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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LAMTOR4
late endosomal/lysosomal adaptor, MAPK and MTOR activator 4
Chromosome 7 · 7q22.1
NCBI Gene: 389541Ensembl: ENSG00000188186.11HGNC: HGNC:33772UniProt: A0A087WT92
39PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
guanyl-nucleotide exchange factor activitymolecular adaptor activityprotein bindingregulation of cell sizeneurodegenerative diseasemicrocephaly 25, primary, autosomal recessiveposterior cortical atrophythyroid hormone resistance, generalized, autosomal dominant
✦AI Summary

LAMTOR4 (late endosomal/lysosomal adaptor, MAPK and mTOR activator 4) is a critical component of the pentameric Ragulator complex that functions as a lysosomal scaffold for amino acid sensing and mTORC1 activation 1. The protein plays an essential role in stabilizing the Ragulator complex assembly, where the HBXIP-LAMTOR4 dimer acts as a nucleator that binds and stabilizes p18, allowing subsequent binding of other subunits 1. Structurally, LAMTOR4 forms a roadblock domain protein pair with LAMTOR5, with extensive hydrophobic interactions mediated by Lamtor1 2. The complex serves dual functions: acting as a guanine nucleotide exchange factor for Rag GTPases and recruiting them to the lysosomal membrane, ultimately leading to mTORC1 recruitment and activation in response to amino acid availability. LAMTOR4 expression is clinically significant, being elevated in various cancers including prostate cancer, where high expression correlates with poor survival outcomes 3. In hepatocellular carcinoma, LAMTOR4 upregulation is associated with mTOR signaling activation and worse prognosis 4. Additionally, LAMTOR4 shows differential requirements under fed versus starved conditions and exhibits synthetic-sick interactions with tumor suppressor folliculin, suggesting potential therapeutic targets 5.

Sources cited
1
LAMTOR4 is part of the pentameric Ragulator complex and HBXIP-LAMTOR4 dimer acts as nucleator for complex assembly
PMID: 31314152
2
LAMTOR4 forms roadblock domain protein pair with LAMTOR5 with structural interactions mediated by Lamtor1
PMID: 29285400
3
High LAMTOR4 expression in prostate cancer correlates with poor overall survival and cause-specific survival
PMID: 39125671
4
LAMTOR4 upregulation is associated with mTOR signaling activation in hepatocellular carcinoma
PMID: 38498682
5
LAMTOR4 shows differential requirements under fed vs starved conditions and synthetic-sick interaction with folliculin
PMID: 32934076
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.48Moderate
microcephaly 25, primary, autosomal recessiveOpen Targets
0.12Weak
posterior cortical atrophyOpen Targets
0.05Suggestive
thyroid hormone resistance, generalized, autosomal dominantOpen Targets
0.05Suggestive
familial hyperthyroidism due to mutations in TSH receptorOpen Targets
0.05Suggestive
coronary artery diseaseOpen Targets
0.04Suggestive
papillary thyroid carcinomaOpen Targets
0.04Suggestive
thyroid cancer, nonmedullary, 1Open Targets
0.04Suggestive
familial gestational hyperthyroidismOpen Targets
0.04Suggestive
hypothyroidism due to TSH receptor mutationsOpen Targets
0.03Suggestive
resistance to thyroid hormone due to a mutation in thyroid hormone receptor betaOpen Targets
0.03Suggestive
Graves diseaseOpen Targets
0.03Suggestive
thyroid dyshormonogenesis 1Open Targets
0.03Suggestive
Familial multinodular goiterOpen Targets
0.03Suggestive
goiter, multinodular 1, with or without Sertoli-Leydig cell tumorsOpen Targets
0.03Suggestive
hypothyroidism, congenital, nongoitrous, 7Open Targets
0.03Suggestive
hypothyroidism, congenital, nongoitrous, 5Open Targets
0.03Suggestive
thyroid hormone resistance, generalized, autosomal recessiveOpen Targets
0.03Suggestive
cancerOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DOCK1Protein interaction100%BLOC1S1Protein interaction100%TFEBProtein interaction100%RGP1Protein interaction100%ELMO1Protein interaction100%BORCS6Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
78%
Ovary
74%
Liver
71%
Heart
66%
Brain
53%
Gene Interaction Network
Click a node to explore
LAMTOR4DOCK1BLOC1S1TFEBRGP1ELMO1BORCS6
PROTEIN STRUCTURE
Preparing viewer…
PDB6B9X · 1.42 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.74LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.09 [0.69–1.74]
RankingsWhere LAMTOR4 stands among ~20K protein-coding genes
  • #10,345of 20,598
    Most Researched39
  • #16,279of 17,882
    Most Constrained (LOEUF)1.74
Genes detectedLAMTOR4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Aberrant hyper-expression of the RNA binding protein GIGYF2 in endothelial cells modulates vascular aging and function.
PMID: 37517320
Redox Biol · 2023
1.00
2
Elevated LAMTOR4 Expression Is Associated with Lethal Prostate Cancer and Its Knockdown Decreases Cell Proliferation, Invasion, and Migration In Vitro.
PMID: 39125671
Int J Mol Sci · 2024
0.90
3
The Absence of Intra-Tumoral Tertiary Lymphoid Structures is Associated with a Worse Prognosis and mTOR Signaling Activation in Hepatocellular Carcinoma with Liver Transplantation: A Multicenter Retrospective Study.
PMID: 38498682
Adv Sci (Weinh) · 2024
0.80
4
Heterogeneity of late endosome/lysosomes shown by multiplexed DNA-PAINT imaging.
PMID: 39485275
J Cell Biol · 2025
0.70
5
C7orf59/LAMTOR4 phosphorylation and structural flexibility modulate Ragulator assembly.
PMID: 31314152
FEBS Open Bio · 2019
0.60