NRN1

Chr 6

neuritin 1

Also known as: NRN, dJ380B8.2

NCBI Gene: 51299ENSG00000124785UniProt: Q9NPD7

This gene encodes a member of the neuritin family, and is expressed in postmitotic-differentiating neurons of the developmental nervous system and neuronal structures associated with plasticity in the adult. The expression of this gene can be induced by neural activity and neurotrophins. The encoded protein contains a consensus cleavage signal found in glycosylphoshatidylinositol (GPI)-anchored proteins. The encoded protein promotes neurite outgrowth and arborization, suggesting its role in promoting neuritogenesis. Overexpression of the encoded protein may be associated with astrocytoma progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

53
ClinVar variants
38
Pathogenic / LP
0.86
pLI score
0
Active trials
Clinical Summary— NRN1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.86) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
38 Pathogenic / Likely Pathogenic· 12 VUS of 53 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.
0.46LOEUF
pLI 0.860
Z-score 2.35
OE 0.00 (0.00–0.46)
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.
1.14Z-score
OE missense 0.64 (0.52–0.81)
53 obs / 82.2 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.0.00 (0.00–0.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.64 (0.52–0.81)
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.1.10
0≤1.21.6
LoF obs/exp: 0 / 6.4Missense obs/exp: 53 / 82.2Syn Z: -0.47

ClinVar Variant Classifications

53 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic4
VUS12
Likely Benign2
Benign1
34
Pathogenic
4
Likely Pathogenic
12
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
34
0
34
Likely Pathogenic
0
0
4
0
4
VUS
0
11
1
0
12
Likely Benign
0
2
0
0
2
Benign
0
1
0
0
1
Total01439053

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

View in ClinVar →

Protein Context — Lollipop Plot

NRN1 · 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
NEURITIN 1; NRN1
MIM #607409 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Exome sequencing identifies genes for socioeconomic status in 350,770 individuals.
Wu XR et al.·Proc Natl Acad Sci U S A
2025
HIF1α inhibitor 2-methoxyestradiol decreases NRN1 expression and represses in vivo and in vitro growth of patient-derived testicular germ cell tumor spheroids.
Namekawa T et al.·Cancer Lett
2020
NRN1 epistasis with BDNF and CACNA1C: mediation effects on symptom severity through neuroanatomical changes in schizophrenia.
Almodóvar-Payá C et al.·Brain Struct Funct
2024
Analysis and experimental validation of necroptosis-related molecular classification, immune signature and feature genes in Alzheimer's disease.
Lian P et al.·Apoptosis
2024
Neurotrophins role in depressive symptoms and executive function performance: Association analysis of NRN1 gene and its interaction with BDNF gene in a non-clinical sample.
Prats C et al.·J Affect Disord
2017
Nrn1 Overexpression Attenuates Retinal Ganglion Cell Apoptosis, Promotes Axonal Regeneration, and Improves Visual Function Following Optic Nerve Crush in Rats.
Huang T et al.·J Mol Neurosci
2021
The impact of DNA demethylation on the upregulation of the NRN1 and TNFAIP3 genes associated with advanced gastric cancer.
Wisnieski F et al.·J Mol Med (Berl)
2020
Integrated Proteomics to Understand the Role of Neuritin (NRN1) as a Mediator of Cognitive Resilience to Alzheimer's Disease.
Hurst C et al.·Mol Cell Proteomics
2023
Biomarkers in Schizophrenia: Current Approaches and New Developments-A Literature Review.
Sierakowska A et al.·Behav Neurol
2025Review
Ovarian cancer detection by DNA methylation in cervical scrapings.
Wu TI et al.·Clin Epigenetics
2019
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