LCP1

Summary

LCP1 (lymphocyte cytosolic protein 1, HGNC:6528) is a protein-coding gene on chromosome 13q14.13, encoding Plastin-2 (P13796). Actin-binding protein.

Plastins are a family of actin-binding proteins that are conserved throughout eukaryote evolution and expressed in most tissues of higher eukaryotes. In humans, two ubiquitous plastin isoforms (L and T) have been identified. Plastin 1 (otherwise known as Fimbrin) is a third distinct plastin isoform which is specifically expressed at high levels in the small intestine. The L isoform is expressed only in hemopoietic cell lineages, while the T isoform has been found in all other normal cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). However, L-plastin has been found in many types of malignant human cells of non-hemopoietic origin suggesting that its expression is induced accompanying tumorigenesis in solid tissues.

Source: NCBI Gene 3936 — RefSeq curated summary.

At a glance

• Gene–disease (curated): bone marrow failure syndrome (Moderate, GenCC)
• Clinical variants (ClinVar): 77 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_002298

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6528
Approved symbol	LCP1
Name	lymphocyte cytosolic protein 1
Location	13q14.13
Locus type	gene with protein product
Status	Approved
Aliases	PLS2, CP64, L-PLASTIN, LC64P
Ensembl gene	ENSG00000136167
Ensembl biotype	protein_coding
OMIM	153430
Entrez	3936

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000323076, ENST00000398576, ENST00000416500, ENST00000442275, ENST00000460190, ENST00000469227, ENST00000494531, ENST00000674665, ENST00000903164, ENST00000957338

RefSeq mRNA: 1 — MANE Select: NM_002298 NM_002298

CCDS: CCDS9403

Canonical transcript exons

ENST00000323076 — 16 exons

Exon	Start	End
ENSE00001003934	46182111	46182177
ENSE00001244603	46125923	46127723
ENSE00003464636	46148352	46148447
ENSE00003505694	46152780	46152945
ENSE00003589874	46150936	46151078
ENSE00003890607	46159599	46159686
ENSE00003891046	46143290	46143404
ENSE00003891147	46154805	46154886
ENSE00003891517	46134127	46134250
ENSE00003891663	46130814	46130938
ENSE00003893380	46158522	46158651
ENSE00003893517	46146908	46147103
ENSE00003894413	46144442	46144520
ENSE00003894596	46142292	46142425
ENSE00003895036	46156438	46156570
ENSE00003895087	46158826	46158989

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 99.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 164.1141 / max 9554.1871, expressed in 1092 samples.

FANTOM5 promoters (22 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137183	138.8222	934
137184	12.9764	711
137180	7.2022	429
137166	0.7605	310
137167	0.7531	292
137164	0.6148	248
137165	0.5901	268
137188	0.5881	238
137177	0.4725	231
207025	0.2429	96

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.70	gold quality
leukocyte	CL:0000738	99.69	gold quality
mononuclear cell	CL:0000842	99.69	gold quality
granulocyte	CL:0000094	99.61	gold quality
blood	UBERON:0000178	99.44	gold quality
bone marrow cell	CL:0002092	99.16	gold quality
spleen	UBERON:0002106	98.93	gold quality
bone marrow	UBERON:0002371	98.81	gold quality
vermiform appendix	UBERON:0001154	98.55	gold quality
corpus epididymis	UBERON:0004359	97.91	gold quality
trabecular bone tissue	UBERON:0002483	97.36	gold quality
gall bladder	UBERON:0002110	97.19	gold quality
right lung	UBERON:0002167	97.17	gold quality
upper lobe of left lung	UBERON:0008952	96.92	gold quality
lymph node	UBERON:0000029	96.65	gold quality
colonic epithelium	UBERON:0000397	96.50	gold quality
upper lobe of lung	UBERON:0008948	96.32	gold quality
rectum	UBERON:0001052	96.10	gold quality
ileal mucosa	UBERON:0000331	95.32	gold quality
thymus	UBERON:0002370	94.22	gold quality
caecum	UBERON:0001153	94.14	gold quality
tonsil	UBERON:0002372	93.81	gold quality
lung	UBERON:0002048	93.47	gold quality
prostate gland	UBERON:0002367	93.33	gold quality
right coronary artery	UBERON:0001625	93.16	gold quality
superficial temporal artery	UBERON:0001614	93.01	gold quality
decidua	UBERON:0002450	93.01	gold quality
omental fat pad	UBERON:0010414	92.66	gold quality
peritoneum	UBERON:0002358	92.58	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.05	gold quality

Single-cell (SCXA)

Detected in 32 experiment(s), a significant marker in 27.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	2515.31
E-MTAB-9388	yes	1176.66
E-MTAB-6819	yes	1009.64
E-MTAB-3929	yes	475.53
E-MTAB-8205	yes	182.42
E-MTAB-6701	yes	93.93
E-HCAD-1	yes	83.04
E-MTAB-8142	yes	71.22
E-GEOD-135922	yes	48.45
E-MTAB-10287	yes	42.26
E-HCAD-6	yes	42.02
E-CURD-122	yes	40.50
E-GEOD-84465	yes	38.01
E-HCAD-10	yes	32.93
E-MTAB-9467	yes	32.17

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ESR1, ETS1, GFI1, PGR, SP1, TBP, TFAP4

miRNA regulators (miRDB)

112 targeting LCP1, 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-518D-5P	100.00	67.51	979
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1271-5P	99.91	71.99	1972
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-4753-3P	99.90	71.03	3786
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-153-5P	99.89	73.86	6317

Literature-anchored findings (GeneRIF, showing 40)

• Data show that the serine protease plasmin cleaved both propeptides from human vascular endothelial growth factor (VEGF)-D, generating mature forms, and also activated VEGF-C. (PMID:12963694)
• association of L-plastin overexpression with increased rate of proliferation and invasion, and loss of E-cadherin expression in the SW480 colon cancer cell line indicates that L-plastin plays an important mechanistic role in colorectal cancer metastasis (PMID:16287074)
• Data suggest that phosphorylated L-plastin might act as an integrator of signals controlling the assembly of the actin cytoskeleton and cell motility in a 3D-space. (PMID:16636079)
• Data show that an increase in melanoma cell invasiveness requires not only expression but also phosphorylation of L-plastin. (PMID:17290393)
• Phosphorylation of the actin bundling protein L-plastin represents a mechanism by which costimulation controls the transport of activation receptors to the T cell surface. (PMID:17294403)
• L-plastin and S100A9 were differentially expressed in nasopharyngeal carcinoma and normal nasopharyngeal epithelial tissue (PMID:19142861)
• This study discloses a novel unexpected role of the actin bundling protein L-plastin as a cell protective protein against TNF-cytotoxicity. (PMID:19799649)
• Data demonstrate for the first time that L-plastin contributes to the fine-tuning of actin turn-over, an activity which is regulated by Ser5 phosphorylation promoting its high affinity binding to the cytoskeleton. (PMID:20169155)
• Data show that the L-plastin/integrin complex is regulated by mu-calpain cleavage and is not directly dissociated by calcium. (PMID:20183869)
• required for immune synapse formation (PMID:20683899)
• Plasmic L-plastin level in patients with colorectal cancer was higher than that in healthy adults, and was associated with tumor size, penetration, and lymphatic metastasis. (PMID:20878578)
• Results establish a causative role for PKCbetaII and L-plastin in linking GM-CSF-induced eosinophil priming for chemotaxis. (PMID:21525390)
• our data introduce costimulation-induced L-plastin phosphorylation as an important event for immune synapse formation and its inhibition by dexamethasone as a novel mode of function of this immunosuppressive glucocorticoid. (PMID:21805466)
• This study adds L-plastin to a growing list of proteins implicated in T lymphocyte polarity and migration (PMID:22581862)
• A single domain antibody directed against functional and structural modules of L-plastin reduced the association between LFA-1 and L-plastin, impaired MTOC docking, immune synapse formation and T cell activation. (PMID:23001012)
• Hepatic LCP1 mRNA was increased (by 300%) in liver biopsy samples from patients with nonalcoholic fatty liver disease compared to controls (PMID:23213074)
• High serum LCP1 is associated with kidney cancer. (PMID:23479363)
• LCP1 is functionally relevant to CXCL12 induced B-cell migration. (PMID:24009233)
• Data suggest that several single-nucleotide polymorphisms (SNPs) of the plastin genes PLS3 and LCP1 could serve as gender- and/or stage-specific molecular predictors of tumor recurrence in stage II/III colorectal cancer as well as therapeutic targets. (PMID:24170770)
• expression of L-plastin promotes tumor metastasis and, importantly, that this effect depends on an additionally required phosphorylation of L-plastin (PMID:24438191)
• L-plastin plays an important role in the clustering of NKG2D into lipid rafts, and it participates in NKG2D-mediated inhibition of NK cell chemotaxis. (PMID:24803550)
• The proteins (HSP90b, TSM1 and L-plastin) in the current study may hold potential in differentiating between melanoma and benign nevi in diagnostically challenging cases. (PMID:25191796)
• Enhanced nitroxidative stress may results in LPL S-glutathionylation leading to impaired chemotaxis, polarization, and bactericidal activity of human neutrophils. (PMID:25881549)
• An NKX3.1 binding site polymorphism in the l-plastin promoter leads to differential gene expression in human prostate cancer (PMID:26148677)
• association of SNPs in LCP1 and CTIF with hearing (PMID:26264041)
• elevated L-plastin expression promotes elongation and reduces protrusion density in cells with relatively lower L-plastin than fascin levels. (PMID:26945069)
• L-plastin regulates the stability of the immune synapse of naive and effector T-cells. (Review) (PMID:27720134)
• LCP1-positive oral squamous cell carcnome samples were correlated closely with the primary tumor size and regional lymph node metastasis. (PMID:28230172)
• The findings support a mechanism in which miR-375 suppresses RUNX1 levels, resulting in reduced vimentin and L-plastin expression. Knockdown of RUNX1, L-plastin, and vimentin resulted in significant reductions in cell invasion in vitro, indicating the functional significance of miR-375 regulation of specific proteins involved in head and neck squamous cell carcinoma (HNSCC) invasion. (PMID:28499703)
• Mutated LCP1 is a driver of chronic lymphocytic leukemia. (PMID:28679620)
• In this study, the authors found that the actin filament bundling abilities of PLS1 and PLS2 were similarly sensitive to Ca(2+) (pCa50 ~6.4), whereas PLS3 was less sensitive (pCa50 ~5.9). (PMID:28694070)
• AngII-dependent phosphorylation of LCP1 in cultured podocytes was mediated by the kinases ERK, p90 ribosomal S6 kinase, PKA, or PKC. LCP1 phosphorylation increased filopodia formation. (PMID:28768720)
• these findings support a plausible mechanism by which the AP4/L-plastin axis is regulated by the PI3K/AKT pathway in human prostate cancer (PCa)and may represent a novel therapeutic target in PCa treatment. (PMID:28981098)
• MOLP8/R cells display a very high overexpression of LCP1 gene (l-Plastin) controlled by HIF1&alpha. (PMID:29882856)
• Among the proteins found to preferentially bind clasped rather than the isolated alphaM and beta2 subunits was L-plastin (LCP1, also known as plastin-2), which binds to and maintains the inactive state of alphaMbeta2 integrin in vivo and thereby regulates leukocyte adhesion to integrin ligands under flow. (PMID:30333137)
• LPL oxidation diminishes its actin-bundling capacity. (PMID:31501427)
• The actin-bundling protein L-plastin-A double-edged sword: Beneficial for the immune response, maleficent in cancer. (PMID:32859369)
• LCP1 is a prognostic biomarker correlated with immune infiltrates in gastric cancer. (PMID:32986657)
• Transcriptome Profiling Analysis Identifies LCP1 as a Contributor for Chidamide Resistance in Gastric Cancer. (PMID:35578065)
• Targeted proteomics using parallel reaction monitoring confirms salivary proteins indicative of metastatic triple-negative breast cancer. (PMID:35995384)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	lcp1	ENSDARG00000023188
mus_musculus	Lcp1	ENSMUSG00000021998
rattus_norvegicus	Lcp1	ENSRNOG00000010319
drosophila_melanogaster	Fim	FBGN0024238
caenorhabditis_elegans		WBGENE00022223
caenorhabditis_elegans		WBGENE00022425

Paralogs (2): PLS3 (ENSG00000102024), PLS1 (ENSG00000120756)

Protein

Protein identifiers

Plastin-2 — P13796 (reviewed: P13796)

Alternative names: L-plastin, LC64P, Lymphocyte cytosolic protein 1

All UniProt accessions (3): P13796, Q5TBN3, Q5TBN5

UniProt curated annotations — full annotation on UniProt →

Function. Actin-binding protein. Plays a role in the activation of T-cells in response to costimulation through TCR/CD3 and CD2 or CD28. Modulates the cell surface expression of IL2RA/CD25 and CD69.

Subunit / interactions. Monomer. Interacts with AIF1. Interacts with actin.

Subcellular location. Cytoplasm. Cytoskeleton. Cell junction. Cell projection. Ruffle membrane.

Tissue specificity. Detected in intestinal microvilli, hair cell stereocilia, and fibroblast filopodia, in spleen and other lymph node-containing organs. Expressed in peripheral blood T-lymphocytes, neutrophils, monocytes, B-lymphocytes, and myeloid cells.

Post-translational modifications. Phosphorylated on a serine residue in response to costimulation through TCR/CD3 and CD2 or CD28. Serine phosphorylation promotes association with the actin cytoskeleton and targeting to peripheral cell projections.

Disease relevance. Chromosomal aberrations involving LCP1 is a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;13)(q27;q14), with BCL6. Defects in LCP1 has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea.

Isoforms (2)

UniProt ID	Names	Canonical?
P13796-1	1	yes
P13796-2	2

RefSeq proteins (1): NP_002289* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001589	Actinin_actin-bd_CS	Conserved_site
IPR001715	CH_dom	Domain
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR036872	CH_dom_sf	Homologous_superfamily
IPR039959	Fimbrin/Plastin	Family

Pfam: PF00307, PF13499

UniProt features (68 total): modified residue 21, helix 12, binding site 10, domain 6, sequence variant 4, turn 4, splice variant 2, mutagenesis site 2, strand 2, region of interest 2, initiator methionine 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6VEC	ELECTRON MICROSCOPY	3.9
2D85	SOLUTION NMR
5JOJ	SOLUTION NMR
5JOL	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13796-F1	89.97	0.71

Functional residue map

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

Ligand- & substrate-binding residues (10): 22; 24; 26; 28; 33; 62; 64; 66; 68; 73

Post-translational modifications (21): 2, 5, 7, 28, 30, 76, 88, 124, 257, 290, 291, 294, 297, 323, 353, 361, 406, 472, 474, 542 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
5	abolishes phosphorylation and reduces the cell surface expression of cd69 and il2ra. reduces association with the actin
5	promotes association with the actin cytoskeleton.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation

MSigDB gene sets: 361 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MCLACHLAN_DENTAL_CARIES_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, MODULE_45, AAGCCAT_MIR135A_MIR135B, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOCC_RUFFLE, MODULE_16, GOMF_GTPASE_BINDING, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_2NM_UP

GO Biological Process (11): T cell activation involved in immune response (GO:0002286), obsolete protein kinase A signaling (GO:0010737), cell migration (GO:0016477), cortical actin cytoskeleton organization (GO:0030866), animal organ regeneration (GO:0031100), regulation of intracellular protein transport (GO:0033157), actin filament bundle assembly (GO:0051017), actin filament network formation (GO:0051639), actin crosslink formation (GO:0051764), extracellular matrix disassembly (GO:0022617), positive regulation of podosome assembly (GO:0071803)

GO Molecular Function (8): actin binding (GO:0003779), integrin binding (GO:0005178), calcium ion binding (GO:0005509), identical protein binding (GO:0042802), actin filament binding (GO:0051015), GTPase binding (GO:0051020), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (22): ruffle (GO:0001726), phagocytic cup (GO:0001891), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), cytosol (GO:0005829), actin filament (GO:0005884), plasma membrane (GO:0005886), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), cell junction (GO:0030054), filopodium (GO:0030175), actin filament bundle (GO:0032432), ruffle membrane (GO:0032587), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), glial cell projection (GO:0097386), stress fiber (GO:0001725), podosome (GO:0002102), cytoskeleton (GO:0005856), membrane (GO:0016020), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interleukin-12 signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
actin filament organization	2
protein-containing complex binding	2
plasma membrane bounded cell projection	2
cytoplasm	2
actin cytoskeleton	2
actin-based cell projection	2
lymphocyte activation involved in immune response	1
immune response	1
T cell activation	1
cell motility	1
actin cytoskeleton organization	1
cortical cytoskeleton organization	1
regeneration	1
animal organ development	1
intracellular protein transport	1
regulation of intracellular transport	1
regulation of protein transport	1
cellular component assembly	1
actin filament bundle organization	1
cellular component disassembly	1
extracellular matrix organization	1
positive regulation of protein-containing complex assembly	1
podosome assembly	1
regulation of podosome assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
cytoskeletal protein binding	1
signaling receptor binding	1
cell adhesion molecule binding	1
metal ion binding	1
protein binding	1
actin binding	1
enzyme binding	1
binding	1
cation binding	1
cell leading edge	1
plasma membrane	1
intracellular anatomical structure	1
polymeric cytoskeletal fiber	1
membrane	1

Protein interactions and networks

STRING

2076 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCP1	FSCN1	Q16658	811
LCP1	GCA	P28676	765
LCP1	ACTG1	P02571	618
LCP1	ACTB	P02570	583
LCP1	CFL1	P23528	566
LCP1	MPEG1	Q2M385	531
LCP1	TUBB2A	Q13885	525
LCP1	CALM1	P02593	518
LCP1	CFL2	Q9Y281	515
LCP1	CALML3	P27482	515
LCP1	CALML5	Q9NZT1	515
LCP1	MYB	P10242	514
LCP1	TPM1	P09493	511
LCP1	SH3GL3	Q99963	510
LCP1	CALML6	Q8TD86	506

IntAct

83 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
LCP1	PLS3	psi-mi:“MI:0914”(association)	0.640
PLS3	LCP1	psi-mi:“MI:0914”(association)	0.640
AP3M1	AP3B1	psi-mi:“MI:0914”(association)	0.640
IKBKE	HSPA8	psi-mi:“MI:0914”(association)	0.560
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
FRMD1	A2ML1	psi-mi:“MI:0914”(association)	0.530
LHFPL4	IFNA17	psi-mi:“MI:0914”(association)	0.530
SSBP2	CLEC18A	psi-mi:“MI:0914”(association)	0.530
SERPINB13	TTC4	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
ATXN2	LCP1	psi-mi:“MI:0915”(physical association)	0.460
LCP1	ATXN2	psi-mi:“MI:0403”(colocalization)	0.460
ATXN2	LCP1	psi-mi:“MI:0403”(colocalization)	0.460
LCP1	rep	psi-mi:“MI:0915”(physical association)	0.370
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
Cyfip2	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
DAG1	AGRN	psi-mi:“MI:0914”(association)	0.350
CXCR2	ARPC2	psi-mi:“MI:0914”(association)	0.350
DDX19B	IGLL5	psi-mi:“MI:0914”(association)	0.350
	AP3B1	psi-mi:“MI:0914”(association)	0.350
MED23	PGRMC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (146): LCP1 (Affinity Capture-MS), LCP1 (Affinity Capture-MS), CNDP2 (Co-fractionation), LCP1 (Co-fractionation), LCP1 (Co-fractionation), LCP1 (Co-fractionation), LCP1 (Co-fractionation), LCP1 (Affinity Capture-MS), LCP1 (Affinity Capture-MS), LCP1 (Affinity Capture-MS), LCP1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), PLS3 (Affinity Capture-MS), RNF41 (Affinity Capture-MS), TTL (Affinity Capture-MS)

ESM2 similar proteins: A6H742, A7E3Q8, O13728, O14134, O14185, O59945, O88818, P05095, P13796, P13797, P19179, P19966, P32599, P37803, P37804, P37805, P41810, P53585, P53978, P54680, P78820, P87078, Q00955, Q01995, Q08873, Q14651, Q3V0K9, Q3ZBY2, Q4R5J4, Q54BC6, Q54HG2, Q550R2, Q55BP5, Q5R6R2, Q61233, Q63598, Q6DG81, Q6FIR8, Q6FM46, Q6P698

Diamond homologs: A0A2I0BVG8, A6H742, A7E3Q8, O23184, O50064, O59945, O88818, P13796, P13797, P19179, P28470, P32599, P48451, P54680, P62343, P62344, P87072, Q0DJ94, Q14651, Q24214, Q25088, Q338P8, Q3E9C0, Q3V0K9, Q61233, Q63598, Q63811, Q6DG81, Q6P698, Q6Z2M9, Q7F0J0, Q7G188, Q7XHW4, Q84UL5, Q8C5W0, Q96LZ3, Q99K51, Q9FI19, Q9FJ70, Q9FKI0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKACA	up-regulates	LCP1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	53
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
981804	NM_002298.5(LCP1):c.1122C>A (p.Tyr374Ter)	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

4166 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:46146969:A:C	F371L	1.000
13:46146969:A:T	F371L	1.000
13:46146971:A:G	F371L	1.000
13:46146973:A:G	L370P	1.000
13:46146979:G:T	A368D	1.000
13:46146988:G:T	A365D	1.000
13:46147018:A:T	V355D	1.000
13:46147033:A:T	V350D	1.000
13:46147035:A:C	F349L	1.000
13:46147035:A:T	F349L	1.000
13:46147037:A:G	F349L	1.000
13:46147061:C:G	A341P	1.000
13:46148425:A:G	L302P	1.000
13:46150985:A:G	L278P	1.000
13:46150999:C:A	W273C	1.000
13:46150999:C:G	W273C	1.000
13:46151001:A:G	W273R	1.000
13:46151001:A:T	W273R	1.000
13:46151009:A:C	L270W	1.000
13:46151009:A:G	L270S	1.000
13:46152834:A:G	W229R	1.000
13:46152834:A:T	W229R	1.000
13:46127619:A:G	L619P	0.999
13:46127625:G:T	A617D	0.999
13:46127679:G:T	A599D	0.999
13:46127703:C:G	R591P	0.999
13:46130901:A:G	L555P	0.999
13:46130918:A:C	S549R	0.999
13:46130918:A:T	S549R	0.999
13:46130920:T:G	S549R	0.999

dbSNP variants (sampled 300 via entrez): RS1000022692 (13:46164720 A>G), RS1000255814 (13:46161801 A>G), RS1000266183 (13:46174190 T>C), RS1000274038 (13:46161557 C>A,T), RS1000289456 (13:46137369 C>G,T), RS1000365821 (13:46174204 C>A), RS1000367003 (13:46129971 G>A,T), RS1000371853 (13:46130649 A>G), RS1000381224 (13:46168036 A>C,G), RS1000477223 (13:46137663 T>C), RS1000625468 (13:46155815 T>A,G), RS1000636664 (13:46163439 A>G), RS1000712077 (13:46169325 T>C), RS1000737421 (13:46175591 A>G), RS1000744735 (13:46169577 C>T)

Disease associations

OMIM: gene MIM:153430 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
bone marrow failure syndrome	Moderate	Autosomal dominant

Mondo (2): hereditary breast ovarian cancer syndrome (MONDO:0003582), bone marrow failure syndrome (MONDO:0000159)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295718 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases mutagenesis	3
Dihydrotestosterone	affects reaction, increases expression	3
Valproic Acid	decreases methylation, increases expression	3
sodium arsenite	decreases expression, increases expression	2
1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane	increases expression, affects reaction	2
(+)-JQ1 compound	decreases expression	2
Arsenic Trioxide	decreases expression, increases expression	2
Air Pollutants	increases abundance, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Progesterone	increases expression	2
Tetradecanoylphorbol Acetate	affects cotreatment, decreases reaction, increases expression, increases phosphorylation	2
Cyclosporine	increases expression	2
Particulate Matter	increases expression, increases abundance	2
OTX015	decreases expression	1
mivebresib	decreases expression	1
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
hydroxyflutamide	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, decreases reaction, increases expression	1
bathocuproine sulfonate	affects cotreatment, decreases reaction, increases expression	1
brequinar	increases expression	1
calyculin A	increases phosphorylation, decreases reaction	1
KT 5926	decreases reaction, increases phosphorylation	1
tanespimycin	affects cotreatment, increases expression	1

ChEMBL screening assays

13 unique, capped per target: 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118994	Binding	Binding affinity to LCP1 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00774527	PHASE3	COMPLETED	Comparison of Cy-Atg Vs Cy-Flu-Atg for the Conditioning Therapy in Allo-HCT
NCT02393508	PHASE3	UNKNOWN	The Impact of Red Cell Age on Product Utilization in the Chronically Transfused Outpatient Population
NCT06940570	PHASE3	SUSPENDED	Methadone as an Alternative Treatment for Children Underdoing HSCT
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT01050439	PHASE2	TERMINATED	Unrelated Donor Transplant for Malignant and Non-Malignant Disorders
NCT01596699	PHASE2	TERMINATED	Pilot Trial of Clofarabine Added to Standard Busulfan and Fludarabine for Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation
NCT01757145	PHASE2	UNKNOWN	Eltrombopag for Enhancing Platelet Engraftment in Adult Patients Undergoing Cord Blood Transplantation
NCT02224872	PHASE2	COMPLETED	Transplantation of Partially Mismatched Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia
NCT02277639	PHASE2	COMPLETED	Reduced Intensity Conditioning Using CD3+/CD19+ Depletion for Non Malignant Transplantable Diseases
NCT02349906	PHASE2	COMPLETED	Treosulfan-based Versus Busulfan-based Conditioning in Paediatric Patients With Non-malignant Diseases
NCT02722668	PHASE2	COMPLETED	UCB Transplant for Hematological Diseases Using a Non Myeloablative Prep
NCT04356469	PHASE2	RECRUITING	TCR Alpha Beta T-cell Depleted Haploidentical HCT in the Treatment of Non-Malignant Hematological Disorders in Children
NCT04558736	PHASE2	RECRUITING	Haploidentical HCT for Severe Aplastic Anemia
NCT04965597	PHASE2	COMPLETED	Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT07585136	PHASE1	NOT_YET_RECRUITING	Stem Cell Mobilization and Apheresis for Life-threatening Blood Disorders
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT01419704	PHASE1/PHASE2	WITHDRAWN	Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies
NCT01966367	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation
NCT02055456	PHASE1/PHASE2	COMPLETED	Nandrolone Decanoate in the Treatment of Telomeropathies
NCT02337595	PHASE1/PHASE2	COMPLETED	Memory T-cell Infusion to Improve Immunity After TCR-alpha/Beta Depleted Hematopoietic Stem Cell Transplantation
NCT03128996	PHASE1/PHASE2	RECRUITING	Reduced Intensity Conditioning and Familial HLA-Mismatched BMT for Non-Malignant Disorders
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT02356653	EARLY_PHASE1	RECRUITING	Expanded Access Protocol Using CD3+/CD19+ Depleted PBSC
NCT02928991	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Fludarabine Based RIC for Bone Marrow Failure Syndromes
NCT06787560	EARLY_PHASE1	RECRUITING	CD7 CAR-T Cell Sequential Allo-HSCT for Non-malignant Blood and Immune System Diseases
NCT00315419	Not specified	UNKNOWN	Identifying Characteristics of Bone Marrow Failure Syndromes
NCT00897260	Not specified	COMPLETED	Umbilical Cord Blood Transplantation As Treatment Of Adult Patients With Hematologic Disorders
NCT02720679	Not specified	RECRUITING	Investigation of the Genetics of Hematologic Diseases
NCT02958462	Not specified	RECRUITING	Pre-myeloid Cancer and Bone Marrow Failure Clinic Study
NCT03145545	Not specified	AVAILABLE	Expanded Access Protocol Using Alpha/Beta T and CD19+ Depleted PBSC
NCT04781790	Not specified	RECRUITING	French National Registry of Bone Marrow Failures