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LATS1 (Large Tumor Suppressor 1)

Written2015-07Stacy Visser-Grieve, Helena J Janse van Rensburg, Xiaolong Yang
Department of Pathology and Molecular Medicine, Queen's University Kingston, ON, Canada. yang@path.queensu.ca

Abstract LATS1 tumor suppressor is a serine/threonine kinase of the AGC kinase family and a core component of the Hippo pathway in mammals. LATS1 regulates various biological processes such as cell cycle progression, genetic stability, cell motility and adhesion, apoptosis, stem cell renewal and differentiation (Visser and Yang, 2010; Mo et al., 2014). LATS1 performs these functions by phosphorylating various substrates such as transcriptional co-activators YAP and TAZ (Zhao et al., 2007; Hao et al., 2008). LATS1 is also required for tissue homeostasis in both flies and mice (Visser et al., 2010). In addition to its roles in a broad spectrum of normal biological processes, loss of LATS1 has been shown to be important for the development of cancer and resistance to chemotherapeutic drugs (Visser et al., 2010). Therefore, understanding the molecular mechanisms underlying loss-of-LATS1-induced tumorigenesis and drug resistance will shed light on the design of new cancer treatment strategies in the future.

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Identity

Alias_namesLATS (large tumor suppressor, Drosophila) homolog 1
LATS, large tumor suppressor, homolog 1 (Drosophila)
Alias_symbol (synonym)WARTS
Other aliasWarts
HGNC (Hugo) LATS1
LocusID (NCBI) 9113
Atlas_Id 41127
Location LATS1 is localized to chromosome 6q24-25.1  [Link to chromosome band 1]
Location_base_pair Starts at 149658153 and ends at 149718256 bp from pter ( according to hg19-Feb_2009)  [Mapping LATS1.png]
Local_order KATNA1. . LATS1. . LOC645967. . NUP43
Fusion genes
(updated 2017)		Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
KATNA1 (6q25.1) / LATS1 (6q25.1)LATS1 (6q25.1) / AFG1L (6q21)PCMT1 (6q25.1) / LATS1 (6q25.1)
SCAF8 (6q25.2) / LATS1 (6q25.1)

DNA/RNA

Description The LATS1 gene contains 8 exons, ranging in size from 106 bp to 1513 bp. The mRNA transcript spans 4756 bp (NM_004690).
Transcription An alternatively spiced variant was identified in vertebrate retina and testis. This smaller variant has deletions of exon 6, 7, and 8 (NM_001270519). Furthermore, a non-coding third transcript variant that is comprised of alternate 5' and internal exons has recently been proposed to exist (NR_073033). In this transcript, an upstream open reading frame (ORF) is predicted to interfere with translation of the longer ORF. The functional significance of these splice variants remains unclear.

Protein

 
Description LATS1 is a highly conserved Ser/Thr kinase that belongs to the AGC (Protein kinase A/G/C) family of protein kinases. Within the C-terminal kinase domain lie two conserved residues, Ser909 and Thr1079, which are phosphorylated upon activation. The N-terminus of LATS1 contains two PPxY motifs, which bind to WW-domain transcriptional co-activators TAZ and YAP or E3 ubiquitin ligases ITCH, WWP1, and NEDD4 as well as a protein binding domain (PBD) that has been shown to bind to MOB1 and cytoskeletal proteins LIMK1 and Zyxin. In addition, an ubiquitin binding domain (UBA) and a proline-rich region (P-stretch) have been identified in the N-terminal region of LATS1, although the functional significance of these domains has not yet been determined.
Expression LATS1 is ubiquitously expressed.
Localisation LATS1 is primarily localized within the cytoplasm, however, LATS1 possesses functions that require its translocation to the nucleus. The mechanism of translocation is not yet understood.
Function As a tumor suppressor, LATS1 functions as a key regulator of cell cycle progression, apoptosis, and cell migration. As cell cycle regulator, LATS1 is able to modulate multiple aspects of the cell cycle, including G2/M arrest, mitotic exit, activation of the G1 tetraploidy checkpoint, and regulation of cytokinesis. LATS1 also promotes apoptosis by inducing expression of pro-apoptotic proteins BAX, caspase 3 and tumor suppressor p53. Finally, loss of LATS1 has been shown to enhance the rate of cell migration.
HIPPO Signaling Pathway LATS1 is a key player in the conserved Hippo signaling pathway. Core components of this pathway include the adaptor proteins Sav1 and MOB1, which aid in bringing LATS in contact with the kinase MST1/2. MST1/2 can then phosphorylate and activate LATS1. Upstream core components of the Hippo pathway lay FERM domain proteins Willin/FRMD6 and Merlin/NF2, as well as a protocadherin FAT4 and G-protein-coupled receptor (GPCR) and many other regulators (see Figure). Downstream of LATS1 lay two transcriptional co-activators, YAP and TAZ, which are phosphorylated and inhibited by LATS1, thereby sequestering them in the cytoplasm. Finally, YAP and TAZ have been shown to act through the TEAD/TEF family of transcription factors to modulate the expression of a variety of genes (See Figure). Functionally, the Hippo pathway has been implicated in cell proliferation, apoptosis, the epithelial mesenchymal transition, cell migration, and stem cell differentiation and renewal.
 
Homology The LATS1 kinase domain is conserved across species. Human homologs include LATS2 and the nuclear Dbf2-related kinases, NDR1 and NDR2.

Mutations

Note The Catalogue of Somatic Mutations in Cancer (COSMIC), lists 491 unique mutations in the LATS1 gene. In the COSMIC Cell Lines Project, there are 135 unique mutations in the LATS1 gene listed.

Implicated in

Note
  
Entity Breast cancer
Note In breast cancers, loss of heterozygosity is often observed on chromosome 6q suggesting a role for LATS1 in breast cancer carcinogenesis (Morinaga et al., 2000). In a study of breast cancer patients, low LATS1 expression has been associated with a biologically aggressive phenotype (Takahashi et al., 2005). In a study of breast cancer tissues, the LATS1 promoter was found to be hypermethylated in 56.7% (17/30) of tumors causing a significant decrease in LATS1 mRNA expression. In breast cancer patients, decreased LATS1 mRNA expression was associated with large tumor size, lymph node metastasis, and estrogen and progesterone negativity. Thus, loss of LATS1 is associated with poor prognosis in breast cancer.
  
  
Entity Cervical cancer
Note In clinical samples of normal and neoplastic cervix, increased expression of upstream regulator ITCH and decreased expression of LATS1 was associated with transformation of cervical epithelial cells and progression of cervical squamous cell carcinoma (Zhou et al., 2014). In cervical cancer patients high ITCH or low LATS1 expression was associated with increased clinical stage and tumor size. Recently, miRNA-21 (miR-21) was found to regulate LATS1 to promote radioresistance in HR-HPV positive cervical cancer implicating LATS1 in cervical cancer sensitivity to treatment (Liu et al., 2015).
  
  
Entity Ovarian cancer
Note Lats1 deficient mice develop soft-tissue sarcomas as well as ovarian stromal cell tumours (St John et al., 1999). In human ovarian cancer, reduced LATS1 expression has been observed in ovarian serous borderline cystadenomas and ovarian serous carcinoma while the opposite pattern is found in ovarian mucinous borderline cystadenomas and ovarian mucinous carcinoma (Xu et al., 2015). In clear cell carcinoma, LATS1 expression was decreased. In ovarian serous carcinoma (but not in mucinous or clear cell carcinomas), LATS1 expression levels were correlated with disease recurrence, clinical stage and tumor grade.
  
  
Entity Renal cell carcinoma
Note LATS1 mRNA expression is reduced in samples from renal cell carcinoma patients (Chen et al., 2014). In these patients, LATS1 expression was associated with cancer pathological grade and clinical stage. The renal cancer cell line 786-O shows hypermethylation of the LATS1 promoter and pharmacological demethylation of the promoter in 786-O reduced cell proliferation while increasing apoptosis and G1 arrest.
  
  
Entity Bladder cancer
Note A recent study identified 29 total and 18 novel single nucleotide polymorphisms (SNPs) in the LATS1 gene using tissues from urinary bladder or colon cancer patients (Saadeldin et al., 2015). 13 SNPs mapped to intronic and untranslated sequences while 5 SNPs mapped to the coding sequences of LATS1 with 4/5 of these novel SNPs representing missense mutations in the serine/threonine kinase catalytic domain of LATS1. The functional significance of these mutations remains unclear.
  
  
Entity Colon cancer
Note In tissue from patients with colorectal cancer, the LATS1 gene was found to be hypermethylated in 57% (25/44) of cases and this hypermethylation was associated with decreased LATS1 mRNA levels (Wierzbicki et al., 2013). 89.4% (127/142) of all colorectal cancer samples analyzed showed decreased LATS1 mRNA. Another study identified 18 novel SNPs in the LATS1 gene using tissues from urinary bladder or colon cancer patients (Saadeldin et al., 2015). 13 SNPs mapped to intronic and untranslated sequences while 5 SNPs mapped to the coding sequences of LATS1 with 4/5 of these novel SNPs representing missense mutations in the serine/threonine kinase catalytic domain of LATS1. The functional significance of these SNPs remains poorly understood.
  
  
Entity Lung cancer
Note In Japanese lung cancer patients, the LATS1 promoter has been found to be hypermethylated in 79.8% (95/119) of tumors (Sasaki et al., 2010). In this study, the methylation status of the LATS1 promoter was associated with squamous histology and smoking status but not patient survival. In a study of non-small cell lung cancer (NSCLC), LATS1 expression is higher in normal lung tissue than in samples from NSCLC tumors (Lin et al., 2014). Low LATS1 expression in NSCLC patients was associated with higher p-TMN stage, increased lymph node metastasis and shorter overall survival. LATS1 overexpression in NSCLC cell lines reduces cell proliferation and invasion.
  
  
Entity Nervous system tumors
Note LATS1 has been reported to be downregulated in human astrocytomas by promoter hypermethylation (Jiang et al., 2006). In tissues from astrocytomas, 63.66% (56/88) showed hypermethylation of the LATS1 promoter while no methylation of the LATS1 promoter was found in 10 normal brain controls. The LATS1 mRNA level was significantly decreased in hypermethylated astrocytoma tissues compared to unmethylated controls. A similar study has shown that LATS1 is downregulated in gliomas (Ji et al., 2012). In gliomas, decreased LATS1 expression was correlated with higher WHO grade, lower Karnofsky Performance Status and shorter overall survival. Therefore, LATS1 is an independent prognostic indicator for survival of glioma patients. In the glioma cell line U251, overexpression of LATS1 reduced cell proliferation, migration and invasion. Recently, a germline LATS1 mutation (c.286C>T; p.R96W) was identified in a family with Li-Fraumeni syndrome (TP53 germline mutation), a MSH4 germline mutation and multiple cases of nervous system tumours (Kim et al., 2014). Peripheral shwannomas were observed in family members lacking the TP53 mutation but who instead carried mutations in MSH4 and LATS1. To examine how LATS1 might drive sporadic nervous system tumorigenesis, the authors screened 81 sporadic nervous system patients for mutations in the LATS1 gene but only identified one such case (a spinal schwannoma with c.2480delG; p.*R827Kfs*8).
  
  
Entity Head and neck squamous cell carcinoma (HNSCC)
Note LATS1 is one of 15 tumor-related genes that frequently show promoter hypermethylation in HNSCC (Steinmann et al. 2009). Increased methylation of these tumor-related genes is associated with less cellular differentiation and higher tumor stage.
  
  
Entity Oral squamous cell carcinoma
Note A pilot study in India examined the methylation status of the LATS1 gene in tumor samples from 13 patients with oral squamous cell carcinoma (Reddy et al., 2015). 54% (7/13) of tumor samples showed hypermethylation of the LATS1 gene.
  
  
Entity Soft-tissue sarcoma
Note Lats1 deficient mice develop soft-tissue sarcomas as well as ovarian stromal cell tumours (St John et al., 1999). Further, in multiple subtypes of human soft tissue sarcoma (myxoid liposarcoma, leiomyosarcoma and malignant fibrous histiocytoma), a missense point mutation in LATS1 gene locus and reduced LATS1 mRNA levels have been observed (Hisaoka et al., 2002). This decreased expression was suggested to be the result of promoter hypermethylation.
  
  
Entity Nevoid basal cell carcinoma syndrome (NBCCS)
Note A recent case report describes biallelic disruptions of the LATS1 gene in tissues from a patient with NBCCS (Tate et al., 2014). The authors compared superficial basal cell carcinoma (BCC) cells with more infiltrative BCCs by whole-exome sequencing. The infiltrative but not superficial BCCs showed mutations in the LATS1 gene. Specifically, infiltrative BCCs had one allele with the nonsense mutation c.943C>T (p.Q315X) as well as the loss of the other wild-type allele of LATS1. Loss of heterozygosity analysis showed a deletion in the distal region of chromosome 6q.
  

Bibliography

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Tumor suppressor WARTS ensures genomic integrity by regulating both mitotic progression and G1 tetraploidy checkpoint function
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Decreased expression of LATS1 is correlated with the progression and prognosis of glioma
Ji T, Liu D, Shao W, Yang W, Wu H, Bian X
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Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma
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Neurosci Res 2006 Dec;56(4):450-8
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The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment
Johnson R, Halder G
Nat Rev Drug Discov 2014 Jan;13(1):63-79
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TP53, MSH4, and LATS1 germline mutations in a family with clustering of nervous system tumors
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TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway
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Mol Cell Biol 2008 Apr;28(7):2426-36
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Expression of LATS1 contributes to good prognosis and can negatively regulate YAP oncoprotein in non-small-cell lung cancer
Lin XY, Zhang XP, Wu JH, Qiu XS, Wang EH
Tumour Biol 2014 Jul;35(7):6435-43
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miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1
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Reddy VR, Annamalai T, Narayanan V, Ramanathan A
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New genetic variants of LATS1 detected in urinary bladder and colon cancer
Saadeldin MK, Shawer H, Mostafa A, Kassem NM, Amleh A, Siam R
Front Genet 2015 Jan 13;5:425
PMID 25628642
 
NEDD4 E3 ligase inhibits the activity of the Hippo pathway by targeting LATS1 for degradation
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Cell Cycle 2013 Dec 15;12(24):3817-23
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LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1
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Yeung B, Ho KC, Yang X
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Yu FX, Guan KL
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Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling
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Zeng Q, Hong W
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Zhang J, Smolen GA, Haber DA
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Up-regulation of ITCH is associated with down-regulation of LATS1 during tumorigenesis and progression of cervical squamous cell carcinoma
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Citation

This paper should be referenced as such :
Stacy Visser-Grieve, Helena J Janse van Rensburg, Xiaolong Yang
LATS1 (Large Tumor Suppressor 1)
Atlas Genet Cytogenet Oncol Haematol. 2016;20(4):179-184.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/LATS1ID41127ch6q25.html

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  KATNA1/LATS1 (6q25)

External links

Nomenclature
HGNC (Hugo)LATS1   6514
Cards
AtlasLATS1ID41127ch6q25
Entrez_Gene (NCBI)LATS1  9113  large tumor suppressor kinase 1
AliasesWARTS; wts
GeneCards (Weizmann)LATS1
Ensembl hg19 (Hinxton)ENSG00000131023 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000131023 [Gene_View]  ENSG00000131023 [Sequence]  chr6:149658153-149718256 [Contig_View]  LATS1 [Vega]
ICGC DataPortalENSG00000131023
TCGA cBioPortalLATS1
AceView (NCBI)LATS1
Genatlas (Paris)LATS1
WikiGenes9113
SOURCE (Princeton)LATS1
Genetics Home Reference (NIH)LATS1
Genomic and cartography
GoldenPath hg38 (UCSC)LATS1  -     chr6:149658153-149718256 -  6q25.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)LATS1  -     6q25.1   [Description]    (hg19-Feb_2009)
GoldenPathLATS1 - 6q25.1 [CytoView hg19]  LATS1 - 6q25.1 [CytoView hg38]
ImmunoBaseENSG00000131023
Mapping of homologs : NCBILATS1 [Mapview hg19]  LATS1 [Mapview hg38]
OMIM603473   
Gene and transcription
Genbank (Entrez)AF104413 AF164041 AK310422 AW021064 BC002767
RefSeq transcript (Entrez)NM_001270519 NM_001350339 NM_001350340 NM_001350392 NM_004690
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)LATS1
Cluster EST : UnigeneHs.549084 [ NCBI ]
CGAP (NCI)Hs.549084
Alternative Splicing GalleryENSG00000131023
Gene ExpressionLATS1 [ NCBI-GEO ]   LATS1 [ EBI - ARRAY_EXPRESS ]   LATS1 [ SEEK ]   LATS1 [ MEM ]
Gene Expression Viewer (FireBrowse)LATS1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9113
GTEX Portal (Tissue expression)LATS1
Human Protein AtlasENSG00000131023-LATS1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO95835   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO95835  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO95835
Splice isoforms : SwissVarO95835
Catalytic activity : Enzyme2.7.11.1 [ Enzyme-Expasy ]   2.7.11.12.7.11.1 [ IntEnz-EBI ]   2.7.11.1 [ BRENDA ]   2.7.11.1 [ KEGG ]   
PhosPhoSitePlusO95835
Domaine pattern : Prosite (Expaxy)AGC_KINASE_CTER (PS51285)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)    UBA (PS50030)   
Domains : Interpro (EBI)AGC-kinase_C    Kinase-like_dom_sf    LATS1    Prot_kinase_dom    Ser/Thr_kinase_AS    UBA    UBA-like_sf   
Domain families : Pfam (Sanger)Pkinase (PF00069)    UBA (PF00627)   
Domain families : Pfam (NCBI)pfam00069    pfam00627   
Domain families : Smart (EMBL)S_TKc (SM00220)  
Conserved Domain (NCBI)LATS1
DMDM Disease mutations9113
Blocks (Seattle)LATS1
PDB (RSDB)4ZRK    5B5W    5BRK   
PDB Europe4ZRK    5B5W    5BRK   
PDB (PDBSum)4ZRK    5B5W    5BRK   
PDB (IMB)4ZRK    5B5W    5BRK   
Structural Biology KnowledgeBase4ZRK    5B5W    5BRK   
SCOP (Structural Classification of Proteins)4ZRK    5B5W    5BRK   
CATH (Classification of proteins structures)4ZRK    5B5W    5BRK   
SuperfamilyO95835
Human Protein Atlas [tissue]ENSG00000131023-LATS1 [tissue]
Peptide AtlasO95835
HPRD09147
IPIIPI00005858   IPI00470672   IPI00745100   IPI01014780   
Protein Interaction databases
DIP (DOE-UCLA)O95835
IntAct (EBI)O95835
FunCoupENSG00000131023
BioGRIDLATS1
STRING (EMBL)LATS1
ZODIACLATS1
Ontologies - Pathways
QuickGOO95835
Ontology : AmiGOG1/S transition of mitotic cell cycle  G2/M transition of mitotic cell cycle  magnesium ion binding  sister chromatid segregation  spindle pole  spindle pole  inner cell mass cell fate commitment  inner cell mass cellular morphogenesis  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein binding  ATP binding  microtubule organizing center  cytosol  protein phosphorylation  hormone-mediated signaling pathway  peptidyl-serine phosphorylation  protein kinase binding  keratinocyte differentiation  estrogen receptor binding  regulation of actin filament polymerization  positive regulation of peptidyl-serine phosphorylation  regulation of intracellular estrogen receptor signaling pathway  cellular protein localization  hippo signaling  hippo signaling  hippo signaling  intracellular signal transduction  positive regulation of apoptotic process  regulation of protein complex assembly  negative regulation of cyclin-dependent protein serine/threonine kinase activity  regulation of organ growth  cytoplasmic sequestering of protein  cell division  mammary gland epithelial cell differentiation  negative regulation of canonical Wnt signaling pathway  regulation of ubiquitin-dependent protein catabolic process  
Ontology : EGO-EBIG1/S transition of mitotic cell cycle  G2/M transition of mitotic cell cycle  magnesium ion binding  sister chromatid segregation  spindle pole  spindle pole  inner cell mass cell fate commitment  inner cell mass cellular morphogenesis  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein binding  ATP binding  microtubule organizing center  cytosol  protein phosphorylation  hormone-mediated signaling pathway  peptidyl-serine phosphorylation  protein kinase binding  keratinocyte differentiation  estrogen receptor binding  regulation of actin filament polymerization  positive regulation of peptidyl-serine phosphorylation  regulation of intracellular estrogen receptor signaling pathway  cellular protein localization  hippo signaling  hippo signaling  hippo signaling  intracellular signal transduction  positive regulation of apoptotic process  regulation of protein complex assembly  negative regulation of cyclin-dependent protein serine/threonine kinase activity  regulation of organ growth  cytoplasmic sequestering of protein  cell division  mammary gland epithelial cell differentiation  negative regulation of canonical Wnt signaling pathway  regulation of ubiquitin-dependent protein catabolic process  
Pathways : KEGGHippo signaling pathway   
NDEx NetworkLATS1
Atlas of Cancer Signalling NetworkLATS1
Wikipedia pathwaysLATS1
Orthology - Evolution
OrthoDB9113
GeneTree (enSembl)ENSG00000131023
Phylogenetic Trees/Animal Genes : TreeFamLATS1
HOGENOMO95835
Homologs : HomoloGeneLATS1
Homology/Alignments : Family Browser (UCSC)LATS1
Gene fusions - Rearrangements
Fusion : MitelmanKATNA1/LATS1 [6q25.1/6q25.1]  [t(6;6)(q25;q25)]  
Fusion : MitelmanLATS1/LACE1 [6q25.1/6q21]  [t(6;6)(q21;q25)]  
Fusion PortalKATNA1 6q25.1 LATS1 6q25.1 BRCA
Fusion PortalLATS1 6q25.1 LACE1 6q21 LUSC
Fusion : FusionGDB18199    19506    32747   
Fusion : Fusion_HubCES2--LATS1    ESR1--LATS1    GLIS3--LATS1    KATNA1--LATS1    LACE1--LATS1    LATS1--AHI1    LATS1--FAM188A    LATS1--GINM1    LATS1--LACE1    LATS1--MYO1D    LATS1--NUP43    LATS1--PCMT1    LATS1--PEX3    LATS1--PSEN1    LATS1--REPS1   
PCMT1--LATS1    PSEN1--LATS1    RPL36--LATS1    SCAF8--LATS1   
Fusion : QuiverLATS1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerLATS1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)LATS1
dbVarLATS1
ClinVarLATS1
1000_GenomesLATS1 
Exome Variant ServerLATS1
ExAC (Exome Aggregation Consortium)ENSG00000131023
GNOMAD BrowserENSG00000131023
Varsome BrowserLATS1
Genetic variants : HAPMAP9113
Genomic Variants (DGV)LATS1 [DGVbeta]
DECIPHERLATS1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisLATS1 
Mutations
ICGC Data PortalLATS1 
TCGA Data PortalLATS1 
Broad Tumor PortalLATS1
OASIS PortalLATS1 [ Somatic mutations - Copy number]
Mutations and Diseases : HGMDLATS1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch LATS1
DgiDB (Drug Gene Interaction Database)LATS1
DoCM (Curated mutations)LATS1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)LATS1 (select a term)
intoGenLATS1
NCG5 (London)LATS1
Cancer3DLATS1(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM603473   
Orphanet
DisGeNETLATS1
MedgenLATS1
Genetic Testing Registry LATS1
NextProtO95835 [Medical]
TSGene9113
GENETestsLATS1
Target ValidationLATS1
Huge Navigator LATS1 [HugePedia]
snp3D : Map Gene to Disease9113
BioCentury BCIQLATS1
ClinGenLATS1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9113
Chemical/Pharm GKB GenePA30301
Clinical trialLATS1
Miscellaneous
canSAR (ICR)LATS1 (select the gene name)
DataMed IndexLATS1
Probes
Litterature
PubMed133 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineLATS1
EVEXLATS1
GoPubMedLATS1
iHOPLATS1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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