NPTX1

Chr 17AD

neuronal pentraxin 1

Also known as: NP1, SCA50

NCBI Gene: 4884ENSG00000171246UniProt: Q15818

NPTX1 is a member of the neuronal pentraxin gene family. Neuronal pentraxin 1 is similar to the rat NP1 gene which encodes a binding protein for the snake venom toxin taipoxin. Human NPTX1 mRNA is exclusively localized to the nervous system. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Spinocerebellar ataxia 50MIM #620158
AD
87
ClinVar variants
22
Pathogenic / LP
0.63
pLI score
0
Active trials
Clinical Summary— NPTX1
🧬
Gene-Disease Validity (ClinGen)
autosomal dominant cerebellar ataxia · ADLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.63) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 59 VUS of 87 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.48LOEUF
pLI 0.625
Z-score 3.03
OE 0.19 (0.08–0.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.87Z-score
OE missense 0.67 (0.59–0.76)
168 obs / 251.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.19 (0.08–0.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.59–0.76)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 3 / 16.1Missense obs/exp: 168 / 251.5Syn Z: -0.10

ClinVar Variant Classifications

87 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic6
VUS59
Likely Benign4
Benign2
16
Pathogenic
6
Likely Pathogenic
59
VUS
4
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
15
0
16
Likely Pathogenic
0
4
2
0
6
VUS
0
52
7
0
59
Likely Benign
0
3
1
0
4
Benign
0
0
0
2
2
Total06025287

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NPTX1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spinocerebellar ataxia 50

MIM #620158

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autosomal dominant cerebellar ataxias: new genes and progress towards treatments.
Coarelli G et al.·Lancet Neurol
2023Review
Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer's disease.
Zeng X et al.·Mol Neurodegener
2024
NPTX1 mutations trigger endoplasmic reticulum stress and cause autosomal dominant cerebellar ataxia.
Coutelier M et al.·Brain
2022
Targeted Proteomics upon Treatment with Tofersen Identifies Novel Response Markers for Superoxide Dismutase 1-Linked Amyotrophic Lateral Sclerosis.
Steffke C et al.·Ann Neurol
2025
Low synaptic and neurosecretory proteins in cerebrospinal fluid in early parkinsonian disease.
Jakobsson P et al.·J Neurol Sci
2025
As a downstream target of the AKT pathway, NPTX1 inhibits proliferation and promotes apoptosis in hepatocellular carcinoma.
Zhao Y et al.·Biosci Rep
2019
Development of a prognostic model based on the ceRNA network in Triple-Negative Breast cancer.
Zhu Y et al.·PeerJ
2025Functional
A Novel NPTX1 de novo Variant in a Late-Onset Ataxia Patient.
Deppe J et al.·Mov Disord
2022
Neuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia.
van der Ende EL et al.·J Neurol Neurosurg Psychiatry
2020
Development and verification of lymphangiogenesis score for prediction of prognosis and immune landscape in gastric cancer.
Liu S et al.·Front Immunol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Cerebrospinal fluid NPTX1 and NPTXR predict neurodegeneration and clinical progression in Alzheimer's disease.
Dai L et al.·Nat Commun
2026
SIGMAR1 Drives the Development of Neuropathic Pain by Promoting AMPA Receptor Membrane Trafficking Through Interacting with NPTX1 in Male Mice.
Ren J et al.·Neurosci Bull
2025
IRX2 and NPTX1 differential regulation of β-catenin underlies MEK-mediated proliferation in human neuroglial cells.
Chen A et al.·Genes Dev
2025🔓 Open Access
[Knockdown of NPTX1 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells].
Shuai T et al.·Beijing Da Xue Xue Bao Yi Xue Ban
2025
β-Elemene Inhibits Adrenocortical Carcinoma Cell Proliferation and Migration, and Induces Apoptosis by Up-Regulating miR-486-3p/Targeting NPTX1 Axis.
Lin Y et al.·Mol Carcinog
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools