LAMTOR5

Summary

LAMTOR5 (late endosomal/lysosomal adaptor, MAPK and MTOR activator 5, HGNC:17955) is a protein-coding gene on chromosome 1p13.3, encoding Ragulator complex protein LAMTOR5 (O43504). As part of the Ragulator complex it is 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.

This gene encodes a protein that specifically complexes with the C-terminus of hepatitis B virus X protein (HBx). The function of this protein is to negatively regulate HBx activity and thus to alter the replication life cycle of the virus.

Source: NCBI Gene 10542 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 25 total
• MANE Select transcript: NM_001382293

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17955
Approved symbol	LAMTOR5
Name	late endosomal/lysosomal adaptor, MAPK and MTOR activator 5
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	XIP, MGC71071
Ensembl gene	ENSG00000134248
Ensembl biotype	protein_coding
OMIM	608521
Entrez	10542

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 retained_intron

ENST00000256644, ENST00000464240, ENST00000474861, ENST00000483260, ENST00000531779, ENST00000602318, ENST00000602858, ENST00000872833

RefSeq mRNA: 2 — MANE Select: NM_001382293 NM_001382293, NM_006402

CCDS: CCDS824, CCDS91022

Canonical transcript exons

ENST00000602318 — 4 exons

Exon	Start	End
ENSE00001123830	110401253	110401583
ENSE00003368250	110407586	110407694
ENSE00003550712	110406318	110406379
ENSE00003580514	110403919	110404036

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 87.6996 / max 424.9813, expressed in 1824 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13746	87.5876	1824
13748	0.0439	21
13747	0.0390	8
13745	0.0290	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nephron tubule	UBERON:0001231	99.48	gold quality
adult mammalian kidney	UBERON:0000082	99.20	gold quality
islet of Langerhans	UBERON:0000006	98.95	gold quality
kidney epithelium	UBERON:0004819	98.94	gold quality
adult organism	UBERON:0007023	98.92	gold quality
metanephros cortex	UBERON:0010533	98.89	gold quality
cortex of kidney	UBERON:0001225	98.88	gold quality
palpebral conjunctiva	UBERON:0001812	98.83	gold quality
monocyte	CL:0000576	98.80	gold quality
apex of heart	UBERON:0002098	98.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.74	gold quality
eye	UBERON:0000970	98.70	gold quality
mononuclear cell	CL:0000842	98.67	gold quality
kidney	UBERON:0002113	98.67	gold quality
heart left ventricle	UBERON:0002084	98.66	gold quality
cardiac ventricle	UBERON:0002082	98.64	gold quality
adenohypophysis	UBERON:0002196	98.64	gold quality
leukocyte	CL:0000738	98.61	gold quality
renal glomerulus	UBERON:0000074	98.58	gold quality
right atrium auricular region	UBERON:0006631	98.49	gold quality
renal medulla	UBERON:0000362	98.45	gold quality
metanephric glomerulus	UBERON:0004736	98.43	gold quality
pituitary gland	UBERON:0000007	98.40	gold quality
heart	UBERON:0000948	98.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.40	gold quality
heart right ventricle	UBERON:0002080	98.39	gold quality
metanephros	UBERON:0000081	98.38	gold quality
ventricular zone	UBERON:0003053	98.36	gold quality
stromal cell of endometrium	CL:0002255	98.35	gold quality
ganglionic eminence	UBERON:0004023	98.35	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-75367	yes	266.89
E-HCAD-10	yes	37.01
E-GEOD-134144	yes	27.62
E-MTAB-10042	yes	5.21
E-CURD-10	no	776.81
E-MTAB-7303	no	617.70
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CXCL8	Activation
LIN28B	Activation
S100A4	Activation

Upstream regulators (CollecTRI, top): ERCC2, MYC, NFKB, SP1, TBP

miRNA regulators (miRDB)

21 targeting LAMTOR5, 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-3185	99.99	68.12	1959
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-148B-5P	97.29	66.30	992
HSA-MIR-6874-3P	97.29	66.34	975
HSA-MIR-4661-3P	96.81	66.02	342
HSA-MIR-4522	95.76	66.23	742

Literature-anchored findings (GeneRIF, showing 40)

• Hepatitis B virus pX interacts with HBXAP (PMID:11788598)
• Elevated levels of GDN/PN1 and XIP mRNAs induced by Allitridi provide valuable molecular evidence for elucidating garlic’s efficacies against neurodegenerative and inflammatory diseases. (PMID:11925594)
• Survivin-HBXIP complexes, but neither survivin nor HBXIP individually, bind pro-caspase-9, preventing its recruitment to Apaf1, and thereby selectively suppressing apoptosis. (PMID:12773388)
• HBXIP up-regulates LTA expression in hepatocytes. (PMID:15955450)
• HBXIP sensitizes HepG2 cells to UV light-induced DNA damage. (PMID:16055925)
• suppressor of var1, 3-like 1 protein interacts with HBXIP, previously identified as a cofactor of survivin in suppression of apoptosis (PMID:16176273)
• The codon-38 change in genotype C is an independent risk factor for the development of HCC and may serve as a useful molecular marker for predicting the clinical outcomes in patients infected with HBV. (PMID:17050029)
• One of the functions of HBXIP is its involvement in cell proliferation (PMID:17303008)
• Hepatitis B virus X protein stimulates the mitochondrial translocation of Raf-1 via oxidative stress (PMID:17428866)
• HBXIP is a critical target of viral HBx for promoting genetic instability through formation of defective spindles and subsequent aberrant chromosome segregation. (PMID:18032378)
• HBXIP significantly stimulated the transcription and expression of telomerase reverse transcriptase and increased the activity of telomerase (PMID:18158869)
• the overexpression of survivin in the majority of NSCLCs together with the abundant or upregulated expression of HBXIP and XIAP suggest that tumours are endowed with resistance against a variety of apoptosis-inducing conditions. (PMID:19885569)
• The x gene of HBV (HBx) is the most common open reading frame integrated into the host genome in hepatocellular carcinoma and the integrated HBx is frequently mutated in hepatocellular carcinoma. (PMID:20811532)
• miR-520b is involved in regulating breast cancer cell migration by targeting HBXIP and IL-8 via a network in which HBXIP promotes migration by stimulating NF-kappaB-mediated IL-8 expression. (PMID:21343296)
• The different structure forms of HBx protein influence their intracellular distribution in hepatocellular carcinoma HepG2 cells (PMID:21651858)
• overexpression of HBXIP increased HepG2 cell-induced endothelial cells migration, proliferation, and angiogenesis, which may be related to increasing phosphorylation of endothelial NO synthase in HUVECs. (PMID:22209835)
• Data suggest that HBXIP upregulates CD46, CD55 and CD59 through p-ERK1/2/NF-kappaB signaling to protect breast cancer from complement-dependent cytotoxicity. (PMID:22293503)
• HBXIP up-regulates S100A4 through activating S100A4 promoter involving STAT4 and inducing PTEN/PI3K/AKT signaling to promote growth and migration of breast cancer cells. (PMID:22740693)
• Study identified HBXIP and C7orf59 as two additional Ragulator components that are required for mTORC1 activation by amino acids. (PMID:22980980)
• knockdown of HBXIP rescued the inhibition of HBV that occurred after the loss of miR-501 in HepG2.2.15 cells, suggesting that miR-501 induced HBV replication partially by targeting HBXIP. (PMID:23266610)
• oncoprotein HBXIP is able to activate the transcriptional coregulatory protein LMO4 through transcription factor Sp1 in promotion of proliferation of breast cancer cells. (PMID:23291272)
• found that HBXIP was able to stimulate the promoter of Skp2 through binding to the -640/-443 region in Skp2 promoter involving activating E2F transcription factor 1 (PMID:23352642)
• conclude that the oncoprotein HBXIP as a co-activator of TF II D transactivates Lin28B promoter via directly binding to TBP to upregulate the expression of Lin28B in promotion of proliferation of breast cancer cells (PMID:23494474)
• HBXIP promotes the proliferation of breast cancer cells via upregulating PDGFB. (PMID:23537647)
• HBXIP nuclear import requires interaction with c-Fos and phosphorylation of both proteins in breast cancer cells (PMID:23667255)
• The oncoprotein HBXIP enhances angiogenesis and growth of breast cancer through modulating FGF8 and VEGF. (PMID:24464787)
• Dta show that HBXIP was able to stimulate the activity of Skp2 promoter via transcription factor Sp1 thus promoting the migration of ovarian cancer cells. (PMID:24788380)
• HBXIP facilitates the proliferation of hepatoma cells by up-regulating SCG3 via E2F1 and miR-509-3p modulation. (PMID:24882622)
• Hepatitis B protein HBx accelerates hepatocarcinogenesis with partner survivin through modulating tumor suppressor miR-520b and oncoprotein HBXIP. (PMID:24886421)
• Our study suggested that high HBXIP is associated with the progression of breast cancer. HBXIP could be a valuable prognostic marker as well as a potential molecular therapy target for breast cancer patients. (PMID:25178941)
• HBXIP promotes the migration of breast cancer cells through modulating microtubule acetylation mediated by GCN5. (PMID:25686500)
• Upon HBV infection, cellular mechanisms involving SETDB1-mediated H3K9me3 and HP1 induce silencing of HBV cccDNA transcription through modulation of chromatin structure. (PMID:26143443)
• highly expressed HBXIP accelerates the MDM2-mediated degradation of p53 in breast cancer through modulating the feedback loop of MDM2/p53, resulting in the fast growth of breast cancer cells. (PMID:26229107)
• oncoprotein HBXIP enhances glucose metabolism reprogramming through suppressing SCO2 and PDHA1 in breast cancer (PMID:26309161)
• deacetylation of MST1 mediated by HBXIP-enhanced HDAC6 results in MST1 degradation in a CMA manner in promotion of breast cancer growth. (PMID:26657153)
• Results support a model in which the HBXIP/Hotair/LSD1 complex serves as a critical effector of c-Myc in activating transcription of its target genes, illuminating long-standing questions on how c-Myc drives carcinogenesis. (PMID:26719542)
• Thus, we conclude that the oncoprotein HBXIP up-regulates FGF4 through activating transcriptional factor Sp1 to promote the migration of breast cancer cells. Therapeutically, HBXIP may serve as a novel target in breast cancer. (PMID:26828265)
• we conclude that the oncoprotein HBXIP contributes to the abnormal lipid metabolism in breast cancer (PMID:26980761)
• HBXIP is able to depress the gluconeogenesis in hepatoma cells by suppressing PCK1 to promote hepatocarcinogenesis, involving miR-135a/FOXO1 axis and PI3K/Akt/p-FOXO1 pathway. (PMID:27609066)
• HBXIP up-regulates YAP expression via activating transcription factor c-Myb to facilitate the growth of hepatoma cells. (PMID:27765671)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lamtor5	ENSDARG00000090194
mus_musculus	Lamtor5	ENSMUSG00000087260
rattus_norvegicus	Lamtor5	ENSRNOG00000018186
drosophila_melanogaster	Lamtor5	FBGN0026090

Protein

Protein identifiers

Ragulator complex protein LAMTOR5 — O43504 (reviewed: O43504)

Alternative names: Hepatitis B virus X-interacting protein, Late endosomal/lysosomal adaptor and MAPK and MTOR activator 5

All UniProt accessions (4): A0A8Z5A536, E9PLX3, O43504, R4GMU8

UniProt curated annotations — full annotation on UniProt →

Function. As part of the Ragulator complex it is 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. When complexed to BIRC5, interferes with apoptosome assembly, preventing recruitment of pro-caspase-9 to oligomerized APAF1, thereby selectively suppressing apoptosis initiated via the mitochondrial/cytochrome c pathway.

Subunit / interactions. Homodimer. 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. 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. Interacts with phosphorylated BIRC5; the resulting complex binds pro-caspase-9, as well as active caspase-9, but much less efficiently. Interacts with SUPV3L1. (Microbial infection) Interacts with hepatitis B virus (HBV) oncoprotein HBX C-terminus.

Subcellular location. Lysosome. Cytoplasm. Cytosol.

Tissue specificity. Highly expressed in skeletal and cardiac muscle, followed by pancreas, kidney, liver, brain, placenta and lung. Elevated levels in both cancerous and non-cancerous liver tissue of patients with chronic HBV infection compared with hepatic tissue without HBV infection.

Similarity. Belongs to the LAMTOR5 family.

RefSeq proteins (2): NP_001369222, NP_006393 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024135	LAMTOR5	Family

Pfam: PF16672

UniProt features (17 total): strand 9, helix 4, mutagenesis site 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

27 structures.

PDB	Method	Resolution (Å)
6B9X	X-RAY DIFFRACTION	1.42
3MSH	X-RAY DIFFRACTION	1.51
5X6V	X-RAY DIFFRACTION	2.02
5YK5	X-RAY DIFFRACTION	2.03
3MS6	X-RAY DIFFRACTION	2.08
6EHP	X-RAY DIFFRACTION	2.3
5X6U	X-RAY DIFFRACTION	2.4
5Y39	X-RAY DIFFRACTION	2.65
5Y38	X-RAY DIFFRACTION	2.8
5VOK	X-RAY DIFFRACTION	2.89
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-O43504-F1	96.55	0.95

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 (1): 1

Mutagenesis-validated functional residues (2):

Position	Phenotype
12	no change.
36	no interaction with xabx14-154 (truncated form of hbx).

Function

Pathways and Gene Ontology

Reactome pathways

19 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-8943724	Regulation of PTEN gene transcription
R-HSA-9639288	Amino acids regulate mTORC1
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-162582	Signal Transduction
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-9612973	Autophagy
R-HSA-9711097	Cellular response to starvation

MSigDB gene sets: 200 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOCC_VACUOLAR_MEMBRANE, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_CELLULAR_RESPONSE_TO_ACID_CHEMICAL, GOBP_PROTEIN_LOCALIZATION_TO_LYSOSOME, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION_TO_NUCLEUS, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_PROTEIN_LOCALIZATION_TO_VACUOLE, GOBP_CYTOKINE_PRODUCTION

GO Biological Process (13): regulation of cell size (GO:0008361), response to virus (GO:0009615), positive regulation of gene expression (GO:0010628), viral genome replication (GO:0019079), positive regulation of TOR signaling (GO:0032008), positive regulation of interleukin-8 production (GO:0032757), TORC1 signaling (GO:0038202), negative regulation of apoptotic process (GO:0043066), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), protein localization to lysosome (GO:0061462), cellular response to amino acid stimulus (GO:0071230), positive regulation of protein localization to nucleus (GO:1900182), positive regulation of TORC1 signaling (GO:1904263)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515), molecular adaptor activity (GO:0060090)

GO Cellular Component (8): lysosome (GO:0005764), lysosomal membrane (GO:0005765), cytosol (GO:0005829), late endosome membrane (GO:0031902), protein-containing complex (GO:0032991), Ragulator complex (GO:0071986), FNIP-folliculin RagC/D GAP (GO:1990877), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Signal Transduction	2
MTOR signalling	2
Autophagy	1
Transcriptional Regulation by TP53	1
PTEN Regulation	1
Cellular response to starvation	1
Intracellular signaling by second messengers	1
RNA Polymerase II Transcription	1
Cellular responses to stimuli	1
Generic Transcription Pathway	1
PIP3 activates AKT signaling	1
Gene expression (Transcription)	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
TOR signaling	2
positive regulation of intracellular signal transduction	2
binding	2
cellular anatomical structure	2
regulation of cellular component size	1
response to other organism	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
viral process	1
viral life cycle	1
regulation of TOR signaling	1
positive regulation of cytokine production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
protein localization to vacuole	1
response to amino acid	1
cellular response to acid chemical	1
protein localization to nucleus	1
regulation of protein localization to nucleus	1
positive regulation of protein localization	1
positive regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
molecular_function	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
cytoplasm	1
late endosome	1
endosome membrane	1
cellular_component	1

Protein interactions and networks

STRING

1312 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LAMTOR5	LAMTOR4	Q0VGL1	996
LAMTOR5	LAMTOR1	Q6IAA8	995
LAMTOR5	LAMTOR3	Q9UHA4	995
LAMTOR5	LAMTOR2	Q9Y2Q5	995
LAMTOR5	XIAP	P98170	803
LAMTOR5	KDM1A	O60341	766
LAMTOR5	RRAGC	Q9HB90	692
LAMTOR5	RRAGB	Q5VZM2	669
LAMTOR5	SLC38A9	Q8NBW4	665
LAMTOR5	RRAGA	Q7L523	643
LAMTOR5	EFNA5	P52803	621
LAMTOR5	METTL3	Q86U44	606
LAMTOR5	RRAGD	Q9NQL2	605
LAMTOR5	MYC	P01106	587
LAMTOR5	CETN2	P41208	583

IntAct

184 interactions, top by confidence:

A	B	Type	Score
LAMTOR4	LAMTOR5	psi-mi:“MI:0915”(physical association)	0.960
LAMTOR4	LAMTOR5	psi-mi:“MI:0407”(direct interaction)	0.960
LAMTOR5	LAMTOR4	psi-mi:“MI:0915”(physical association)	0.960
LAMTOR4	LAMTOR5	psi-mi:“MI:0914”(association)	0.960
LAMTOR5	LAMTOR4	psi-mi:“MI:0914”(association)	0.960
LAMTOR1	LAMTOR5	psi-mi:“MI:0915”(physical association)	0.870
LAMTOR1	LAMTOR5	psi-mi:“MI:0914”(association)	0.870
LAMTOR5	LAMTOR1	psi-mi:“MI:0914”(association)	0.870
LAMTOR1	LAMTOR5	psi-mi:“MI:0403”(colocalization)	0.870
LAMTOR2	LAMTOR5	psi-mi:“MI:0914”(association)	0.860

BioGRID (208): LAMTOR5 (Two-hybrid), LAMTOR5 (Two-hybrid), LAMTOR5 (Two-hybrid), CEP70 (Two-hybrid), LAMTOR4 (Two-hybrid), LAMTOR5 (Affinity Capture-RNA), LAMTOR5 (Affinity Capture-RNA), ASGR1 (Two-hybrid), BHMT (Two-hybrid), DBI (Two-hybrid), TGFB1 (Two-hybrid), RBP4 (Two-hybrid), CFB (Two-hybrid), CD74 (Two-hybrid), MT2A (Two-hybrid)

ESM2 similar proteins: A0JN27, A6H7F7, B2RYU6, B5FXJ6, B5FYY5, B5X7X4, B5XGE7, O43504, P55168, P61201, P61202, P61203, P79101, Q05048, Q13888, Q28F72, Q2TBL9, Q2TBV5, Q2YDH6, Q3T132, Q4KLA0, Q4R9A8, Q4VC33, Q5BJQ6, Q5F398, Q5M8X5, Q5R532, Q5R8K2, Q5R9J9, Q5RKJ1, Q63ZJ2, Q6DEG4, Q6DF40, Q6GR10, Q6IQT4, Q6IR75, Q6P1K8, Q7L5Y9, Q7SXR3, Q7ZXB7

Diamond homologs: A7RT29, A9UL91, O43504, Q3SZ68, Q4PM15, Q54QW5, Q66X52, Q6IRS2, Q9D1L9

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
LAMTOR5	“form complex”	LAMTOR	binding
STAT4	“up-regulates activity”	LAMTOR5	binding
LAMTOR5	“up-regulates quantity by expression”	S100A4	“transcriptional regulation”
LAMTOR5	“up-regulates quantity by expression”	LIN28B	“transcriptional regulation”
hsa-miR-520a-5p	“down-regulates quantity by repression”	LAMTOR5	“post transcriptional regulation”
ATM	“up-regulates activity”	LAMTOR5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 114 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	11	60.9×	3e-15
Energy dependent regulation of mTOR by LKB1-AMPK	9	41.2×	1e-10
MTOR signalling	9	27.8×	3e-09
PTEN Regulation	10	26.6×	5e-10
Amino acids regulate mTORC1	9	21.0×	3e-08
Regulation of PTEN gene transcription	10	20.8×	4e-09
Cellular response to starvation	9	17.3×	1e-07
Autophagy	9	15.5×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
TORC1 signaling	5	37.9×	4e-05
positive regulation of TOR signaling	7	32.7×	5e-07
cellular response to amino acid stimulus	9	26.0×	4e-08
positive regulation of TORC1 signaling	9	25.1×	4e-08
negative regulation of autophagy	5	12.2×	7e-03

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	17
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

644 predictions. Top by Δscore:

Variant	Effect	Δscore
1:110403913:ACT:A	donor_loss	1.0000
1:110403914:CTCA:C	donor_loss	1.0000
1:110403915:TCACC:T	donor_loss	1.0000
1:110403916:C:CG	donor_loss	1.0000
1:110403917:A:AC	donor_gain	1.0000
1:110403917:AC:A	donor_gain	1.0000
1:110403917:ACC:A	donor_gain	1.0000
1:110403918:C:CC	donor_gain	1.0000
1:110403918:CC:C	donor_gain	1.0000
1:110403918:CCC:C	donor_gain	1.0000
1:110403976:G:C	donor_gain	1.0000
1:110404033:CGGC:C	acceptor_gain	1.0000
1:110404034:GGC:G	acceptor_gain	1.0000
1:110404035:GC:G	acceptor_gain	1.0000
1:110404035:GCC:G	acceptor_loss	1.0000
1:110404036:CC:C	acceptor_gain	1.0000
1:110404037:C:CC	acceptor_gain	1.0000
1:110404037:CTGG:C	acceptor_loss	1.0000
1:110404038:T:A	acceptor_loss	1.0000
1:110406316:ACAAC:A	donor_gain	1.0000
1:110406317:CAACC:C	donor_gain	1.0000
1:110406388:A:T	acceptor_gain	1.0000
1:110406393:C:CT	acceptor_gain	1.0000
1:110406408:G:GC	acceptor_gain	1.0000
1:110406411:CATAA:C	acceptor_gain	1.0000
1:110406412:A:AC	acceptor_gain	1.0000
1:110406415:A:AC	acceptor_gain	1.0000
1:110407494:C:CA	donor_gain	1.0000
1:110407584:A:AC	donor_gain	1.0000
1:110407585:C:CC	donor_gain	1.0000

AlphaMissense

587 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:110406356:C:T	G20E	1.000
1:110406357:C:G	G20R	1.000
1:110406357:C:T	G20R	1.000
1:110401545:G:T	A85E	0.999
1:110404030:C:A	G35V	0.999
1:110404030:C:T	G35E	0.999
1:110404031:C:A	G35W	0.999
1:110406332:C:T	G28E	0.999
1:110406333:C:G	G28R	0.999
1:110406333:C:T	G28R	0.999
1:110406348:A:G	C23R	0.999
1:110406356:C:A	G20V	0.999
1:110401546:C:G	A85P	0.998
1:110401572:A:T	I76N	0.998
1:110403940:A:T	V65E	0.998
1:110403979:G:T	A52E	0.998
1:110404000:A:T	I45K	0.998
1:110404006:C:T	G43E	0.998
1:110404007:C:G	G43R	0.998
1:110404007:C:T	G43R	0.998
1:110404031:C:G	G35R	0.998
1:110404031:C:T	G35R	0.998
1:110406332:C:A	G28V	0.998
1:110406346:G:C	C23W	0.998
1:110403929:A:G	S69P	0.997
1:110403934:A:G	L67P	0.997
1:110403980:C:G	A52P	0.997
1:110404009:G:T	A42D	0.997
1:110406323:A:G	L31P	0.997
1:110406329:A:G	L29P	0.997

dbSNP variants (sampled 300 via entrez): RS1000550829 (1:110407305 G>A,C,T), RS1000583292 (1:110407508 C>T), RS1001168298 (1:110401015 A>G), RS1001249039 (1:110407239 C>T), RS1001585531 (1:110408827 G>C), RS1001814183 (1:110402493 G>A), RS1002139755 (1:110405486 CAT>C,CATAT), RS1002183071 (1:110402203 A>G), RS1002780237 (1:110403974 T>C), RS1002802591 (1:110408127 GAC>G), RS1003159854 (1:110403624 A>C,G), RS1003753604 (1:110405253 C>A,T), RS1004189604 (1:110405596 G>T), RS1004210891 (1:110407059 G>A), RS1004754721 (1:110409839 T>C)

Disease associations

OMIM: gene MIM:608521 | 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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, increases abundance	4
Cadmium	increases abundance, increases expression, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
nuciferine	affects binding	1
methylparaben	decreases expression	1
diallyl trisulfide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
chloropicrin	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression, increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Plant Extracts	decreases expression, increases expression, affects cotreatment	1
Tretinoin	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, 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_E0YL	Ubigene MDA-MB-231 LAMTOR5 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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