Human Gene Module / Chromosome 7 / FOXP2

FOXP2forkhead box P2

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
24 / 58
Rare Variants / Common Variants
81 / 8
Aliases
FOXP2, SPCH1,  CAGH44,  TNRC10,  DKFZp686H1726
Associated Syndromes
-
Chromosome Band
7q31.1
Associated Disorders
SCZ, ADHD, ASD
Relevance to Autism

Studies have found genetic association and rare variants in the FOXP2 gene that are identified with autism. Positive associations have been found in the Chinese Han population and mutations were identified in the Japanese population. However, several other studies have either found no genetic association or no rare genetic variation in the FOXP2 gene identified with autism. Separately, rare variations in the FMR1 gene have been identified with verbal dyspraxia.

Molecular Function

This gene encodes a member of the forkhead/winged-helix (FOX) family of transcription factors. It is expressed in fetal and adult brain as well as in several other organs such as the lung and gut. The protein product contains a FOX DNA-binding domain and a large polyglutamine tract and is an evolutionarily conserved transcription factor, which may bind directly to approximately 300 to 400 gene promoters in the human genome to regulate the expression of a variety of genes. This gene is required for proper development of speech and language regions of the brain during embryogenesis, and may be involved in a variety of biological pathways and cascades that may ultimately influence language development. Mutations in this gene cause speech-language disorder 1 (SPCH1), also known as autosomal dominant speech and language disorder with orofacial dyspraxia.

SFARI Genomic Platforms
Reports related to FOXP2 (58 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support A forkhead-domain gene is mutated in a severe speech and language disorder Lai CS , et al. (2001) No -
2 Negative Association FOXP2 is not a major susceptibility gene for autism or specific language impairment Newbury DF , et al. (2002) Yes -
3 Negative Association Evaluation of FOXP2 as an autism susceptibility gene Wassink TH , et al. (2002) Yes -
4 Highly Cited Molecular evolution of FOXP2, a gene involved in speech and language Enard W , et al. (2002) No -
5 Negative Association Mutation screening of FOXP2 in individuals diagnosed with autistic disorder Gauthier J , et al. (2003) Yes -
6 Primary Association between the FOXP2 gene and autistic disorder in Chinese population Gong X , et al. (2004) Yes -
7 Positive Association Absence of causative mutations and presence of autism-related allele in FOXP2 in Japanese autistic patients Li H , et al. (2005) Yes -
8 Recent Recommendation Identification of FOXP2 truncation as a novel cause of developmental speech and language deficits MacDermot KD , et al. (2005) No -
9 Negative Association No association of FOXP2 and PTPRZ1 on 7q31 with autism from the Japanese population Marui T , et al. (2005) Yes -
10 Support Speech, prosody, and voice characteristics of a mother and daughter with a 7;13 translocation affecting FOXP2 Shriberg LD , et al. (2006) No -
11 Support Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia Feuk L , et al. (2006) No -
12 Recent Recommendation Incomplete and inaccurate vocal imitation after knockdown of FoxP2 in songbird basal ganglia nucleus Area X Haesler S , et al. (2007) No -
13 Recent Recommendation Impaired synaptic plasticity and motor learning in mice with a point mutation implicated in human speech deficits Groszer M , et al. (2008) No -
14 Recent Recommendation Expression of FOXP2 in the developing monkey forebrain: comparison with the expression of the genes FOXP1, PBX3, and MEIS2 Takahashi K , et al. (2008) No -
15 Recent Recommendation Conservation and diversity of Foxp2 expression in muroid rodents: functional implications Campbell P , et al. (2008) No -
16 Recent Recommendation A functional genetic link between distinct developmental language disorders Vernes SC , et al. (2008) No -
17 Recent Recommendation A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice Enard W , et al. (2009) No -
18 Support Language features in a mother and daughter of a chromosome 7;13 translocation involving FOXP2 Tomblin JB , et al. (2009) No -
19 Recent Recommendation Human-specific transcriptional regulation of CNS development genes by FOXP2 Konopka G , et al. (2009) No -
20 Support Molecular networks implicated in speech-related disorders: FOXP2 regulates the SRPX2/uPAR complex Roll P , et al. (2010) No -
21 Negative Association Association study of the CNS patterning genes and autism in Han Chinese in Taiwan Chien YL , et al. (2011) Yes -
22 Support Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders Schaaf CP , et al. (2011) Yes -
23 Support Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link with autism Lesca G , et al. (2012) No ADHD
24 Recent Recommendation Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization Laffin JJ , et al. (2012) No -
25 Negative Association Analysis of two language-related genes in autism: a case-control association study of FOXP2 and CNTNAP2 Toma C , et al. (2013) Yes -
26 Recent Recommendation FOXP2 targets show evidence of positive selection in European populations Ayub Q , et al. (2013) No -
27 Support Small intragenic deletion in FOXP2 associated with childhood apraxia of speech and dysarthria Turner SJ , et al. (2013) No -
28 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No -
29 Support Comprehensive molecular testing in patients with high functioning autism spectrum disorder Alvarez-Mora MI , et al. (2016) Yes -
30 Recent Recommendation Sumoylation of FOXP2 Regulates Motor Function and Vocal Communication Through Purkinje Cell Development Usui N , et al. (2016) No -
31 Support FOXP2 variants in 14 individuals with developmental speech and language disorders broaden the mutational and clinical spectrum Reuter MS , et al. (2016) No ASD or autistic features
32 Recent Recommendation Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c Chen YC , et al. (2016) No -
33 Support The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies Redin C , et al. (2016) No -
34 Support Functional characterization of rare FOXP2 variants in neurodevelopmental disorder Estruch SB , et al. (2016) No -
35 Positive Association The central nervous system patterning gene variants associated with clinical symptom severity of autism spectrum disorders Chien YL , et al. (2017) Yes Severity of social reciprocity deficits (ADI-R, SC
36 Positive Association A common genetic variant in FOXP2 is associated with language-based learning (dis)abilities: Evidence from two Italian independent samples Mozzi A , et al. (2017) No -
37 Support Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder Lim ET , et al. (2017) Yes -
38 Recent Recommendation Proteomic analysis of FOXP proteins reveals interactions between cortical transcription factors associated with neurodevelopmental disorders Estruch SB , et al. (2018) No -
39 Recent Recommendation Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder Demontis D , et al. (2018) No -
40 Support Genome sequencing identifies multiple deleterious variants in autism patients with more severe phenotypes Guo H , et al. (2018) Yes -
41 Recent Recommendation Chromatin Decondensation by FOXP2 Promotes Human Neuron Maturation and Expression of Neurodevelopmental Disease Genes Hickey SL , et al. (2019) No -
42 Support Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder Munnich A , et al. (2019) Yes -
43 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
44 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes -
45 Support - Herrero MJ et al. (2021) Yes -
46 Support - Pode-Shakked B et al. (2021) No -
47 Support - Mahjani B et al. (2021) Yes -
48 Support - Lüffe TM et al. (2021) No -
49 Support - Hu C et al. (2022) Yes -
50 Support - Krgovic D et al. (2022) Yes ID
51 Positive Association - Tielbeek JJ et al. (2022) No -
52 Support - Haghighatfard A et al. (2022) Yes -
53 Support - Spataro N et al. (2023) No -
54 Support - Hu C et al. (2023) Yes -
55 Support - Sanchis-Juan A et al. (2023) No -
56 Support - Sheth F et al. (2023) Yes DD, ID
57 Support - Newaz I Ahmed et al. (2024) Yes -
58 Support - Axel Schmidt et al. (2024) No -
Rare Variants   (81)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
delCAA - inframe_deletion - - - 15737702 Li H , et al. (2005)
- - translocation Unknown - - 11586359 Lai CS , et al. (2001)
- - translocation Unknown - - 17033973 Feuk L , et al. (2006)
A>G p.(=) synonymous_variant - - - 15737702 Li H , et al. (2005)
A>T p.(=) synonymous_variant - - - 15737702 Li H , et al. (2005)
C>T p.(=) synonymous_variant - - - 15737702 Li H , et al. (2005)
G>T p.(=) synonymous_variant - - - 15737702 Li H , et al. (2005)
- - copy_number_loss Unknown - - 31406558 Munnich A , et al. (2019)
G>A - 5_prime_UTR_variant - - - 15877281 MacDermot KD , et al. (2005)
A>G p.(=) synonymous_variant - - - 11894222 Newbury DF , et al. (2002)
C>G p.(=) synonymous_variant - - - 11894222 Newbury DF , et al. (2002)
G>A p.(=) synonymous_variant - - - 11894222 Newbury DF , et al. (2002)
T>A p.(=) synonymous_variant - - - 11894222 Newbury DF , et al. (2002)
T>C p.(=) synonymous_variant - - - 11894222 Newbury DF , et al. (2002)
T>G p.(=) synonymous_variant - - - 11894222 Newbury DF , et al. (2002)
T>G p.(=) synonymous_variant - - - 12116195 Wassink TH , et al. (2002)
A>G p.(=) synonymous_variant - - - 12655497 Gauthier J , et al. (2003)
C>G p.(=) synonymous_variant - - - 12655497 Gauthier J , et al. (2003)
T>G p.(=) synonymous_variant - - - 12655497 Gauthier J , et al. (2003)
- - insertion Unknown - Simplex 37541188 Sanchis-Juan A et al. (2023)
C>G p.(=) synonymous_variant - - - 15877281 MacDermot KD , et al. (2005)
C>T p.(=) synonymous_variant - - - 15877281 MacDermot KD , et al. (2005)
T>A p.(=) synonymous_variant - - - 15877281 MacDermot KD , et al. (2005)
T>C p.(=) synonymous_variant - - - 15877281 MacDermot KD , et al. (2005)
T>G p.(=) synonymous_variant - - - 15877281 MacDermot KD , et al. (2005)
c.495A>G p.Gln165= synonymous_variant - - - 15737702 Li H , et al. (2005)
c.987-1G>A - splice_site_variant Unknown - - 33004838 Wang T et al. (2020)
c.233G>C p.Ser78Thr missense_variant Unknown - - 35741772 Hu C et al. (2022)
c.741C>T p.Leu247= synonymous_variant - - - 12116195 Wassink TH , et al. (2002)
c.570A>G p.Gln190= synonymous_variant - - - 12655497 Gauthier J , et al. (2003)
c.1831T>A p.Leu611Met missense_variant Unknown - - 35741772 Hu C et al. (2022)
- - copy_number_loss Familial Paternal Multiplex 30504930 Guo H , et al. (2018)
c.1468+9T>C - intron_variant Unknown - Unknown 22738016 Lesca G , et al. (2012)
c.1201C>T p.Arg401Ter stop_gained Unknown - - 34615535 Mahjani B et al. (2021)
c.1674G>A p.Leu558%3D stop_gained Unknown - - 35813072 Krgovic D et al. (2022)
- - translocation Familial Maternal Simplex 19797137 Tomblin JB , et al. (2009)
c.1770-33G>A - intron_variant Unknown - Unknown 22738016 Lesca G , et al. (2012)
del18 - inframe_deletion Familial Maternal - 12116195 Wassink TH , et al. (2002)
c.1664T>C p.Ile555Thr missense_variant De novo - - 33004838 Wang T et al. (2020)
c.628C>T p.Gln210Ter stop_gained Unknown - - 39039281 Axel Schmidt et al. (2024)
- - complex_structural_alteration De novo - Simplex 27841880 Redin C , et al. (2016)
c.1429C>T p.Arg477Ter stop_gained De novo - Simplex 28714951 Lim ET , et al. (2017)
insCAGCAG - inframe_insertion Familial Maternal - 11894222 Newbury DF , et al. (2002)
c.1690C>T p.Arg564Ter stop_gained Familial - - 34580403 Pode-Shakked B et al. (2021)
c.1761G>A p.(=) synonymous_variant Unknown - Unknown 22738016 Lesca G , et al. (2012)
c.934C>T p.His312Tyr stop_gained De novo - Simplex 27572252 Reuter MS , et al. (2016)
insCAGCAGCAACAA - inframe_insertion - - Multiplex 15877281 MacDermot KD , et al. (2005)
c.1765C>T p.Arg589Ter stop_gained De novo - Simplex 27572252 Reuter MS , et al. (2016)
c.1067G>A p.Cys356Tyr missense_variant Familial Paternal - 37007974 Hu C et al. (2023)
del15 - inframe_deletion Familial Maternal Multiplex 12116195 Wassink TH , et al. (2002)
c.1217T>C p.Met406Thr missense_variant Unknown - Unknown 22738016 Lesca G , et al. (2012)
c.1368T>C p.Ile456= synonymous_variant Unknown - Unknown 22738016 Lesca G , et al. (2012)
c.1321C>A p.Pro441Thr missense_variant Unknown - Simplex 21624971 Schaaf CP , et al. (2011)
c.2012A>G p.Asn671Ser missense_variant Unknown - Simplex 21624971 Schaaf CP , et al. (2011)
c.2175A>T p.Glu725Asp missense_variant Unknown - Simplex 21624971 Schaaf CP , et al. (2011)
c.1786A>C p.Asn596His missense_variant Unknown - Multiplex 22766611 Laffin JJ , et al. (2012)
- - copy_number_loss De novo - Multiplex (monozygotic twins) 27572252 Reuter MS , et al. (2016)
c.50A>T p.Gln17Leu missense_variant Unknown - Multiplex 15877281 MacDermot KD , et al. (2005)
c.1842_1843del p.Gly615LysfsTer19 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.1088del p.Leu363Ter frameshift_variant Familial Maternal - 36980980 Spataro N et al. (2023)
c.613del p.Gln205SerfsTer82 frameshift_variant Unknown - - 39039281 Axel Schmidt et al. (2024)
c.1654C>T p.Arg552Cys missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.917C>T p.Ala306Val stop_gained Familial Paternal Multiplex 27572252 Reuter MS , et al. (2016)
c.1217T>C p.Met406Thr missense_variant Familial Paternal Simplex 20858596 Roll P , et al. (2010)
c.1057C>T p.Arg353Ter stop_gained Familial Maternal Multiplex 27572252 Reuter MS , et al. (2016)
c.979C>T p.Arg327Ter stop_gained Familial Maternal Multiplex 15877281 MacDermot KD , et al. (2005)
c.1549G>A p.Ala517Thr missense_variant Unknown Not maternal Simplex 37543562 Sheth F et al. (2023)
c.1637C>T p.Thr546Ile missense_variant Familial Paternal Simplex 27572252 Reuter MS , et al. (2016)
c.1321C>A p.Pro441Thr missense_variant Familial Maternal Multiplex 23918746 Turner SJ , et al. (2013)
c.1682G>C p.Arg561Pro missense_variant Familial Paternal Multiplex 27572252 Reuter MS , et al. (2016)
c.1611del p.Phe537LeufsTer28 frameshift_variant De novo - Multiplex 27572252 Reuter MS , et al. (2016)
c.1165_1166del p.Gln389ValfsTer7 frameshift_variant De novo - Simplex 23918746 Turner SJ , et al. (2013)
c.522_524del p.Gln174_Leu175delinsHis inframe_deletion Unknown - Unknown 22738016 Lesca G , et al. (2012)
c.426G>T p.Gln142His missense_variant Familial Paternal Simplex 26845707 Alvarez-Mora MI , et al. (2016)
c.-11+3115T>C - intron_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
c.1092-3370C>T - intron_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
c.1264-1709A>G - intron_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
c.324dup p.Gln109SerfsTer156 frameshift_variant Familial Paternal Simplex 23160955 O'Roak BJ , et al. (2012)
c.1655G>A p.Arg552His missense_variant Familial Maternal and Paternal Multi-generational 11586359 Lai CS , et al. (2001)
c.615_617dup p.Gln208dup inframe_insertion De novo (1 case); unknown (3 cases) - Simplex 21624971 Schaaf CP , et al. (2011)
c.2159A>C p.His720Pro missense_variant Familial (1 case); De novo (1 case) Maternal (1 case) Simplex 21624971 Schaaf CP , et al. (2011)
Common Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.169-26341C>A;c.168+81597C>A;c.*228+9183C>A - intron_variant - - - 28081867 Chien YL , et al. (2017)
c.-11+5061A>T;c.-345+5061A>T;c.-11+5879A>T;c.-344-6081A>T;c.-10-6081A>T - intron_variant - - - 28081867 Chien YL , et al. (2017)
c.1264-2019T>C;c.1267-2019T>C;c.1342-2019T>C;c.1318-2019T>C;c.1411-2019T>C;c.433-2019T>C - intron_variant - - - 15108192 Gong X , et al. (2004)
c.1264-2019T>C;c.1267-2019T>C;c.1342-2019T>C;c.1318-2019T>C;c.1411-2019T>C;c.433-2019T>C - intron_variant - - - 28081867 Chien YL , et al. (2017)
G to T N/A intron_variant - - - 15737702 Li H , et al. (2005)
c.169-11932G>A - intron_variant - - - 28436202 Mozzi A , et al. (2017)
c.-10-23398A>G - intron_variant - - - 36284158 Tielbeek JJ et al. (2022)
c.168+19400_168+19401delTC - intron_variant - - - 30478444 Demontis D , et al. (2018)
SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

1

High Confidence

See all Category 1 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
2
icon
1

Decreased from 2 to 1

10/1/2020
2
icon
2

Decreased from 2 to 2

Description

A significant but unreplicated association study of FOXP2 in ASD has been reported. FOXP2 is mutated in specific language impairment, and also physically interacts with FOXP1, which has been implicated in ASD (PMID: 21572417)

1/1/2020
2
icon
2

Decreased from 2 to 2

Description

A significant but unreplicated association study of FOXP2 in ASD has been reported. FOXP2 is mutated in specific language impairment, and also physically interacts with FOXP1, which has been implicated in ASD (PMID: 21572417)

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

A significant but unreplicated association study of FOXP2 in ASD has been reported. FOXP2 is mutated in specific language impairment, and also physically interacts with FOXP1, which has been implicated in ASD (PMID: 21572417)

Reports Added
[New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

A significant but unreplicated association study of FOXP2 in ASD has been reported. FOXP2 is mutated in specific language impairment, and also physically interacts with FOXP1, which has been implicated in ASD (PMID: 21572417)

4/1/2019
3
icon
3

Decreased from 3 to 3

Description

A significant but unreplicated association study of FOXP2 in ASD has been reported. FOXP2 is mutated in specific language impairment, and also physically interacts with FOXP1, which has been implicated in ASD (PMID: 21572417)

10/1/2018
3
icon
3

Decreased from 3 to 3

Description

A significant but unreplicated association study of FOXP2 in ASD has been reported. FOXP2 is mutated in specific language impairment, and also physically interacts with FOXP1, which has been implicated in ASD (PMID: 21572417)

7/1/2017
3
icon
3

Decreased from 3 to 3

Description

A significant but unreplicated association study of FOXP2 in ASD has been reported. FOXP2 is mutated in specific language impairment, and also physically interacts with FOXP1, which has been implicated in ASD (PMID: 21572417)

4/1/2017
3
icon
3

Decreased from 3 to 3

Description

A significant but unreplicated association study of FOXP2 in ASD has been reported. FOXP2 is mutated in specific language impairment, and also physically interacts with FOXP1, which has been implicated in ASD (PMID: 21572417)

Reports Added
[FOXP2 is not a major susceptibility gene for autism or specific language impairment.2002] [Evaluation of FOXP2 as an autism susceptibility gene.2002] [Mutation screening of FOXP2 in individuals diagnosed with autistic disorder.2003] [Absence of causative mutations and presence of autism-related allele in FOXP2 in Japanese autistic patients.2005] [No association of FOXP2 and PTPRZ1 on 7q31 with autism from the Japanese population.2005] [Association study of the CNS patterning genes and autism in Han Chinese in Taiwan.2011] [Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.2011] [Analysis of two language-related genes in autism: a case-control association study of FOXP2 and CNTNAP2.2013] [Association between the FOXP2 gene and autistic disorder in Chinese population.2004] [Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization.2012] [Small intragenic deletion in FOXP2 associated with childhood apraxia of speech and dysarthria.2013] [Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia.2006] [Language features in a mother and daughter of a chromosome 7;13 translocation involving FOXP2.2009] [Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link wi...2012] [A forkhead-domain gene is mutated in a severe speech and language disorder.2001] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Identification of FOXP2 truncation as a novel cause of developmental speech and language deficits.2005] [Molecular evolution of FOXP2, a gene involved in speech and language.2002] [Speech, prosody, and voice characteristics of a mother and daughter with a 7;13 translocation affecting FOXP2.2006] [Incomplete and inaccurate vocal imitation after knockdown of FoxP2 in songbird basal ganglia nucleus Area X.2007] [Impaired synaptic plasticity and motor learning in mice with a point mutation implicated in human speech deficits.2008] [Expression of FOXP2 in the developing monkey forebrain: comparison with the expression of the genes FOXP1, PBX3, and MEIS2.2008] [Conservation and diversity of Foxp2 expression in muroid rodents: functional implications.2008] [A functional genetic link between distinct developmental language disorders.2008] [A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice.2009] [Human-specific transcriptional regulation of CNS development genes by FOXP2.2009] [FOXP2 targets show evidence of positive selection in European populations.2013] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016] [Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c.2016] [FOXP2 variants in 14 individuals with developmental speech and language disorders broaden the mutational and clinical spectrum.2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016] [Functional characterization of rare FOXP2 variants in neurodevelopmental disorder.2016] [Molecular networks implicated in speech-related disorders: FOXP2 regulates the SRPX2/uPAR complex.2010] [The central nervous system patterning gene variants associated with clinical symptom severity of autism spectrum disorders.2017] [Sumoylation of FOXP2 Regulates Motor Function and Vocal Communication Through Purkinje Cell Development.2016] [A common genetic variant in FOXP2 is associated with language-based learning (dis)abilities: Evidence from two Italian independent samples.2017]
1/1/2017
3
icon
3

Decreased from 3 to 3

Description

A significant but unreplicated association study of FOXP2 in ASD has been reported. FOXP2 is mutated in specific language impairment, and also physically interacts with FOXP1, which has been implicated in ASD (PMID: 21572417)

10/1/2016
3
icon
3

Decreased from 3 to 3

Description

A significant but unreplicated association study of FOXP2 in ASD has been reported. FOXP2 is mutated in specific language impairment, and also physically interacts with FOXP1, which has been implicated in ASD (PMID: 21572417)

7/1/2016
3
icon
3

Decreased from 3 to 3

Description

A significant but unreplicated association study of FOXP2 in ASD has been reported. FOXP2 is mutated in specific language impairment, and also physically interacts with FOXP1, which has been implicated in ASD (PMID: 21572417)

1/1/2016
3
icon
3

Decreased from 3 to 3

Description

A significant but unreplicated association study of FOXP2 in ASD has been reported. FOXP2 is mutated in specific language impairment, and also physically interacts with FOXP1, which has been implicated in ASD (PMID: 21572417)

Reports Added
[FOXP2 is not a major susceptibility gene for autism or specific language impairment.2002] [Evaluation of FOXP2 as an autism susceptibility gene.2002] [Mutation screening of FOXP2 in individuals diagnosed with autistic disorder.2003] [Absence of causative mutations and presence of autism-related allele in FOXP2 in Japanese autistic patients.2005] [No association of FOXP2 and PTPRZ1 on 7q31 with autism from the Japanese population.2005] [Association study of the CNS patterning genes and autism in Han Chinese in Taiwan.2011] [Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.2011] [Analysis of two language-related genes in autism: a case-control association study of FOXP2 and CNTNAP2.2013] [Association between the FOXP2 gene and autistic disorder in Chinese population.2004] [Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization.2012] [Small intragenic deletion in FOXP2 associated with childhood apraxia of speech and dysarthria.2013] [Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia.2006] [Language features in a mother and daughter of a chromosome 7;13 translocation involving FOXP2.2009] [Epileptic encephalopathies of the Landau-Kleffner and continuous spike and waves during slow-wave sleep types: genomic dissection makes the link wi...2012] [A forkhead-domain gene is mutated in a severe speech and language disorder.2001] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [Identification of FOXP2 truncation as a novel cause of developmental speech and language deficits.2005] [Molecular evolution of FOXP2, a gene involved in speech and language.2002] [Speech, prosody, and voice characteristics of a mother and daughter with a 7;13 translocation affecting FOXP2.2006] [Incomplete and inaccurate vocal imitation after knockdown of FoxP2 in songbird basal ganglia nucleus Area X.2007] [Impaired synaptic plasticity and motor learning in mice with a point mutation implicated in human speech deficits.2008] [Expression of FOXP2 in the developing monkey forebrain: comparison with the expression of the genes FOXP1, PBX3, and MEIS2.2008] [Conservation and diversity of Foxp2 expression in muroid rodents: functional implications.2008] [A functional genetic link between distinct developmental language disorders.2008] [A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice.2009] [Human-specific transcriptional regulation of CNS development genes by FOXP2.2009] [FOXP2 targets show evidence of positive selection in European populations.2013] [Comprehensive molecular testing in patients with high functioning autism spectrum disorder.2016]
1/1/2015
3
icon
3

Decreased from 3 to 3

Description

A significant but unreplicated association study of FOXP2 in ASD has been reported. FOXP2 is mutated in specific language impairment, and also physically interacts with FOXP1, which has been implicated in ASD (PMID: 21572417)

7/1/2014
No data
icon
3

Increased from No data to 3

Description

A significant but unreplicated association study of FOXP2 in ASD has been reported. FOXP2 is mutated in specific language impairment, and also physically interacts with FOXP1, which has been implicated in ASD (PMID: 21572417)

4/1/2014
No data
icon
3

Increased from No data to 3

Description

A significant but unreplicated association study of FOXP2 in ASD has been reported. FOXP2 is mutated in specific language impairment, and also physically interacts with FOXP1, which has been implicated in ASD (PMID: 21572417)

Krishnan Probability Score

Score 0.4932417615921

Ranking 4225/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
ExAC Score

Score 0.99617883109285

Ranking 1434/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.93899153449755

Ranking 14054/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Larsen Cumulative Evidence Score

Score 18

Ranking 111/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Zhang D Score

Score 0.36747956931788

Ranking 1815/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
0610006I08RIK transmembrane protein 223 Mouse Protein Binding 66836 Q9CQE2
1110064P04RIK AHA1, activator of heat shock protein ATPase homolog 2 (yeast) Mouse Protein Binding 268390 Q8N9S3
1200013P24RIK N-acetyltransferase 15 (GCN5-related, putative) Mouse Protein Binding 74763 Q9DBU2
1300010M03RIK family with sequence similarity 134, member C Mouse Protein Binding 67998 Q9CQV4
1700009P03RIK RNA binding motif protein 26 Mouse Protein Binding 74213 Q6NZN0
1700054O13RIK RIKEN cDNA 1700054O13 gene Mouse Protein Binding 67334 A2AF56
1810011O10RIK RIKEN cDNA 1810011O10 gene Mouse Protein Binding 69068 Q9D915
1810037C20RIK family with sequence similarity 3, member A Mouse Protein Binding 66294 Q9D8T0
2010321M09RIK RIKEN cDNA 2010321M09 gene Mouse Protein Binding 69882 Q8R3P6
2200002K05RIK RIKEN cDNA 2200002K05 gene Mouse Protein Binding 69137 Q9D806
2310028H24RIK RIKEN cDNA 2310028H24 gene Mouse Protein Binding 71901 A2ANP1
2310057M21RIK RIKEN cDNA 2310057M21 gene Mouse Protein Binding 68277 Q9D2Q3
2310061I09RIK coiled-coil domain containing 115 Mouse Protein Binding 69668 Q8VE99
2510048L02RIK coiled-coil domain containing 159 Mouse Protein Binding 67119 Q8C963
2810002I04RIK family with sequence similarity 164, member C Mouse Protein Binding 72350 Q8CCG1
2810430M08RIK ribosomal RNA processing 15 homolog (S. cerevisiae) Mouse Protein Binding 67223 Q9CYX7
2900041A09RIK tubulin polymerization promoting protein Mouse Protein Binding 72948 Q7TQD2
3110043J09RIK Rho GTPase activating protein 8 Mouse Protein Binding 73167 Q9CXP4
3200002M19RIK RIKEN cDNA 3200002M19 gene Mouse Protein Binding 75430 P60007
4930408O21RIK PDZ domain containing 9 Mouse Protein Binding 67983 Q9D9M4
4933403G14RIK RIKEN cDNA 4933403G14 gene Mouse Protein Binding 74393 Q8BJS7
8430419L09RIK RIKEN cDNA 8430419L09 gene Mouse Protein Binding 74525 Q8BYI8
9230117E20RIK serine peptidase inhibitor, Kazal type 11 Mouse Protein Binding 78242 Q9D256
A130033B22 predicted gene 5094 Mouse Protein Binding 328839 N/A
A530082C11RIK solute carrier family 35, member E2 Mouse Protein Binding 320541 Q8C811
A730085E03RIK RIKEN cDNA A730085E03 gene Mouse Protein Binding 328983 N/A
A930001M12RIK transmembrane protein 215 Mouse Protein Binding 320500 A7E1Z1
AARD alanine and arginine rich domain containing protein Mouse Protein Binding 239435 Q811W1
ABCA6 ATP-binding cassette, sub-family A (ABC1), member 6 Mouse Protein Binding 76184 Q8K441
ALOX12E arachidonate lipoxygenase, epidermal Mouse Protein Binding 11685 P55249
ARL11 ADP-ribosylation factor-like 11 Mouse Protein Binding 219144 Q6P3A9
ARPM1 actin related protein M1 Mouse Protein Binding 76652 Q8BXF8
BATF2 basic leucine zipper transcription factor, ATF-like 2 Mouse Protein Binding 74481 Q8R1H8
BC019537 solute carrier family 17, member 9 Mouse Protein Binding 228993 Q8VCL5
BC021442 zinc finger protein 758 Mouse Protein Binding 224598 E9Q462
BC035954 cDNA sequence BC035954 Mouse Protein Binding 194162 N/A
BC050188 tripartite motif family-like 1 Mouse Protein Binding 244448 Q8BVP1
BET1 blocked early in transport 1 homolog (S. cerevisiae) Mouse Protein Binding 12068 O35623
C78339 expressed sequence C78339 Mouse Protein Binding 97863 Q3URQ4
CATSPER3 cation channel, sperm associated 3 Mouse Protein Binding 76856 Q80W99
CBLN2 cerebellin 2 precursor protein Mouse Protein Binding 12405 Q8BGU2
CD53 CD53 antigen Mouse Protein Binding 12508 Q61451
CD59A CD59a antigen Mouse Protein Binding 12509 O55186
CDC2L6 cyclin-dependent kinase 19 Mouse Protein Binding 78334 Q8BWD8
CGA glycoprotein hormones, alpha subunit Mouse Protein Binding 12640 P01216
CHRNA1 cholinergic receptor, nicotinic, alpha polypeptide 1 (muscle) Mouse Protein Binding 11435 P04756
COL24A1 collagen, type XXIV, alpha 1 Mouse Protein Binding 71355 Q30D77
COL3A1 collagen, type III, alpha 1 Mouse Protein Binding 12825 P08121
CTRB1 chymotrypsinogen B1 Mouse Protein Binding 66473 Q9CR35
D030041N04RIK leucine zipper-EF-hand containing transmembrane protein 2 Mouse Protein Binding 270035 Q7TNU7
D11ERTD730E SLU7 splicing factor homolog (S. cerevisiae) Mouse Protein Binding 193116 Q8BHJ9
D330045A20RIK RIKEN cDNA D330045A20 gene Mouse Protein Binding 102871 Q8C779
D830007B15RIK shisa homolog 3 (Xenopus laevis) Mouse Protein Binding 330096 Q3UPR0
DSG4 Desmoglein-4 Human Protein Binding 147409 Q86SJ6-2
DSPG3 epiphycan Mouse Protein Binding 13516 P70186
EIF3S10 eukaryotic translation initiation factor 3, subunit A Mouse Protein Binding 13669 P23116
EMX2 empty spiracles homolog 2 (Drosophila) Mouse Protein Binding 13797 Q04744
FAM124A family with sequence similarity 124A Human Protein Binding 220108 Q86V42
FGF1 fibroblast growth factor 1 Mouse Protein Binding 14164 P61148
FMO2 flavin containing monooxygenase 2 Mouse Protein Binding 55990 Q8K2I3
FXYD2 FXYD domain-containing ion transport regulator 2 Mouse Protein Binding 11936 Q04646
GALNACT2 chondroitin sulfate N-acetylgalactosaminyltransferase 2 Mouse Protein Binding 78752 Q8C1F4
GGN gametogenetin Mouse Protein Binding 243897 Q80WJ1
GM1553 predicted gene 1553 Mouse Protein Binding 432480 Q66VB7
IL12B interleukin 12b Mouse Protein Binding 16160 P43432
KLRE1 killer cell lectin-like receptor family E member 1 Mouse Protein Binding 243655 Q8CJC7
LIPC lipase, hepatic Mouse Protein Binding 15450 P27656
LOC433178 serine peptidase inhibitor, Kazal type 14 Mouse Protein Binding 433178 B9EJP9
LRRC15 leucine rich repeat containing 15 Human Protein Binding 131578 Q8TF66
MAGOH mago-nashi homolog, proliferation-associated (Drosophila) Mouse Protein Binding 17149 P61327
MMU-LET-7A-1 microRNA let7a-1 Mouse Protein Binding 387244 N/A
MMU-MIR-137 microRNA 137 Mouse Protein Binding 387155 N/A
MMU-MIR-19B-1 microRNA 19b-2 Mouse Protein Binding 387195 N/A
MMU-MIR-469 microRNA 469 Mouse Protein Binding 723872 N/A
NRN1 neuritin 1 Mouse Protein Binding 68404 Q8CFV4
NSG1 neuron specific gene family member 1 Mouse Protein Binding 18196 Q62092
OC90 otoconin 90 Mouse Protein Binding 18256 Q9Z0L3
OLFR113 olfactory receptor 113 Mouse Protein Binding 258286 Q8VEU4
OLFR1184 olfactory receptor 1184 Mouse Protein Binding 258820 Q8VG86
OLFR131 olfactory receptor 131 Mouse Protein Binding 258867 Q8VGC8
OLFR1388 olfactory receptor 1388 Mouse Protein Binding 258459 Q8VFA3
OLFR139 olfactory receptor 139 Mouse Protein Binding 259005 Q60891
OLFR1465 olfactory receptor 1465 Mouse Protein Binding 258121 Q7TQR2
OLFR26 olfactory receptor 26 Mouse Protein Binding 18324 Q7TRB7
OLFR284 olfactory receptor 284 Mouse Protein Binding 258278 Q8VET7
OLFR305 olfactory receptor 305 Mouse Protein Binding 258609 Q7TS02
OLFR461 olfactory receptor 461 Mouse Protein Binding 258380 Q8VF30
OLFR487 olfactory receptor 487 Mouse Protein Binding 258042 Q7TRU9
OLFR711 olfactory receptor 711 Mouse Protein Binding 259037 Q9EPG2
OLFR723 olfactory receptor 723 Mouse Protein Binding 259147 E9PZU2
OLFR978 olfactory receptor 978 Mouse Protein Binding 259109 E9Q985
PBEF1 nicotinamide phosphoribosyltransferase Mouse Protein Binding 59027 Q99KQ4
PCDHA2 protocadherin alpha 2 Mouse Protein Binding 353234 Q05C01
PCOLN3 chromatin modifying protein 1A Mouse Protein Binding 234852 Q921W0
PIGC phosphatidylinositol glycan anchor biosynthesis, class C Mouse Protein Binding 67292 Q9CXR4
PKDREJ polycystic kidney disease (polycystin) and REJ (sperm receptor for egg jelly homolog, sea urchin) Mouse Protein Binding 18766 Q9Z0T6
PKP3 Plakophilin-3 Human Protein Binding 11187 Q9Y446
PLA2G10 phospholipase A2, group X Mouse Protein Binding 26565 Q9QXX3
PRLPM prolactin family 2, subfamily a, member 1 Mouse Protein Binding 56635 Q9JHK0
PRMT4 coactivator-associated arginine methyltransferase 1 Mouse Protein Binding 59035 Q9WVG6
PRSS2 protease, serine, 2 Mouse Protein Binding 22072 P07146
PSTK phosphoseryl-tRNA kinase Mouse Protein Binding 214580 Q8BP74
PTTG1 pituitary tumor-transforming gene 1 Mouse Protein Binding 30939 Q9CQJ7
RAB3C RAB3C, member RAS oncogene family Mouse Protein Binding 67295 P62823
RAB9B RAB9B, member RAS oncogene family Mouse Protein Binding 319642 Q8BHH2
RHOJ ras homolog gene family, member J Mouse Protein Binding 80837 Q9ER71
RLN1 relaxin 1 Mouse Protein Binding 19773 A2RTV8
RNF17 ring finger protein 17 Mouse Protein Binding 30054 Q99MV7
ROBO4 roundabout homolog 4 (Drosophila) Mouse Protein Binding 74144 Q8C310
S100A2 S100 calcium binding protein A2 Human Protein Binding 6273 P29034
SEMA6D sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6D Mouse Protein Binding 214968 Q76KF0
SLC12A9 solute carrier family 12 (potassium/chloride transporters), member 9 Mouse Protein Binding 83704 Q99MR3
SLC13A3 solute carrier family 13 (sodium-dependent dicarboxylate transporter), member 3 Mouse Protein Binding 114644 Q91Y63
SLC14A1 solute carrier family 14 (urea transporter), member 1 Mouse Protein Binding 108052 Q8VHL0
SLC22A6 solute carrier family 22 (organic anion transporter), member 6 Mouse Protein Binding 18399 Q8VC69
SLC24A1 solute carrier family 24 (sodium/potassium/calcium exchanger), member 1 Mouse Protein Binding 214111 Q91WD8
SMC5L1 structural maintenance of chromosomes 5 Mouse Protein Binding 226026 Q8CG46
SPATA17 spermatogenesis associated 17 Mouse Protein Binding 74717 Q9D552
SPESP1 sperm equatorial segment protein 1 Mouse Protein Binding 66712 Q9D5A0
SRPX2 sushi-repeat containing protein, X-linked 2 Human DNA Binding 27286 O60687
STEAP1 six transmembrane epithelial antigen of the prostate 1 Mouse Protein Binding 70358 Q9CWR7
SVS1 seminal vesicle secretory protein 1 Mouse Protein Binding 243377 Q6WIZ7
TAAR5 trace amine-associated receptor 5 Mouse Protein Binding 215854 Q5QD14
TBC1D19 TBC1 domain family, member 19 Mouse Protein Binding 67249 Q8VDV7
TCFAP2D transcription factor AP-2, delta Mouse Protein Binding 226896 Q91ZK0
TCTE1 t-complex-associated testis expressed 1 Mouse Protein Binding 21645 A6H639
TMEM55A transmembrane protein 55A Mouse Protein Binding 72519 Q9CZX7
TRAF3IP3 TRAF3 interacting protein 3 Mouse Protein Binding 215243 Q8C0G2
TSACC TSSK6 activating co-chaperone Human Protein Binding 128229 Q96A04
TSPAN10 tetraspanin 10 Mouse Protein Binding 208634 Q8VCF5
V1RB1 vomeronasal 1 receptor 50 Mouse Protein Binding 113852 Q9EP51
WBP5 WW domain binding protein 5 Mouse Protein Binding 22381 Q9DD24
ZCCHC5 zinc finger, CCHC domain containing 5 Mouse Protein Binding 213436 Q6P1Y1
ZFP248 zinc finger protein 248 Mouse Protein Binding 72720 Q640N4
ZFP36 zinc finger protein 36 Mouse Protein Binding 22695 P22893
ZFP521 zinc finger protein 521 Mouse Protein Binding 225207 Q6KAS7
ZSWIM2 zinc finger, SWIM domain containing 2 Mouse Protein Binding 71861 Q9D9X6
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