LAMP3

Summary

LAMP3 (lysosome associated membrane protein 3, HGNC:14582) is a protein-coding gene on chromosome 3q27.1, encoding Lysosome-associated membrane glycoprotein 3 (Q9UQV4). Lysosomal membrane glycoprotein which plays a role in the unfolded protein response (UPR) that contributes to protein degradation and cell survival during proteasomal dysfunction.

This gene encodes lysosome-associated membrane glycoprotein 3, a type 1 integral membrane protein that belongs to a family of lysosome associated membrane proteins which form part of the glycoconjugate coat present on the inside of the lysosomal membrane. It is predominantly expressed in mature dendritic cells and serves as a marker of dendritic cell maturation. The encoded protein localizes primarily to late endosomes/lysosomes and the MHC class II compartment, where it contributes to antigen processing and presentation during adaptive immune responses. The expression of this gene is inducible under hypoxic conditions via hypoxia-inducible factor 1-alpha signaling. In cancer, this gene is frequently overexpressed and is associated with tumor progression, metastasis, therapy resistance, and poor clinical prognosis in multiple malignancies including breast, cervical, and ovarian cancers.

Source: NCBI Gene 27074 — RefSeq curated summary.

At a glance

• Gene–disease (curated): interstitial lung disease (Strong, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 67 total
• MANE Select transcript: NM_014398

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14582
Approved symbol	LAMP3
Name	lysosome associated membrane protein 3
Location	3q27.1
Locus type	gene with protein product
Status	Approved
Aliases	LAMP, TSC403, DC-LAMP, DCLAMP, CD208
Ensembl gene	ENSG00000078081
Ensembl biotype	protein_coding
OMIM	605883
Entrez	27074

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000265598, ENST00000466939, ENST00000470251, ENST00000476015, ENST00000486686, ENST00000948307

RefSeq mRNA: 1 — MANE Select: NM_014398 NM_014398

CCDS: CCDS3242

Canonical transcript exons

ENST00000265598 — 6 exons

Exon	Start	End
ENSE00000780953	183152375	183152503
ENSE00001056743	183140538	183140595
ENSE00001236375	183135717	183135887
ENSE00001236403	183122215	183124214
ENSE00001861941	183162607	183162734
ENSE00003488986	183153682	183154391

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 99.47.

FANTOM5 (CAGE): breadth broad, TPM avg 21.3404 / max 3300.1086, expressed in 774 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45798	15.1740	476
45799	4.9284	591
45797	0.9364	217
203045	0.2708	151
45796	0.0238	6
45800	0.0071	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	99.47	gold quality
sperm	CL:0000019	96.84	gold quality
visceral pleura	UBERON:0002401	96.19	gold quality
lung	UBERON:0002048	93.70	gold quality
male germ cell	CL:0000015	93.62	gold quality
adult organism	UBERON:0007023	93.37	gold quality
palpebral conjunctiva	UBERON:0001812	92.48	gold quality
epithelium of nasopharynx	UBERON:0001951	92.32	gold quality
nasopharynx	UBERON:0001728	92.31	gold quality
upper lobe of lung	UBERON:0008948	91.19	gold quality
vermiform appendix	UBERON:0001154	91.08	gold quality
upper lobe of left lung	UBERON:0008952	90.63	gold quality
hair follicle	UBERON:0002073	87.95	gold quality
gingival epithelium	UBERON:0001949	87.45	gold quality
bronchial epithelial cell	CL:0002328	87.35	gold quality
gingiva	UBERON:0001828	87.07	gold quality
epithelium of bronchus	UBERON:0002031	85.46	gold quality
thymus	UBERON:0002370	85.46	gold quality
bronchus	UBERON:0002185	84.86	gold quality
right lung	UBERON:0002167	84.82	gold quality
caecum	UBERON:0001153	83.36	gold quality
lymph node	UBERON:0000029	82.68	gold quality
esophagus squamous epithelium	UBERON:0006920	82.54	gold quality
tonsil	UBERON:0002372	81.62	gold quality
left testis	UBERON:0004533	81.05	gold quality
squamous epithelium	UBERON:0006914	80.91	gold quality
testis	UBERON:0000473	80.01	gold quality
secondary oocyte	CL:0000655	79.29	gold quality
skin of hip	UBERON:0001554	79.29	gold quality
right testis	UBERON:0004534	79.12	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	6698.58
E-MTAB-7381	yes	3924.36
E-ANND-2	yes	2493.02
E-MTAB-8142	yes	1186.56
E-MTAB-8410	yes	874.00
E-CURD-120	yes	769.22
E-MTAB-8530	yes	759.56
E-MTAB-6653	yes	665.69
E-GEOD-139324	yes	637.64
E-MTAB-8207	yes	464.98
E-HCAD-1	yes	103.49
E-CURD-46	yes	24.46
E-GEOD-130148	yes	19.23
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF4

miRNA regulators (miRDB)

120 targeting LAMP3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587

Literature-anchored findings (GeneRIF, showing 40)

• Findings indicate that LAMP3 overexpression is associated with an enhanced metastatic potential and may be a prognostic factor for cervical cancer. (PMID:16204031)
• 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)
• DC-LAMP staining was lost in solid type adenocarcinomas but persisted in well-differentiated areas and there was no prognostic difference in tumors that reacted with DC-LAMP. (PMID:17056097)
• DC-LAMP has a role in preventing the progression of micrometastatic melanoma in lymph nodes (PMID:17606713)
• In rheumatoid arthritis patients, the number of CD304(+) plasmacytoid DCs (pDCs) exceeded that of CD1c(+) myeloid DCs (mDCs), with the majority of infiltrating DCs being CD83(-) or DC-LAMP(-). (PMID:18292234)
• Because a defect of the granular layer in psoriatic lesions has been recognized, increased expression of lysosome-related CD208 in the basal and suprabasal keratinocytes of psoriatic lesions might represent aberrant epidermal differentiation. (PMID:19335688)
• Data show that the ABCA3 N-terminus is proteolytically removed inside acidic LAMP3-positive vesicles MVB/LB. (PMID:20863830)
• In the current breast cancer cohorts, LAMP3 had independent prognostic value. (PMID:21319150)
• Both DC-LAMP and DC-SIGN proteins may be involved in the pathogenesis of psoriasis vulgaris. (PMID:21596034)
• LAMP3 is an influenza A virus inducible gene, and plays an important role in viral post-entry steps. (PMID:21810281)
• The crystal structure of the conserved domain of human DC-LAMP was solved. (PMID:22809326)
• the PERK/ATF4/LAMP3-arm of the UPR is an additional pathway mediating hypoxia-induced breast cancer cell migration (PMID:23294542)
• DC-LAMP and DC-SIGN may be involved in the pathogenesis of condyloma acuminatum. (PMID:23569139)
• LAMP3 is a driver of interferon related genes as demonstrated by siRNA experiments and by gene expression in cervical carcer samples. (PMID:23651994)
• These results suggest that Treg-DC interactions may promote chronic H. pylori infection by rendering gastric DCs tolerogenic. (PMID:23876802)
• the association between hypoxia, metastasis, and poor prognosis is due, in part, to hypoxic activation of the unfolded protein response and expression of LAMP3. (PMID:24045183)
• Increase in CD208+ dendritic cells in tonsils is associated with immunoglobulin A nephropathy (PMID:24081865)
• LAMP3 knockdown in MCF7 breast cancer cells increases tamoxifen sensitivity. (PMID:24434718)
• the MCCC1/LAMP3 gene can decrease the risk of Parkinson disease in Chinese population. (PMID:24631562)
• LAMP3 gene expression is relevant for prognosis in squamous cell carcinoma of head and neck. (PMID:24634103)
• LAMP3 and TP53 protein expression was significantly higher in cancerous gastrointestinal tissues compared to normal and benign tissues; only LAMP3 expression correlated with poor overall survival (PMID:25362357)
• LAMP3 regulation as part of the unfolded protein response contributes to protein degradation and cell survival during proteasomal dysfunction. (PMID:25681212)
• In laryngeal squamous cell carcinoma, high LAMP3 and high TP53 protein expression was significantly associated with tumor stage and size and patients with high expression of these proteins had poor overall survival. (PMID:26191259)
• our results suggest that epithelial LAMP3 expression is an independent prognostic biomarker for esophageal squamous cell carcinoma . (PMID:26263981)
• study indicates that LAMP-3 is induced by Salmonella infection and recruited to the Salmonella pathogen for intracellular proliferation. (PMID:27329040)
• this study shows that the vitamin D3 reduce the LAMP3 expression during the dendritic cells differentiation and maturation, via NFkappaB pathways (PMID:27697285)
• LAMP3 variants found to be associated with Bipolar disorder or Schizophrenia in other populations are also associated with Bipolar disorder risk in Latinos. (PMID:27759212)
• Immunohistochemical results showed that high lysosome-associated membrane protein 3 cytoplasmic expression was significantly related to tumor grade ( p = 0.038), lymph node metastasis ( p = 0.049), metastasis ( p < 0.001), level of CA125 ( p = 0.030), and International Federation of Gynecology and Obstetrics (FIGO) ( p < 0.001). (PMID:28349821)
• mRNA and protein levels of LAMP3 were significantly higher in oral squamous carcinoma tissues than in adjacent normal tissues. High LAMP3 expression was linked to the degree of tumor differentiation and stage. (PMID:28607528)
• LAMP3 promotes the invasion of osteosarcoma cells via SPP1 signaling. (PMID:28849219)
• LAMP3 is an important regulator of hepatic lipid metabolism. (PMID:29056532)
• Knockdown of LAMP3 significantly inhibited OS cell viability and promoted apoptosis. TP53, which is involved in the apoptosis pathway, was found to be highly upregulated after knockdown of LAMP3. (PMID:30008754)
• Elevated LAMP3 expression is associated with epithelial-mesenchymal transition and metastatic potential in esophageal cancer. (PMID:31311326)
• Depletion of LAMP3 enhances PKA-mediated VASP phosphorylation to suppress invasion and metastasis in esophageal squamous cell carcinoma. (PMID:32200035)
• Lysosome-Associated Membrane Proteins Support the Furin-Mediated Processing of the Mumps Virus Fusion Protein. (PMID:32295904)
• The gene for the lysosomal protein LAMP3 is a direct target of the transcription factor ATF4. (PMID:32312748)
• LAMP3 induces apoptosis and autoantigen release in Sjogren’s syndrome patients. (PMID:32939030)
• Novel Associations of BST1 and LAMP3 With REM Sleep Behavior Disorder. (PMID:33397775)
• Association study of MCCC1/LAMP3 and DGKQ variants with Parkinson’s disease in patients of Malay ancestry. (PMID:33559030)
• LAMP3 inhibits autophagy and contributes to cell death by lysosomal membrane permeabilization. (PMID:34802379)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Lysosome-associated membrane glycoprotein 3 — Q9UQV4 (reviewed: Q9UQV4)

Alternative names: DC-lysosome-associated membrane glycoprotein, Protein TSC403

All UniProt accessions (4): Q9UQV4, C9JDI8, C9JYP5, E7ETP9

UniProt curated annotations — full annotation on UniProt →

Function. Lysosomal membrane glycoprotein which plays a role in the unfolded protein response (UPR) that contributes to protein degradation and cell survival during proteasomal dysfunction. Plays a role in the process of fusion of the lysosome with the autophagosome, thereby modulating the autophagic process. Promotes hepatocellular lipogenesis through activation of the PI3K/Akt pathway. May also play a role in dendritic cell function and in adaptive immunity. (Microbial infection) Plays a positive role in post-entry steps of influenza A virus replication, either virus uncoating, cytosolic transport, or nuclear import of viral components, and promotes nuclear accumulation of influenza nucleoprotein/NP at early stages of viral infection. (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. (Microbial infection) Promotes the intracellular proliferation of Salmonella typhimuium.

Subunit / interactions. Monomer. Interacts with FURIN. (Microbial infection) Interacts with mumps virus protein F; this interaction promotes protein F cleavage by FURIN.

Subcellular location. Cell surface. Lysosome membrane. Cytoplasmic vesicle membrane. Early endosome membrane.

Tissue specificity. Detected in tonsil interdigitating dendritic cells, in spleen, lymph node, Peyer’s patches in the small instestine, in thymus medulla and in B-cells (at protein level). Expressed in lymphoid organs and dendritic cells. Expressed in lung. Up-regulated in carcinomas of the esophagus, colon, rectum, ureter, stomach, breast, fallopian tube, thyroid and parotid tissues.

Induction. By UPR transcription factor ATF4 signaling. (Microbial infection) Upon Salmonella typhimurium infection, at both transcriptional and translational levels.

Similarity. Belongs to the LAMP family.

RefSeq proteins (1): NP_055213* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002000	Lysosome-assoc_membr_glycop	Family
IPR048528	Lamp2-like_luminal	Domain

Pfam: PF01299

UniProt features (37 total): strand 14, glycosylation site 7, disulfide bond 2, sequence variant 2, topological domain 2, sequence conflict 2, region of interest 2, compositionally biased region 2, signal peptide 1, chain 1, helix 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4AKM	X-RAY DIFFRACTION	2.69

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UQV4-F1	68.32	0.39

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 (2): 237–274, 339–376

Glycosylation sites (7): 158, 164, 200, 232, 266, 291, 112

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 297 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GOBP_REGULATION_OF_AUTOPHAGY, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_RESPONSE_TO_PEPTIDE, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, PEREZ_TP63_TARGETS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOCC_CELL_SURFACE, KEGG_LYSOSOME, BROWNE_HCMV_INFECTION_16HR_UP, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (8): adaptive immune response (GO:0002250), regulation of autophagy (GO:0010506), positive regulation of gene expression (GO:0010628), response to interferon-alpha (GO:0035455), establishment of protein localization to organelle (GO:0072594), negative regulation of proteasomal protein catabolic process (GO:1901799), regulation of viral life cycle (GO:1903900), immune system process (GO:0002376)

GO Molecular Function (0):

GO Cellular Component (16): lysosomal membrane (GO:0005765), early endosome (GO:0005769), plasma membrane (GO:0005886), cell surface (GO:0009986), early endosome membrane (GO:0031901), late endosome membrane (GO:0031902), vesicle (GO:0031982), perinuclear region of cytoplasm (GO:0048471), alveolar lamellar body membrane (GO:0097233), cytoplasm (GO:0005737), lysosome (GO:0005764), endosome (GO:0005768), endomembrane system (GO:0012505), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
endosome membrane	2
cytoplasm	2
cytoplasmic vesicle	2
immune response	1
autophagy	1
regulation of catabolic process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
response to cytokine	1
establishment of protein localization	1
proteasomal protein catabolic process	1
negative regulation of protein catabolic process	1
regulation of proteasomal protein catabolic process	1
viral life cycle	1
regulation of viral process	1
biological_process	1
lysosome	1
lytic vacuole membrane	1
endosome	1
membrane	1
cell periphery	1
early endosome	1
late endosome	1
membrane-bounded organelle	1
alveolar lamellar body	1
lamellar body membrane	1
intracellular anatomical structure	1
lytic vacuole	1
endomembrane system	1
vacuole	1
plasma membrane	1
vesicle membrane	1
intracellular vesicle	1

Protein interactions and networks

STRING

976 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LAMP3	CD207	Q9UJ71	750
LAMP3	CD83	Q01151	693
LAMP3	CD1C	P29017	657
LAMP3	ITGAX	P20702	649
LAMP3	CCL19	Q99731	646
LAMP3	CD1A	P06126	620
LAMP3	CD1B	P29016	620
LAMP3	CD1E	P15812	610
LAMP3	CD1D	P15813	582
LAMP3	CD209	Q9NNX6	582
LAMP3	NTAN1	Q96AB6	570
LAMP3	CD86	P42081	551
LAMP3	CCL22	O00626	543
LAMP3	TSLP	Q969D9	541
LAMP3	CCL17	Q92583	527
LAMP3	LY75	O60449	527

IntAct

12 interactions, top by confidence:

A	B	Type	Score
LAMP3	METTL15	psi-mi:“MI:0914”(association)	0.530
SGTB	LAMP3	psi-mi:“MI:0915”(physical association)	0.370
ABCA3	LAMP3	psi-mi:“MI:0403”(colocalization)	0.270
LAMP3	ABCA3	psi-mi:“MI:0403”(colocalization)	0.270
LAMP3	Rab14	psi-mi:“MI:0403”(colocalization)	0.270
LAMP3	RAB9A	psi-mi:“MI:0403”(colocalization)	0.270
RAB9A	LAMP3	psi-mi:“MI:0403”(colocalization)	0.270
LAMP3	FLOT2	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (539): GALNT4 (Affinity Capture-MS), MARCH5 (Affinity Capture-MS), NEK6 (Affinity Capture-MS), HUS1 (Affinity Capture-MS), NEK7 (Affinity Capture-MS), SEC14L1 (Affinity Capture-MS), MAPK8 (Affinity Capture-MS), ZRANB3 (Affinity Capture-MS), DOPEY2 (Affinity Capture-MS), INTS8 (Affinity Capture-MS), SEL1L3 (Affinity Capture-MS), SGPP1 (Affinity Capture-MS), NARS2 (Affinity Capture-MS), TAMM41 (Affinity Capture-MS), MAP2K7 (Affinity Capture-MS)

ESM2 similar proteins: A0A1Z2R986, A5D7U1, A6NHS7, F5H9T4, O02671, P11322, P15137, P15139, P16721, P16743, P20826, P21581, P21583, P22596, P23515, P35767, P35768, P35769, P35770, P40200, P48357, P79169, P79368, Q06220, Q28132, Q29030, Q3U0X8, Q5BK49, Q5HZW7, Q5W9T8, Q5XI99, Q62959, Q63912, Q66608, Q6SWB9, Q6SWC3, Q6SWC9, Q6UC88, Q6UQ28, Q7TST5

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1047 predictions. Top by Δscore:

Variant	Effect	Δscore
3:183135710:AACTT:A	donor_loss	1.0000
3:183135711:ACTT:A	donor_loss	1.0000
3:183135712:CTTAC:C	donor_loss	1.0000
3:183135713:TTACC:T	donor_loss	1.0000
3:183135714:T:TG	donor_loss	1.0000
3:183135715:A:C	donor_loss	1.0000
3:183135716:C:CT	donor_loss	1.0000
3:183135888:C:CC	acceptor_gain	1.0000
3:183135715:A:AC	donor_gain	0.9900
3:183135716:C:CC	donor_gain	0.9900
3:183135883:TGTCT:T	acceptor_gain	0.9900
3:183135885:TCTC:T	acceptor_loss	0.9900
3:183135886:CT:C	acceptor_gain	0.9900
3:183135887:TCTG:T	acceptor_loss	0.9900
3:183135888:CT:C	acceptor_loss	0.9900
3:183135889:T:A	acceptor_loss	0.9900
3:183153675:AACTT:A	donor_loss	0.9900
3:183153676:ACTT:A	donor_loss	0.9900
3:183153677:CTTAC:C	donor_loss	0.9900
3:183153678:TTA:T	donor_loss	0.9900
3:183153680:A:AC	donor_gain	0.9900
3:183153680:A:C	donor_loss	0.9900
3:183153681:C:CC	donor_gain	0.9900
3:183153681:CCGA:C	donor_gain	0.9900
3:183154389:TTA:T	acceptor_gain	0.9900
3:183154390:TA:T	acceptor_gain	0.9900
3:183154392:C:CC	acceptor_gain	0.9900
3:183162599:CCACT:C	donor_loss	0.9900
3:183162600:CACTC:C	donor_loss	0.9900
3:183162601:ACTCA:A	donor_loss	0.9900

AlphaMissense

2677 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:183135745:A:C	F363L	0.994
3:183135745:A:T	F363L	0.994
3:183135747:A:G	F363L	0.994
3:183153723:C:G	A240P	0.994
3:183135818:C:G	C339S	0.993
3:183135819:A:T	C339S	0.993
3:183152421:A:G	L281P	0.992
3:183152415:A:G	L283S	0.991
3:183152382:A:G	F294S	0.990
3:183153704:A:G	L246P	0.990
3:183135819:A:G	C339R	0.989
3:183153731:C:G	C237S	0.987
3:183153732:A:T	C237S	0.987
3:183153759:A:C	Y228D	0.987
3:183135755:A:G	L360P	0.986
3:183124205:C:G	C376S	0.985
3:183124206:A:T	C376S	0.985
3:183135724:A:C	F370L	0.985
3:183135724:A:T	F370L	0.985
3:183135726:A:G	F370L	0.985
3:183135823:G:C	F337L	0.985
3:183135823:G:T	F337L	0.985
3:183135825:A:G	F337L	0.985
3:183152388:A:G	L292P	0.985
3:183152442:C:G	C274S	0.985
3:183152443:A:T	C274S	0.985
3:183135725:A:C	F370C	0.984
3:183152408:A:C	F285L	0.984
3:183152408:A:T	F285L	0.984
3:183152410:A:G	F285L	0.984

dbSNP variants (sampled 300 via entrez): RS1000075977 (3:183147865 C>T), RS1000182044 (3:183147244 A>G), RS1000249733 (3:183153463 T>C), RS1000266479 (3:183162843 G>C), RS1000341747 (3:183141578 T>C), RS1000349213 (3:183160023 G>A), RS1000414252 (3:183159749 G>A,C), RS1000431302 (3:183127639 A>C,G), RS1000623449 (3:183152510 C>T), RS1000837057 (3:183124310 A>G), RS1000864672 (3:183123978 T>C,G), RS1000891360 (3:183164377 G>C), RS1000942389 (3:183144484 T>C), RS1000997181 (3:183152227 T>A,C), RS1001035195 (3:183130479 T>C)

Disease associations

OMIM: gene MIM:605883 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
interstitial lung disease	Strong	Autosomal recessive

Mondo (1): interstitial lung disease (MONDO:0015925)

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000959_6	Parkinson’s disease	8.000000e-12
GCST001126_4	Parkinson’s disease	3.000000e-10
GCST003158_3	Subjective response to lithium treatment	9.000000e-07
GCST003922_1	Parkinson’s disease	3.000000e-08
GCST009441_12	Age-related cognitive decline (memory) (slope of z-scores)	5.000000e-06
GCST011739_2	Cutaneous leishmaniasis	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D017563	Lung Diseases, Interstitial	C08.381.483

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	9
sodium arsenite	affects methylation, decreases expression, increases expression	6
Estradiol	affects cotreatment, decreases expression, decreases reaction, increases expression	4
Benzo(a)pyrene	increases methylation, decreases expression, increases expression	3
Cyclosporine	increases expression, increases methylation	3
Aflatoxin B1	affects expression, increases expression	3
bisphenol A	affects expression, decreases expression	2
trichostatin A	increases expression, decreases reaction, affects cotreatment	2
cobaltous chloride	affects cotreatment, decreases expression	2
nickel sulfate	increases expression	2
Acetaminophen	increases expression	2
Air Pollutants	increases abundance, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
tungsten carbide	affects binding, decreases expression	1
daidzein	decreases expression	1
lasiocarpine	increases expression	1
propionaldehyde	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	increases expression	1
perfluorooctanoic acid	increases expression	1
tobacco tar	increases expression	1
butylbenzyl phthalate	decreases expression	1
4,4’-dichlorobiphenyl	decreases expression	1
lead chloride	affects cotreatment, decreases expression	1
cadmium sulfate	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, decreases reaction, affects cotreatment	1
4-nonylphenol	decreases expression	1
pentanal	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1G7	Abcam A-549 LAMP3 KO 1	Cancer cell line	Male
CVCL_B1VK	Abcam HeLa LAMP3 KO	Cancer cell line	Female
CVCL_B2NR	Abcam A-549 LAMP3 KO 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00637065	PHASE4	UNKNOWN	Bosentan in Pulmonary Hypertension in Interstitial Lung Disease Treatment Study
NCT00882817	PHASE4	COMPLETED	Pulmonary Rehabilitation in Interstitial Lung Diseases
NCT02143687	PHASE4	COMPLETED	Patients With Pulmonary Hypertension or Interstitial Lung Disease at Altitude - Effect of Oxygen on Exercise Performance
NCT02150616	PHASE4	UNKNOWN	Patients With Pulmonary Hypertension or Interstitial Lung Disease at Altitude - Effect of Oxygen on Breathing and Sleep
NCT02622022	PHASE4	COMPLETED	Palliation of Dyspnea With Morphine in Patients With Interstitial Lung Disease
NCT02821689	PHASE4	UNKNOWN	Pirfenidone in Progressive Interstitial Lung Disease Associated With Clinically Amyopathic Dermatomyositis
NCT04036721	PHASE4	SUSPENDED	Coorticosteroid Regimen in Patients With Anti-PD-1/PD-L1 Induced Pneumonitis
NCT04311567	PHASE4	TERMINATED	Effects of Tofacitinib vs Methotrexate on Rheumatoid Arthritis Interstitial Lung Disease
NCT04619680	PHASE4	COMPLETED	The Study of the Use of Nintedanib in Slowing Lung Disease in Patients With Fibrotic or Non-Fibrotic Interstitial Lung Disease Related to COVID-19
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT04988282	PHASE4	COMPLETED	Systemic Corticosteroids in Treatment of Post-COVID-19 Interstitial Lung Disease
NCT05129410	PHASE4	UNKNOWN	Clinical Study of MMF in Treatment of IIM-ILD and Its Effect on Peripheral Blood Treg Cells
NCT05375435	PHASE4	UNKNOWN	Efficacy and Safety of Triple Therapy in Patients With Anti-MDA5 Antibody-positive Dermatomyositis
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT07077486	PHASE4	RECRUITING	Effects of Telitacicept vs Cyclophosphamide on Lupus Related Interstitial Lung Disease
NCT07319598	PHASE4	RECRUITING	A Study to Test Tetrandrine Tablets for Connective Tissue Disease-Related Lung Disease
NCT07570888	PHASE4	NOT_YET_RECRUITING	This is a Trial Designed to Evaluate the Combination of Nerandomilast With Mycophenolate Across a Wide Variety of Pulmonary Fibrosis Subtypes, With the Aim of Providing Clinicians With Assurance That This is an Appropriate Therapeutic Combination.
NCT01570764	PHASE3	COMPLETED	Cyclophosphamide Systemic Sclerosis Associated Interstitial Lung Disease
NCT02896205	PHASE3	COMPLETED	Study to Compare the Efficacy of Mycophenolate Mofetil in Systemic Sclerosis Related Early Interstitial Lung Disease
NCT03018756	PHASE3	COMPLETED	Nebulized Fentanyl in Patients With Mild to Moderate Interstitial Lung Disease and Chronic Dyspnea
NCT03770663	PHASE3	UNKNOWN	Cyclophosphamide and Azathioprine vs Tacrolimus in Antisynthetase Syndrome-related Interstitial Lung Disease
NCT04708782	PHASE3	COMPLETED	Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis
NCT04905693	PHASE3	ENROLLING_BY_INVITATION	Extension Study of Inhaled Treprostinil in Subjects With Fibrotic Lung Disease
NCT05255991	PHASE3	COMPLETED	Multinational Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis
NCT05943535	PHASE3	RECRUITING	Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)
NCT06297096	PHASE3	RECRUITING	Study of the Efficacy of Nintedanib+Tocilizumab in Patients With Systemic Sclerosis and Interstitial Lung Disease
NCT06806592	PHASE3	RECRUITING	A Study to Test Whether Nerandomilast Helps People With Lungfibrosis Related to Rheumatic Diseases
NCT07179380	PHASE3	RECRUITING	Efficacy and Safety Study of Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD)
NCT07201922	PHASE3	RECRUITING	A Study to Test Whether Nerandomilast Can Help Slow Down Changes in the Lung in People With a Family History of Pulmonary Fibrosis
NCT07234032	PHASE3	NOT_YET_RECRUITING	An Open-Label Extension Study of Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD)
NCT07540988	PHASE3	NOT_YET_RECRUITING	FIBRONEER-ACT: A Study to Test Whether Nerandomilast Helps People With Fibrosing Interstitial Lung Disease at Risk for Disease Progression
NCT07613099	PHASE3	NOT_YET_RECRUITING	Evaluation of Fibrotic Disease Activity in Cardiopulmonary Disorders Using 18F-Fibroblast Activation Protein Inhibitor (18F-FAPI-74 PET/CT Imaging)
NCT00678821	PHASE2	COMPLETED	Aerobic Exercise in Patients With Pulmonary Hypertension
NCT00705133	PHASE2	COMPLETED	Treprostinil Therapy For Patients With Interstitial Lung Disease And Severe Pulmonary Arterial Hypertension
NCT00883129	PHASE2	COMPLETED	Comparison of Therapeutic Regimens for Scleroderma Interstitial Lung Disease (The Scleroderma Lung Study II)
NCT01203943	PHASE2	TERMINATED	A Study to Characterize the Safety, PK and Biological Activity of CC-930 in Idiopathic Pulmonary Fibrosis (IPF)
NCT01280994	PHASE2	RECRUITING	Hyperpolarized 129Xe MRI for Imaging Pulmonary Function
NCT01381666	PHASE2	TERMINATED	Evaluation of the Diagnostic Utility of INS316 in Patients With Interstitial Lung Diseases (01-701)
NCT01559129	PHASE2	TERMINATED	Study of Pomalidomide (CC-4047) to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Effectiveness for Patients With Systemic Sclerosis With Interstitial Lung Disease