Details for: CNTNAP1

Gene ID: 8506

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CNTNAP1

Ensembl ID: ENSG00000108797

Description: contactin associated protein 1

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • conventional dendritic cell CL0000990
    CSI 49.76
    rCSI 41.54%
    PRS 68.81
  • chondrocyte CL0000138
    CSI 37.55
    rCSI 59.72%
    PRS 45.05
  • regulatory T cell CL0000815
    CSI 35.08
    rCSI 40.67%
    PRS 68.34
  • basal cell of epidermis CL0002187
    CSI 31.98
    rCSI 56.67%
    PRS 30.97
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 29.42
    rCSI 35.64%
    PRS 43.83
  • melanocyte of skin CL1000458
    CSI 25.45
    rCSI 34.69%
    PRS 26.81
  • helper T cell CL0000912
    CSI 24.96
    rCSI 35.3%
    PRS 59.71
  • suprabasal keratinocyte CL4033013
    CSI 24.61
    rCSI 40.17%
    PRS 27.26
  • innate lymphoid cell CL0001065
    CSI 21.12
    rCSI 43.6%
    PRS 56.38
  • inhibitory interneuron CL0000498
    CSI 15.35
    rCSI 35.44%
    PRS 42.76
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 15.12
    rCSI 25.37%
    PRS 35.48
  • sncg GABAergic cortical interneuron CL4023015
    CSI 14.8
    rCSI 23.81%
    PRS 37.58
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 13.6
    rCSI 16.92%
    PRS 33.78
  • ependymal cell CL0000065
    CSI 13.22
    rCSI 26.83%
    PRS 33.38
  • retinal bipolar neuron CL0000748
    CSI 11.66
    rCSI 21.83%
    PRS 41.49
  • cerebral cortex neuron CL0010012
    CSI 9.01
    rCSI 36.71%
    PRS 48.59
  • sst GABAergic cortical interneuron CL4023017
    CSI 8.85
    rCSI 11.41%
    PRS 36.55
  • VIP GABAergic cortical interneuron CL4023016
    CSI 8.85
    rCSI 10.57%
    PRS 35.33
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 8.78
    rCSI 31.59%
    PRS 34.16
  • L6b glutamatergic cortical neuron CL4023038
    CSI 8.04
    rCSI 25.12%
    PRS 36.86
  • cytotoxic T cell CL0000910
    CSI 7
    rCSI 40.09%
    PRS 63.37
  • dopaminergic neuron CL0000700
    CSI 6.88
    rCSI 38.88%
    PRS 38.21
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 5.95
    rCSI 14.46%
    PRS 34.25
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 4.85
    rCSI 15.16%
    PRS 39.3
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 4.68
    rCSI 15.38%
    PRS 40.46
  • retinal ganglion cell CL0000740
    CSI 4.39
    rCSI 9.7%
    PRS 39.7
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 4.12
    rCSI 15.57%
    PRS 36.29
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 3.25
    rCSI 19.12%
    PRS 36.88
  • glutamatergic neuron CL0000679
    CSI 2.75
    rCSI 5.65%
    PRS 44.67
  • central nervous system neuron CL2000029
    CSI 2.49
    rCSI 18.28%
    PRS 39.85
  • medium spiny neuron CL1001474
    CSI 1.84
    rCSI 15.86%
    PRS 39.59
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.51
    rCSI 2.66%
    PRS 34.5
  • ON parasol ganglion cell CL4033052
    CSI 1.39
    rCSI 19.65%
    PRS 44.21
  • direct pathway medium spiny neuron CL4023026
    CSI 1.24
    rCSI 29.74%
    PRS 34.9
  • ON midget ganglion cell CL4033046
    CSI 1.11
    rCSI 22.7%
    PRS 44.1
  • OFF midget ganglion cell CL4033047
    CSI 1.08
    rCSI 21.93%
    PRS 45.42
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.04
    rCSI 25.09%
    PRS 35.86
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 0.45
    rCSI 1.07%
    PRS 40.72

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CNTNAP1](/details-gene/8506), or Contactin-associated protein 1, is a protein-coding gene located on chromosome 17q21.2. It encodes a transmembrane receptor primarily known for its critical roles in the nervous system, particularly in the formation and maintenance of paranodal junctions, myelination, and axon guidance ([GO:0030913](https://www.ebi.ac.uk/QuickGO/term/GO:0030913), [R-HSA-422475](https://reactome.org/content/detail/R-HSA-422475)). Clinically, mutations in [CNTNAP1](/details-gene/8506) are associated with severe congenital hypomyelinating neuropathy and arthrogryposis multiplex congenita ([602346](https://omim.org/entry/602346)) ([Link](https://doi.org/10.1093/hmg/ddt618), [Link](https://doi.org/10.1038/ejhg.2016.142)). While its function in the nervous system is well-documented, expression data reveals a surprisingly broad cellular landscape. **Overall**, it shows high significance not only in various neuron subtypes but also as a top marker in non-neuronal cells, including [conventional dendritic cell](/details-cell/CL0000990), [chondrocyte](/details-cell/CL0000138), and multiple T cell populations, suggesting its functional roles may extend beyond neurodevelopment into immunity and structural tissue biology. ## Cellular Roles and Expression Landscape The expression profile of [CNTNAP1](/details-gene/8506) indicates a more diverse biological role than its name and primary functional annotations might suggest. **Overall**, the gene exhibits its highest significance in a mix of immune, structural, epithelial, and neuronal cell types. Its most significant expression is observed in [conventional dendritic cell](/details-cell/CL0000990) (CSI: 49.76), pointing towards a potential, yet uncharacterized, role in antigen presentation or immune surveillance. This is complemented by high significance scores in other immune populations, including [regulatory T cell](/details-cell/CL0000815), [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203), [helper T cell](/details-cell/CL0000912), and [innate lymphoid cell](/details-cell/CL0001065), suggesting a broad involvement in adaptive and innate immune cell interactions. Beyond the immune system, [CNTNAP1](/details-gene/8506) is a significant marker for [chondrocyte](/details-cell/CL0000138) (CSI: 37.55), implicating it in cartilage biology, possibly related to cell adhesion functions analogous to its role in the nervous system. Furthermore, it is highly expressed in epidermal cells, such as [basal cell of epidermis](/details-cell/CL0002187) and [suprabasal keratinocyte](/details-cell/CL4033013), and in [melanocyte of skin](/details-cell/CL1000458), suggesting functions in skin architecture and cell-cell communication. Consistent with its established role, [CNTNAP1](/details-gene/8506) also shows notable significance in several neuronal subtypes, including various GABAergic cortical interneurons like [inhibitory interneuron](/details-cell/CL0000498), [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011), and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018), as well as [retinal bipolar neuron](/details-cell/CL0000748). This diverse expression pattern across multiple major tissue types suggests that [CNTNAP1](/details-gene/8506) may be a pleiotropic cell adhesion molecule whose specific function is tailored to its cellular context. ## Pathways and Molecular Function Functionally, [CNTNAP1](/details-gene/8506) is deeply integrated into the development and maintenance of the nervous system. Gene Ontology annotations highlight its involvement in fundamental processes such as [axonogenesis](/details-cell/GO:0007409), [central nervous system myelination](/details-cell/GO:0022010), and general [cell adhesion](/details-cell/GO:0007155). Its molecular function as a [signaling receptor activity](/details-cell/GO:0038023) protein that facilitates [protein binding](/details-cell/GO:0005515) is central to these roles. A key aspect of its function is its localization and role at the paranodal junctions of myelinated axons ([GO:0033010](https://www.ebi.ac.uk/QuickGO/term/GO:0033010)), where it is crucial for [paranodal junction assembly](/details-cell/GO:0030913) and the propagation of action potentials ([GO:0019227](https://www.ebi.ac.uk/QuickGO/term/GO:0019227)). This is supported by its involvement in Reactome pathways like [Nervous system development](/details-cell/R-HSA-9675108) and specific protein interaction networks such as [L1cam interactions](/details-cell/R-HSA-373760) and [Neurofascin interactions](/details-cell/R-HSA-447043). The severe neurological phenotypes observed in patients with [CNTNAP1](/details-gene/8506) mutations, including defects in myelination and axon-glia integrity, directly reflect the disruption of these critical pathways ([Link](https://doi.org/10.1093/jnen/nlw093), [Link](https://doi.org/10.1212/nxg.0000000000000144)). The high expression in non-neuronal cells, particularly immune cells, remains enigmatic as it is not clearly explained by the current canonical pathway annotations, suggesting novel, uncharacterized functions in these cellular contexts. ## Research Directions The well-established role of [CNTNAP1](/details-gene/8506) in the nervous system contrasts sharply with its high expression in immune and structural cells, opening up several avenues for future research. The discrepancy suggests that our understanding of this gene's function is incomplete. Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis 1:** Given its high significance in [conventional dendritic cell](/details-cell/CL0000990) and multiple T cell subsets, [CNTNAP1](/details-gene/8506) may function as a co-stimulatory or adhesion molecule that mediates the formation or stability of the immunological synapse between dendritic cells and T cells, thereby modulating T cell activation. 2. **Hypothesis 2:** The prominent expression of [CNTNAP1](/details-gene/8506) in [chondrocyte](/details-cell/CL0000138) suggests it plays a role in cartilage homeostasis. It could be involved in mediating cell-matrix interactions or cell-cell communication required for maintaining the structural integrity of cartilage tissue, a role analogous to its function at the paranodal junction. **Experimental Approach:** To test Hypothesis 1, one could employ a CRISPR-Cas9-based knockout of [CNTNAP1](/details-gene/8506) in primary human monocyte-derived dendritic cells (mo-DCs). The ability of these CNTNAP1-null mo-DCs to stimulate T cells could be assessed in a mixed lymphocyte reaction (MLR). T cell proliferation could be quantified using CFSE dye dilution assays via flow cytometry, and cytokine profiles (e.g., IL-2, IFN-gamma) in the co-culture supernatant could be measured by ELISA or multiplex bead array. A significant reduction in T cell proliferation or altered cytokine production in the absence of [CNTNAP1](/details-gene/8506) would support its role in T cell activation. **Therapeutic Potential:** The clinical relevance of [CNTNAP1](/details-gene/8506) is currently linked to severe, autosomal recessive loss-of-function disorders. Therefore, therapeutic strategies would likely focus on functional restoration rather than inhibition. For congenital hypomyelinating neuropathies caused by [CNTNAP1](/details-gene/8506) mutations, gene therapy represents a potential long-term approach. AAV-mediated delivery of a functional [CNTNAP1](/details-gene/8506) transgene targeted to Schwann cells in the peripheral nervous system or oligodendrocytes in the central nervous system could potentially correct the underlying molecular defect. However, the broad expression profile of [CNTNAP1](/details-gene/8506) would necessitate careful consideration of the delivery vector and promoter to ensure targeted expression and avoid off-target effects.

Genular Protein ID: 3427920779

Symbol: CNTP1_HUMAN

Name: Contactin-associated protein 1

UniProtKB Accession Codes:

P78357

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 3 CORUM 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 1 ExpressionAtlas 1 GO 26 Gene3D 4 GeneCards 1 GeneReviews 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 9 KEGG 1 MANE-Select 1 MIM 5 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 6 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 2 SIGNOR 1 SMART 3 SMR 1 STRING 1 SUPFAM 4 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9118959

Title: Identification of a novel contactin-associated transmembrane receptor with multiple domains implicated in protein-protein interactions.

PubMed ID: 9118959

DOI: 10.1093/emboj/16.5.978

PubMed ID: 24319099

Title: Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis multiplex congenita with axoglial defects.

PubMed ID: 24319099

DOI: 10.1093/hmg/ddt618

PubMed ID: 27782105

Title: Two novel variants in CNTNAP1 in two siblings presenting with congenital hypotonia and hypomyelinating neuropathy.

PubMed ID: 27782105

DOI: 10.1038/ejhg.2016.142

PubMed ID: 27818385

Title: Contactin-Associated Protein 1 (CNTNAP1) Mutations Induce Characteristic Lesions of the Paranodal Region.

PubMed ID: 27818385

DOI: 10.1093/jnen/nlw093

PubMed ID: 28254648

Title: Identification of a novel CNTNAP1 mutation causing arthrogryposis multiplex congenita with cerebral and cerebellar atrophy.

PubMed ID: 28254648

DOI: 10.1016/j.ejmg.2017.02.006

PubMed ID: 27668699

Title: Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy.

PubMed ID: 27668699

DOI: 10.1002/mus.25416

PubMed ID: 28374019

Title: CNTNAP1 mutations cause CNS hypomyelination and neuropathy with or without arthrogryposis.

PubMed ID: 28374019

DOI: 10.1212/nxg.0000000000000144

PubMed ID: 29511323

Title: Phenotype of CNTNAP1: a study of patients demonstrating a specific severe congenital hypomyelinating neuropathy with survival beyond infancy.

PubMed ID: 29511323

DOI: 10.1038/s41431-018-0110-x

Sequence Information:

  • Length: 1384
  • Mass: 156267
  • Checksum: 7727A13DF626DDCA
  • Sequence:
    • MMHLRLFCIL LAAVSGAEGW GYYGCDEELV GPLYARSLGA SSYYSLLTAP RFARLHGISG 
WSPRIGDPNP WLQIDLMKKH RIRAVATQGS FNSWDWVTRY MLLYGDRVDS WTPFYQRGHN 
STFFGNVNES AVVRHDLHFH FTARYIRIVP LAWNPRGKIG LRLGLYGCPY KADILYFDGD 
DAISYRFPRG VSRSLWDVFA FSFKTEEKDG LLLHAEGAQG DYVTLELEGA HLLLHMSLGS 
SPIQPRPGHT TVSAGGVLND QHWHYVRVDR FGRDVNFTLD GYVQRFILNG DFERLNLDTE 
MFIGGLVGAA RKNLAYRHNF RGCIENVIFN RVNIADLAVR RHSRITFEGK VAFRCLDPVP 
HPINFGGPHN FVQVPGFPRR GRLAVSFRFR TWDLTGLLLF SRLGDGLGHV ELTLSEGQVN 
VSIAQSGRKK LQFAAGYRLN DGFWHEVNFV AQENHAVISI DDVEGAEVRV SYPLLIRTGT 
SYFFGGCPKP ASRWDCHSNQ TAFHGCMELL KVDGQLVNLT LVEGRRLGFY AEVLFDTCGI 
TDRCSPNMCE HDGRCYQSWD DFICYCELTG YKGETCHTPL YKESCEAYRL SGKTSGNFTI 
DPDGSGPLKP FVVYCDIREN RAWTVVRHDR LWTTRVTGSS MERPFLGAIQ YWNASWEEVS 
ALANASQHCE QWIEFSCYNS RLLNTAGGYP YSFWIGRNEE QHFYWGGSQP GIQRCACGLD 
RSCVDPALYC NCDADQPQWR TDKGLLTFVD HLPVTQVVIG DTNRSTSEAQ FFLRPLRCYG 
DRNSWNTISF HTGAALRFPP IRANHSLDVS FYFRTSAPSG VFLENMGGPY CQWRRPYVRV 
ELNTSRDVVF AFDVGNGDEN LTVHSDDFEF NDDEWHLVRA EINVKQARLR VDHRPWVLRP 
MPLQTYIWME YDQPLYVGSA ELKRRPFVGC LRAMRLNGVT LNLEGRANAS EGTSPNCTGH 
CAHPRLPCFH GGRCVERYSY YTCDCDLTAF DGPYCNHDIG GFFEPGTWMR YNLQSALRSA 
AREFSHMLSR PVPGYEPGYI PGYDTPGYVP GYHGPGYRLP DYPRPGRPVP GYRGPVYNVT 
GEEVSFSFST SSAPAVLLYV SSFVRDYMAV LIKDDGTLQL RYQLGTSPYV YQLTTRPVTD 
GQPHSINITR VYRNLFIQVD YFPLTEQKFS LLVDSQLDSP KALYLGRVME TGVIDPEIQR 
YNTPGFSGCL SGVRFNNVAP LKTHFRTPRP MTAELAEALR VQGELSESNC GAMPRLVSEV 
PPELDPWYLP PDFPYYHDEG WVAILLGFLV AFLLLGLVGM LVLFYLQNHR YKGSYHTNEP 
KAAHEYHPGS KPPLPTSGPA QVPTPTAAPN QAPASAPAPA PTPAPAPGPR DQNLPQILEE 
SRSE