes nasopharyngeal carcinoma proliferation, migration and invasion.	9
31754215	2020	Indispensable role of STIL in the regulation of cancer cell motility through the lamellipodial accumulation of ARHGEF7-PAK1 complex.	12
32107292	2020	Direct interaction between CEP85 and STIL mediates PLK4-driven directed cell migration.	4
33132204	2020	Novel compound heterozygous variants in the STIL gene identified in a Chinese family with presentation of foetal microcephaly.	1
31187582	2019	Knockdown of STIL suppresses the progression of gastric cancer by down-regulating the IGF-1/PI3K/AKT pathway.	19

Citation

Asher Castiel ; Shai Izraeli

STIL (SCL/TAL1 interrupting locus)

Atlas Genet Cytogenet Oncol Haematol. 2005-10-01

Online version: http://atlasgeneticsoncology.org/gene/524/silid524ch1p32