LST1

Summary

LST1 (leukocyte specific transcript 1, HGNC:14189) is a protein-coding gene on chromosome 6p21.33, encoding Leukocyte-specific transcript 1 protein (O00453). Possible role in modulating immune responses. It is a selective cancer dependency (DepMap: 25.2% of cell lines).

The protein encoded by this gene is a membrane protein that can inhibit the proliferation of lymphocytes. Expression of this gene is enhanced by lipopolysaccharide, interferon-gamma, and bacteria. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7940 — RefSeq curated summary.

At a glance

• GWAS associations: 27
• Clinical variants (ClinVar): 19 total
• Cancer dependency (DepMap): dependent in 25.2% of screened cell lines
• MANE Select transcript: NM_205839

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14189
Approved symbol	LST1
Name	leukocyte specific transcript 1
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	LST-1, B144, D6S49E
Ensembl gene	ENSG00000204482
Ensembl biotype	protein_coding
OMIM	109170
Entrez	7940

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 28 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000211921, ENST00000303757, ENST00000339530, ENST00000376086, ENST00000376089, ENST00000376090, ENST00000376092, ENST00000376093, ENST00000376096, ENST00000376099, ENST00000376110, ENST00000396101, ENST00000396112, ENST00000418507, ENST00000419073, ENST00000433492, ENST00000438075, ENST00000460834, ENST00000464044, ENST00000464526, ENST00000490742, ENST00000868366, ENST00000868367, ENST00000868368, ENST00000868369, ENST00000868370, ENST00000868371, ENST00000953352, ENST00000953353, ENST00000953354, ENST00000953355

RefSeq mRNA: 6 — MANE Select: NM_205839 NM_001166538, NM_007161, NM_205837, NM_205838, NM_205839, NM_205840

CCDS: CCDS43450, CCDS4705, CCDS54984, CCDS54985, CCDS54986, CCDS54987

Canonical transcript exons

ENST00000427507 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 99.61.

FANTOM5 (CAGE): breadth broad, TPM avg 51.1864 / max 5845.2855, expressed in 662 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66955	28.7020	572
66965	5.5450	342
66961	5.3938	388
66962	2.7084	273
66964	2.2298	255
66956	1.7509	288
66958	1.3621	207
66967	1.1770	303
66960	0.9463	247
66966	0.5322	145

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.61	gold quality
monocyte	CL:0000576	99.57	gold quality
leukocyte	CL:0000738	99.55	gold quality
mononuclear cell	CL:0000842	99.55	gold quality
blood	UBERON:0000178	98.82	gold quality
bone marrow	UBERON:0002371	98.70	gold quality
bone marrow cell	CL:0002092	98.37	gold quality
spleen	UBERON:0002106	98.20	gold quality
periodontal ligament	UBERON:0008266	95.63	gold quality
trabecular bone tissue	UBERON:0002483	95.12	gold quality
vermiform appendix	UBERON:0001154	95.02	gold quality
right lung	UBERON:0002167	93.50	gold quality
lymph node	UBERON:0000029	91.75	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.61	gold quality
upper lobe of left lung	UBERON:0008952	91.59	gold quality
caecum	UBERON:0001153	91.50	gold quality
superficial temporal artery	UBERON:0001614	91.42	silver quality
upper lobe of lung	UBERON:0008948	90.92	gold quality
spinal cord	UBERON:0002240	90.26	gold quality
gall bladder	UBERON:0002110	88.40	gold quality
diaphragm	UBERON:0001103	87.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.42	gold quality
middle frontal gyrus	UBERON:0002702	87.15	gold quality
lung	UBERON:0002048	87.12	gold quality
cranial nerve II	UBERON:0000941	86.57	gold quality
rectum	UBERON:0001052	86.56	gold quality
substantia nigra	UBERON:0002038	85.95	gold quality
epithelium of nasopharynx	UBERON:0001951	85.82	silver quality
midbrain	UBERON:0001891	85.10	gold quality
lower lobe of lung	UBERON:0008949	84.95	silver quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-CURD-126	yes	3919.44
E-MTAB-9467	yes	341.90
E-HCAD-4	yes	204.27
E-MTAB-9388	yes	111.13
E-CURD-46	yes	34.08
E-MTAB-10287	yes	29.49
E-MTAB-6678	yes	25.84
E-MTAB-9221	yes	21.76
E-MTAB-8498	yes	11.30
E-HCAD-1	yes	10.63
E-MTAB-9067	yes	10.20
E-GEOD-70580	no	308.88
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting LST1, 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-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-3938	98.72	66.07	834
HSA-MIR-6883-3P	97.97	67.35	643
HSA-MIR-4329	97.68	66.26	1003
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-6857-3P	96.70	65.43	915
HSA-MIR-3974	96.56	66.22	928
HSA-MIR-4740-5P	96.25	67.96	726
HSA-MIR-1269A	92.75	64.61	542
HSA-MIR-1269B	92.75	64.73	538

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 25.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 13)

• Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells. (PMID:11828009)
• Expression of this receptor, inhibited by TGF-beta1, affects NK-mediated killing of dendritic cells (PMID:12646700)
• The expression of LST1, specifically splice variants encoding soluble isoforms and NCR3, was increased in rheumatoid-arthritis-affected blood and synovium and was associated with more severe inflammation in the synovium. (PMID:16362817)
• LST1 protein expression in human cell lines was found to be tightly regulated, allowing the expression of transmembrane isoforms but suppressing soluble isoforms (PMID:19663701)
• Study found association between extended LTA, TNF, LST1 and HLA gene haplotypes and rubella vaccine-induced immunity. (PMID:20668555)
• LST1 is expressed specifically in leukocytes of the myeloid lineage, where it localizes to the tetraspanin-enriched microdomains andit binds SHP-1 and SHP-2 phosphatases. (PMID:22589543)
• induces the formation of functional nanotubes (PMID:23239025)
• This is the first report demonstrating regulated LST1 expression in human intestinal epithelial and microvascular endothelial cells and in inflamed colonic tissue from IBD patients. (PMID:24682411)
• Psoriasis was associated with promoter variant, rs9267502 of LST1.Promoter activity was examined and it was larger than that of the other genetic variants, most probably due to changes in binding affinity to transcription factors. (PMID:24803336)
• Data indicate that the MHC class III gene LST1 5’ untranslated regions (5’-UTR) contains several upstream open reading frames (uORFs). (PMID:24816991)
• Increased expression of LST1 in GC-responders before therapy warrants further investigation into their role as potential predictors for the response to GC, and in the inflammatory process of rheumatoid arthritis. (PMID:27384923)
• the present review describes LST1 promotor, gene organization, splice variants and expression in human tissues, cell lines and cancer with the focus on LST1 expression in inflammation, autoimmune diseases and cancer (PMID:30055863)
• Significance of leukocyte-specific transcript 1 levels in nasal mucosal tissue to predict recurrence of nasal polyps. (PMID:36754676)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lst1	ENSMUSG00000073412
rattus_norvegicus	Lst1	ENSRNOG00000000855

Protein

Protein identifiers

Leukocyte-specific transcript 1 protein — O00453 (reviewed: O00453)

Alternative names: Protein B144

All UniProt accessions (7): O00453, F2Z2M1, H7C4M3, H7C4Z3, Q2HNT4, Q5HYT5, Q5STB1

UniProt curated annotations — full annotation on UniProt →

Function. Possible role in modulating immune responses. Induces morphological changes including production of filopodia and microspikes when overexpressed in a variety of cell types and may be involved in dendritic cell maturation. Isoform 1 and isoform 2 have an inhibitory effect on lymphocyte proliferation.

Subcellular location. Membrane. Golgi apparatus membrane. Endomembrane system.

Tissue specificity. Expressed in lung, tonsil, thymus, placenta, kidney, fetal spleen, fetal liver and brain.

Induction. By IFNG/IFN-gamma. Up-regulated upon autoimmune and bacterially-induced inflammation.

Similarity. Belongs to the LST1 family.

Isoforms (13)

UniProt ID	Names	Canonical?
O00453-1	1, LST1/A	yes
O00453-2	2, LST1/C
O00453-3	3, pLst1
O00453-4	4, LST1/E
O00453-5	5, LST1/K
O00453-6	6, LST1/L
O00453-7	7, LST1/J
O00453-8	8, LST1/M
O00453-9	9, LST1/N
O00453-10	10
O00453-11	11, LST1/P
O00453-12	12
O00453-13	13

RefSeq proteins (6): NP_001160010, NP_009092, NP_995309, NP_995310, NP_995311, NP_995312 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007775	Leukocyte-sp_tscrpt_1_LST1	Family

Pfam: PF05083

UniProt features (19 total): splice variant 12, sequence conflict 2, chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00453-F1	70.03	0.20

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): 58

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 213 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_DENDRITE_DEVELOPMENT, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, MODULE_45, MATTIOLI_MGUS_VS_PCL, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_NEUROGENESIS, MODULE_16, BOHN_PRIMARY_IMMUNODEFICIENCY_SYNDROM_DN, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, MODULE_75, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS

GO Biological Process (7): cell morphogenesis (GO:0000902), immune response (GO:0006955), regulation of cell shape (GO:0008360), anatomical structure morphogenesis (GO:0009653), dendrite development (GO:0016358), negative regulation of lymphocyte proliferation (GO:0050672), immune system process (GO:0002376)

GO Molecular Function (0):

GO Cellular Component (7): Golgi membrane (GO:0000139), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), endomembrane system (GO:0012505)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
anatomical structure development	2
cytoplasm	2
anatomical structure morphogenesis	1
immune system process	1
response to stimulus	1
regulation of cell morphogenesis	1
regulation of biological quality	1
developmental process	1
neuron projection development	1
negative regulation of mononuclear cell proliferation	1
lymphocyte proliferation	1
regulation of lymphocyte proliferation	1
negative regulation of lymphocyte activation	1
biological_process	1
Golgi apparatus	1
bounding membrane of organelle	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

840 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LST1	LTB	P78370	782
LST1	ABHD16A	O95870	761
LST1	LTA	P01374	752
LST1	NCR3	O14931	747
LST1	RALGPS2	Q86X27	733
LST1	NFKBIL1	Q9UBC1	716
LST1	DDX39B	Q13838	697
LST1	MYOF	Q9NZM1	654
LST1	RALA	P11233	638
LST1	FLNB	O75369	615
LST1	FLNC	Q14315	607
LST1	FLNA	P21333	583
LST1	TNF	P01375	475
LST1	HLA-B	P01889	469
LST1	PTPN11	Q06124	415

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CUL4A	DDX39A	psi-mi:“MI:0914”(association)	0.350
LST1	G2E3	psi-mi:“MI:0915”(physical association)	0.000
LST1	CACTIN	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): LST1 (Affinity Capture-MS), LST1 (Affinity Capture-MS), LST1 (Affinity Capture-RNA), LST1 (Positive Genetic), LST1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A4F4L0, O00453, O14669, O43914, O54885, P04234, P04235, P07766, P0CAN6, P18438, P19377, P20963, P24161, P29328, P29329, P59646, Q13113, Q28072, Q28073, Q2KIP5, Q3TYX2, Q5R1Q1, Q5RA41, Q63113, Q64159, Q6AYD4, Q6ITQ4, Q6X9T7, Q764N2, Q8K1T1, Q8MII8, Q8N386, Q8NET5, Q8R182, Q8WNQ8, Q923S2, Q925F2, Q95J79, Q95LI5, Q95LI8

Diamond homologs: O00453, O08843, Q5TM23

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

587 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31586312:CTGGG:C	donor_loss	0.9900
6:31586314:GG:G	donor_gain	0.9900
6:31586315:GG:G	donor_gain	0.9900
6:31586316:G:A	donor_loss	0.9900
6:31586317:T:G	donor_loss	0.9900
6:31586316:G:GG	donor_gain	0.9800
6:31587199:GAT:G	acceptor_gain	0.9800
6:31587198:A:AG	acceptor_gain	0.9600
6:31587199:G:GG	acceptor_gain	0.9600
6:31587194:TCACA:T	acceptor_loss	0.9500
6:31587195:CACA:C	acceptor_loss	0.9500
6:31587196:ACAG:A	acceptor_loss	0.9500
6:31587197:CA:C	acceptor_loss	0.9500
6:31587199:G:C	acceptor_loss	0.9500
6:31587539:A:G	acceptor_gain	0.9400
6:31586313:TGG:T	donor_gain	0.9300
6:31586314:GGG:G	donor_gain	0.9300
6:31588516:AGGCC:A	acceptor_gain	0.9300
6:31587199:GATGA:G	acceptor_gain	0.9200
6:31587538:A:AG	acceptor_gain	0.9200
6:31588515:CAGG:C	acceptor_gain	0.9100
6:31587943:G:GA	acceptor_gain	0.9000
6:31586311:TCTGG:T	donor_gain	0.8800
6:31586312:CTGG:C	donor_gain	0.8800
6:31586318:AA:A	donor_loss	0.8700
6:31587541:A:G	acceptor_gain	0.8700
6:31587198:AGAT:A	acceptor_gain	0.8600
6:31587199:GATG:G	acceptor_gain	0.8600
6:31587942:A:AG	acceptor_gain	0.8600
6:31587317:TGG:T	donor_loss	0.8500

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000228388 (6:31588957 A>G), RS1000791610 (6:31587071 C>T), RS1001966262 (6:31586604 C>A,T), RS1002410742 (6:31586819 T>C), RS1003587055 (6:31584601 C>A), RS1004777542 (6:31588195 TGAGA>T), RS1005155147 (6:31587868 G>A), RS1005210994 (6:31588242 G>A), RS1006321912 (6:31589371 T>A), RS1007597248 (6:31585516 C>T), RS1008534926 (6:31587464 C>A), RS1009322795 (6:31587155 C>T), RS1010325118 (6:31585504 A>C,G), RS1010886665 (6:31588374 A>G), RS1011079947 (6:31585377 C>A)

Disease associations

OMIM: gene MIM:109170 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST000879_24	Crohn’s disease	4.000000e-11
GCST003450_2	Clozapine-induced agranulocytosis/granulocytopenia in treatment-resistant schizophrenia	3.000000e-09
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004185_15	Lung function (FEV1/FVC)	2.000000e-10
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_265	Autism spectrum disorder or schizophrenia	7.000000e-14
GCST004521_3	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST004608_24	Granulocyte percentage of myeloid white cells	1.000000e-14
GCST005014_61	Tonsillectomy	3.000000e-17
GCST008916_111	Asthma	2.000000e-14
GCST008916_114	Asthma	1.000000e-09
GCST008916_30	Asthma	1.000000e-09
GCST008917_2	Asthma (childhood onset)	4.000000e-07
GCST008921_1	Asthma and major depressive disorder	2.000000e-16
GCST010725_43	Malaria	5.000000e-07
GCST010725_62	Malaria	3.000000e-06
GCST010989_266	Body size at age 10	4.000000e-13
GCST90002399_322	Neutrophil percentage of white cells	5.000000e-37
GCST90002407_247	White blood cell count	3.000000e-16

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007924	tonsillectomy risk measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

6 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1800629	Efficacy	3	diclofenac	Migraine without Aura
rs1800629	Efficacy	3	ibuprofen	Migraine without Aura
rs1800629	Efficacy	3	indomethacin	Migraine without Aura
rs1800629	Efficacy	3	ketorolac	Migraine without Aura
rs1800629	Efficacy	3	naproxen	Migraine without Aura
rs3093726	Toxicity	3	abacavir	Drug Hypersensitivity

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1800629	LST1, LTA, TNF	2B	14.62	14	etanercept;carbamazepine;ethambutol;isoniazid;pyrazinamide;rifampin;sorafenib;Tumor necrosis factor alpha (TNF-alpha) inhibitors;cyclosporine;mycophenolate mofetil;atorvastatin;carboplatin;gemcitabine;aspirin;diclofenac
rs3093726	LST1, LTA, LTB, TNF	3	0.00	1	abacavir
rs1052248	LST1, NCR3		0.00	0

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	increases expression	3
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
sodium bichromate	decreases expression	1
sulforaphane	increases expression	1
tetrathiomolybdate	increases expression	1
tamibarotene	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	affects cotreatment, increases methylation	1
(+)-JQ1 compound	decreases expression	1
Bortezomib	decreases expression	1
Decitabine	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Diuron	decreases expression	1
Mercuric Chloride	affects cotreatment, decreases expression	1
Nickel	increases expression	1
Testosterone	increases expression	1
Theophylline	increases expression	1
Gold Compounds	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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