NPTX1

Chr 17

neuronal pentraxin 1

Also known as: NP1, SCA50

Neuronal pentraxin 1 mediates uptake of synaptic material during synapse remodeling and synaptic clustering of AMPA glutamate receptors at excitatory synapses. Mutations cause spinocerebellar ataxia 50 with autosomal dominant inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.48), suggesting intolerance to complete protein loss.

ResearchSummary from RefSeq, OMIM, UniProt
DNmechanismLOEUF 0.48
Clinical SummaryNPTX1
🧬
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.
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.625
Z-score 3.03
OE 0.19 (0.080.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.87Z-score
OE missense 0.67 (0.590.76)
168 obs / 251.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.19 (0.080.48)
00.351.4
Missense OE0.67 (0.590.76)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 3 / 16.1Missense obs/exp: 168 / 251.5Syn Z: -0.10
DN
0.5967th %ile
GOF
0.5562th %ile
LOF
0.50top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DN1 literature citation

Literature Evidence

DNWe suggest that variants in NPTX1 can lead to cerebellar ataxia due to endoplasmic reticulum stress, mediated by ATF6, and associated to a destabilization of NP1 polymers in a dominant-negative manner for one of the variants.PMID:34788392

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗