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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PITPNM3
PITPNM family member 3
Chromosome 17 · 17p13.2-p13.1
NCBI Gene: 83394Ensembl: ENSG00000091622.16HGNC: HGNC:21043UniProt: A1A5C9
26PubMed Papers
21Diseases
0Drugs
3Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingcalcium ion bindingreceptor tyrosine kinase bindingcytoplasmCone rod dystrophyRod-cone dystrophycone-rod dystrophycone dystrophy
✦AI Summary

PITPNM3 (phosphatidylinositol transfer protein 3) functions as a membrane-associated protein that catalyzes phospholipid transfer between membranes and serves as a functional receptor for the chemokine CCL18 1. The protein mediates CCL18-induced signaling cascades that promote cancer metastasis through multiple mechanisms. Upon CCL18 binding, PITPNM3 activates intracellular calcium signaling and forms complexes with Pyk2 kinase, leading to Src kinase activation and integrin clustering 12. This signaling cascade enhances cancer cell adherence to extracellular matrix, migration, invasion, and epithelial-mesenchymal transition (EMT) 3. PITPNM3 also activates NF-κB signaling pathways, promoting the production of pro-metastatic cytokines IL-6 and IL-8 43. The clinical significance of PITPNM3 is substantial, as its expression correlates with tumor metastasis, poor differentiation, and chemotherapy resistance in multiple cancer types including breast and hepatocellular carcinomas 13. Recent therapeutic developments include PITPNM3-selective small molecule inhibitors that effectively reduce cancer metastasis in preclinical models, establishing PITPNM3 as a promising therapeutic target for metastatic cancers 5.

Sources cited
1
PITPNM3 serves as a functional receptor for CCL18 and mediates calcium signaling
PMID: 21481794
2
PITPNM3 forms complexes with Pyk2 and activates Src kinase upon CCL18 binding
PMID: 24142406
3
PITPNM3 expression correlates with tumor metastasis and activates NF-κB signaling
PMID: 26449829
4
CCL18-PITPNM3 signaling enhances IL-6 and IL-8 production via NF-κB activation
PMID: 36418470
5
Small molecule PITPNM3 inhibitors reduce cancer metastasis in preclinical models
PMID: 36285700
Disease Associationsⓘ21
Cone rod dystrophyOpen Targets
0.52Moderate
Rod-cone dystrophyOpen Targets
0.37Weak
cone-rod dystrophyOpen Targets
0.37Weak
Cerebral arteriovenous malformationOpen Targets
0.34Weak
cone dystrophyOpen Targets
0.34Weak
chronic pancreatitisOpen Targets
0.26Weak
musculoskeletal system diseaseOpen Targets
0.21Weak
cone-rod dystrophy, dominantOpen Targets
0.19Weak
Retinal dystrophyOpen Targets
0.19Weak
Benign Thyroid Gland NeoplasmOpen Targets
0.14Weak
retinitis pigmentosaOpen Targets
0.14Weak
coronary artery diseaseOpen Targets
0.08Suggestive
oral squamous cell carcinomaOpen Targets
0.08Suggestive
intrahepatic cholangiocarcinomaOpen Targets
0.07Suggestive
Gorham-Stout diseaseOpen Targets
0.07Suggestive
cancerOpen Targets
0.06Suggestive
hypothyroidismOpen Targets
0.06Suggestive
hepatocellular carcinomaOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.05Suggestive
breast cancerOpen Targets
0.05Suggestive
Cone-rod dystrophy 5UniProt
Pathogenic Variants3
NM_031220.4(PITPNM3):c.61C>T (p.Arg21Ter)Likely pathogenic
not provided
★☆☆☆2023→ Residue 21
NM_031220.4(PITPNM3):c.1657_1660dup (p.Tyr554Ter)Pathogenic
Cone dystrophy
★☆☆☆2020→ Residue 554
NM_031220.4(PITPNM3):c.274C>T (p.Arg92Ter)Pathogenic
Cerebral arteriovenous malformation
★☆☆☆2018→ Residue 92
View on ClinVar ↗
Related Genes
CCL18Protein interaction100%PITPNAProtein interaction93%PITPNBProtein interaction93%PTK2BProtein interaction88%GUCY2DProtein interaction82%UNC119Protein interaction82%
Tissue Expression6 tissues
Ovary
100%
Brain
20%
Lung
5%
Liver
4%
Heart
2%
Bone Marrow
2%
Gene Interaction Network
Click a node to explore
PITPNM3CCL18PITPNAPITPNBPTK2BGUCY2DUNC119
PROTEIN STRUCTURE
Preparing viewer…
PDB9C38 · 1.95 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.35Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.26 [0.19–0.35]
RankingsWhere PITPNM3 stands among ~20K protein-coding genes
  • #12,849of 20,598
    Most Researched26
  • #4,135of 5,498
    Most Pathogenic Variants3
  • #1,572of 17,882
    Most Constrained (LOEUF)0.35 · top 10%
Genes detectedPITPNM3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
CCL18 signaling from tumor-associated macrophages activates fibroblasts to adopt a chemoresistance-inducing phenotype.
PMID: 36418470
Oncogene · 2023
1.00
2
CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3.
PMID: 21481794
Cancer Cell · 2011
0.90
3
CCL18 in the Progression of Cancer.
PMID: 33114763
Int J Mol Sci · 2020
0.80
4
CCL18/PITPNM3 enhances migration, invasion, and EMT through the NF-κB signaling pathway in hepatocellular carcinoma.
PMID: 26449829
Tumour Biol · 2016
0.70
5
Small Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3.
PMID: 36285700
Adv Sci (Weinh) · 2022
0.60