CNTNAP2 explained

Contactin-associated protein-like 2 is a protein that in humans is encoded by the CNTNAP2 gene.^{[1] [2]} Since the most recent reference human genome GRCh38, CNTNAP2 is the longest gene in the human genome ^[3]

This gene encodes a member of the neurexin family which functions in the vertebrate nervous system as cell adhesion molecules and receptors. This protein, like other neurexin proteins, contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, thrombospondin N-terminal-like domains and a putative PDZ binding site. This protein is localized at the juxtaparanodes of myelinated axons and associated with potassium channels. It may play a role in the local differentiation of the axon into distinct functional subdomains. This gene encompasses almost 1.6% of chromosome 7 and is one of the largest genes in the human genome.^[4] It may represent a positional candidate gene for the DFNB13 form of nonsyndromic deafness.^[5]

Clinical significance

CNTNAP2 has been associated with autism spectrum disorder but accounts for very few cases.^{[6] [7] [8]} CNTNAP2 may also be related to a disorder called specific language impairment.^[9]

Recessive mutations in CNTNAP2 result in a disorder that resembles Pitt–Hopkins syndrome.^{[10] [11]}

Interactions

CNTNAP2 has been shown to interact with CNTN2.^[12]

See also

• Brett Abrahams, geneticist and neuroscientist

Further reading

• Nakabayashi K, Scherer SW . 16120451 . The human contactin-associated protein-like 2 gene (CNTNAP2) spans over 2 Mb of DNA at chromosome 7q35 . Genomics . 73 . 1 . 108–12 . April 2001 . 11352571 . 10.1006/geno.2001.6517 .
• Spiegel I, Salomon D, Erne B, Schaeren-Wiemers N, Peles E . Caspr3 and caspr4, two novel members of the caspr family are expressed in the nervous system and interact with PDZ domains . Molecular and Cellular Neurosciences . 20 . 2 . 283–97 . June 2002 . 12093160 . 10.1006/mcne.2002.1110 . 25024421 .
• Nakayama M, Kikuno R, Ohara O . Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs . Genome Research . 12 . 11 . 1773–84 . November 2002 . 12421765 . 187542 . 10.1101/gr.406902 .
• Denisenko-Nehrbass N, Oguievetskaia K, Goutebroze L, Galvez T, Yamakawa H, Ohara O, Carnaud M, Girault JA . Protein 4.1B associates with both Caspr/paranodin and Caspr2 at paranodes and juxtaparanodes of myelinated fibres . The European Journal of Neuroscience . 17 . 2 . 411–6 . January 2003 . 12542678 . 10.1046/j.1460-9568.2003.02441.x . 21570541 .
• Verkerk AJ, Mathews CA, Joosse M, Eussen BH, Heutink P, Oostra BA . CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder . Genomics . 82 . 1 . 1–9 . July 2003 . 12809671 . 10.1016/S0888-7543(03)00097-1 .
• Traka M, Goutebroze L, Denisenko N, Bessa M, Nifli A, Havaki S, Iwakura Y, Fukamauchi F, Watanabe K, Soliven B, Girault JA, Karagogeos D . Association of TAG-1 with Caspr2 is essential for the molecular organization of juxtaparanodal regions of myelinated fibers . The Journal of Cell Biology . 162 . 6 . 1161–72 . September 2003 . 12975355 . 2172849 . 10.1083/jcb.200305078 .
• Fu GK, Wang JT, Yang J, Au-Young J, Stuve LL . Circular rapid amplification of cDNA ends for high-throughput extension cloning of partial genes . Genomics . 84 . 1 . 205–10 . July 2004 . 15203218 . 10.1016/j.ygeno.2004.01.011 .
• Strauss KA, Puffenberger EG, Huentelman MJ, Gottlieb S, Dobrin SE, Parod JM, Stephan DA, Morton DH . Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2 . The New England Journal of Medicine . 354 . 13 . 1370–7 . March 2006 . 16571880 . 10.1056/NEJMoa052773 . free .
• Belloso JM, Bache I, Guitart M, Caballin MR, Halgren C, Kirchhoff M, Ropers HH, Tommerup N, Tümer Z . Disruption of the CNTNAP2 gene in a t(7;15) translocation family without symptoms of Gilles de la Tourette syndrome . European Journal of Human Genetics . 15 . 6 . 711–3 . June 2007 . 17392702 . 10.1038/sj.ejhg.5201824 . free .

Notes and References

1. Poliak S, Gollan L, Martinez R, Custer A, Einheber S, Salzer JL, Trimmer JS, Shrager P, Peles E . Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels . Neuron . 24 . 4 . 1037–47 . December 1999 . 10624965 . 10.1016/S0896-6273(00)81049-1 . 12444497 . free .
2. Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O . Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 5 . 6 . 355–64 . December 1998 . 10048485 . 10.1093/dnares/5.6.355 . free .
3. Ashley. Euan A.. Towards precision medicine. Nature Reviews Genetics. 16 August 2016. 17. 9. 507–522. 10.1038/nrg.2016.86. 27528417. 2609065.
4. Helmrich A, Ballarino M, Tora L . Collisions between replication and transcription complexes cause common fragile site instability at the longest human genes . en . Molecular Cell . 44 . 6 . 966–77 . December 2011 . 22195969 . 10.1016/j.molcel.2011.10.013 . free .
5. Web site: Entrez Gene: CNTNAP2 contactin associated protein-like 2.
6. Alarcón M, Abrahams BS, Stone JL, Duvall JA, Perederiy JV, Bomar JM, Sebat J, Wigler M, Martin CL, Ledbetter DH, Nelson SF, Cantor RM, Geschwind DH . Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene . American Journal of Human Genetics . 82 . 1 . 150–9 . January 2008 . 18179893 . 2253955 . 10.1016/j.ajhg.2007.09.005 . https://web.archive.org/web/20080116062126/http://www.ajhg.org/AJHG/fulltext/S0002-9297%2807%2900011-0 . 2008-01-16 .
   • Web site: Elaine Schmidt . 2008-01-10 . UCLA scientists identify new genetic link to autism . UCLA Newsroom . https://web.archive.org/web/20080117142829/http://newsroom.ucla.edu/portal/ucla/ucla-scientists-identify-new-genetic-42778.aspx . 2008-01-17.
7. Arking DE, Cutler DJ, Brune CW, Teslovich TM, West K, Ikeda M, Rea A, Guy M, Lin S, Cook EH, Chakravarti A . A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism . American Journal of Human Genetics . 82 . 1 . 160–4 . January 2008 . 18179894 . 2253968 . 10.1016/j.ajhg.2007.09.015 . https://web.archive.org/web/20080116062131/http://www.ajhg.org/AJHG/fulltext/S0002-9297%2807%2900021-3 . 2008-01-16 .
   • 2008-01-22 . Hopkins Team Identifies Autism Susceptibility Gene . Johns Hopkins Medicine .
8. Bakkaloglu B, O'Roak BJ, Louvi A, Gupta AR, Abelson JF, Morgan TM, Chawarska K, Klin A, Ercan-Sencicek AG, Stillman AA, Tanriover G, Abrahams BS, Duvall JA, Robbins EM, Geschwind DH, Biederer T, Gunel M, Lifton RP, State MW . Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders . American Journal of Human Genetics . 82 . 1 . 165–73 . January 2008 . 18179895 . 2253974 . 10.1016/j.ajhg.2007.09.017 . dead . https://web.archive.org/web/20080116062226/http://www.ajhg.org/AJHG/fulltext/S0002-9297%2807%2900023-7 . 2008-01-16 .
9. Vernes SC, Newbury DF, Abrahams BS, Winchester L, Nicod J, Groszer M, Alarcón M, Oliver PL, Davies KE, Geschwind DH, Monaco AP, Fisher SE . A functional genetic link between distinct developmental language disorders . The New England Journal of Medicine . 359 . 22 . 2337–45 . November 2008 . 18987363 . 2756409 . 10.1056/NEJMoa0802828.
10. Peippo M, Ignatius J . Pitt-Hopkins Syndrome . Molecular Syndromology . 2 . 3–5 . 171–180 . April 2012 . 22670138 . 10.1159/000335287 . 3366706 .
11. Zweier C, de Jong EK, Zweier M, Orrico A, Ousager LB, Collins AL, Bijlsma EK, Oortveld MA, Ekici AB, Reis A, Schenck A, Rauch A . 6 . CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila . en . American Journal of Human Genetics . 85 . 5 . 655–66 . November 2009 . 19896112 . 2775834 . 10.1016/j.ajhg.2009.10.004 .
12. Traka M, Goutebroze L, Denisenko N, Bessa M, Nifli A, Havaki S, Iwakura Y, Fukamauchi F, Watanabe K, Soliven B, Girault JA, Karagogeos D . Association of TAG-1 with Caspr2 is essential for the molecular organization of juxtaparanodal regions of myelinated fibers . The Journal of Cell Biology . 162 . 6 . 1161–72 . September 2003 . 12975355 . 2172849 . 10.1083/jcb.200305078 .