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
• GTEx eGene: eQTL in 25 tissues, sQTL in 15 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.79 (unconstrained)
• MANE Select transcript: NM_004811
• Notable: 61 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 11 — 7 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000395074

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3

ENST00000395074, ENST00000528489, ENST00000528954, ENST00000529915, ENST00000530561, ENST00000985471, ENST00000985472, ENST00001028164, ENST00001028165, ENST00001110737, ENST00001110738

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.

Highest expression (Bgee): granulocyte, leukocyte, mononuclear cell, monocyte, vermiform appendix.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LPXN is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 25 tissues and its splicing (sQTL) in 15 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 40 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	sqtl	6.9e-56	+1.09	11:58496708:G:A
Whole Blood	sqtl	2.0e-12	+0.31	11:58488290:A:G
Testis	sqtl	1.9e-08	+0.54	11:58506897:T:C
Esophagus Muscularis	eqtl	6.7e-07	+0.58	11:58499826:G:A
Whole Blood	eqtl	4.8e-06	+0.44	11:58539002:A:AAAC
Artery Tibial	eqtl	8.3e-05	-0.46	11:58608052:A:G
Artery Aorta	eqtl	1.8e-04	+0.58	11:58562811:GT:G
Skin Sun Exposed Lower leg	eqtl	2.8e-04	-0.34	11:58381838:G:A
Muscle Skeletal	sqtl	4.5e-04	+0.29	11:58471088:G:T
Lung	eqtl	6.5e-04	+0.51	11:58539002:A:AAAC
Adrenal Gland	eqtl	1.0e-03	+0.77	11:58477915:A:G
Brain Frontal Cortex BA9	eqtl	1.2e-03	+0.98	11:58236584:T:C
Pancreas	eqtl	1.2e-03	+0.74	11:58562811:GT:G
Nerve Tibial	eqtl	1.9e-03	-0.37	11:58231290:T:C
Brain Hypothalamus	eqtl	2.6e-03	+1.03	11:58864461:G:T
Thyroid	sqtl	3.0e-03	-1.20	11:58539002:A:AAAC
Skin Sun Exposed Lower leg	sqtl	5.6e-03	+1.14	11:58539002:A:AAAC
Muscle Skeletal	eqtl	6.1e-03	+0.41	11:58639066:G:A
Pancreas	sqtl	7.3e-03	-0.55	11:58291866:C:G
Brain Cerebellar Hemisphere	sqtl	8.5e-03	-1.09	11:58312613:C:T

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

showing 100 of 280 tissues 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
C1 segment of cervical spinal cord	UBERON:0006469	83.87	gold quality
palpebral conjunctiva	UBERON:0001812	83.86	gold quality
visceral pleura	UBERON:0002401	83.56	gold quality
ascending aorta	UBERON:0001496	83.19	gold quality
thoracic aorta	UBERON:0001515	83.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.01	gold quality
smooth muscle tissue	UBERON:0001135	82.90	gold quality
right lobe of liver	UBERON:0001114	82.75	gold quality
right coronary artery	UBERON:0001625	82.61	gold quality
transverse colon	UBERON:0001157	82.59	gold quality
metanephros cortex	UBERON:0010533	82.43	gold quality
mucosa of stomach	UBERON:0001199	82.31	gold quality
male germ cell	CL:0000015	82.27	gold quality
minor salivary gland	UBERON:0001830	82.16	gold quality
skin of hip	UBERON:0001554	82.01	gold quality
left coronary artery	UBERON:0001626	81.94	gold quality
intestine	UBERON:0000160	81.86	gold quality
aorta	UBERON:0000947	81.84	gold quality
spinal cord	UBERON:0002240	81.84	gold quality
right adrenal gland cortex	UBERON:0035827	81.81	gold quality
right lobe of thyroid gland	UBERON:0001119	81.80	gold quality
right uterine tube	UBERON:0001302	81.73	gold quality
right adrenal gland	UBERON:0001233	81.70	gold quality
left lobe of thyroid gland	UBERON:0001120	81.67	gold quality
left ovary	UBERON:0002119	81.61	gold quality
right testis	UBERON:0004534	81.56	gold quality
calcaneal tendon	UBERON:0003701	81.44	gold quality
urinary bladder	UBERON:0001255	81.40	gold quality
stromal cell of endometrium	CL:0002255	81.24	gold quality
left testis	UBERON:0004533	81.21	gold quality
thyroid gland	UBERON:0002046	81.09	gold quality
popliteal artery	UBERON:0002250	81.07	gold quality
large intestine	UBERON:0000059	81.06	gold quality
tibial artery	UBERON:0007610	81.06	gold quality
colon	UBERON:0001155	80.99	gold quality
right ovary	UBERON:0002118	80.97	gold quality
left adrenal gland	UBERON:0001234	80.93	gold quality
subcutaneous adipose tissue	UBERON:0002190	80.81	gold quality
tibial nerve	UBERON:0001323	80.72	gold quality
superficial temporal artery	UBERON:0001614	80.70	gold quality
left adrenal gland cortex	UBERON:0035825	80.60	gold quality
coronary artery	UBERON:0001621	80.59	gold quality
omental fat pad	UBERON:0010414	80.54	gold quality
peritoneum	UBERON:0002358	80.48	gold quality
pleura	UBERON:0000977	80.30	gold quality
body of pancreas	UBERON:0001150	80.26	gold quality
adipose tissue of abdominal region	UBERON:0007808	80.21	gold quality
left uterine tube	UBERON:0001303	80.00	gold quality
body of stomach	UBERON:0001161	79.94	gold quality
testis	UBERON:0000473	79.75	gold quality
apex of heart	UBERON:0002098	79.75	gold quality
body of uterus	UBERON:0009853	79.53	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.47	gold quality
endocervix	UBERON:0000458	79.25	gold quality
adrenal cortex	UBERON:0001235	79.16	gold quality
adrenal gland	UBERON:0002369	79.13	gold quality
ovary	UBERON:0000992	79.12	gold quality
mouth mucosa	UBERON:0003729	79.11	gold quality
trabecular bone tissue	UBERON:0002483	79.03	gold quality
sigmoid colon	UBERON:0001159	78.99	gold quality
saliva-secreting gland	UBERON:0001044	78.95	gold quality
colonic mucosa	UBERON:0000317	78.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	78.88	gold quality
stomach	UBERON:0000945	78.74	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	78.65	gold quality
duodenum	UBERON:0002114	78.31	gold quality
adipose tissue	UBERON:0001013	78.28	gold quality
adenohypophysis	UBERON:0002196	78.21	gold quality
pancreas	UBERON:0001264	78.20	gold quality
connective tissue	UBERON:0002384	78.10	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Tonsil	tissue	111.0	high
Thymus	tissue	96.2
Lymph node	tissue	81.4	high
Appendix	tissue	45.5	high
Spleen	tissue	35.6	medium
Lung	tissue	31.5	high
Urinary bladder	tissue	30.2	not detected
Rectum	tissue	18.4	low
Postcentral gyrus	tissue	17.8
Gallbladder	tissue	14.2	not detected
Colon	tissue	13.6	low
Liver	tissue	13.1	not detected
Small intestine	tissue	12.9	not detected
Nucleus accumbens	tissue	12.6
Locus coeruleus	tissue	12.6
Stomach 1	tissue	12.3	low
Hypothalamus	tissue	12.3
Periaqueductal gray	tissue	11.8
Spinal cord	tissue	11.7
Epididymis	tissue	11.2	not detected
Hippocampus	tissue	11.0	low
Medulla oblongata	tissue	10.3
Substantia nigra	tissue	10.3
Duodenum	tissue	10.3	not detected
Pons	tissue	10.2
Corpus callosum	tissue	9.6
Bone marrow	tissue	9.6	not detected
Breast	tissue	9.5	not detected
Septum	tissue	9.3
Smooth muscle	tissue	9.0	not detected
Midbrain	tissue	8.8
Prostate	tissue	8.8	not detected
Thalamus	tissue	7.6
Adipose tissue	tissue	7.5	not detected
Cervix	tissue	7.4	not detected
Ovary	tissue	7.4	not detected
Salivary gland	tissue	7.2	not detected
Pituitary gland	tissue	7.0
Testis	tissue	6.9	not detected
Endometrium 1	tissue	6.9	not detected
Seminal vesicle	tissue	6.7	not detected
Kidney	tissue	6.6	low
Adrenal gland	tissue	6.6	not detected
Retina	tissue	6.5
Choroid plexus	tissue	6.5
Thyroid gland	tissue	6.5	low
Superior colliculi	tissue	6.4
Putamen	tissue	6.3
Fallopian tube	tissue	6.3	not detected
Pancreas	tissue	6.2	not detected
Parathyroid gland	tissue	6.1	not detected
Vagina	tissue	5.8	not detected
Amygdala	tissue	5.7
Ventral forebrain	tissue	5.7
Hippocampal formation	tissue	5.4
Skin 1	tissue	5.1	low
Heart muscle	tissue	5.0	not detected
Esophagus	tissue	4.9	not detected
Placenta	tissue	4.9	not detected
Tongue	tissue	4.8

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Lateral funiculus (white matter) (20.5), Posterior thalamic nucleus (18.8), Posteroventral cochlear nucleus (18.3), Cerebellar white matter (17.6), Anterior thalamic nucleus, ventral (17.5).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting LPXN by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 39 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.00068, LOEUF 0.787, missense Z 0.574 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000395074 — one region, missense o/e 0.97.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2147677) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased IgM level	1
abnormal plasma cell differentiation	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R7I1	98.8%	Diamond
Bos taurus	Q3ZBI6	97.1%	Diamond
Oryctolagus cuniculus	Q09YN8	93.6%	Diamond
Gallus gallus	Q90YH9	89.5%	Diamond
Drosophila pseudoobscura pseudoobscura	Q292U5	84.2%	Diamond
Anopheles gambiae	Q7QJT4	83.3%	Diamond
Aedes aegypti	Q174I2	80.3%	Diamond
Xenopus laevis	Q6GLJ6	77.6%	Diamond
Arabidopsis thaliana	Q0WSN2	65.2%	Diamond
Dictyostelium discoideum	Q8MML5	48.7%	Diamond
Schizosaccharomyces pombe 972h-	O43052	41.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
OR5B21	protein-coding	219968
ZFP91-CNTF	ncRNA	386607
OR5B2	protein-coding	390190
OR5B12	protein-coding	390191
ZFP91	protein-coding	80829
GLYAT	protein-coding	10249
CNTF	protein-coding	1270
OR5B3	protein-coding	441608

Protein

Protein identifiers

Leupaxin — O60711 (reviewed: O60711)

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

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 by resolution:

PDB	Title	Method	Resolution (Å)
4XEK	Pyk2-FAT domain in complex with leupaxin LD4 motif	X-RAY DIFFRACTION	1.79
4XEV	Fusion of Pyk2-FAT domain with Leupaxin LD1 motif, complexed with Leupaxin LD4 peptide	X-RAY DIFFRACTION	2.01
4XEF	Pyk2-FAT complexed with Leupaxin LD motif LD1	X-RAY DIFFRACTION	2.5
1X3H	Solution structure of the LIM domain of human Leupaxin	SOLUTION NMR

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): focal adhesion sites; cytosol; nuclear speckles

Antibody reliability (HPA): IH enhanced · IF supported

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)

Type	Positions
Phosphoserine	19, 54, 81
Phosphotyrosine	22, 62, 72
N-acetylmethionine	1

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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): DNA-templated transcription (GO:0006351), cell adhesion (GO:0007155), negative regulation of cell adhesion (GO:0007162), signal transduction (GO:0007165), 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 (11): podosome (GO:0002102), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), focal adhesion (GO:0005925), membrane (GO:0016020), nuclear speck (GO:0016607), perinuclear region of cytoplasm (GO:0048471), cytoskeleton (GO:0005856)

GO top-level categories

32 GO namespaces:

Category	Terms
cellular anatomical structure	4
cellular process	2
regulation of cell adhesion	2
cytoplasm	2
gene expression	1
RNA biosynthetic process	1
cell adhesion	1
negative regulation of cellular process	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	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
anchoring junction	1
cell-substrate junction	1
nuclear ribonucleoprotein granule	1
intracellular membraneless organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 23 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of B cell receptor signaling pathway	BP	direct assay
negative regulation of cell adhesion	BP	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
focal adhesion	CC	direct assay
membrane	CC	high-throughput assay
nuclear speck	CC	direct assay
nucleus	CC	direct assay
plasma membrane	CC	direct assay
podosome	CC	direct assay
transcription coregulator activity	MF	direct assay

Protein interactions and networks

STRING

showing 17 of 854 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LPXN	PTK2B	Q14289	812
LPXN	VCL	P18206	789
LPXN	APOB	P04114	655
LPXN	APOA1	P02647	497
LPXN	TMEM217B	A0A494BZU4	442
LPXN	TMEM217	Q8N7C4	434
LPXN	CETP	P11597	423
LPXN	ILK	P57043	421
LPXN	PTPN12	Q05209	400
LPXN	FERMT3	Q86UX7	398
LPXN	FERMT1	Q9BQL6	396
LPXN	PARVA	Q9NVD7	382
LPXN	TLN1	Q9Y490	378
LPXN	NT5C	Q8TCD5	370
LPXN	TUBG2	Q9NRH3	370
LPXN	CLRN3	Q8NCR9	370
LPXN	EPHA6	Q9UF33	370

IntAct

Human interaction partners of LPXN in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 113 partners by confidence:

Partner	Interaction type	MIscore	Records
PLEKHH2	physical association	0.800	3
HOXC9	physical association	0.780	7
LMO1	physical association	0.740	7
PTK2	physical association	0.740	1
PCNT	association	0.640	2
RUNX1T1	physical association	0.560	7
PLEKHN1	physical association	0.560	6
POM121	physical association	0.560	4
VCL	physical association	0.560	4
AGXT	physical association	0.560	3
AQP1	physical association	0.560	3
LMO3	physical association	0.560	3
OPTN	physical association	0.560	3
TGFB1	physical association	0.560	3
TNS2	physical association	0.560	3
TXLNB	physical association	0.560	3
PATJ	direct interaction	0.440	9
GRIP1	direct interaction	0.440	5
MAGI2	direct interaction	0.440	5
GRIP2	direct interaction	0.440	4
DLG1	direct interaction	0.440	3
DLG3	direct interaction	0.440	3
DLG4	direct interaction	0.440	3
FRMPD2	direct interaction	0.440	3
IL16	direct interaction	0.440	3
LNX1	direct interaction	0.440	3
MPDZ	direct interaction	0.440	3
NHERF4	direct interaction	0.440	3
SCRIB	direct interaction	0.440	3
WHRN	direct interaction	0.440	3

BioGRID (110 interactions; top human partners by supporting records): GIT1 (Affinity Capture-MS; 3 records), PLEKHH2 (Two-hybrid; 3 records), PTK2 (Affinity Capture-MS; 3 records), RUNX1T1 (Two-hybrid; 3 records), ARHGEF6 (Affinity Capture-MS; 2 records), ARHGEF7 (Affinity Capture-MS; 2 records), ATXN2 (Affinity Capture-MS; 2 records), CCDC6 (Affinity Capture-MS; 2 records), CDK5RAP2 (Affinity Capture-MS; 2 records), CEP68 (Affinity Capture-MS; 2 records), DCP1B (Affinity Capture-MS; 2 records), EDC3 (Affinity Capture-MS; 2 records), GIT2 (Affinity Capture-MS; 2 records), HOXC9 (Two-hybrid; 2 records), LIMD1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

1 signaling 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 113 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	37.1×	2e-05
Unblocking of NMDA receptors, glutamate binding and activation	5	35.3×	2e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	35.3×	2e-05
Assembly and cell surface presentation of NMDA receptors	10	33.0×	6e-11
Dopamine Neurotransmitter Release Cycle	5	32.2×	2e-05
Long-term potentiation	5	30.9×	2e-05
Neurexins and neuroligins	11	28.1×	5e-11
Protein-protein interactions at synapses	7	24.1×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	53.8×	1e-12
receptor clustering	8	46.2×	2e-09
protein localization to synapse	6	42.6×	7e-07
cell-cell junction organization	5	28.9×	6e-05
regulation of postsynaptic membrane neurotransmitter receptor levels	6	27.5×	9e-06
protein-containing complex assembly	11	11.6×	6e-07
cell-cell adhesion	12	11.3×	2e-07

Disease & clinical

Genetic variants

Variant evidence for LPXN: 61 ClinVar records (0 pathogenic / likely pathogenic); 5 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 1,483):

Position(s)	Effect	Δscore	Sites
11:58551063–58551064	donor_loss	1.0000	5
11:58551067	donor_gain	1.0000
11:58551233–58551234	acceptor_loss	1.0000	6
11:58551239–58551240	acceptor_gain	1.0000	2
11:58554839–58554840	donor_loss	1.0000	5
11:58554941–58554942	acceptor_loss	1.0000	6
11:58554943	acceptor_gain	1.0000
11:58570554–58570555	donor_loss	1.0000	4
11:58570714–58570715	acceptor_loss	1.0000	2
11:58570721	acceptor_gain	1.0000

AlphaMissense

805 missense substitutions predicted likely pathogenic (of 2,567 scored), across 197 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H231	8	0.985	0.996
H290	8	0.983	0.995
F294	8	0.976	0.995
D261	8	0.969	0.985
H234	8	0.968	0.992
H172	8	0.963	0.989
F235	8	0.962	0.996
H349	8	0.960	0.994
F244	8	0.949	0.991
H352	8	0.925	0.970
F176	8	0.920	0.990
F353	8	0.919	0.987
F303	8	0.914	0.984
H175	8	0.908	0.967
D202	8	0.811	0.879
D5	8	0.779	0.908
C237	7	0.998	0.999
C293	7	0.995	0.998
C296	7	0.995	0.998
C355	7	0.995	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	favorable	0.000374

Disease associations

OMIM: gene MIM:605390 | disease phenotypes:

GWAS associations

5 associations:

Study	Trait	p-value
GCST001725_9	Inflammatory bowel disease	7e-10
GCST007269_324	Pulse pressure	2e-8
GCST001826_12	Lymphoma	4e-8
GCST001826_11	Lymphoma	1e-7
GCST004133_23	Ulcerative colitis	9e-6

EFO canonical traits (from GWAS)

1 canonical traits:

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 (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

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	increases reaction, increases methylation, affects binding	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	decreases expression, affects cotreatment	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	affects cotreatment, decreases expression	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for LPXN across ~30M SureChEMBL compounds — explore on Sugi Predict.