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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CNTN6
contactin 6
Chromosome 3 Β· 3p26.3
NCBI Gene: 27255Ensembl: ENSG00000134115.14HGNC: HGNC:2176UniProt: B4DGV0
32PubMed Papers
20Diseases
0Drugs
5Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cell-cell adhesion mediator activityaxon guidancesynapse organizationdendrite self-avoidanceCOVID-19oligodendrogliomahead and neck malignant neoplasiasevere acute respiratory syndrome
✦AI Summary

CNTN6 (contactin 6) encodes a cell adhesion molecule of the immunoglobulin superfamily that plays critical roles in nervous system development and function. The protein participates in oligodendrocyte generation by serving as a ligand for NOTCH1, promoting NOTCH1 activation through release of the notch intracellular domain (NICD) and its nuclear translocation 1. CNTN6 functions in axon guidance, synapse organization, and formation of axon connections during nervous system development 2. Copy number variations affecting CNTN6, including microdeletions and microduplications in the 3p26.3 region, are associated with neurodevelopmental disorders such as intellectual disability, developmental delay, and autism spectrum disorders 234. Notably, CNTN6 deletions and coding variants are enriched in autism spectrum disorder patients, particularly those with abnormal auditory sensory perception and hyperacusis 3. Recent studies have identified CNTN6 as a novel causative gene for congenital hypothyroidism, where it mediates thyroid hormone biosynthesis through Notch signaling by regulating expression of key thyroid genes including SLC5A5, TPO, and DUOX2 1. Interestingly, CNTN6 duplications show variable penetrance and allele-specific biased expression in patient-derived neurons 5, suggesting complex regulatory mechanisms underlying CNTN6-related pathologies.

Sources cited
1
CNTN6 microdeletions are associated with intellectual disability and autism, and the protein functions in axon connection formation during nervous system development
PMID: 25606055
2
CNTN6 is a novel causative gene for congenital hypothyroidism, mediating thyroid hormone biosynthesis through Notch signaling by promoting NOTCH1 activation
PMID: 38183624
3
CNTN6 deletions and coding variants are enriched in autism spectrum disorder patients, particularly those with abnormal auditory sensory perception
PMID: 27166760
4
Copy number variants affecting CNTN6 are associated with neurodevelopmental disorders
PMID: 38674362
5
CNTN6 duplications show allele-specific biased expression in patient-derived neurons
PMID: 29327201
Disease Associationsβ“˜20
COVID-19Open Targets
0.39Weak
oligodendrogliomaOpen Targets
0.35Weak
head and neck malignant neoplasiaOpen Targets
0.34Weak
severe acute respiratory syndromeOpen Targets
0.32Weak
neuroendocrine neoplasmOpen Targets
0.31Weak
poisoningOpen Targets
0.29Weak
response to stimulusOpen Targets
0.29Weak
pyogenic granulomaOpen Targets
0.28Weak
adverse effectOpen Targets
0.27Weak
autism spectrum disorderOpen Targets
0.27Weak
Autistic behaviorOpen Targets
0.27Weak
ovarian neoplasmOpen Targets
0.27Weak
ulcerative colitisOpen Targets
0.27Weak
gastric ulcerOpen Targets
0.25Weak
hemorrhageOpen Targets
0.25Weak
diabetic ketoacidosisOpen Targets
0.23Weak
Peyronie diseaseOpen Targets
0.23Weak
skull disorderOpen Targets
0.23Weak
nervous system benign neoplasmOpen Targets
0.23Weak
ocular hypotensionOpen Targets
0.23Weak
Pathogenic Variants5
NM_001289080.2(CNTN6):c.1492+1G>TLikely pathogenic
Autism spectrum disorder
β˜…β˜†β˜†β˜†2022
NM_001289080.2(CNTN6):c.566C>A (p.Ser189Ter)Likely pathogenic
Autistic behavior
β˜…β˜†β˜†β˜†2018β†’ Residue 189
NC_000003.12:g.(?_1133359)_(1192637_?)delLikely pathogenic
Autism
β˜…β˜†β˜†β˜†2018
NC_000003.12:g.(?_1247669)_(1285156_?)delLikely pathogenic
Autism
β˜…β˜†β˜†β˜†2018
NC_000003.12:g.(?_1264992)_(1295956_?)delLikely pathogenic
Schizophrenia
β˜…β˜†β˜†β˜†2018
View on ClinVar β†—
Related Genes
CHL1Protein interaction98%PTPRGProtein interaction93%CD177Protein interaction84%ALCAMProtein interaction81%CD6Protein interaction81%BCAMProtein interaction79%
Tissue Expression6 tissues
Lung
100%
Brain
52%
Bone Marrow
5%
Ovary
2%
Heart
2%
Liver
1%
Gene Interaction Network
Click a node to explore
CNTN6CHL1PTPRGCD177ALCAMCD6BCAM
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9UQ52
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.32LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.12 [0.96–1.32]
RankingsWhere CNTN6 stands among ~20K protein-coding genes
  • #11,487of 20,598
    Most Researched32
  • #3,614of 5,498
    Most Pathogenic Variants5
  • #13,833of 17,882
    Most Constrained (LOEUF)1.32
Genes detectedCNTN6
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Single gene microdeletions and microduplication of 3p26.3 in three unrelated families: CNTN6 as a new candidate gene for intellectual disability.
PMID: 25606055
Mol Cytogenet Β· 2014
1.00
2
Targeted correction of megabase-scale
PMID: 39850828
PeerJ Β· 2025
0.90
3
Contactin 6, A Novel Causative Gene for Congenital Hypothyroidism, Mediates Thyroid Hormone Biosynthesis Through Notch Signaling.
PMID: 38183624
Thyroid Β· 2024
0.80
4
Genetic Alterations in a Large Population of Italian Patients Affected by Neurodevelopmental Disorders.
PMID: 38674362
Genes (Basel) Β· 2024
0.70
5
CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders.
PMID: 27166760
Mol Psychiatry Β· 2017
0.60