NPTX1

Chr 17

neuronal pentraxin 1

Also known as: NP1, SCA50

NCBI Gene: 4884 ENSG00000171246 UniProt: Q15818

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

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]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.48

Clinical Summary— NPTX1

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Gene-Disease Validity (ClinGen)

autosomal dominant cerebellar ataxia · ADLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.63) — some intolerance to loss-of-function variants.

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 52 VUS of 68 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.87Z-score

OE missense 0.67 (0.59–0.76)

168 obs / 251.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.19 (0.08–0.48)

0≤0.351.4

Missense OE?0.67 (0.59–0.76)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 3 / 16.1Missense obs/exp: 168 / 251.5Syn Z: -0.10

This gene — mechanism propensity

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.1

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

References

1.PMID 34788392 ↗

ClinVar Variant Classifications

68 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic5

VUS52

Likely Benign6

Benign2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	1
Likely Pathogenic	4	1	0	5
VUS	52	0	0	52
Likely Benign	4	1	1	6
Benign	0	0	2	2
Total	61	2	3	66

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap NPTX1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →