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FLASH GENE

Symbol

FOXP2

contributors: mct/npt/pgu/shn - updated : 09-11-2018

HGNC name	forkhead box P2
HGNC id	13875

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

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 Digestive esophagus           intestine         Nervous brain basal nuclei striatum   predominantly Homo sapiens   brain forebrain cerebral cortex     Homo sapiens   brain diencephalon thalamus     Homo sapiens   brain basal nuclei striatum   predominantly Danio rerio Respiratory lung

cell lineage
cell lines	normal human neuronal progenitor cells, NHNPs
fluid/secretion

at STAGE

physiological period

fetal

Text	intestinal, cardiovascular tissues
	preferentially expressed in distinct cell populations in the developing striatum
	expressed in the developing CNS, including the striatum, cerebral cortex, and thalamus

IMPRINTING	paternally
text	paternally imprinted in Developmental Verbal Dyspraxia

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a transcriptional repression domain including a zinc-finger motif in the N-terminal region
	a nuclear localization signal domains
	a polyglutamine tract
	a forkhead (FH, winged helix) domain evolutionally conserved domain of approximately 110 AA, important for both DNA binding ability and nuclear localization, forming a helix-turn-helix DNA binding motif dubbed the winged-helix
	one C2H2 type zinc finger

HOMOLOGY

interspecies	ortholog to Foxp2, Mus musculus
	ortholog to Foxp2, Rattus norvegicus
	ortholog to foxp2, Danio rerio
	ortholog to FOXP2, Pan troglodytes

intraspecies

homolog to FOXP1

Homologene

FAMILY

forkhead box (FOX) transcription factors

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus,chromatin/chromosome
text	nuclear localization depended on two distally separated nuclear localization signals in the forkhead domain

basic FUNCTION	involved in neural mechanisms mediating the development of speech and language
	transcriptional repressor playing an important role in the specification and differentiation of lung epithelium
	playing a role in the development of corticostriatal and olivocerebellar circuits involved in motor control
	involved in acquiring human speech/language ability
	involved in multiple functions not related to higher cognitive functions, including sensorimotor integration and vocal learning in birds and lung development outside the CNS
	crucial regulator of lung and esophageal development, underscoring the necessity of this transcription factor in the development of anterior foregut-derived tissues
	implicated in developmental verbal dyspraxia, a speech and language disorder
	is important for modulating the plasticity of relevant neural circuits
	FOXP1 and FOXP2 may be involved in the determination of the cell type identities during late embryogenesis
	has an important role in speech and language in humans, and its targets may have a critical function in the development and evolution of language circuitry
	in combination with PBX3 and MEIS2, may play a pivotal role in the development of striosomal neurons of the striatum and the islands of Calleja
	down-regulates both the SRPX2 and the PLAUR genes and this transcriptional regulation is lost when FOXP2 bears a pathogenic p.R553H mutation that is known to cause DVD (developmental verbal dyspraxia)
	modulates neuronal network formation, by directly and indirectly regulating mRNAs involved in the development and plasticity of neuronal connections
	FOXP2 might functionally regulate DISC1 expression
	FOXP2, DISC1 and the NRXN family in a molecular network that, when altered, confers risk for neurodevelopmental conditions in which various aspects of linguistic and cognitive function are disturbed, possibly via aberrant synaptic function
	implicated in the development of cortico-striatal circuits, which are involved in sensorimotor integration required for vocal motor learning
	implicated in pathways regulating neurite outgrowth, axon guidance and synaptic plasticity, which is in agreement with a role of FOXP2 in the development of neural circuits for language development

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

a component

FOXP2-SRPX2/PLAUR network provides exciting insights into molecular pathways underlying speech-related disorders

INTERACTION

DNA	5' regulatory region of MET

RNA

small molecule

protein	C-terminal binding protein 1, CTBP1
	CNTNAP2
	p66beta
	SRPX2 and the PLAUR
	POT1
	FOXP1 may compensate for the loss of FOXP2 and a level of redundancy exists between these two genes

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

DEL7Q31 , SPCH1

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional imprinting       absence of paternal FOXP2(paternal imprinting) is the cause of developmental verbal dyspraxia in patients with Silver-russel with maternal UPD7 constitutional       loss of function in orofacial dyspraxia, abnormalities in cortex and basal ganglia, expressive and receptive language impairment

Susceptibility

to SPCH1 and other langage impairment to dyslexia

Variant & Polymorphism other	nonsense mutation increasing the risk of SPCH1 and other langage impairment
	role of FOXP2 genetic variants in dyslexia-specific brain activation

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	mice with a disruption in the Foxp2 display severe motor impairment, premature death, and an absence of ultrasonic vocalizations
	Foxp2 (R552H) knockin mice showed reduced weight, immature development of the cerebellum with incompletely folded folia, Purkinje cells with poor dendritic arbors and less synaptophysin immunoreactivity, and achieved crisis stage for survival 3 weeks after birth