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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NCAN
neurocan
Chromosome 19 · 19p13.11
NCBI Gene: 1463Ensembl: ENSG00000130287.15HGNC: HGNC:2465UniProt: O14594
46PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GO:0005615synapseperineuronal netskeletal system developmentmetabolic diseasechronic bronchitishyperlipidemiatooth disease
✦AI Summary

NCAN (neurocan) is a chondroitin sulfate proteoglycan that modulates neuronal development and brain structure. During development, NCAN binds to neural cell adhesion molecules (NG-CAM and N-CAM) and hyaluronic acid to regulate neuronal adhesion and neurite growth, functioning as a component of the perineuronal net and extracellular matrix 1. NCAN variants significantly associate with brain structure variation, particularly in white matter volume of temporoparietal and inferior frontal regions in adults, and grey matter volumes in infants 2. The protein shows robust associations with cognitive function, with plasma NCAN levels linked to digit symbol substitution test performance, partially mediated through structural brain phenotypes 3. NCAN genetic variants contribute to bipolar disorder susceptibility as a polygenic risk factor 4. Elevated circulating NCAN levels associate with depression-like behavior in primate models and may serve as a potential biomarker for major depressive disorder through inflammatory pathways 5. Additionally, NCAN variants show associations with serum lipid levels in population studies 6. Proteomic analyses identify NCAN among the most significantly associated proteins with brain structure variation, implicating roles in neurogenesis and neuronal function 7. The gene represents a candidate locus for developmental dyslexia 2, suggesting critical involvement in neurodevelopmental processes.

Sources cited
1
CSPGs including NCAN are components of the extracellular matrix and perineuronal nets that regulate neuronal plasticity
PMID: 12424383
2
NCAN variants (rs1064395) associate with white matter and grey matter volumes in brain regions and is a candidate gene for developmental dyslexia
PMID: 28839234
3
Plasma NCAN levels associate with cognitive function (DSST performance) and this association is partially mediated by brain structural phenotypes
PMID: 38762535
4
NCAN variants show genome-wide significant associations with bipolar disorder susceptibility as polygenic risk factors
PMID: 23663951
5
Elevated NCAN levels are associated with depressive-like behavior in primate models and identified as a potential biomarker for major depressive disorder
PMID: 40081592
6
NCAN SNPs and their gene-gene interactions associate with serum lipid levels and hyperlipidemia risk
PMID: 32568739
7
NCAN shows the most associations among 1143 proteins with 256 brain structure measures and is implicated in neurogenesis and neuronal function
PMID: 40456753
Disease Associationsⓘ20
metabolic diseaseOpen Targets
0.29Weak
chronic bronchitisOpen Targets
0.29Weak
hyperlipidemiaOpen Targets
0.27Weak
tooth diseaseOpen Targets
0.26Weak
familial hypercholesterolemiaOpen Targets
0.10Weak
familial hyperlipidemiaOpen Targets
0.09Suggestive
Abnormality of the skeletal systemOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.08Suggestive
Nijmegen breakage syndromeOpen Targets
0.08Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.07Suggestive
alcoholic liver diseaseOpen Targets
0.06Suggestive
liver diseaseOpen Targets
0.06Suggestive
Disorder of lipid metabolismOpen Targets
0.06Suggestive
bipolar disorderOpen Targets
0.06Suggestive
Merkel cell skin cancerOpen Targets
0.05Suggestive
gliomaOpen Targets
0.05Suggestive
esophageal varicesOpen Targets
0.05Suggestive
AscitesOpen Targets
0.05Suggestive
bipolar I disorderOpen Targets
0.05Suggestive
schizophreniaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
HAPLN1Shared pathway100%HAPLN3Shared pathway100%HAPLN2Shared pathway100%PTPRZ1Protein interaction98%NCAM1Protein interaction97%L1CAMProtein interaction97%
Tissue Expression6 tissues
Brain
100%
Liver
0%
Bone Marrow
0%
Ovary
0%
Lung
0%
Heart
0%
Gene Interaction Network
Click a node to explore
NCANHAPLN1HAPLN3HAPLN2PTPRZ1NCAM1L1CAM
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O14594
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.53Moderately Constrained
pLIⓘ
0.23Tolerant
Observed/Expected LoF0.41 [0.32–0.53]
RankingsWhere NCAN stands among ~20K protein-coding genes
  • #9,353of 20,598
    Most Researched46
  • #3,320of 17,882
    Most Constrained (LOEUF)0.53 · top quartile
Genes detectedNCAN
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Genetics of bipolar disorder.
PMID: 23663951
Lancet · 2013
1.00
2
Atlas of Proteomic signatures of brain structure and its links to brain disorders.
PMID: 40456753
Nat Commun · 2025
0.90
3
Reactivation of ocular dominance plasticity in the adult visual cortex.
PMID: 12424383
Science · 2002
0.80
4
Association of the
PMID: 32568739
Aging (Albany NY) · 2020
0.70
5
The circulating proteome and brain health: Mendelian randomisation and cross-sectional analyses.
PMID: 38762535
Transl Psychiatry · 2024
0.60