CNTNAP2

Protein identityUniProt · HPA

UniProt accession

Q9UHC6

Gene

CNTNAP2

Ensembl

ENSG00000174469

Chromosome

7

Canonical length

1331 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

OverviewNCBI Gene

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 mediates interactions between neurons and glia during nervous system development and is also involved in localization of potassium channels within differentiating axons. This gene encompasses almost 1.5% of chromosome 7 and is one of the largest genes in the human genome. It is directly bound and regulated by forkhead box protein P2, a transcription factor related to speech and language development. This gene has been implicated in multiple neurodevelopmental disorders, including Gilles de la Tourette syndrome, schizophrenia, epilepsy, autism, ADHD and intellectual disability. [provided by RefSeq, Jul 2017]

Canonical amino-acid sequenceUniProt

1331 residues, UniProt reviewed canonical sequence.

>Q9UHC6|CNTNAP2
     1  MQAAPRAGCG AALLLWIVSS CLCRAWTAPS TSQKCDEPLV SGLPHVAFSS SSSISGSYSP
    61  GYAKINKRGG AGGWSPSDSD HYQWLQVDFG NRKQISAIAT QGRYSSSDWV TQYRMLYSDT
   121  GRNWKPYHQD GNIWAFPGNI NSDGVVRHEL QHPIIARYVR IVPLDWNGEG RIGLRIEVYG
   181  CSYWADVINF DGHVVLPYRF RNKKMKTLKD VIALNFKTSE SEGVILHGEG QQGDYITLEL
   241  KKAKLVLSLN LGSNQLGPIY GHTSVMTGSL LDDHHWHSVV IERQGRSINL TLDRSMQHFR
   301  TNGEFDYLDL DYEITFGGIP FSGKPSSSSR KNFKGCMESI NYNGVNITDL ARRKKLEPSN
   361  VGNLSFSCVE PYTVPVFFNA TSYLEVPGRL NQDLFSVSFQ FRTWNPNGLL VFSHFADNLG
   421  NVEIDLTESK VGVHINITQT KMSQIDISSG SGLNDGQWHE VRFLAKENFA ILTIDGDEAS
   481  AVRTNSPLQV KTGEKYFFGG FLNQMNNSSH SVLQPSFQGC MQLIQVDDQL VNLYEVAQRK
   541  PGSFANVSID MCAIIDRCVP NHCEHGGKCS QTWDSFKCTC DETGYSGATC HNSIYEPSCE
   601  AYKHLGQTSN YYWIDPDGSG PLGPLKVYCN MTEDKVWTIV SHDLQMQTPV VGYNPEKYSV
   661  TQLVYSASMD QISAITDSAE YCEQYVSYFC KMSRLLNTPD GSPYTWWVGK ANEKHYYWGG
   721  SGPGIQKCAC GIERNCTDPK YYCNCDADYK QWRKDAGFLS YKDHLPVSQV VVGDTDRQGS
   781  EAKLSVGPLR CQGDRNYWNA ASFPNPSSYL HFSTFQGETS ADISFYFKTL TPWGVFLENM
   841  GKEDFIKLEL KSATEVSFSF DVGNGPVEIV VRSPTPLNDD QWHRVTAERN VKQASLQVDR
   901  LPQQIRKAPT EGHTRLELYS QLFVGGAGGQ QGFLGCIRSL RMNGVTLDLE ERAKVTSGFI
   961  SGCSGHCTSY GTNCENGGKC LERYHGYSCD CSNTAYDGTF CNKDVGAFFE EGMWLRYNFQ
  1021  APATNARDSS SRVDNAPDQQ NSHPDLAQEE IRFSFSTTKA PCILLYISSF TTDFLAVLVK
  1081  PTGSLQIRYN LGGTREPYNI DVDHRNMANG QPHSVNITRH EKTIFLKLDH YPSVSYHLPS
  1141  SSDTLFNSPK SLFLGKVIET GKIDQEIHKY NTPGFTGCLS RVQFNQIAPL KAALRQTNAS
  1201  AHVHIQGELV ESNCGASPLT LSPMSSATDP WHLDHLDSAS ADFPYNPGQG QAIRNGVNRN
  1261  SAIIGGVIAV VIFTILCTLV FLIRYMFRHK GTYHTNEAKG AESAESADAA IMNNDPNFTE
  1321  TIDESKKEWL I

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CNTNAP2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.29

Highest tissue expression

35 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CNTNAP2.

Disease | AllUniProt

Conditions CNTNAP2 is implicated in, by any mechanism.

• Autism 15 (AUTS15) MIM:612100
• Pitt-Hopkins-like syndrome 1 (PTHSL1) MIM:610042

Disease | GeneticClinVar

112 pathogenic / likely-pathogenic of 1,956 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cortical dysplasia-focal epilepsy syndrome
• Inborn genetic diseases
• Autism, susceptibility to, 15
• See cases
• Autism spectrum disorder

Disease | AutoantibodyPubMed

Conditions in which antibodies against CNTNAP2 are reported. Each links to that disease's full target list.

• Encephalitis 59
• Hashimoto Disease 32
• Limbic Encephalitis 32
• Autoimmune Diseases of the Nervous System 23
• Epilepsy 12
• Seizures 11
• Thymoma 9
• Brain Diseases 8
• Thymus Neoplasms 8
• Pain 7
• Neoplasm Recurrence, Local 6
• Paraneoplastic Syndromes, Nervous System 6
• Peripheral Nervous System Diseases 5
• Guillain-Barre Syndrome 4
• Myasthenia Gravis 4
• Ataxia 3
• Cerebellar Ataxia 3
• Lung Neoplasms 3

Showing 18 of 30 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for CNTNAP2 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.55

gnomAD pLI

0

gnomAD missense Z

-0.29

DepMap mean gene effect

-0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adult behavior
• brain development
• cell adhesion
• cell population proliferation
• cerebral cortex development
• clustering of voltage-gated potassium channels
• learning
• limbic system development
• neuron projection development
• neuron projection morphogenesis
• neuron recognition
• positive regulation of gap junction assembly
• prepulse inhibition
• protein localization to juxtaparanode region of axon
• social behavior
• striatum development
• superior temporal gyrus development
• thalamus development
• transmission of nerve impulse
• vocal learning
• vocalization behavior

Molecular functions

• enzyme binding
• protease binding
• transmembrane transporter binding

Cellular components

• axolemma
• axon
• cell surface
• dendrite
• early endosome
• GABA-ergic synapse
• glutamatergic synapse
• Golgi apparatus
• juxtaparanode region of axon
• membrane
• neuronal cell body
• paranodal junction
• paranode region of axon
• perikaryon
• presynaptic membrane
• voltage-gated potassium channel complex

Protein domainsUniProt · Pfam · InterPro

• Coagulation factor 5/8, C-terminal domain
• EGF-like domain
• Laminin G domain
• Fibrinogen, alpha/beta/gamma chain, C-terminal globular domain
• Neurexin/syndecan/glycophorin C
• Galactose-binding-like domain superfamily
• Concanavalin A-like lectin/glucanase domain superfamily
• Fibrinogen-like, C-terminal
• Neurexin-related cell adhesion and synaptic protein
• F5/8 type C domain
• Laminin G domain

KeywordsUniProt

• Autism
• Autism spectrum disorder
• Cell adhesion
• Cell junction
• Cell projection
• Chromosomal rearrangement
• Disulfide bond
• EGF-like domain
• Epilepsy
• Glycoprotein
• Intellectual disability
• Membrane
• Phosphoprotein
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of CNTNAP2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GPR37
• KCNA2
• MEOX2