CNTNAP1

Protein identityUniProt · HPA

UniProt accession

P78357

Gene

CNTNAP1

Ensembl

ENSG00000108797

Chromosome

17

Canonical length

1384 aa

Protein class

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

Subcellular location

Nucleoplasm

OverviewNCBI Gene

The gene product was initially identified as a 190-kD protein associated with the contactin-PTPRZ1 complex. The 1,384-amino acid protein, also designated p190 or CASPR for 'contactin-associated protein,' includes an extracellular domain with several putative protein-protein interaction domains, a putative transmembrane domain, and a 74-amino acid cytoplasmic domain. Northern blot analysis showed that the gene is transcribed predominantly in brain as a transcript of 6.2 kb, with weak expression in several other tissues tested. The architecture of its extracellular domain is similar to that of neurexins, and this protein may be the signaling subunit of contactin, enabling recruitment and activation of intracellular signaling pathways in neurons. [provided by RefSeq, Jan 2009]

Canonical amino-acid sequenceUniProt

1384 residues, UniProt reviewed canonical sequence.

>P78357|CNTNAP1
     1  MMHLRLFCIL LAAVSGAEGW GYYGCDEELV GPLYARSLGA SSYYSLLTAP RFARLHGISG
    61  WSPRIGDPNP WLQIDLMKKH RIRAVATQGS FNSWDWVTRY MLLYGDRVDS WTPFYQRGHN
   121  STFFGNVNES AVVRHDLHFH FTARYIRIVP LAWNPRGKIG LRLGLYGCPY KADILYFDGD
   181  DAISYRFPRG VSRSLWDVFA FSFKTEEKDG LLLHAEGAQG DYVTLELEGA HLLLHMSLGS
   241  SPIQPRPGHT TVSAGGVLND QHWHYVRVDR FGRDVNFTLD GYVQRFILNG DFERLNLDTE
   301  MFIGGLVGAA RKNLAYRHNF RGCIENVIFN RVNIADLAVR RHSRITFEGK VAFRCLDPVP
   361  HPINFGGPHN FVQVPGFPRR GRLAVSFRFR TWDLTGLLLF SRLGDGLGHV ELTLSEGQVN
   421  VSIAQSGRKK LQFAAGYRLN DGFWHEVNFV AQENHAVISI DDVEGAEVRV SYPLLIRTGT
   481  SYFFGGCPKP ASRWDCHSNQ TAFHGCMELL KVDGQLVNLT LVEGRRLGFY AEVLFDTCGI
   541  TDRCSPNMCE HDGRCYQSWD DFICYCELTG YKGETCHTPL YKESCEAYRL SGKTSGNFTI
   601  DPDGSGPLKP FVVYCDIREN RAWTVVRHDR LWTTRVTGSS MERPFLGAIQ YWNASWEEVS
   661  ALANASQHCE QWIEFSCYNS RLLNTAGGYP YSFWIGRNEE QHFYWGGSQP GIQRCACGLD
   721  RSCVDPALYC NCDADQPQWR TDKGLLTFVD HLPVTQVVIG DTNRSTSEAQ FFLRPLRCYG
   781  DRNSWNTISF HTGAALRFPP IRANHSLDVS FYFRTSAPSG VFLENMGGPY CQWRRPYVRV
   841  ELNTSRDVVF AFDVGNGDEN LTVHSDDFEF NDDEWHLVRA EINVKQARLR VDHRPWVLRP
   901  MPLQTYIWME YDQPLYVGSA ELKRRPFVGC LRAMRLNGVT LNLEGRANAS EGTSPNCTGH
   961  CAHPRLPCFH GGRCVERYSY YTCDCDLTAF DGPYCNHDIG GFFEPGTWMR YNLQSALRSA
  1021  AREFSHMLSR PVPGYEPGYI PGYDTPGYVP GYHGPGYRLP DYPRPGRPVP GYRGPVYNVT
  1081  GEEVSFSFST SSAPAVLLYV SSFVRDYMAV LIKDDGTLQL RYQLGTSPYV YQLTTRPVTD
  1141  GQPHSINITR VYRNLFIQVD YFPLTEQKFS LLVDSQLDSP KALYLGRVME TGVIDPEIQR
  1201  YNTPGFSGCL SGVRFNNVAP LKTHFRTPRP MTAELAEALR VQGELSESNC GAMPRLVSEV
  1261  PPELDPWYLP PDFPYYHDEG WVAILLGFLV AFLLLGLVGM LVLFYLQNHR YKGSYHTNEP
  1321  KAAHEYHPGS KPPLPTSGPA QVPTPTAAPN QAPASAPAPA PTPAPAPGPR DQNLPQILEE
  1381  SRSE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CNTNAP1 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

73 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CNTNAP1.

Disease | AllUniProt

Conditions CNTNAP1 is implicated in, by any mechanism.

• Lethal congenital contracture syndrome 7 (LCCS7) MIM:616286
• Neuropathy, congenital hypomyelinating, 3 (CHN3) MIM:618186

Disease | GeneticClinVar

46 pathogenic / likely-pathogenic of 643 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neuropathy, congenital hypomyelinating, 3
• Lethal congenital contracture syndrome 7
• CNTNAP1-related disorder
• Fetal akinesia deformation sequence 1
• Arthrogryposis multiplex congenita

ReferencesPubMed · IEDB

Publications for CNTNAP1 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)

0.42

gnomAD pLI

0

gnomAD missense Z

3.22

DepMap mean gene effect

-0.25

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• axonogenesis
• cell adhesion
• central nervous system myelination
• cytoskeleton organization
• mitochondrion organization
• myelination in peripheral nervous system
• neuromuscular process controlling balance
• neuromuscular process controlling posture
• neuron projection morphogenesis
• neuronal action potential propagation
• paranodal junction assembly
• paranodal junction maintenance
• postsynaptic density organization
• protein localization to juxtaparanode region of axon
• protein localization to paranode region of axon
• regulation of synapse maturation
• signal transduction
• neuromuscular junction development, skeletal muscle fiber

Molecular functions

• SH3 domain binding
• signaling receptor activity

Cellular components

• glutamatergic synapse
• membrane
• paranodal junction
• paranode region of axon

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

• Cell adhesion
• Cell junction
• Disulfide bond
• EGF-like domain
• Glycoprotein
• Membrane
• Neuropathy
• Phosphoprotein
• Repeat
• SH3-binding
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of CNTNAP1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CNTN1
• CANX
• FBXO6