NPTX2

Chr 7

neuronal pentraxin 2

Also known as: NARP, NP-II, NP2

NCBI Gene: 4885ENSG00000106236UniProt: P47972

This gene encodes a member of the family of neuronal petraxins, synaptic proteins that are related to C-reactive protein. This protein is involved in excitatory synapse formation. It also plays a role in clustering of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors at established synapses, resulting in non-apoptotic cell death of dopaminergic nerve cells. Up-regulation of this gene in Parkinson disease (PD) tissues suggests that the protein may be involved in the pathology of PD. [provided by RefSeq, Feb 2009]

98
ClinVar variants
14
Pathogenic / LP
0.03
pLI score
0
Active trials
Clinical Summary— NPTX2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 81 VUS of 98 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.73LOEUF
pLI 0.031
Z-score 2.29
OE 0.35 (0.18–0.73)
Tolerant

Typical tolerance to LoF variation

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.
0.68Z-score
OE missense 0.87 (0.78–0.98)
194 obs / 222.5 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.0.35 (0.18–0.73)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.78–0.98)
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.1.06
0≤1.21.6
LoF obs/exp: 5 / 14.4Missense obs/exp: 194 / 222.5Syn Z: -0.45

ClinVar Variant Classifications

98 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
VUS81
Likely Benign3
14
Pathogenic
81
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
0
0
0
VUS
0
76
5
0
81
Likely Benign
0
3
0
0
3
Benign
0
0
0
0
0
Total07919098

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

View in ClinVar →

Protein Context — Lollipop Plot

NPTX2 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Biomarker treatment effects in two phase 3 trials of gantenerumab.
Bittner T et al.·Alzheimers Dement
2025
Neuronal pentraxin-2 (NPTX2) serum levels during an acute psychotic episode in patients with schizophrenia.
Göverti D et al.·Psychopharmacology (Berl)
2022Cohort
Circulating NPTX2 methylation as a non-invasive biomarker for prognosis and monitoring of metastatic pancreatic cancer.
García-Ortiz MV et al.·Clin Epigenetics
2023
NPTX2 is associated with neoadjuvant therapy response in rectal cancer.
Karagkounis G et al.·J Surg Res
2016
Early Epigenetic Markers for Precision Medicine.
Dumitrescu RG·Methods Mol Biol
2018Review
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
Serum NPTX2 and cognitive impairment in geriatric diabetes.
Çadırcı K et al.·Biomol Biomed
2025
Association between serum NPTX2 and cognitive function in patients with vascular dementia.
Shao K et al.·Brain Behav
2020Cohort
Cerebrospinal fluid proteome profiling across the Alzheimer's disease continuum: a step towards solving the equation for 'X'.
Weiner S et al.·Mol Neurodegener
2025
Neuronal pentraxin 2 correlates with neurodegeneration but not cognition in idiopathic normal pressure hydrocephalus (iNPH).
Patel M et al.·Neurol Neurochir Pol
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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