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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NRGN
neurogranin
Chromosome 11 · 11q24.2
NCBI Gene: 4900Ensembl: ENSG00000154146.14HGNC: HGNC:8000UniProt: Q92686
73PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Swiss-Prot Reviewed
nervous system developmentcytosolsignal transductioncalmodulin bindingschizophrenianeurodegenerative diseasesmoking initiationattention deficit hyperactivity disorder
✦AI Summary

NRGN encodes neurogranin, a brain-specific 78-amino acid postsynaptic protein that functions as a calmodulin-binding substrate in calcium-independent signaling cascades 1. The protein acts as a 'third messenger' in protein kinase C-mediated pathways during synaptic development and plasticity, particularly in telencephalic neurons 1. NRGN expression is regulated by thyroid hormone through a T3-responsive element in its first intron, suggesting involvement in thyroid hormone-dependent neuronal processes 2. The gene shows significant clinical relevance in neuropsychiatric and neurodegenerative diseases. Genetic variants, particularly rs12807809, are associated with schizophrenia risk and altered hippocampal functional connectivity 34. Reduced NRGN expression correlates with the high-risk haplotype and may contribute to schizophrenia pathophysiology 4. In Alzheimer's disease, NRGN serves as a neurodegeneration biomarker, with elevated levels in neuron-derived extracellular vesicles correlating with disease progression and cognitive decline 56. Additionally, NRGN appears to modulate immune responses in hepatocellular carcinoma by promoting TGF-β1 secretion, suggesting broader roles beyond neuronal function 7. These findings establish NRGN as both a critical synaptic regulatory protein and a clinically relevant biomarker across multiple disease contexts.

Sources cited
1
NRGN encodes a brain-specific 78-amino acid postsynaptic protein expressed in telencephalic neurons
PMID: 9143500
2
NRGN is regulated by thyroid hormone through a T3-responsive element in its first intron
PMID: 9886843
3
NRGN genetic variants (rs12807809) are associated with schizophrenia and altered hippocampal functional connectivity
PMID: 30953482
4
Reduced NRGN expression correlates with high-risk haplotype and schizophrenia risk
PMID: 22461181
5
NRGN serves as a biomarker in neuron-derived extracellular vesicles for Alzheimer's disease
PMID: 37842184
6
NRGN levels correlate with Alzheimer's disease progression and cognitive decline
PMID: 38695174
7
NRGN modulates immune responses in hepatocellular carcinoma by promoting TGF-β1 secretion
PMID: 40316076
Disease Associationsⓘ20
schizophreniaOpen Targets
0.47Moderate
neurodegenerative diseaseOpen Targets
0.44Moderate
smoking initiationOpen Targets
0.41Moderate
attention deficit hyperactivity disorderOpen Targets
0.40Weak
substance abuseOpen Targets
0.33Weak
autism spectrum disorderOpen Targets
0.29Weak
major depressive disorderOpen Targets
0.24Weak
bipolar disorderOpen Targets
0.24Weak
anorexia nervosaOpen Targets
0.23Weak
obsessive-compulsive disorderOpen Targets
0.23Weak
Tourette syndromeOpen Targets
0.23Weak
intelligenceOpen Targets
0.23Weak
Alzheimer diseaseOpen Targets
0.12Weak
Creutzfeldt Jacob DiseaseOpen Targets
0.09Suggestive
infectionOpen Targets
0.09Suggestive
deliriumOpen Targets
0.08Suggestive
dementiaOpen Targets
0.07Suggestive
7q11.23 microduplication syndromeOpen Targets
0.07Suggestive
Monoamine oxidase A deficiencyOpen Targets
0.07Suggestive
schizophrenia 19Open Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CALM3Protein interaction99%CALML6Protein interaction99%CALML3Protein interaction99%CALML5Protein interaction99%CALML4Protein interaction99%CALM1Protein interaction93%
Tissue Expression6 tissues
Brain
100%
Lung
11%
Bone Marrow
8%
Heart
2%
Ovary
1%
Liver
1%
Gene Interaction Network
Click a node to explore
NRGNCALM3CALML6CALML3CALML5CALML4CALM1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q92686
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.54LoF Tolerant
pLIⓘ
0.48Tolerant
Observed/Expected LoF0.00 [0.00–1.54]
RankingsWhere NRGN stands among ~20K protein-coding genes
  • #6,490of 20,598
    Most Researched73
  • #15,396of 17,882
    Most Constrained (LOEUF)1.54
Genes detectedNRGN
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Association between NRGN gene polymorphism and resting-state hippocampal functional connectivity in schizophrenia.
PMID: 30953482
BMC Psychiatry · 2019
1.00
2
Structure, organization, and chromosomal mapping of the human neurogranin gene (NRGN).
PMID: 9143500
Genomics · 1997
0.90
3
Synaptic proteins in neuron-derived extracellular vesicles as biomarkers for Alzheimer's disease: novel methodology and clinical proof of concept.
PMID: 37842184
Extracell Vesicles Circ Nucl Acids · 2023
0.80
4
Neurogranin facilitates maintaining the immunosuppressive state of hepatocellular carcinoma by promoting TGF-β1 secretion.
PMID: 40316076
Int J Biol Macromol · 2025
0.70
5
The human RC3 gene homolog, NRGN contains a thyroid hormone-responsive element located in the first intron.
PMID: 9886843
Endocrinology · 1999
0.60