LPXN

Summary

LPXN (leupaxin, HGNC:14061) is a protein-coding gene on chromosome 11q12.1, encoding Leupaxin (O60711). Transcriptional coactivator for androgen receptor (AR) and serum response factor (SRF).

The product encoded by this gene is preferentially expressed in hematopoietic cells and belongs to the paxillin protein family. Similar to other members of this focal-adhesion-associated adaptor-protein family, it has four leucine-rich LD-motifs in the N-terminus and four LIM domains in the C-terminus. It may function in cell type-specific signaling by associating with PYK2, a member of focal adhesion kinase family. As a substrate for a tyrosine kinase in lymphoid cells, this protein may also function in, and be regulated by, tyrosine kinase activity. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 9404 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 61 total
• Druggable target: yes
• MANE Select transcript: NM_004811

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14061
Approved symbol	LPXN
Name	leupaxin
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	LDPL
Ensembl gene	ENSG00000110031
Ensembl biotype	protein_coding
OMIM	605390
Entrez	9404

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000395074, ENST00000528489, ENST00000528954, ENST00000529915, ENST00000530561

RefSeq mRNA: 3 — MANE Select: NM_004811 NM_001143995, NM_001307951, NM_004811

CCDS: CCDS53635, CCDS76407, CCDS7969

Canonical transcript exons

ENST00000395074 — 9 exons

Exon	Start	End
ENSE00002146350	58575760	58575856
ENSE00002517537	58554841	58554940
ENSE00003554727	58564155	58564201
ENSE00003595240	58549973	58550146
ENSE00003613275	58570556	58570713
ENSE00003636313	58526871	58527723
ENSE00003646737	58528043	58528191
ENSE00003647277	58551065	58551232
ENSE00003690182	58549786	58549867

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 96.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.5716 / max 959.5576, expressed in 1776 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119817	42.5717	1114
119822	4.4971	1545
119819	1.0287	246
119821	0.3264	130
119820	0.1476	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.46	gold quality
leukocyte	CL:0000738	95.37	gold quality
mononuclear cell	CL:0000842	95.32	gold quality
monocyte	CL:0000576	95.25	gold quality
vermiform appendix	UBERON:0001154	95.06	gold quality
lymph node	UBERON:0000029	94.90	gold quality
blood	UBERON:0000178	94.67	gold quality
thymus	UBERON:0002370	93.80	gold quality
spleen	UBERON:0002106	93.06	gold quality
ileal mucosa	UBERON:0000331	92.12	gold quality
epithelium of nasopharynx	UBERON:0001951	90.73	gold quality
tonsil	UBERON:0002372	89.96	gold quality
caecum	UBERON:0001153	89.82	gold quality
rectum	UBERON:0001052	88.42	gold quality
bone marrow cell	CL:0002092	88.09	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.23	gold quality
gall bladder	UBERON:0002110	87.16	gold quality
upper lobe of left lung	UBERON:0008952	86.88	gold quality
upper lobe of lung	UBERON:0008948	86.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.90	gold quality
colonic epithelium	UBERON:0000397	85.55	gold quality
bone marrow	UBERON:0002371	85.45	gold quality
sperm	CL:0000019	85.25	gold quality
lung	UBERON:0002048	85.15	gold quality
right lung	UBERON:0002167	85.01	gold quality
small intestine	UBERON:0002108	84.86	gold quality
amniotic fluid	UBERON:0000173	84.81	gold quality
mucosa of transverse colon	UBERON:0004991	84.76	gold quality
lower lobe of lung	UBERON:0008949	84.47	gold quality
descending thoracic aorta	UBERON:0002345	83.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.61
E-MTAB-6678	yes	5.15
E-CURD-112	no	2.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting LPXN, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-508-3P	98.66	69.62	887
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-138-1-3P	98.25	67.89	867

Literature-anchored findings (GeneRIF, showing 15)

• leupaxin may be a critical nucleating component of the osteoclast podosomal signaling complex (PMID:12674328)
• Leupaxin binding to tyrosine phosphatase PEP suggests that leupaxin may function as a signal-transducing complex with PEP. (PMID:15786712)
• These data demonstrate that LPXN forms a signaling complex with Pyk2, c-Src, and PTP-PEST to regulate migration of prostate cancer cells. (PMID:17329398)
• Leupaxin plays an inhibitory role in BCR signaling and B cell function. (PMID:17640867)
• leupaxin could serve as a potential progression marker for a subset of PCa and may represent a novel coactivator of the androgen receptor (PMID:18451096)
• Leupaxin is enriched in vascular smooth nuscle. It undergoes cytoplasmic/nuclear shuttling & functions as an serum response factor cofactor. It associates with CArG-containing regions. Its ectopic expression induces smooth muscle marker gene expression. (PMID:18497331)
• LPXN, a member of the paxillin superfamily, is fused to RUNX1 in an acute myeloid leukemia patient with a t(11;21)(q12;q22) translocation. (PMID:19760607)
• leupaxin functions as a paxillin counterpart that potently suppresses the tyrosine phosphorylation of paxillin during integrin signaling. (PMID:19917054)
• first evidence of dynamic regulation of leupaxin localization and tyrosine phosphorylation by G-Protein Coupled Receptors (PMID:20543562)
• Results show that leupaxin has particular influence on the progression and invasion of breast cancer cells and may therefore represent an interesting candidate protein for diagnosis and therapeutic interventions. (PMID:25955236)
• Authors demonstrate that LPXN directly influences cytoskeletal dynamics via interaction with the actin-binding protein CaD and regulates CaD phosphorylation by recruiting ERK to highly dynamic structures within PCa cells. (PMID:26079947)
• this is the first demonstration of a role for the leupaxin in the regulation of hepatocellular carcinoma progression, at least in part, by enhancing beta-catenin transcription activity. (PMID:26361959)
• The full-length leupaxin binds to the Pyk2-focal adhesion targeting domain. (PMID:26866573)
• LPXN may facilitate bladder cancer progression by upregulating the expression of S100P via PI3K/AKT pathway. These results provide a novel insight into the role of LPXN in tumorigenesis and progression of bladder cancer and potential therapeutic target of bladder cancer. (PMID:29975926)
• Paxillin family proteins Hic-5 and LPXN promote lipid storage by regulating the ubiquitination degradation of CIDEC. (PMID:38159847)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	lpxn	ENSDARG00000079315
mus_musculus	Lpxn	ENSMUSG00000024696
rattus_norvegicus	Lpxn	ENSRNOG00000012611
drosophila_melanogaster	Pax	FBGN0041789
drosophila_melanogaster	CG30178	FBGN0050178
drosophila_melanogaster	CG31624	FBGN0051624
drosophila_melanogaster	CG31988	FBGN0051988
drosophila_melanogaster	CG34325	FBGN0085354
caenorhabditis_elegans		WBGENE00016197
caenorhabditis_elegans	C34B2.4	WBGENE00016389
caenorhabditis_elegans	F33D11.1	WBGENE00018000

Paralogs (2): PXN (ENSG00000089159), TGFB1I1 (ENSG00000140682)

Protein

Protein identifiers

Leupaxin — O60711 (reviewed: O60711)

All UniProt accessions (3): O60711, B7Z5P7, E9PNX9

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional coactivator for androgen receptor (AR) and serum response factor (SRF). Contributes to the regulation of cell adhesion, spreading and cell migration and acts as a negative regulator in integrin-mediated cell adhesion events. Suppresses the integrin-induced tyrosine phosphorylation of paxillin (PXN). May play a critical role as an adapter protein in the formation of the adhesion zone in osteoclasts. Negatively regulates B-cell antigen receptor (BCR) signaling.

Subunit / interactions. Interacts with PTPN22. Interacts with unphosphorylated ITGA4. Interacts with PTK2B/PYK2, PTPN12, AR and SRF. Interacts (via LD motif 3) with LYN and the interaction is induced upon B-cell antigen receptor (BCR) activation. Interacts (via LD motif 3) with PTK2/FAK.

Subcellular location. Cytoplasm. Cell junction. Focal adhesion. Nucleus. Perinuclear region. Cell projection. Podosome. Cell membrane.

Tissue specificity. Macrophages, monocytes and osteoclasts (at protein level). Strongly expressed in cells and tissues of hematopoietic origin. Highest expression in lymphoid tissues such as spleen, lymph node, thymus and appendix and in the vascular smooth muscle. Lower levels in bone marrow and fetal liver. Also expressed in peripheral blood lymphocytes and a number of hematopoietic cell lines. Very low levels found in epithelial cell lines. Expressed in prostate cancer (PCa) cells and its expression intensity is directly linked to PCa progression.

Post-translational modifications. Phosphorylated on tyrosine residues. Phosphorylation on Tyr-72 is important for its inhibitory function. Bombesin stimulates phosphorylation on Tyr-22, Tyr-62 and Tyr-72.

Domain organisation. The LIM domain 3 is critical for focal adhesion targeting and the suppression of paxillin (PXN) tyrosine phosphorylation. The LIM domain 3 alone or both LIM domains 3 and 4 can mediate interaction with AR.

Similarity. Belongs to the paxillin family.

Isoforms (2)

UniProt ID	Names	Canonical?
O60711-1	1	yes
O60711-2	2

RefSeq proteins (3): NP_001137467, NP_001294880, NP_004802* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain
IPR017305	Tgfb1i1/Leupaxin/TGFB1I1	Family

Pfam: PF00412

UniProt features (30 total): modified residue 7, domain 4, strand 4, sequence conflict 3, helix 3, short sequence motif 3, turn 2, chain 1, splice variant 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4XEK	X-RAY DIFFRACTION	1.79
4XEV	X-RAY DIFFRACTION	2.01
4XEF	X-RAY DIFFRACTION	2.5
1X3H	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60711-F1	76.70	0.51

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 (7): 19, 22, 54, 62, 72, 81, 1

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 318 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_B_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, MODULE_45, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, MODULE_16, WIELAND_UP_BY_HBV_INFECTION, PUJANA_CHEK2_PCC_NETWORK, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_REGULATION_OF_IMMUNE_RESPONSE, ROZANOV_MMP14_TARGETS_UP, GOBP_REGULATION_OF_CELL_ADHESION_MEDIATED_BY_INTEGRIN, BROWNE_HCMV_INFECTION_14HR_DN, RIGGI_EWING_SARCOMA_PROGENITOR_DN, TGACATY_UNKNOWN

GO Biological Process (9): cell adhesion (GO:0007155), negative regulation of cell adhesion (GO:0007162), signal transduction (GO:0007165), transforming growth factor beta receptor signaling pathway (GO:0007179), regulation of cell adhesion mediated by integrin (GO:0033628), substrate adhesion-dependent cell spreading (GO:0034446), endothelial cell migration (GO:0043542), negative regulation of B cell receptor signaling pathway (GO:0050859), protein-containing complex assembly (GO:0065003)

GO Molecular Function (3): transcription coregulator activity (GO:0003712), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (12): podosome (GO:0002102), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), membrane (GO:0016020), nuclear speck (GO:0016607), perinuclear region of cytoplasm (GO:0048471), cytoskeleton (GO:0005856), cell projection (GO:0042995), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cellular process	2
regulation of cell adhesion	2
cytoplasm	2
cell adhesion	1
negative regulation of cellular process	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cell adhesion mediated by integrin	1
cell-substrate adhesion	1
cell migration	1
B cell receptor signaling pathway	1
regulation of B cell receptor signaling pathway	1
negative regulation of antigen receptor-mediated signaling pathway	1
cellular component assembly	1
protein-containing complex organization	1
transcription regulator activity	1
cation binding	1
binding	1
actin-based cell projection	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
cell-substrate junction	1
nuclear ribonucleoprotein granule	1
intracellular membraneless organelle	1
cell junction	1

Protein interactions and networks

STRING

1298 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LPXN	PTK2B	Q14289	901
LPXN	VCL	P18206	806
LPXN	PTPN12	Q05209	783
LPXN	APOB	P04114	765
LPXN	ILK	P57043	583
LPXN	TLN2	Q9Y4G6	531
LPXN	APOA1	P02647	524
LPXN	HCLS1	P14317	515
LPXN	GSN	P06396	509
LPXN	CTTN	Q14247	508
LPXN	SCIN	Q9Y6U3	496
LPXN	STX3	Q13277	465
LPXN	ZNF614	Q8N883	458
LPXN	PARVA	Q9NVD7	443
LPXN	ETV6	P41212	432

IntAct

225 interactions, top by confidence:

A	B	Type	Score
PLEKHH2	LPXN	psi-mi:“MI:0915”(physical association)	0.800
LPXN	PLEKHH2	psi-mi:“MI:0915”(physical association)	0.800
LPXN	HOXC9	psi-mi:“MI:0915”(physical association)	0.780
LMO1	LPXN	psi-mi:“MI:0915”(physical association)	0.740
LPXN	LMO1	psi-mi:“MI:0915”(physical association)	0.740
LPXN	PCNT	psi-mi:“MI:0914”(association)	0.640
LPXN	Hoxa1	psi-mi:“MI:0915”(physical association)	0.570
Hoxa1	LPXN	psi-mi:“MI:0915”(physical association)	0.570
LPXN		psi-mi:“MI:0915”(physical association)	0.560
LPXN	RUNX1T1	psi-mi:“MI:0915”(physical association)	0.560
LPXN	PLEKHN1	psi-mi:“MI:0915”(physical association)	0.560
TXLNB	LPXN	psi-mi:“MI:0915”(physical association)	0.560
	LPXN	psi-mi:“MI:0915”(physical association)	0.560
RUNX1T1	LPXN	psi-mi:“MI:0915”(physical association)	0.560
LPXN	TXLNB	psi-mi:“MI:0915”(physical association)	0.560
PLEKHN1	LPXN	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (110): LPXN (Two-hybrid), LPXN (Two-hybrid), LPXN (Two-hybrid), SFI1 (Two-hybrid), PLEKHN1 (Two-hybrid), PLEKHH2 (Two-hybrid), TXLNB (Two-hybrid), ZNF426 (Two-hybrid), PHF21A (Two-hybrid), IMP3 (Two-hybrid), LPXN (Two-hybrid), LPXN (Two-hybrid), POM121 (Two-hybrid), LPXN (PCA), Hoxa1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1L8F1M4, A8WH69, B1AK53, D3ZQL6, E1BBG2, O43294, O60711, O75112, P36202, P49023, P49024, P50479, P70271, Q09476, Q0VA45, Q2TCH4, Q3MHZ4, Q3SX40, Q3T005, Q3TJD7, Q4V882, Q5R7I1, Q5U464, Q62219, Q62920, Q63618, Q66H76, Q679P3, Q6INU3, Q6P7E4, Q80VP1, Q8BGT6, Q8BYZ1, Q8CI51, Q8K382, Q8N3F8, Q8TDY4, Q8TEH3, Q8VI36, Q91W69

Diamond homologs: A0A1L8F1M4, A0M8R4, A0M8S5, A0M8U6, A1Z6W3, A8WH69, O35115, O43294, O43900, O60711, O70433, O94929, P47226, P48059, P49023, P49024, P50464, P97447, Q00PK1, Q07DW1, Q07DX3, Q07DY3, Q07DZ4, Q07E27, Q07E40, Q07E51, Q09476, Q09YI0, Q09YJ2, Q09YK3, Q09YL5, Q09YN8, Q108U9, Q13642, Q13643, Q14192, Q174I2, Q17QE2, Q28FG2, Q292U2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
LYN	“up-regulates activity”	LPXN	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 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
Ras activation upon Ca2+ influx through NMDA receptor	5	46.0×	6e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	43.9×	6e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	43.9×	6e-06
Long-term potentiation	5	38.4×	8e-06
Assembly and cell surface presentation of NMDA receptors	9	36.8×	3e-10
Neurexins and neuroligins	10	31.8×	2e-10
Protein-protein interactions at synapses	6	25.7×	6e-06
Extracellular matrix organization	6	6.1×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
receptor clustering	8	53.7×	9e-10
establishment or maintenance of epithelial cell apical/basal polarity	8	50.0×	9e-10
protein localization to synapse	6	49.4×	4e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	5	26.6×	1e-04
protein-containing complex assembly	9	11.0×	1e-05
cell-cell adhesion	10	10.9×	5e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2645 predictions. Top by Δscore:

Variant	Effect	Δscore
11:58549864:CTTT:C	acceptor_gain	1.0000
11:58551059:TCTCA:T	donor_loss	1.0000
11:58551060:CTCA:C	donor_loss	1.0000
11:58551061:TCA:T	donor_loss	1.0000
11:58551062:CA:C	donor_loss	1.0000
11:58551064:C:CT	donor_loss	1.0000
11:58551067:T:A	donor_gain	1.0000
11:58551229:CAAC:C	acceptor_gain	1.0000
11:58551233:C:CC	acceptor_gain	1.0000
11:58551239:C:CT	acceptor_gain	1.0000
11:58551239:C:T	acceptor_gain	1.0000
11:58551240:A:T	acceptor_gain	1.0000
11:58554835:ACTC:A	donor_loss	1.0000
11:58554837:TCACC:T	donor_loss	1.0000
11:58554839:A:AG	donor_loss	1.0000
11:58554840:C:CA	donor_loss	1.0000
11:58554936:CTTCA:C	acceptor_gain	1.0000
11:58554937:TTCA:T	acceptor_gain	1.0000
11:58554938:TCA:T	acceptor_gain	1.0000
11:58554939:CA:C	acceptor_gain	1.0000
11:58554939:CAC:C	acceptor_gain	1.0000
11:58554941:C:CA	acceptor_loss	1.0000
11:58554941:C:CC	acceptor_gain	1.0000
11:58554942:T:G	acceptor_loss	1.0000
11:58554943:A:AC	acceptor_gain	1.0000
11:58554943:A:C	acceptor_gain	1.0000
11:58570551:TTTA:T	donor_loss	1.0000
11:58570552:TTAC:T	donor_loss	1.0000
11:58570553:TAC:T	donor_loss	1.0000
11:58570554:ACCG:A	donor_loss	1.0000

AlphaMissense

2567 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:58549817:G:C	C237W	0.999
11:58549819:A:G	C237R	0.999
11:58527550:A:C	C355W	0.998
11:58527552:A:G	C355R	0.998
11:58528048:A:G	C296R	0.998
11:58528057:A:G	C293R	0.998
11:58549818:C:G	C237S	0.998
11:58549818:C:T	C237Y	0.998
11:58549819:A:T	C237S	0.998
11:58549840:A:G	W230R	0.998
11:58549840:A:T	W230R	0.998
11:58550002:A:G	C211R	0.998
11:58527551:C:T	C355Y	0.997
11:58527630:A:G	C329R	0.997
11:58528046:A:C	C296W	0.997
11:58528047:C:T	C296Y	0.997
11:58528056:C:G	C293S	0.997
11:58528057:A:T	C293S	0.997
11:58528069:A:G	W289R	0.997
11:58528069:A:T	W289R	0.997
11:58528125:C:G	C270S	0.997
11:58528126:A:G	C270R	0.997
11:58528126:A:T	C270S	0.997
11:58528165:A:C	Y257D	0.997
11:58528187:A:C	F249L	0.997
11:58528187:A:T	F249L	0.997
11:58528189:A:G	F249L	0.997
11:58549818:C:A	C237F	0.997
11:58549991:G:C	C214W	0.997
11:58549992:C:G	C214S	0.997

dbSNP variants (sampled 300 via entrez): RS1000012721 (11:58548848 G>C), RS1000029468 (11:58550936 A>G), RS1000058376 (11:58558028 G>C), RS1000085467 (11:58538942 G>A,C), RS1000090422 (11:58557647 C>T), RS1000118168 (11:58539340 C>T), RS1000274182 (11:58564663 G>A), RS1000323341 (11:58545858 CATCT>C), RS1000435339 (11:58552546 T>C), RS1000497762 (11:58565835 A>G), RS1000574280 (11:58563614 T>A), RS1000619552 (11:58569699 A>G), RS1000645764 (11:58564976 G>A,C), RS1000684644 (11:58528773 T>C), RS1000733303 (11:58569536 G>A,C,T)

Disease associations

OMIM: gene MIM:605390 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001725_9	Inflammatory bowel disease	7.000000e-10
GCST001826_11	Lymphoma	1.000000e-07
GCST001826_12	Lymphoma	4.000000e-08
GCST004133_47	Ulcerative colitis	9.000000e-06
GCST007269_201	Pulse pressure	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066504 (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
6.20	Kd	631.2	nM	CHEMBL5653589
6.20	ED50	631.2	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	2148663: Binding affinity to human LPXN incubated for 45 mins by Kinobead based pull down assay	kd	0.6312	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	4
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
Nickel	decreases expression, increases expression	3
Tetrachlorodibenzodioxin	decreases reaction, increases expression	3
arsenite	affects binding, increases reaction, increases methylation	2
chloropicrin	affects expression, decreases expression	2
(+)-JQ1 compound	affects cotreatment, decreases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	decreases expression	1
lead acetate	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
potassium chromate(VI)	decreases expression	1
rutecarpine	increases expression	1
ferrous chloride	decreases expression	1
resorcinol	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	increases expression	1
abrine	increases expression	1
mirdametinib	decreases expression, affects cotreatment	1
2,2’,4,4’-tetrabromodiphenyl ether	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
CHEMBL5651705	Binding	Binding affinity to human LPXN 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

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D2K6	Abcam Raji LPXN KO	Cancer cell line	Male
CVCL_UQ87	Abcam Jurkat LPXN KO	Cancer cell line	Male

Clinical trials (associated diseases)

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