LAMP1

Summary

LAMP1 (lysosome associated membrane protein 1, HGNC:6499) is a protein-coding gene on chromosome 13q34, encoding Lysosome-associated membrane glycoprotein 1 (P11279). Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis.

The protein encoded by this gene is a member of a family of membrane glycoproteins. This glycoprotein provides selectins with carbohydrate ligands. It may also play a role in tumor cell metastasis.

Source: NCBI Gene 3916 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 86 total
• Druggable target: yes
• MANE Select transcript: NM_005561

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6499
Approved symbol	LAMP1
Name	lysosome associated membrane protein 1
Location	13q34
Locus type	gene with protein product
Status	Approved
Aliases	CD107a
Ensembl gene	ENSG00000185896
Ensembl biotype	protein_coding
OMIM	153330
Entrez	3916

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000332556, ENST00000471046, ENST00000472564, ENST00000886113, ENST00000886114, ENST00000886115, ENST00000886116, ENST00000886117, ENST00000886118, ENST00000886119, ENST00000886120, ENST00000929071, ENST00000945470

RefSeq mRNA: 1 — MANE Select: NM_005561 NM_005561

CCDS: CCDS41909

Canonical transcript exons

ENST00000332556 — 9 exons

Exon	Start	End
ENSE00001303147	113321404	113321470
ENSE00001304165	113322282	113323672
ENSE00001317057	113320345	113320470
ENSE00001323112	113321557	113321727
ENSE00001329432	113306485	113306606
ENSE00001417808	113297239	113297495
ENSE00003500971	113309643	113309862
ENSE00003528410	113310709	113310867
ENSE00003656373	113319469	113319656

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 301.8125 / max 1824.4073, expressed in 1829 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136212	284.3538	1829
136213	8.6233	1759
136211	5.7844	1731
136215	1.7027	1071
136216	0.7787	471
136217	0.3900	177
136210	0.0985	49
136214	0.0810	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.94	gold quality
parotid gland	UBERON:0001831	99.94	gold quality
inferior olivary complex	UBERON:0002127	99.94	gold quality
visceral pleura	UBERON:0002401	99.94	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.93	gold quality
renal glomerulus	UBERON:0000074	99.92	gold quality
nephron tubule	UBERON:0001231	99.92	gold quality
esophagus squamous epithelium	UBERON:0006920	99.92	gold quality
gingival epithelium	UBERON:0001949	99.91	gold quality
metanephric glomerulus	UBERON:0004736	99.91	gold quality
pancreatic ductal cell	CL:0002079	99.90	gold quality
squamous epithelium	UBERON:0006914	99.90	gold quality
kidney epithelium	UBERON:0004819	99.88	gold quality
epithelium of esophagus	UBERON:0001976	99.87	gold quality
pleura	UBERON:0000977	99.86	gold quality
gingiva	UBERON:0001828	99.85	gold quality
cervix squamous epithelium	UBERON:0006922	99.85	gold quality
germinal epithelium of ovary	UBERON:0001304	99.84	gold quality
parietal pleura	UBERON:0002400	99.84	gold quality
medial globus pallidus	UBERON:0002477	99.84	gold quality
renal medulla	UBERON:0000362	99.83	gold quality
tibia	UBERON:0000979	99.83	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.82	gold quality
palpebral conjunctiva	UBERON:0001812	99.81	gold quality
globus pallidus	UBERON:0001875	99.81	gold quality
decidua	UBERON:0002450	99.81	gold quality
tendon of biceps brachii	UBERON:0008188	99.81	gold quality
tongue squamous epithelium	UBERON:0006919	99.80	gold quality
hair follicle	UBERON:0002073	99.79	gold quality
epithelium of mammary gland	UBERON:0003244	99.78	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	23.24
E-ANND-3	yes	20.91
E-CURD-10	no	265.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HMBOX1, MT3, MYC, VPS35

miRNA regulators (miRDB)

50 targeting LAMP1, 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-9-5P	100.00	72.28	2361
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4487	99.96	64.58	1252
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-LET-7C-3P	99.95	73.42	2862
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-505-3P	99.19	69.71	896
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891

Literature-anchored findings (GeneRIF, showing 40)

• review of structure, function, cell and tissue distribution, intracellular trafficking (PMID:12144129)
• This study identifies two cDNA clones that code for heart extracellular matrix protein, hLAMP-1. Immunohistochemical studies indicate that the myocardial layer of the heart produces hLAMP-1. (PMID:15052658)
• Using human leukemia and lymphoma cell lines, we observed a close correlation between CD107a surface expression and target cell lysis, indicating that NK cell cytotoxicity can be assessed by this method. (PMID:15744340)
• Data identify CD13, CD107a, and CD164 as novel basophil-activation antigens. (PMID:15916720)
• Novel evidence for differential expression of HBGA and LAMPs in proliferative and involutive phases of immunohistochemistry is presented. (PMID:16570122)
• expression in keratinocytes cultured at different cell densities in order to induce differentiation (PMID:16710742)
• Enhanced expression of lysosome-associated membrane protein-1 in melanoma may promote invasion by influencing both adhesion to extracellular matrix and perhaps also binding to endothelial cells. (PMID:16718270)
• CD107a surface expression has a role in Munc13-4 defect in familial hemophagocytic lymphohistiocytosis (PMID:16778144)
• LAMP-1 and DC-LAMP antigen chimeras follow different trafficking pathways, induce distinct modulatory immune responses, and are able to present cryptic epitopes. (PMID:16887987)
• LAMP-1 and LAMP-2 may have roles in accidental involution of the thymic gland (PMID:17048695)
• Data show that cells lacking either LAMP-1 or LAMP-2 alone formed phagosomes that gradually acquired microbicidal activity and curtailed bacterial growth, but LAMP-1 and LAMP-2 double-deficient cells failed to kill engulfed Neisseria gonorrhoeae. (PMID:17506821)
• CD107a expression may be a sensitive marker for the cytotoxic activity determination (PMID:18835598)
• Despite its abundance, LAMP-1 is not essential, but LAMP-2 may be partially important for the Salmonella-containing vacuolar membrane. (PMID:18958159)
• the activation-induced degranulation of Fas ligand has distinct requirements and involves different mechanisms than those of the granule markers CD63 and CD107a/Lamp-1 (PMID:19079288)
• Most Hassal’s corpuscules in thymoma were negative for LAMPs, but positive in normal thymus. Both lymphocytes and epithelial cells in pathological thymus showed higher intensity for LAMP-2 compared with LAMP-1. (PMID:19343823)
• Data show that The cell surface expression levels of (ICAM)-2 and -3 on the apoptotic cells were markedly lower, while those of calnexin, calreticulin, and (LAMP)-1 and -2 were significantly higher compared to non-apoptotic cells. (PMID:19524015)
• Immunohistochemistry studies showed EGBs to exhibit pronounced reactivity to antibodies against lysosome-associated membrane proteins (LAMP)-1 and LAMP-2, and the lysosomal enzyme cathepsin D. (PMID:20926008)
• Human full-length amelogenin increases the proliferation of mesenchymal stem cells by interaction with LAMP1 through the MAPK-ERK signaling pathway. (PMID:20967466)
• nucleolin and LAMP-1 have a role in promoting infection of human monocytes by Francisella tularensis (PMID:21152024)
• Report expression of NKG2D and CD107 in CD8(+) effector memory lymphocytes in Churg-Strauss syndrome. (PMID:22640649)
• LAMP proteins retain TAPL on the limiting membrane of endosomes and prevent its sorting to intraluminal vesicles. (PMID:22641697)
• Data indicate that lysosomally targeted cameleon Ca2+ probe LAMP1-YCaM accurately and sensitively responds to both global and lysosome-specific Ca2+ signals. (PMID:23098255)
• Simultaneous expression of LAMP1 and EGFR correlates with the ovarian neoplasm grading. (PMID:23172893)
• Data indicate that monoclonal antibodies specific to CD107a (LAMP-1) or CD107b (LAMP-2) enhanced LPS-induced IL-8 secretion of THP-1 cells. (PMID:23603048)
• LAMP1 is required for efficient perforin delivery to lytic granules and NK-cell cytotoxicity. (PMID:23632890)
• LAMP-1/GFAP showed pronounced co-expression and LAMP-1/CD133 was co-expressed as well in astrocytomas suggesting that tumor cells including the proposed tumor stem cells contain lysosomes. (PMID:23826410)
• CD107a/LAMP-1 has a role in the protection of NK cells from degranulation-associated suicide (PMID:23847195)
• in TB pleurisy regulatory T lymphocytes effectively inhibit CD107a expression (PMID:24134738)
• Caveolin-1 associated adenovirus entry into human corneal cells. (PMID:24147000)
• LAMP-1 and LAMP-2 could be used as additional markers with which to assess enzyme replacement therapy effectiveness in Fabry disease. (PMID:24334114)
• The LAMP-1 had preferential localization in the high density secondary lysosomes where endogenous human LAMP-1 was enriched. In contrast, a major portion of I382L was located in a low density fraction. (PMID:24695761)
• Synergistic defects of different molecules in the cytotoxic pathway lead to clinical familial hemophagocytic lymphohistiocytosis. (PMID:24916509)
• study has shown that Lassa virus entry requires a pH-regulated engagement of alpha-DG and LAMP1 both of which need to be glycosylated (PMID:24970085)
• Human miR-373 is silenced by histone modification in lung cancer cells and is a negative regulator of the mesenchymal phenotype through downstream IRAK2 and LAMP1 target genes. (PMID:25063738)
• Downregulation of miR-184 was consistent with significantly lower levels of LAMP-1 (PMID:25251993)
• A unique triad of histidines of Lassa Virus GP1 forms a binding site for host LAMP1. (PMID:25972533)
• The data support a viral entry mechanism dependent on binding to the lysosome-resident receptor LAMP1 and further dissociation of the membrane-distal GP1 subunits. (PMID:26849049)
• Overexpression of LAMP1 was observed in prostate cancer (PCa) and castration-resistant prostate cancer clinical specimens. Moreover, downstream pathways were identified using si-LAMP1-transfected cells. The discovery of tumor-suppressive miR320a-mediated pathways may provide important insights into the potential mechanisms of PCa metastasis. (PMID:27212625)
• LAMP1 has a role in fratricide amongst T cell receptor transgenic CD8+ T cells directed against tumor-associated antigens (PMID:27447745)
• downregulation of FUT1, which leads to the perinuclear localization of LAMP-1 and 2, is correlated with increased rate of autophagic flux by decreasing mTOR signaling and increasing autolysosome formation. (PMID:27560716)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lamp1	ENSMUSG00000031447
rattus_norvegicus	Lamp1	ENSRNOG00000019629

Paralogs (3): LAMP2 (ENSG00000005893), LAMP5 (ENSG00000125869), CD68 (ENSG00000129226)

Protein

Protein identifiers

Lysosome-associated membrane glycoprotein 1 — P11279 (reviewed: P11279)

Alternative names: CD107 antigen-like family member A

All UniProt accessions (1): P11279

UniProt curated annotations — full annotation on UniProt →

Function. Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis. Acts as an important regulator of lysosomal lumen pH regulation by acting as a direct inhibitor of the proton channel TMEM175, facilitating lysosomal acidification for optimal hydrolase activity. Also plays an important role in NK-cells cytotoxicity. Mechanistically, participates in cytotoxic granule movement to the cell surface and perforin trafficking to the lytic granule. In addition, protects NK-cells from degranulation-associated damage induced by their own cytotoxic granule content. Presents carbohydrate ligands to selectins. (Microbial infection) Acts as a receptor for Lassa virus glycoprotein. Also promotes fusion of the virus with host membrane in less acidic endosomes. (Microbial infection) Supports the FURIN-mediated cleavage of mumps virus fusion protein F by interacting with both FURIN and the unprocessed form but not the processed form of the viral protein F.

Subunit / interactions. Interacts with ABCB9; this interaction strongly stabilizes ABCB9 and protects ABCB9 against lysosomal degradation. Interacts with FURIN. Interacts with TMEM175; inhibiting the proton channel activity of TMEM175. (Microbial infection) Interacts with Lassa virus protein glycoprotein. (Microbial infection) Interacts with mumps virus protein F; this interaction promotes protein F cleavage by FURIN.

Subcellular location. Lysosome membrane. Endosome membrane. Late endosome membrane. Cell membrane. Cytolytic granule membrane.

Post-translational modifications. O- and N-glycosylated; some of the 18 N-linked glycans are polylactosaminoglycans. (Microbial infection) The glycosylation of Asn-76 is essential for Lassa virus entry into cells.

Similarity. Belongs to the LAMP family.

Isoforms (2)

UniProt ID	Names	Canonical?
P11279-1	1	yes
P11279-2	2

RefSeq proteins (1): NP_005552* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002000	Lysosome-assoc_membr_glycop	Family
IPR018134	LAMP_CS	Conserved_site
IPR048524	Lamp2-like_TM	Domain
IPR048528	Lamp2-like_luminal	Domain

Pfam: PF01299, PF21222

UniProt features (67 total): glycosylation site 24, strand 13, sequence conflict 7, disulfide bond 4, region of interest 4, turn 4, topological domain 2, helix 2, signal peptide 1, chain 1, transmembrane region 1, splice variant 1, sequence variant 1, mutagenesis site 1, compositionally biased region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8ATH	X-RAY DIFFRACTION	2.37
8FYF	ELECTRON MICROSCOPY	3.4
8FY5	ELECTRON MICROSCOPY	3.5
9C5A	ELECTRON MICROSCOPY	4.2
9C59	ELECTRON MICROSCOPY	4.3
9C5B	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11279-F1	86.89	0.70

Antibody-complex structures (SAbDab): 1 — 8ATH

Functional residue map

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

Disulfide bonds (4): 41–80, 155–191, 231–269, 338–375

Glycosylation sites (24): 37, 45, 62, 76, 84, 103, 107, 121, 130, 165, 181, 197, 199, 200, 207, 209, 211, 223, 228, 241 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
76	complete loss of interaction with lassa virus protein gpc.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 412 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_LYSOSOMAL_TRANSPORT, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_VACUOLE_ORGANIZATION, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_DEGRANULATION, DITTMER_PTHLH_TARGETS_UP, GOBP_REGULATION_OF_EXOCYTOSIS, GOCC_CELL_SURFACE, HSIAO_HOUSEKEEPING_GENES, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_VACUOLAR_TRANSPORT, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY

GO Biological Process (11): lysosomal lumen acidification (GO:0007042), positive regulation of natural killer cell degranulation (GO:0043323), positive regulation of natural killer cell mediated cytotoxicity (GO:0045954), protein stabilization (GO:0050821), establishment of protein localization to organelle (GO:0072594), Golgi to lysosome transport (GO:0090160), granzyme-mediated programmed cell death signaling pathway (GO:0140507), regulation of organelle transport along microtubule (GO:1902513), lysosomal lumen pH elevation (GO:0035752), symbiont entry into host cell (GO:0046718), proton transmembrane transport (GO:1902600)

GO Molecular Function (5): virus receptor activity (GO:0001618), ion channel inhibitor activity (GO:0008200), enzyme binding (GO:0019899), protein domain specific binding (GO:0019904), protein binding (GO:0005515)

GO Cellular Component (27): autophagosome membrane (GO:0000421), cytoplasm (GO:0005737), lysosome (GO:0005764), lysosomal membrane (GO:0005765), late endosome (GO:0005770), multivesicular body (GO:0005771), cytosol (GO:0005829), plasma membrane (GO:0005886), synaptic vesicle (GO:0008021), external side of plasma membrane (GO:0009897), endosome membrane (GO:0010008), membrane (GO:0016020), late endosome membrane (GO:0031902), azurophil granule membrane (GO:0035577), sarcolemma (GO:0042383), melanosome (GO:0042470), autolysosome (GO:0044754), perinuclear region of cytoplasm (GO:0048471), phagolysosome membrane (GO:0061474), extracellular exosome (GO:0070062), ficolin-1-rich granule membrane (GO:0101003), cytolytic granule membrane (GO:0101004), endosome (GO:0005768), cell surface (GO:0009986), vesicle (GO:0031982), cytolytic granule (GO:0044194), phagocytic vesicle (GO:0045335)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein binding	2
endosome	2
late endosome	2
cytoplasm	2
plasma membrane	2
lysosomal membrane	2
vacuolar acidification	1
positive regulation of leukocyte degranulation	1
natural killer cell degranulation	1
regulation of natural killer cell degranulation	1
positive regulation of natural killer cell mediated cytotoxicity	1
positive regulation of leukocyte mediated cytotoxicity	1
positive regulation of natural killer cell mediated immunity	1
natural killer cell mediated cytotoxicity	1
regulation of natural killer cell mediated cytotoxicity	1
regulation of protein stability	1
establishment of protein localization	1
Golgi to vacuole transport	1
lysosomal transport	1
cytosolic transport	1
signal transduction	1
programmed cell death	1
regulation of intracellular transport	1
regulation of microtubule-based movement	1
organelle transport along microtubule	1
intracellular pH elevation	1
viral life cycle	1
symbiont entry into host	1
monoatomic cation transmembrane transport	1
symbiont entry into host cell	1
exogenous protein binding	1
monoatomic ion channel activity	1
channel inhibitor activity	1
transmembrane transporter binding	1
ion channel regulator activity	1
binding	1
vacuolar membrane	1
autophagosome	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

4506 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LAMP1	CD63	P08962	984
LAMP1	CTSD	P07339	920
LAMP1	EEA1	Q15075	919
LAMP1	LAMP2	P13473	904
LAMP1	CIDEB	Q9UHD4	871
LAMP1	BECN1	Q14457	850
LAMP1	PRF1	P14222	845
LAMP1	RAB5A	P20339	841
LAMP1	TSG101	Q99816	820
LAMP1	IFNG	P01579	804
LAMP1	NEU1	Q99519	800
LAMP1	CANX	P27824	797
LAMP1	TFRC	P02786	796
LAMP1	ATG5	Q9H1Y0	793
LAMP1	CD8A	P01732	792

IntAct

84 interactions, top by confidence:

A	B	Type	Score
LAMTOR2	LAMTOR5	psi-mi:“MI:0914”(association)	0.860
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
LAMP1	SLC48A1	psi-mi:“MI:0915”(physical association)	0.560
LAMP1	VSTM1	psi-mi:“MI:0915”(physical association)	0.560
LAMP1	GPC	psi-mi:“MI:0915”(physical association)	0.540
GPC	LAMP1	psi-mi:“MI:0407”(direct interaction)	0.540
GPC	LAMP1	psi-mi:“MI:0915”(physical association)	0.540
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
LAMP1	FZD7	psi-mi:“MI:0914”(association)	0.530
SOD1	GAPDH	psi-mi:“MI:0914”(association)	0.500
sseJ	AGPS	psi-mi:“MI:0914”(association)	0.460
EGFR	LAMP1	psi-mi:“MI:0403”(colocalization)	0.430
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
LAMP1	RRAGB	psi-mi:“MI:0915”(physical association)	0.400
RRAGB	LAMP1	psi-mi:“MI:0915”(physical association)	0.400
LMP2	WWP2	psi-mi:“MI:0914”(association)	0.350
LAMP1	NPRL3	psi-mi:“MI:0403”(colocalization)	0.350
LAMP1	SZT2	psi-mi:“MI:0403”(colocalization)	0.350
LAMP1	HAX1	psi-mi:“MI:0914”(association)	0.350
PB2	DNAJB6	psi-mi:“MI:0914”(association)	0.350
LAMP1	ORC4	psi-mi:“MI:0914”(association)	0.350
TEX101	PSMD12	psi-mi:“MI:0914”(association)	0.350

BioGRID (893): LAMP1 (Affinity Capture-MS), ZFPL1 (Co-fractionation), LAMP1 (Proximity Label-MS), LAMP1 (Affinity Capture-Western), STK17B (Affinity Capture-MS), SLC38A7 (Affinity Capture-MS), FZD7 (Affinity Capture-MS), RAB4A (Affinity Capture-MS), FZD2 (Affinity Capture-MS), PLAA (Affinity Capture-MS), C4A (Affinity Capture-MS), LEMD3 (Affinity Capture-MS), LGALS1 (Affinity Capture-MS), ELP6 (Affinity Capture-MS), RARS (Affinity Capture-MS)

ESM2 similar proteins: A0A5B9, A6NDV4, A6QLK4, B1AWJ5, E9PTA2, O75051, O94759, P01850, P01851, P01852, P01857, P01859, P01860, P01861, P01870, P01906, P01909, P03987, P06333, P0DSE2, P0DTU4, P11279, P11364, P48030, P54900, P55259, Q0VBP7, Q1WIM1, Q1WIM3, Q2YDG0, Q3TMX7, Q5M7U7, Q6NW40, Q6ZRP7, Q71DR4, Q7TQ33, Q812F8, Q864L3, Q8BHK2, Q8K297

Diamond homologs: P05300, P11279, P11438, P13473, P14562, P17046, P17047, P31996, P49129, P49130, Q05204, Q90617, P34810, Q8MJJ2, Q9UQV4, Q5XI99, Q7TST5

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
TFEB	“up-regulates quantity by expression”	LAMP1	“transcriptional regulation”
ACSS2	“up-regulates quantity by expression”	LAMP1	“transcriptional regulation”
TFE3	“up-regulates quantity by expression”	LAMP1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 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
Amino acids regulate mTORC1	6	22.3×	1e-04
RHOQ GTPase cycle	5	16.8×	2e-03
Cellular response to starvation	5	15.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	7
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1890 predictions. Top by Δscore:

Variant	Effect	Δscore
13:113306473:T:TA	acceptor_gain	1.0000
13:113309636:A:AG	acceptor_gain	1.0000
13:113309638:TCTA:T	acceptor_loss	1.0000
13:113309639:CTAG:C	acceptor_loss	1.0000
13:113309640:TAGAA:T	acceptor_loss	1.0000
13:113309641:A:AG	acceptor_gain	1.0000
13:113309642:G:GG	acceptor_gain	1.0000
13:113309642:GA:G	acceptor_gain	1.0000
13:113309642:GAAC:G	acceptor_gain	1.0000
13:113309861:AGG:A	donor_loss	1.0000
13:113309863:GTAA:G	donor_loss	1.0000
13:113309864:T:G	donor_loss	1.0000
13:113310707:A:AG	acceptor_gain	1.0000
13:113310708:G:GG	acceptor_gain	1.0000
13:113310865:G:T	donor_gain	1.0000
13:113319644:G:GT	donor_gain	1.0000
13:113320340:T:G	acceptor_gain	1.0000
13:113320340:T:TA	acceptor_gain	1.0000
13:113320342:CAGA:C	acceptor_loss	1.0000
13:113320343:A:AG	acceptor_gain	1.0000
13:113320343:AGAC:A	acceptor_gain	1.0000
13:113320343:AGACG:A	acceptor_gain	1.0000
13:113320344:G:GA	acceptor_gain	1.0000
13:113320344:GA:G	acceptor_gain	1.0000
13:113320344:GAC:G	acceptor_gain	1.0000
13:113320344:GACG:G	acceptor_gain	1.0000
13:113320344:GACGG:G	acceptor_gain	1.0000
13:113320461:G:GG	donor_gain	1.0000
13:113320466:GGATG:G	donor_gain	1.0000
13:113320467:GATG:G	donor_gain	1.0000

AlphaMissense

2735 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:113321625:T:A	C338S	0.995
13:113321626:G:C	C338S	0.995
13:113322290:T:A	C375S	0.989
13:113322290:T:C	C375R	0.989
13:113322291:G:C	C375S	0.989
13:113321625:T:C	C338R	0.988
13:113321718:T:C	F369L	0.986
13:113321720:T:A	F369L	0.986
13:113321720:T:G	F369L	0.986
13:113321627:C:G	C338W	0.985
13:113321697:T:C	F362L	0.985
13:113321699:C:A	F362L	0.985
13:113321699:C:G	F362L	0.985
13:113322347:G:A	G394R	0.983
13:113322347:G:C	G394R	0.983
13:113321626:G:T	C338F	0.982
13:113322292:T:G	C375W	0.982
13:113322327:C:A	A387D	0.982
13:113319601:T:C	L232P	0.981
13:113319607:C:A	A234D	0.981
13:113306553:G:C	A44P	0.980
13:113319606:G:C	A234P	0.980
13:113321626:G:A	C338Y	0.980
13:113322348:G:A	G394E	0.980
13:113322354:T:A	V396D	0.980
13:113322372:C:A	A402D	0.980
13:113320399:T:A	C269S	0.978
13:113320400:G:C	C269S	0.978
13:113321719:T:G	F369C	0.978
13:113322333:G:A	G389D	0.978

dbSNP variants (sampled 300 via entrez): RS1000001261 (13:113315738 A>G), RS1000293289 (13:113313444 G>A,C), RS1000373041 (13:113297366 C>T), RS1000552257 (13:113299550 A>C), RS1000570531 (13:113308321 G>A,C,T), RS1000716946 (13:113296327 G>C), RS1000815113 (13:113301361 G>A), RS1001175306 (13:113324160 A>G), RS1001278830 (13:113319202 C>G), RS1001297419 (13:113318840 G>A,C,T), RS1001410719 (13:113313013 C>A), RS1001899142 (13:113317500 G>A), RS1001915688 (13:113295579 G>C), RS1001952757 (13:113322428 G>A), RS1002019013 (13:113300747 G>C)

Disease associations

OMIM: gene MIM:153330 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008103_78	Bipolar disorder	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066964 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.50	Kd	31.64	nM	CHEMBL5653589
7.50	ED50	31.7	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148635: Binding affinity to human LAMP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0316	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	7
sodium arsenite	increases reaction, affects reaction, affects expression, decreases expression, increases abundance (+1 more)	4
Acetylcysteine	decreases reaction, increases expression, increases abundance	3
Doxorubicin	decreases expression, decreases reaction, affects expression	3
Cadmium Chloride	increases palmitoylation, increases expression, affects reaction, decreases reaction, increases abundance	3
bisphenol A	decreases expression, increases expression	2
lead acetate	decreases expression, decreases reaction, increases expression	2
alpha-Chlorohydrin	decreases expression, decreases reaction	2
Antimycin A	decreases expression, affects cotreatment, affects expression, affects response to substance	2
Cadmium	decreases reaction, increases abundance, increases palmitoylation, increases expression, affects reaction	2
Tobacco Smoke Pollution	affects expression, increases expression	2
triphenyl phosphate	affects expression	1
1,12-benzoperylene	decreases expression	1
cepharanthine	increases expression	1
25-hydroxycholesterol	increases expression	1
nuciferine	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
arsenite	decreases expression, increases abundance	1
xanthatin	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
sulindac sulfide	decreases expression	1
3-methyladenine	decreases expression, decreases reaction	1
4-hydroxy-2-nonenal	increases expression, decreases reaction, affects reaction	1
cupric chloride	increases expression	1
oligomycin A	affects expression, affects response to substance, affects cotreatment	1
1,3-dichloro-2-propanol	decreases expression	1
allyl sulfide	decreases expression	1
beta-methylcholine	affects expression	1
leucyl-leucine-methyl ester	increases expression	1
epigallocatechin gallate	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651677	Binding	Binding affinity to human LAMP1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8JJ	Abcam HCT 116 LAMP1 KO	Cancer cell line	Male
CVCL_B9LT	Abcam A-549 LAMP1 KO	Cancer cell line	Male
CVCL_D1TE	Abcam U-87MG LAMP1 KO	Cancer cell line	Male
CVCL_D2G3	Abcam MCF-7 LAMP1 KO	Cancer cell line	Female
CVCL_D9IB	Ubigene HEK293 LAMP1 KO	Transformed cell line	Female
CVCL_SV26	HAP1 LAMP1 (-) 1	Cancer cell line	Male
CVCL_SV27	HAP1 LAMP1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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