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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LATS1
large tumor suppressor kinase 1
Chromosome 6 · 6q25.1
NCBI Gene: 9113Ensembl: ENSG00000131023.14HGNC: HGNC:6514UniProt: O95835
246PubMed Papers
20Diseases
0Drugs
3Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedKinaseTumor Suppressor
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
spindle polemicrotubule organizing centerATP bindingprotein kinase bindingcervical squamous cell carcinomaskin basal cell carcinomacarcinoma of liver and intrahepatic biliary tractHepatobiliary Neoplasm
✦AI Summary

LATS1 (large tumor suppressor kinase 1) is a serine/threonine kinase and core component of the Hippo signaling pathway that functions as a critical tumor suppressor 1. LATS1 operates within a kinase cascade where MST1/2 phosphorylates and activates LATS1 in complex with its regulatory protein MOB1, which then phosphorylates and inactivates the oncoproteins YAP1 and TAZ 1. This phosphorylation prevents YAP1 nuclear translocation, inhibiting expression of genes promoting cell proliferation and migration while suppressing apoptosis 1. Beyond canonical Hippo signaling, LATS1 maintains chr6 stability through regulation of mitotic progression and G1 tetraploidy checkpoints, controls G2/M transition by downregulating CDK1 activity, and affects cytokinesis through negative modulation of actin polymerization 2. LATS1 expression and activity are dynamically regulated by multiple mechanisms: m6A methylation by METTL3 reduces LATS1 mRNA stability in breast cancer 3, while oxidative stress activates LATS1 through MOB1 acetylation 2. LATS1 degradation via WWP1-mediated ubiquitination promotes metastasis in esophageal cancer 4. Recently, LATS1 was identified as a NLRP3 inflammasome activator, phosphorylating NLRP3 to facilitate its interaction with NEK7 5. Loss or reduced LATS1 expression is associated with tumorigenesis, making it a therapeutic target across multiple cancer types.

Sources cited
1
LATS1 is a core Hippo pathway kinase that phosphorylates YAP/TAZ to control cell proliferation and organ size
PMID: 30566373
2
MOB1 acetylation activates LATS1 and suppresses YAP/TAZ nuclear translocation; acetylated MOB1 predicts better survival in lung cancer
PMID: 35349706
3
METTL3-mediated m6A methylation reduces LATS1 mRNA stability and promotes breast cancer progression through YAP/TAZ activation
PMID: 36609396
4
GPRC5A promotes LATS1 degradation via WWP1, activating YAP1 signaling to enhance esophageal cancer lung metastasis
PMID: 39550386
5
LATS1/2 phosphorylate NLRP3 at Ser-265 following palmitoylation to activate the NLRP3 inflammasome
PMID: 39173637
Disease Associationsⓘ20
cervical squamous cell carcinomaOpen Targets
0.41Moderate
skin basal cell carcinomaOpen Targets
0.37Weak
carcinoma of liver and intrahepatic biliary tractOpen Targets
0.37Weak
colorectal adenocarcinomaOpen Targets
0.37Weak
Endometrial Endometrioid AdenocarcinomaOpen Targets
0.37Weak
Hepatobiliary NeoplasmOpen Targets
0.37Weak
skin squamous cell carcinomaOpen Targets
0.37Weak
multiple myelomaOpen Targets
0.34Weak
myoepithelial tumorOpen Targets
0.33Weak
hepatocellular carcinomaOpen Targets
0.30Weak
melanomaOpen Targets
0.30Weak
non-small cell lung carcinomaOpen Targets
0.29Weak
urinary bladder carcinomaOpen Targets
0.29Weak
papillary thyroid carcinomaOpen Targets
0.29Weak
oral squamous cell carcinomaOpen Targets
0.29Weak
lung adenocarcinomaOpen Targets
0.29Weak
schwannomaOpen Targets
0.29Weak
breast carcinomaOpen Targets
0.29Weak
head and neck squamous cell carcinomaOpen Targets
0.28Weak
bladder transitional cell carcinomaOpen Targets
0.28Weak
Pathogenic Variants3
NM_004690.4(LATS1):c.375A>T (p.Lys125Asn)Pathogenic
Myoepithelial tumor
☆☆☆☆2022→ Residue 125
NM_004690.4(LATS1):c.2449G>A (p.Glu817Lys)Likely pathogenic
Multiple myeloma
☆☆☆☆2019→ Residue 817
NM_004690.4(LATS1):c.2636G>A (p.Trp879Ter)Likely pathogenic
Malignant peritoneal mesothelioma
☆☆☆☆2019→ Residue 879
View on ClinVar ↗
Related Genes
NF2Protein interaction100%TEAD1Protein interaction100%LIMD1Protein interaction97%AJUBAProtein interaction97%RASSF1Protein interaction97%MOB1AProtein interaction97%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
69%
Ovary
59%
Heart
44%
Lung
41%
Liver
36%
Gene Interaction Network
Click a node to explore
LATS1NF2TEAD1LIMD1AJUBARASSF1MOB1A
PROTEIN STRUCTURE
Preparing viewer…
PDB7LWH · 1.61 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.32Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.22 [0.16–0.32]
RankingsWhere LATS1 stands among ~20K protein-coding genes
  • #1,573of 20,598
    Most Researched246 · top 10%
  • #3,923of 5,498
    Most Pathogenic Variants3
  • #1,280of 17,882
    Most Constrained (LOEUF)0.32 · top 10%
Genes detectedLATS1
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
The Hippo Pathway: Biology and Pathophysiology.
PMID: 30566373
Annu Rev Biochem · 2019
1.00
2
CircXRN2 suppresses tumor progression driven by histone lactylation through activating the Hippo pathway in human bladder cancer.
PMID: 37684641
Mol Cancer · 2023
0.90
3
Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling.
PMID: 22863277
Cell · 2012
0.80
4
Phase separation of TAZ compartmentalizes the transcription machinery to promote gene expression.
PMID: 32203417
Nat Cell Biol · 2020
0.76
5
Consecutive palmitoylation and phosphorylation orchestrates NLRP3 membrane trafficking and inflammasome activation.
PMID: 39173637
Mol Cell · 2024
0.70