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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NPTX1
neuronal pentraxin 1
Chromosome 17 · 17q25.3
NCBI Gene: 4884Ensembl: ENSG00000171246.7HGNC: HGNC:7952UniProt: Q15818
47PubMed Papers
21Diseases
0Drugs
6Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
glutamatergic synapseaxonogenesis involved in innervationcentral nervous system developmentchemical synaptic transmissionspinocerebellar ataxia 50Irritabilitygenetic disordermorbid obesity
✦AI Summary

NPTX1 (neuronal pentraxin 1) is a secreted pentraxin family protein primarily expressed in the nervous system 1 with established roles in synaptic function and emerging disease relevance beyond neurology. **Primary Function and Mechanism:** NPTX1 mediates synaptic material uptake and AMPA glutamate receptor clustering at excitatory synapses 1. The protein functions through receptor-ligand interactions; it binds AMIGO2 to regulate cellular signaling 2 and stabilizes β-catenin protein levels to control cell proliferation via MEK-mediated pathways 3. **Disease Relevance:** NPTX1 mutations cause spinocerebellar ataxia 50 (SCA50), an autosomal dominant cerebellar ataxia 4. Beyond neurological disease, NPTX1 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) where NPTX1-AMIGO2 signaling drives metastatic colonization by enhancing HIF1α nuclear retention under hypoxic conditions 2. NPTX1 hypermethylation occurs in lung cancer, correlating with reduced expression and poor prognosis 5. Additionally, plasma NPTX1 shows tau pathology-dependent changes in preclinical Alzheimer's disease, emerging as a novel synaptic and neuroinflammation biomarker 6. **Clinical Significance:** NPTX1-targeting monoclonal antibodies substantially reduced PDAC liver metastasis in preclinical models 2. NPTX1 upregulation in hypoxic adipocytes enhances stem cell activation and adipose graft survival 7, suggesting therapeutic applications in regenerative medicine.

Sources cited
1
NPTX1 mutations cause SCA50, an autosomal dominant cerebellar ataxia
PMID: 37479376
2
NPTX1-AMIGO2 signaling drives PDAC metastatic colonization and HIF1α nuclear retention; therapeutic NPTX1 antibodies reduce liver metastasis
PMID: 39028915
3
NPTX1 stabilizes β-catenin protein levels to mediate MEK-controlled proliferation in neuroglial cells
PMID: 40240141
4
Plasma NPTX1 shows tau PET-dependent longitudinal changes as a novel synaptic and neuroinflammation biomarker in preclinical Alzheimer's disease
PMID: 39385222
5
NPTX1 upregulation in hypoxic adipocytes facilitates ADSC activation and improves adipose tissue graft survival
PMID: 38789811
6
NPTX1 promoter hypermethylation in lung cancer correlates with reduced expression and poor overall survival
PMID: 25646694
7
NPTX1 is a nervous system-specific pentraxin protein that mediates synaptic material uptake and is conserved across species
PMID: 8884281
8
NPTX1 is a long pentraxin family member with emerging roles in immune regulation and inflammation
PMID: 37832905
Disease Associationsⓘ21
spinocerebellar ataxia 50Open Targets
0.59Moderate
IrritabilityOpen Targets
0.48Moderate
genetic disorderOpen Targets
0.34Weak
morbid obesityOpen Targets
0.32Weak
injuryOpen Targets
0.16Weak
joint diseaseOpen Targets
0.11Weak
Abnormality of the skeletal systemOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.08Suggestive
melanomaOpen Targets
0.08Suggestive
gastric cancerOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.07Suggestive
smoking initiationOpen Targets
0.06Suggestive
Alzheimer diseaseOpen Targets
0.05Suggestive
breast cancerOpen Targets
0.05Suggestive
Moyamoya diseaseOpen Targets
0.05Suggestive
BlindnessOpen Targets
0.05Suggestive
breast carcinomaOpen Targets
0.05Suggestive
glioblastoma multiformeOpen Targets
0.04Suggestive
type 2 diabetes mellitusOpen Targets
0.04Suggestive
pachyonychia congenitaOpen Targets
0.04Suggestive
Spinocerebellar ataxia 50UniProt
Pathogenic Variants6
NM_002522.4(NPTX1):c.1165G>A (p.Gly389Arg)Pathogenic
not provided|Spinocerebellar ataxia 50|Inborn genetic diseases
★★☆☆2025→ Residue 389
NM_002522.4(NPTX1):c.1261_1287del (p.Thr421_Arg429del)Likely pathogenic
Spinocerebellar ataxia 50
★☆☆☆2024→ Residue 421
NM_002522.4(NPTX1):c.428G>T (p.Arg143Leu)Likely pathogenic
Spinocerebellar ataxia 50
★☆☆☆2024→ Residue 143
NM_002522.4(NPTX1):c.539G>T (p.Arg180Leu)Likely pathogenic
Spinocerebellar ataxia 50
★☆☆☆2024→ Residue 180
NM_002522.4(NPTX1):c.1109A>G (p.Gln370Arg)Likely pathogenic
Spinocerebellar ataxia 50
★☆☆☆2023→ Residue 370
NM_002522.4(NPTX1):c.980A>G (p.Glu327Gly)Pathogenic
Spinocerebellar ataxia 50
☆☆☆☆2022→ Residue 327
View on ClinVar ↗
Related Genes
SLITRK2Protein interaction81%RCN2Protein interaction73%C1QL3Shared pathway18%C1QL2Shared pathway17%RAPSNShared pathway15%MBPShared pathway14%
Tissue Expression6 tissues
Brain
100%
Lung
2%
Bone Marrow
1%
Ovary
0%
Liver
0%
Heart
0%
Gene Interaction Network
Click a node to explore
NPTX1SLITRK2RCN2C1QL3C1QL2RAPSNMBP
PROTEIN STRUCTURE
Preparing viewer…
PDB6YPE · 1.45 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.52Moderately Constrained
pLIⓘ
0.96Intolerant
Observed/Expected LoF0.31 [0.20–0.52]
RankingsWhere NPTX1 stands among ~20K protein-coding genes
  • #9,247of 20,598
    Most Researched47
  • #3,401of 5,498
    Most Pathogenic Variants6
  • #3,216of 17,882
    Most Constrained (LOEUF)0.52 · top quartile
Genes detectedNPTX1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Autosomal dominant cerebellar ataxias: new genes and progress towards treatments.
PMID: 37479376
Lancet Neurol · 2023
1.00
2
A Targetable Secreted Neural Protein Drives Pancreatic Cancer Metastatic Colonization and HIF1α Nuclear Retention.
PMID: 39028915
Cancer Discov · 2024
0.90
3
IRX2 and NPTX1 differential regulation of β-catenin underlies MEK-mediated proliferation in human neuroglial cells.
PMID: 40240141
Genes Dev · 2025
0.80
4
Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer's disease.
PMID: 39385222
Mol Neurodegener · 2024
0.70
5
NPTX1 Mediates the Facilitating Effects of Hypoxia-Stimulated Human Adipocytes on Adipose-Derived Stem Cell Activation and Autologous Adipose Graft Survival Rate.
PMID: 38789811
Aesthetic Plast Surg · 2024
0.60