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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CNTN3
contactin 3
Chromosome 3 · 3p12.3
NCBI Gene: 5067Ensembl: ENSG00000113805.10HGNC: HGNC:2173UniProt: Q9P232
19PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
neuron projectionextracellular regionplasma membranehepatitis B virus infectionpoisoningmastodyniacoronary artery disease
✦AI Summary

CNTN3 (contactin 3) is a cell adhesion molecule that mediates cell surface interactions during nervous system development and has neurite outgrowth-promoting activity 1. The protein functions through its extracellular domains, with the second Fibronectin domain (Fn2) mediating binding to the Amyloid Precursor Protein (APP), specifically to APP's copper binding domain 2. CNTN3 expression is developmentally regulated, peaking around birth and during infancy before declining in the adult brain 3. The protein shows differential expression patterns across various disease contexts. In tuberous sclerosis complex (TSC), CNTN3 is significantly down-regulated in cortical tubers during early postnatal development, which may contribute to neuropsychiatric comorbidities 3. In dementia, CNTN3 levels in cerebrospinal fluid are reduced in Parkinson's disease dementia/dementia with Lewy bodies compared to Alzheimer's disease, suggesting distinct alterations across neurodegenerative conditions 4. CNTN3 also shows dysregulation in various cancers, including colorectal cancer where it may serve as a diagnostic biomarker 5, and glioblastoma where it is underexpressed compared to lower-grade astrocytic tumors 6. The protein is subject to microRNA regulation, with miR-3675b directly targeting CNTN3's 3'-UTR 7.

Sources cited
1
CNTN3 mediates cell surface interactions during nervous system development and has neurite outgrowth-promoting activity
PMID: 25300137
2
The second Fibronectin domain (Fn2) in CNTN3 mediates APP binding, and the most important amino acids for binding reside on one face of CNTN3-Fn2
PMID: 31318883
3
CNTN3 expression peaks around birth and during infancy, declining in adult brain; it is down-regulated in TSC cortical tubers during early postnatal period
PMID: 35030990
4
CNTN3 levels in cerebrospinal fluid are reduced in PDD/DLB compared to AD, showing differential alterations across dementias
PMID: 39317877
5
CNTN3 is differentially expressed in colorectal cancer and may serve as a diagnostic biomarker
PMID: 32566650
6
CNTN3 is underexpressed in glioblastoma compared to lower-grade diffuse astrocytic gliomas
PMID: 32647207
7
miR-3675b directly targets and negatively regulates CNTN3 through its 3'-UTR
PMID: 23153516
Disease Associationsⓘ20
hepatitis B virus infectionOpen Targets
0.34Weak
poisoningOpen Targets
0.32Weak
mastodyniaOpen Targets
0.32Weak
coronary artery diseaseOpen Targets
0.31Weak
agingOpen Targets
0.30Weak
keratoconusOpen Targets
0.29Weak
attention deficit hyperactivity disorderOpen Targets
0.27Weak
substance abuseOpen Targets
0.27Weak
mathematical abilityOpen Targets
0.27Weak
ovarian dysfunctionOpen Targets
0.26Weak
knee fractureOpen Targets
0.26Weak
bile duct disorderOpen Targets
0.26Weak
Benign Ovarian NeoplasmOpen Targets
0.25Weak
smoking initiationOpen Targets
0.25Weak
tooth diseaseOpen Targets
0.24Weak
ThrombophlebitisOpen Targets
0.22Weak
neurodegenerative diseaseOpen Targets
0.21Weak
PhlebitisOpen Targets
0.21Weak
response to xenobiotic stimulusOpen Targets
0.18Weak
response to antibioticOpen Targets
0.17Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PTPRGProtein interaction99%APPProtein interaction72%CNTN5Co-mentioned in literature20%
Tissue Expression6 tissues
Liver
100%
Heart
62%
Brain
39%
Ovary
25%
Lung
7%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
CNTN3PTPRGAPPCNTN5
PROTEIN STRUCTURE
Preparing viewer…
PDB1WJ3 · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.67LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.52 [0.41–0.67]
RankingsWhere CNTN3 stands among ~20K protein-coding genes
  • #14,386of 20,598
    Most Researched19
  • #4,918of 17,882
    Most Constrained (LOEUF)0.67
Genes detectedCNTN3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.
PMID: 28600779
Hum Genet · 2017
1.00
2
Defining the binding interface of Amyloid Precursor Protein (APP) and Contactin3 (CNTN3) by site-directed mutagenesis.
PMID: 31318883
PLoS One · 2019
0.90
3
Down-regulation of the brain-specific cell-adhesion molecule contactin-3 in tuberous sclerosis complex during the early postnatal period.
PMID: 35030990
J Neurodev Disord · 2022
0.80
4
PMID: 32566650
Biomed Res Int · 2020
0.70
5
Contactin proteins in cerebrospinal fluid show different alterations in dementias.
PMID: 39317877
J Neurol · 2024
0.60