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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LPXN
leupaxin
Chromosome 11 · 11q12.1
NCBI Gene: 9404Ensembl: ENSG00000110031.13HGNC: HGNC:14061UniProt: B7Z5P7
53PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
transcription coregulator activityprotein bindingnegative regulation of B cell receptor signaling pathwaypodosomemyopathyhypertrophic cardiomyopathymathematical abilitybreast cancer
✦AI Summary

LPXN (leupaxin) is a focal adhesion adaptor protein with multifaceted regulatory roles in cell migration, transcription, and metabolism. As a transcriptional coactivator, LPXN interacts with hepatic nuclear factor 4α (HNF4α) to promote hepatic gluconeogenesis 1, while also functioning as a coactivator for androgen receptor and serum response factor. LPXN regulates cell adhesion and migration through its interaction with paxillin and Kindlin-3 in integrin adhesion complexes; disruption of Kindlin-3-LPXN binding paradoxically enhances macrophage motility and phagocytosis 2. In prostate cancer, LPXN associates with Pyk2 and PTP-PEST to form signaling complexes that promote migration via Rho GTPase activation 3. LPXN negatively regulates B-cell antigen receptor signaling through Lyn-mediated phosphorylation at Tyr72, suppressing JNK and p38 MAPK activation 4. Pathologically, LPXN expression is elevated in bladder cancer and promotes proliferation, invasion, and angiogenesis through the PI3K/AKT pathway 5. In hepatocellular and renal cancers, LPXN suppression enhances migration and metastasis 6, while in leukemia, LPXN knockdown suppresses proliferation and enhances chemosensitivity 7. Additionally, LPXN promotes lipid storage by stabilizing CIDEC and preventing its ubiquitin-proteasome degradation 8.

Sources cited
1
LPXN acts as a coactivator for HNF4α in regulating hepatic gluconeogenesis and glucose metabolism
PMID: 39603504
2
LPXN directly interacts with Kindlin-3 and paxillin; disruption enhances macrophage migration and phagocytosis
PMID: 32094207
3
LPXN associates with Pyk2 and PTP-PEST to form signaling complexes regulating prostate cancer cell migration via Rho GTPase
PMID: 17329398
4
LPXN negatively regulates BCR signaling through Lyn-mediated tyrosine phosphorylation at Tyr72
PMID: 17640867
5
LPXN is elevated in bladder cancer and promotes proliferation, invasion, and angiogenesis through PI3K/AKT pathway
PMID: 29975926
6
HLF regulates LPXN expression to suppress cancer cell migration and lung metastasis through collagen-cytoskeleton integration
PMID: 40473600
7
LPXN silencing suppresses acute monocytic leukemia cell proliferation and enhances chemosensitivity via JNK and p38 MAPK activation
PMID: 33168498
8
LPXN promotes lipid storage by reducing CIDEC ubiquitination and inhibiting its proteasomal degradation
PMID: 38159847
Disease Associationsⓘ20
myopathyOpen Targets
0.32Weak
hypertrophic cardiomyopathyOpen Targets
0.29Weak
mathematical abilityOpen Targets
0.20Weak
breast cancerOpen Targets
0.09Suggestive
posterior cortical atrophyOpen Targets
0.07Suggestive
open-angle glaucomaOpen Targets
0.07Suggestive
isolated agammaglobulinemiaOpen Targets
0.06Suggestive
classic Hodgkin lymphomaOpen Targets
0.06Suggestive
Hodgkins lymphomaOpen Targets
0.06Suggestive
combined immunodeficiency with skin granulomasOpen Targets
0.05Suggestive
BENTA diseaseOpen Targets
0.05Suggestive
macroglobulinemia, Waldenstrom, 1Open Targets
0.05Suggestive
immunodeficiency 86Open Targets
0.05Suggestive
immunodeficiency, common variable, 14Open Targets
0.05Suggestive
severe combined immunodeficiency due to CARD11 deficiencyOpen Targets
0.05Suggestive
hyper-IgM syndrome type 3Open Targets
0.05Suggestive
immunodeficiency 18Open Targets
0.05Suggestive
immunodeficiency 62Open Targets
0.05Suggestive
combined immunodeficiency due to CTPS1 deficiencyOpen Targets
0.05Suggestive
immunodeficiency, common variable, 4Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GIT1Protein interaction100%PTK2BProtein interaction91%PTPN12Protein interaction86%PSTPIP2Protein interaction86%ARHGEF6Protein interaction71%CD72Shared pathway29%
Tissue Expression6 tissues
Lung
100%
Liver
45%
Ovary
44%
Bone Marrow
34%
Heart
22%
Brain
18%
Gene Interaction Network
Click a node to explore
LPXNGIT1PTK2BPTPN12PSTPIP2ARHGEF6CD72
PROTEIN STRUCTURE
Preparing viewer…
PDB4XEK · 1.79 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.79LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.55 [0.39–0.79]
RankingsWhere LPXN stands among ~20K protein-coding genes
  • #8,451of 20,598
    Most Researched53
  • #6,486of 17,882
    Most Constrained (LOEUF)0.79
Genes detectedLPXN
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
SWI/SNF ATPase silenced HLF potentiates lung metastasis in solid cancers.
PMID: 40473600
Nat Commun · 2025
1.00
2
Leupaxin Promotes Bladder Cancer Proliferation, Metastasis, and Angiogenesis Through the PI3K/AKT Pathway.
PMID: 29975926
Cell Physiol Biochem · 2018
0.90
3
Interaction of Pyk2 and PTP-PEST with leupaxin in prostate cancer cells.
PMID: 17329398
Am J Physiol Cell Physiol · 2007
0.80
4
Leupaxin promotes hepatic gluconeogenesis and glucose metabolism by coactivation with hepatic nuclear factor 4α.
PMID: 39603504
Mol Metab · 2025
0.70
5
Macrophage Migration and Phagocytosis Are Controlled by Kindlin-3's Link to the Cytoskeleton.
PMID: 32094207
J Immunol · 2020
0.60