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FLASH GENE

Symbol

CNTNAP2

contributors: mct/ - updated : 20-10-2015

HGNC name	contactin associated protein-like 2
HGNC id	13830

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	AUTS1 autism spectrum disorder, 1 CDFE cortical dysplasia-focal epilepsy syndrome PTHS3 Pitt-Hopkins syndrome 3 SPCHSL language impairment susceptibility
Location	7q35      Physical location : 145.813.452 - 148.118.086
Synonym name	homolog of Drosophila neurexin IV
	cell recognition molecule Caspr2
Synonym symbol(s)	NRXN4, CASPR2, KIAA0868, AUTS15, CDFE, PTHSL1

DNA

TYPE	functioning gene
STRUCTURE	2304.64 kb     24 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence

cytosine-phosphate-guanine/HTF

MAPPING

cloned

Y

linked

N

status

provisional

Map	cen - ARHGEF5 - D7S1486 - D7S676 - [D7S1925 - D7S498 - D7S2511 ] - D7S2442 - D7S2419 - D7S688 - CUL1 - qter
Text	[CNTNAP2 ]

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_014141 24 - 9890 NP_054860 - 1331 - 2009 19166515 CASPR2 isoform 2 3 - - - - - 2010 20711234 derived from the alternative promoter present between exons 21 and 22 contains only the last three coding exons and, on the protein level, lacks the extracellular domain apparently does not function as a cell adhesion molecule and may compete with expression of full-length CNTNAP2

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain forebrain cerebral cortex temporal cortex highly Homo sapiens   brain diencephalon thalamus   highly Homo sapiens   brain basal nuclei striatum   highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular         Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Nervous glia Homo sapiens Nervous neuron Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	during myelination, CNTNAP2 localizes to the developing nodes of Ranvier

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a signal peptide
	two epidermal growth factor repeats
	three laminin G-like domains
	one F5/8 type C domain
	one GNP motif
	a PDZ binding motif
	13 potential N-linked glycosylation sites in its extracellular domain

HOMOLOGY

interspecies

ortholog to murine Cntnap2

Homologene

FAMILY

neurexin family, contactin-associated protein family

CATEGORY

adhesion , tumor suppressor , signaling

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
text	type 1 membrane protein
	located in a specific compartment at the nodes of Ranvier of axons
	is localized at the axon initial segment, a region that is characterized by a high concentration of K+ channels

basic FUNCTION	may be playing a role in the formation of functional distinct domains critical for saltatory conduction of nerve impulses in myelinated nerve fibers
	playing a role in circuits important for language development
	involved in clustering of K+ channels in the juxtaparanodal region of the nodes of Ranvier
	having dynamic synaptic function, potentially involving synaptic structural reorganization, as observed for other neurexin superfamily members
	regulates neuron-glia contact and colocalize with Shaker-like K+ channels in the juxtaparanodal areas of Ranvier nodes in myelinated axons of both the central and peripheral nervous system
	acts as a tumor suppressor gene in glioma
	functional role for CNTNAP2 in brain development
	involved in the development of cortical circuits and further support alterations in brain synchrony or connectivity in ASD pathophysiology
	necessary for the normal migration of cortical projection neurons
	role for CNTNAP2 in GABAergic interneuron development
	juxtaparanodal proteins CNTNAP2 and CNTN2 regulate diet-induced obesity
	required for normal development of neural networks
	cell-autonomous function of CNTNAP2 in controlling the arborization of dendrites and the maturation of dendritic spines
	essential role for CNTNAP2 in the assembly of the nodes of Ranvier in myelinated axons
	cell-autonomous function for CNTNAP2 in controlling the growth of dendritic arbors and spines before myelination
	plays an important role for neuronal synchronization and brain connectivity
	role for CNTNAP2 fine-regulation in human-specific language and communication traits
	CNTNAP1, CNTNAP2 are required for the organization of the axolemma both radially, manifested as the mesaxonal line, and longitudinally, demarcated by the nodal domains

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

neurotransmission

	transmission of nerve impulse
	FOXP2-CNTNAP2 pathway provides a mechanistic link between clinically distinct syndromes involving disrupted language

a component

INTERACTION

DNA

RNA

small molecule

protein	EPB41
	EPB41L3 (through GNP motif)
	interaction with FOXP2
	carboxypeptidase E (CPE) is a CNTNAP2-interacting candidate protein
	CNTNAP2 associates with micromolar affinity with CNTN1 but, under the same conditions, it does not interact with any of the other members of the contactin family
	CNTN1 is an endogenous ligand for CNTNAP2

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

CDFE , AUTS1 , SPCHSL , PTHS3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional         lead to a disturbed distribution of the K(+) channels in the nervous system, influencing conduction and/or repolarization, causing movements of Gilles de la Tourette syndrome and obsessive compulsive disorder constitutional       loss of function in schizophrenia tumoral     --over   positively correlated with survival and is an independent prognostic factor in glioma

Susceptibility

first widely replicated autism-predisposition gene, see AUTS1, AUTS15 and AUTS19 to Gilles de la Tourette syndrome and obsessive compulsive disorder to autism and language impairment

Variant & Polymorphism	deleterious variant associated with autism : I869T
	SNP rs2710102 associated with autism in male probands (association between variation at rs2710102 and age at first word in ASD samples from male-only families)
	rs7794745 with T allele enriched in probands with autism

Candidate gene	for a subtype of ASD
Marker
Therapy target

ANIMAL & CELL MODELS

Cntnap2-/- mice show deficits in the three core ASD behavioral domains, as well as hyperactivity and epileptic seizures