LAMTOR1

Summary

LAMTOR1 (late endosomal/lysosomal adaptor, MAPK and MTOR activator 1, HGNC:26068) is a protein-coding gene on chromosome 11q13.4, encoding Ragulator complex protein LAMTOR1 (Q6IAA8). Key component of the Ragulator complex, a multiprotein complex involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. It is a selective cancer dependency (DepMap: 15.1% of cell lines).

Enables GTPase binding activity and protein-membrane adaptor activity. Contributes to guanyl-nucleotide exchange factor activity and molecular adaptor activity. Involved in several processes, including cholesterol homeostasis; positive regulation of TORC1 signaling; and regulation of cholesterol transport. Located in lysosome. Part of FNIP-folliculin RagC/D GAP. Is active in Ragulator complex and lysosomal membrane.

Source: NCBI Gene 55004 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 25 total
• Cancer dependency (DepMap): dependent in 15.1% of screened cell lines
• MANE Select transcript: NM_017907

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26068
Approved symbol	LAMTOR1
Name	late endosomal/lysosomal adaptor, MAPK and MTOR activator 1
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20625, p18, p27RF-Rho, Pdro, Ragulator1
Ensembl gene	ENSG00000149357
Ensembl biotype	protein_coding
OMIM	613510
Entrez	55004

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000278671, ENST00000535107, ENST00000535872, ENST00000538404, ENST00000539797, ENST00000541403, ENST00000544594, ENST00000545249, ENST00000877099, ENST00000877100, ENST00000920955, ENST00000920956, ENST00000947239

RefSeq mRNA: 1 — MANE Select: NM_017907 NM_017907

CCDS: CCDS8209

Canonical transcript exons

ENST00000278671 — 5 exons

Exon	Start	End
ENSE00002295093	72103183	72103297
ENSE00003493779	72098781	72098858
ENSE00003592987	72098289	72098415
ENSE00003613404	72099111	72099256
ENSE00003670798	72097292	72097914

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 98.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 126.3411 / max 744.3158, expressed in 1827 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121147	121.7737	1827
121148	3.1934	1533
121146	1.3739	909

Top tissues by expression

262 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.82	gold quality
leukocyte	CL:0000738	98.81	gold quality
ileal mucosa	UBERON:0000331	98.63	gold quality
granulocyte	CL:0000094	98.58	gold quality
right adrenal gland cortex	UBERON:0035827	98.32	gold quality
right adrenal gland	UBERON:0001233	98.29	gold quality
left adrenal gland	UBERON:0001234	98.20	gold quality
left adrenal gland cortex	UBERON:0035825	98.20	gold quality
stromal cell of endometrium	CL:0002255	98.17	gold quality
right lobe of thyroid gland	UBERON:0001119	98.09	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.07	gold quality
metanephros cortex	UBERON:0010533	98.00	gold quality
left lobe of thyroid gland	UBERON:0001120	97.97	gold quality
adrenal cortex	UBERON:0001235	97.86	gold quality
apex of heart	UBERON:0002098	97.84	gold quality
mucosa of transverse colon	UBERON:0004991	97.80	gold quality
adenohypophysis	UBERON:0002196	97.71	gold quality
putamen	UBERON:0001874	97.67	gold quality
caudate nucleus	UBERON:0001873	97.60	gold quality
adrenal gland	UBERON:0002369	97.58	gold quality
amygdala	UBERON:0001876	97.57	gold quality
spleen	UBERON:0002106	97.57	gold quality
nucleus accumbens	UBERON:0001882	97.56	gold quality
body of stomach	UBERON:0001161	97.53	gold quality
hypothalamus	UBERON:0001898	97.49	gold quality
spinal cord	UBERON:0002240	97.47	gold quality
thyroid gland	UBERON:0002046	97.46	gold quality
right lung	UBERON:0002167	97.45	gold quality
tibialis anterior	UBERON:0001385	97.43	gold quality
lower esophagus mucosa	UBERON:0035834	97.41	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	41.88
E-CURD-112	yes	32.80
E-CURD-122	yes	22.68
E-HCAD-6	yes	21.52
E-MTAB-9221	yes	19.40
E-HCAD-10	yes	16.51
E-CURD-88	yes	12.41
E-HCAD-1	yes	5.43
E-MTAB-8911	no	288.02
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting LAMTOR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-657	99.48	66.02	848
HSA-MIR-6165	99.44	67.12	1389

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 15.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 16)

• Studies in rat and mice, identified the rat p18 protein as an endosomal membrane anchoring protein which interacts with MEK1 scaffold p14/MP1 and mobilizes them to late endosome. (PMID:19177150)
• MT1-MMP-associated protein p27RF-Rho binds p27(kip1) and prevents p27(kip1) from binding to RhoA. [p27RF-Rho] (PMID:19654316)
• A complex encoded by the MAPKSP1, ROBLD3, and c11orf59 genes interacts with the Rag GTPases, recruits them to lysosomes, and is essential for mTORC1 activation (PMID:20381137)
• A p27(kip1)-binding protein, p27RF-Rho, promotes cancer metastasis via activation of RhoA and RhoC. (PMID:21087931)
• LAMTOR1 expression affects the tuning of lysosomal activation that can lead to p53-dependent apoptosis through excessive catabolism. (PMID:22513874)
• Data suggest that ablation of p18/LAMTOR1 suppresses starvation-induced cell death by stimulating autophagy through modulation of p27(kip1) activity. (PMID:26032166)
• Western blot experiments designed to detect flotillin 2, TMEM256, Rab3B and LAMTOR1 showed that the level of these proteins was higher in urinary exosomes from prostate cancer patients compared to healthy males (PMID:27664330)
• Study found that NF1 negatively regulates mTOR signaling in a LAMTOR1-dependent manner. In addition, the cell growth and survival of NF1-deficient cells have become dependent on hyperactivation of the mTOR pathway, and the tumorigenic properties of these cells have become dependent on LAMTOR1. (PMID:28174230)
• In vitro reconstitution and experiments with site-directed mutagenesis defined the physiological importance of LAMTOR1 in assembling the remaining components to ensure fidelity of mTORC1 signaling. (PMID:28935770)
• LAMTOR1 is a negative regulator of Arl8b- and BORC-dependent late endosomal positioning. (PMID:28993467)
• We found that under nutrient-rich conditions TMEM127 expression reduces mTORC1 recruitment to Rags. In addition, TMEM127 interacts with LAMTOR in an amino acid-dependent manner and decreases the LAMTOR1-vATPase association, while TMEM127-vATPase binding requires intact lysosomal acidification but is amino acid independent (PMID:29547888)
• The Lamtor1 dynamically controls cellular function via mTORC1 activation and lipid signaling. (PMID:30806216)
• A novel gene fusion between the LAMTOR1 and AKT1 was identified in a histopathologically indeterminate epithelioid neoplasm of a patient. This fusion resulted in oncogenic activatin of AKT1. (PMID:30877085)
• N-myristoyltransferase-1 deficiency blocks myristoylation of LAMTOR1 and inhibits bladder cancer progression. (PMID:34999170)
• LAMTOR1 degrades MHC-II via the endocytic in hepatocellular carcinoma. (PMID:36070764)
• TRAF4-Mediated LAMTOR1 Ubiquitination Promotes mTORC1 Activation and Inhibits the Inflammation-Induced Colorectal Cancer Progression. (PMID:38229144)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lamtor1	ENSDARG00000076464
mus_musculus	Lamtor1	ENSMUSG00000030842
rattus_norvegicus	Lamtor1	ENSRNOG00000004319
rattus_norvegicus	Lamtor1l1	ENSRNOG00000020016
drosophila_melanogaster	Lamtor1	FBGN0036932

Protein

Protein identifiers

Ragulator complex protein LAMTOR1 — Q6IAA8 (reviewed: Q6IAA8)

Alternative names: Late endosomal/lysosomal adaptor and MAPK and MTOR activator 1, Lipid raft adaptor protein p18, Protein associated with DRMs and endosomes, p27Kip1-releasing factor from RhoA

All UniProt accessions (6): Q6IAA8, F5GX19, F5H267, F5H3Y3, F5H479, H0YFI1

UniProt curated annotations — full annotation on UniProt →

Function. Key component of the Ragulator complex, a multiprotein complex involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. LAMTOR1 is directly responsible for anchoring the Ragulator complex to the lysosomal membrane. LAMTOR1 wraps around the other subunits of the Ragulator complex to hold them in place and interacts with the Rag GTPases, thereby playing a key role in the recruitment of the mTORC1 complex to lysosomes. Also involved in the control of embryonic stem cells differentiation via non-canonical RagC/RRAGC and RagD/RRAGD activation: together with FLCN, it is necessary to recruit and activate RagC/RRAGC and RagD/RRAGD at the lysosomes, and to induce exit of embryonic stem cells from pluripotency via non-canonical, mTOR-independent TFE3 inactivation. Also required for late endosomes/lysosomes biogenesis it may regulate both the recycling of receptors through endosomes and the MAPK signaling pathway through recruitment of some of its components to late endosomes. May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes. May also play a role in RHOA activation.

Subunit / interactions. Part of the Ragulator complex composed of LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5. LAMTOR4 and LAMTOR5 form a heterodimer that interacts, through LAMTOR1, with a LAMTOR2, LAMTOR3 heterodimer. Interacts with LAMTOR2 and LAMTOR3; the interaction is direct. The Ragulator complex interacts with both the mTORC1 complex and heterodimers constituted of the Rag GTPases RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and RagD/RRAGD; regulated by amino acid availability. The Ragulator complex interacts with SLC38A9; the probable amino acid sensor. Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator. Associates with the lysosomal V-ATPase complex; interaction promotes the guanine nucleotide exchange factor (GEF) of the Ragulator complex. Interacts with MMP14. Interacts with CDKN1B; prevents the interaction of CDKN1B with RHOA leaving RHOA in a form accessible to activation by ARHGEF2. Interacts with PIP4P1.

Subcellular location. Lysosome membrane. Late endosome membrane.

Post-translational modifications. N-terminal myristoylation and palmitoylation mediates its recruitment to lysosome membranes, thereby promoting localization of the Ragulator complex to lysosomes. N-myristoylation by NMT1 is required for palmitoylation at Cys-3 and Cys-4. May be palmitoylated by ZDHHC3. Ubiquitinated at Lys-60, Lys-103 and Lys-104 by UBE3A, promoting its degradation by the proteasome. Ubiquitination at Lys-20 impairs the association with the lysosomal V-ATPase complex. Deubiquitination at Lys-20 by USP32 promotes the association with the lysosomal V-ATPase complex and subsequent activation of the mTORC1 complex.

Induction. Down-regulated by cholesterol (at protein level).

Similarity. Belongs to the LAMTOR1 family.

RefSeq proteins (1): NP_060377* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028209	LAMTOR1/MEH1	Family

Pfam: PF15454

UniProt features (42 total): mutagenesis site 12, helix 7, cross-link 5, modified residue 5, lipid moiety-binding region 3, sequence conflict 3, region of interest 2, initiator methionine 1, chain 1, sequence variant 1, turn 1, strand 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
6B9X	X-RAY DIFFRACTION	1.42
5X6V	X-RAY DIFFRACTION	2.02
6EHP	X-RAY DIFFRACTION	2.3
5X6U	X-RAY DIFFRACTION	2.4
5Y39	X-RAY DIFFRACTION	2.65
6EHR	X-RAY DIFFRACTION	2.9
5Y3A	X-RAY DIFFRACTION	2.9
7UX2	ELECTRON MICROSCOPY	2.9
5YK3	X-RAY DIFFRACTION	3.01
6U62	ELECTRON MICROSCOPY	3.18
6WJ2	ELECTRON MICROSCOPY	3.2
7UXC	ELECTRON MICROSCOPY	3.2
7UXH	ELECTRON MICROSCOPY	3.2
9ED4	ELECTRON MICROSCOPY	3.23
6ULG	ELECTRON MICROSCOPY	3.31
8DHB	ELECTRON MICROSCOPY	3.53
6NZD	ELECTRON MICROSCOPY	3.6
6WJ3	ELECTRON MICROSCOPY	3.9
7T3B	ELECTRON MICROSCOPY	3.9
9ED6	ELECTRON MICROSCOPY	3.98
7T3A	ELECTRON MICROSCOPY	4
7T3C	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IAA8-F1	80.24	0.60

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (13): 3, 4, 20, 31, 60, 103, 104, 27, 42, 56, 98, 141, 2

Mutagenesis-validated functional residues (12):

Position	Phenotype
2	abolished n-myristoylation and subsequent palmitoylation.
3–4	abolished palmitoylation and recruitment to lysosomes, leading to impaired activation of the mtorc1 complex.
3	decreased palmitoylation.
3	does not affect interaction with zdhhc3.
4	decreased palmitoylation.
4	does not affect interaction with zdhhc3.
119	impaired assembly of the ragulator complex.
132	impaired assembly of the ragulator complex.
148–149	impaired assembly of the ragulator complex.
151–153	impaired recruiment of rag gtpases (rraga and rragc) to the lysosomal membrane.
154–158	does not affect interaction with rraga and rragc in vitro.
154–156	impaired recruiment of rag gtpases (rraga and rragc) to the lysosomal membrane.

Function

Pathways and Gene Ontology

Reactome pathways

33 pathways

ID	Pathway
R-HSA-1632852	Macroautophagy
R-HSA-165159	MTOR signalling
R-HSA-166208	mTORC1-mediated signalling
R-HSA-380972	Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-6798695	Neutrophil degranulation
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013406	RHOQ GTPase cycle
R-HSA-9013407	RHOH GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9639288	Amino acids regulate mTORC1
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-162582	Signal Transduction
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-194315	Signaling by Rho GTPases
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-6807070	PTEN Regulation
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9006925	Intracellular signaling by second messengers
R-HSA-9012999	RHO GTPase cycle

MSigDB gene sets: 224 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ENDOSOME_ORGANIZATION, GOBP_VACUOLE_ORGANIZATION, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_STEROL_HOMEOSTASIS, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_REGULATION_OF_CHOLESTEROL_EFFLUX

GO Biological Process (24): regulation of cell growth (GO:0001558), regulation of receptor recycling (GO:0001919), endosome organization (GO:0007032), lysosome organization (GO:0007040), intracellular protein localization (GO:0008104), regulation of cholesterol efflux (GO:0010874), endosomal transport (GO:0016197), cellular response to nutrient levels (GO:0031669), positive regulation of TOR signaling (GO:0032008), lysosome localization (GO:0032418), TORC1 signaling (GO:0038202), cholesterol homeostasis (GO:0042632), positive regulation of MAPK cascade (GO:0043410), regulation of cholesterol import (GO:0060620), cellular response to amino acid stimulus (GO:0071230), protein localization to membrane (GO:0072657), positive regulation of protein localization to lysosome (GO:0150032), positive regulation of TORC1 signaling (GO:1904263), autophagosome assembly (GO:0000045), cytoplasmic translation (GO:0002181), negative regulation of autophagy (GO:0010507), negative regulation of translational initiation (GO:0045947), positive regulation of translational initiation (GO:0045948), protein localization to lysosome (GO:0061462)

GO Molecular Function (5): protein-membrane adaptor activity (GO:0043495), GTPase binding (GO:0051020), guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515), molecular adaptor activity (GO:0060090)

GO Cellular Component (13): lysosome (GO:0005764), lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), late endosome membrane (GO:0031902), azurophil granule membrane (GO:0035577), specific granule membrane (GO:0035579), membrane raft (GO:0045121), extracellular exosome (GO:0070062), Ragulator complex (GO:0071986), ficolin-1-rich granule membrane (GO:0101003), FNIP-folliculin RagC/D GAP (GO:1990877), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
RHO GTPase cycle	8
MTOR signalling	2
Autophagy	1
Signal Transduction	1
Transcriptional Regulation by TP53	1
Innate Immune System	1
PTEN Regulation	1
Cellular response to starvation	1
Intracellular signaling by second messengers	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
secretory granule membrane	3
regulation of cholesterol transport	2
TOR signaling	2
positive regulation of intracellular signal transduction	2
binding	2
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
receptor recycling	1
regulation of signaling	1
regulation of macromolecule metabolic process	1
endomembrane system organization	1
vesicle organization	1
lytic vacuole organization	1
macromolecule localization	1
cholesterol efflux	1
vesicle-mediated transport	1
intracellular transport	1
response to nutrient levels	1
cellular response to stimulus	1
regulation of TOR signaling	1
vacuolar localization	1
sterol homeostasis	1
MAPK cascade	1
regulation of MAPK cascade	1
cholesterol import	1
response to amino acid	1
cellular response to acid chemical	1
intracellular protein localization	1
localization within membrane	1
protein localization to lysosome	1
regulation of protein localization to lysosome	1
positive regulation of protein localization	1
positive regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1

Protein interactions and networks

STRING

1578 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LAMTOR1	LAMTOR3	Q9UHA4	997
LAMTOR1	LAMTOR2	Q9Y2Q5	997
LAMTOR1	LAMTOR4	Q0VGL1	996
LAMTOR1	LAMTOR5	O43504	995
LAMTOR1	AXIN1	O15169	874
LAMTOR1	RRAGA	Q7L523	827
LAMTOR1	CDKN1B	P46527	802
LAMTOR1	SLC38A9	Q8NBW4	769
LAMTOR1	RRAGC	Q9HB90	748
LAMTOR1	ARHGEF1	Q92888	716
LAMTOR1	RRAGB	Q5VZM2	706
LAMTOR1	RRAGD	Q9NQL2	679
LAMTOR1	EFNA5	P52803	671
LAMTOR1	LAMP1	P11279	641
LAMTOR1	RHEB	Q15382	592

IntAct

225 interactions, top by confidence:

A	B	Type	Score
LAMTOR4	LAMTOR5	psi-mi:“MI:0914”(association)	0.960
LAMTOR5	LAMTOR4	psi-mi:“MI:0914”(association)	0.960
LAMTOR2	LAMTOR1	psi-mi:“MI:0915”(physical association)	0.940
LAMTOR1	LAMTOR2	psi-mi:“MI:2364”(proximity)	0.940
LAMTOR2	LAMTOR1	psi-mi:“MI:2364”(proximity)	0.940
LAMTOR2	LAMTOR1	psi-mi:“MI:0914”(association)	0.940
RRAGC	LAMTOR1	psi-mi:“MI:0914”(association)	0.920
LAMTOR1	RRAGC	psi-mi:“MI:0403”(colocalization)	0.920
RRAGC	LAMTOR1	psi-mi:“MI:2364”(proximity)	0.920
RRAGC	LAMTOR1	psi-mi:“MI:0915”(physical association)	0.920
LAMTOR1	RRAGC	psi-mi:“MI:0915”(physical association)	0.920
LAMTOR4	LAMTOR1	psi-mi:“MI:2364”(proximity)	0.910
LAMTOR1	LAMTOR4	psi-mi:“MI:0915”(physical association)	0.910
LAMTOR4	LAMTOR1	psi-mi:“MI:0914”(association)	0.910
LAMTOR1	LAMTOR4	psi-mi:“MI:0403”(colocalization)	0.910
LAMTOR3	LAMTOR1	psi-mi:“MI:2364”(proximity)	0.900
LAMTOR1	LAMTOR3	psi-mi:“MI:2364”(proximity)	0.900
LAMTOR1	LAMTOR3	psi-mi:“MI:0915”(physical association)	0.900
RRAGC	RRAGB	psi-mi:“MI:0914”(association)	0.870

BioGRID (878): LAMTOR1 (Affinity Capture-MS), LAMTOR1 (Affinity Capture-MS), LAMTOR1 (Affinity Capture-Western), LAMTOR1 (Affinity Capture-Western), LAMTOR1 (Affinity Capture-Western), RRAGB (Co-localization), LAMTOR1 (Affinity Capture-MS), LAMTOR1 (Affinity Capture-MS), LAMTOR1 (Affinity Capture-MS), LAMTOR1 (Affinity Capture-MS), LAMTOR1 (Affinity Capture-MS), LAMTOR1 (Affinity Capture-MS), LAMTOR1 (Affinity Capture-MS), LAMTOR1 (Affinity Capture-MS), LAMTOR1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U2WFX7, A0A1L9WQN2, A0A1R3RGK4, A2R6G8, A2T713, A2T7L8, C6Y4C5, C6Y4D3, M2XJV1, O14948, O49743, O94733, P0CP42, P0CP43, P31962, P31963, P34069, P37934, P37936, P37937, P37938, P40333, P78742, P78743, P78744, Q02594, Q10060, Q21148, Q3T0D8, Q4G2I2, Q4P456, Q4W9W8, Q4WIN1, Q4WMK0, Q5R766, Q6BZZ1, Q6CEU8, Q6IAA8, Q6K1S6, Q6P2W7

Diamond homologs: Q3T0D8, Q5R766, Q6IAA8, Q6P2W7, Q6P791, Q7SYW7, Q9CQ22

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
LAMTOR1	“form complex”	LAMTOR	binding
UBE3A	“down-regulates quantity by destabilization”	LAMTOR1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 134 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
mTORC1-mediated signalling	10	51.2×	6e-13
Energy dependent regulation of mTOR by LKB1-AMPK	10	42.3×	3e-12
MTOR signalling	10	28.6×	1e-10
Amino acids regulate mTORC1	12	25.9×	3e-12
PTEN Regulation	10	24.6×	5e-10
Regulation of PTEN gene transcription	10	19.2×	5e-09
Autophagy	12	19.1×	1e-10
Cellular response to starvation	10	17.8×	9e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein localization to lysosome	5	45.4×	5e-06
TORC1 signaling	6	41.5×	5e-07
lysosomal lumen acidification	7	40.7×	4e-08
lysosome localization	8	36.3×	9e-09
positive regulation of TOR signaling	8	34.2×	1e-08
cellular response to amino acid stimulus	10	26.4×	2e-09
positive regulation of TORC1 signaling	10	25.5×	2e-09
autophagosome maturation	6	18.2×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

25 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1338 predictions. Top by Δscore:

Variant	Effect	Δscore
11:72093492:ACAG:A	acceptor_loss	1.0000
11:72093493:CAGA:C	acceptor_loss	1.0000
11:72093494:A:AG	acceptor_gain	1.0000
11:72093494:A:AT	acceptor_loss	1.0000
11:72093495:G:GA	acceptor_gain	1.0000
11:72093697:ACCCT:A	donor_gain	1.0000
11:72093699:CCTG:C	donor_loss	1.0000
11:72093700:CT:C	donor_gain	1.0000
11:72093701:TG:T	donor_loss	1.0000
11:72093702:G:GG	donor_gain	1.0000
11:72093702:GTGA:G	donor_loss	1.0000
11:72093703:TGAGT:T	donor_loss	1.0000
11:72094989:C:CA	acceptor_gain	1.0000
11:72095090:GGTA:G	donor_gain	1.0000
11:72095094:TAGG:T	donor_loss	1.0000
11:72095095:AGGT:A	donor_loss	1.0000
11:72095096:GGT:G	donor_loss	1.0000
11:72095097:GTA:G	donor_loss	1.0000
11:72098285:TCA:T	donor_loss	1.0000
11:72098288:C:CT	donor_loss	1.0000
11:72098288:CCTG:C	donor_gain	1.0000
11:72098411:GGGTG:G	acceptor_gain	1.0000
11:72098412:GGTG:G	acceptor_gain	1.0000
11:72098413:GTG:G	acceptor_gain	1.0000
11:72098413:GTGC:G	acceptor_loss	1.0000
11:72098414:TG:T	acceptor_gain	1.0000
11:72098416:C:CC	acceptor_gain	1.0000
11:72098416:CTGA:C	acceptor_loss	1.0000
11:72098417:T:C	acceptor_loss	1.0000
11:72098421:C:CT	acceptor_gain	1.0000

AlphaMissense

1054 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:72097892:G:T	A139D	1.000
11:72097901:G:T	A136D	1.000
11:72098850:A:C	I66S	1.000
11:72098850:A:T	I66N	1.000
11:72097834:A:C	F158L	0.999
11:72097834:A:T	F158L	0.999
11:72097835:A:G	F158S	0.999
11:72097836:A:G	F158L	0.999
11:72097844:A:T	V155D	0.999
11:72097847:A:G	L154P	0.999
11:72097883:G:T	A142E	0.999
11:72097884:C:G	A142P	0.999
11:72097893:C:G	A139P	0.999
11:72097902:C:G	A136P	0.999
11:72098785:A:C	Y88D	0.999
11:72098785:A:G	Y88H	0.999
11:72098793:G:T	A85D	0.999
11:72098794:C:G	A85P	0.999
11:72098796:C:G	R84P	0.999
11:72098844:A:T	V68E	0.999
11:72098847:T:C	D67G	0.999
11:72098850:A:G	I66T	0.999
11:72098853:A:C	I65S	0.999
11:72098853:A:G	I65T	0.999
11:72098853:A:T	I65N	0.999
11:72099114:G:T	A62D	0.999
11:72099115:C:G	A62P	0.999
11:72099126:A:G	L58P	0.999
11:72099126:A:T	L58H	0.999
11:72099129:A:C	I57S	0.999

dbSNP variants (sampled 300 via entrez): RS1000813349 (11:72098753 G>T), RS1000886750 (11:72097314 C>T), RS1001460409 (11:72098479 T>C), RS1001585414 (11:72104907 T>A,C), RS1001801476 (11:72103735 G>A), RS1001904171 (11:72096961 C>G,T), RS1001920633 (11:72103513 A>C,G), RS1002033733 (11:72103321 C>A,G), RS1002282550 (11:72102428 C>T), RS1002822751 (11:72099549 A>G), RS1003155944 (11:72101335 C>T), RS1003270950 (11:72101032 T>C), RS1003473819 (11:72102558 C>T), RS1003533482 (11:72097163 C>G,T), RS1003588706 (11:72102204 G>A)

Disease associations

OMIM: gene MIM:613510 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, decreases expression, increases abundance	2
Tretinoin	affects cotreatment, increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
coumarin	decreases phosphorylation	1
nutlin 3	affects cotreatment, increases expression, increases secretion	1
bisphenol B	increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
jinfukang	increases expression	1
bisphenol AF	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Dactinomycin	increases expression, increases secretion, affects cotreatment	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Quercetin	decreases phosphorylation	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1VL	Abcam HeLa LAMTOR1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.