Summary Statistics:
ASD Reports: 11
Recent Reports: 2
Annotated variants: 5
Associated CNVs: 6
Evidence score: 2
Gene Score: 4
Relevance to Autism
Genetic association of common variants in the GTF2I gene have been associated with autism (Malenfant et al., 2011). In addition, rare variants in the region surrounding GTF2I may be associated with Williams syndrome (Morris et al., 2003).
Molecular Function
A multifunctional phosphoprotein with roles in transcription and signal transduction.
References
Primary
Association of GTF2i in the Williams-Beuren syndrome critical region with autism spectrum disorders.
ASD
Support
Autism risk in offspring can be assessed through quantification of male sperm mosaicism.
ASD
Support
Williams-Beuren syndrome
Support
ASD, chromosome 7q11.23 duplication syndrome
Support
Williams-Beuren syndrome, 7q11.23 duplication synd
Highly Cited
GTF2I hemizygosity implicated in mental retardation in Williams syndrome: genotype-phenotype analysis of five families with deletions in the Willia...
Williams syndrome
Highly Cited
Williams syndrome deficits in visual spatial processing linked to GTF2IRD1 and GTF2I on chromosome 7q11.23.
Recent Recommendation
Expression of the transcription factor, TFII-I, during post-implantation mouse embryonic development.
Recent Recommendation
An SNP in an ultraconserved regulatory element affects Dlx5/Dlx6 regulation in the forebrain.
GEN116R001
stop_gained
c.427C>T
p.Arg143Ter
De novo
Simplex
GEN116R002
missense_variant
c.508C>T
p.Leu170%3D
De novo
GEN116R003
splice_site_variant
c.557+2T>G
De novo
Simplex
GEN116C001
intron_variant
rs4717907
c.-6+14101A>G;c.-6+14101G>A;c.10+13152A>G
A/G
AGRE, ASD-CARC
Discovery
GEN116C002
intron_variant
rs13227433
c.-5-8738G>T;c.-5-8738T>G;c.11-8738G>T;c.-6+1165G>T
AGRE, ASD-CARC
Discovery
7
Deletion-Duplication
78
Summary Statistics:
# of Reports: 2
# of Models: 5
Model Summary
Involvement in several aspects of embryonic development and the development of social neurocircuitry; contributor to hypersociability in Williams Syndrome.
References
Primary
Haploinsufficiency of Gtf2i, a gene deleted in Williams Syndrome, leads to increases in social interactions.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Gene-trapping strategy inserted immediately after exon 3 in Gtf2i gene.
Allele Type: Targeted (Knock-out)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Gene-trapping strategy inserted immediately after exon 3 in Gtf2i gene.
Allele Type: Targeted (Knock-out)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
The Gtf2i knockout allele (MGI:3880452) was generated using a gene trap vector inserted into intron 3. The heterozygous mutant was one functional copy of the Gtf2i gene.
Allele Type: Knockout
Strain of Origin: 129P2/OlaHsd
Genetic Background: CD-1
ES Cell Line: Not specified
Mutant ES Cell Line:
Model Source: Bay Genomics
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
A Gtf2i knock-in mutation (MGI:5490970) was generated by Cre-mediated recombination between loxP sites in intron 4 of Gtf2ird1Gt(XS0608)Wtsi and downstream of exon 34 of Gtf2itm1Lro, resulting in a duplication of the intervening sequence. The heterozygous knock-in has a duplication of the Gtf2i gene in one allele, with a total gene dosage of three.
Allele Type: Knockin
Strain of Origin: 129
Genetic Background: CD-1
ES Cell Line: E14TG2a.4; R1
Mutant ES Cell Line:
Model Source: Lucy Osborne
Abnormal
View More
Description: Abnormal brain development resulting in exencephaly
Exp Paradigm: Brain size measurements
Histology
Unreported
Developmental trajectory1
Abnormal
View More
Description: Abnormal developmental trajectory demonstrated by neural tube closure defect
Exp Paradigm: Histology
Histology
Unreported
Increased
View More
Description: Increased lethality demonstrated by no living pups
Exp Paradigm: General observations
General observations
Unreported
Decreased
View More
Description: Decreased expression of gtf2i in embryo
Exp Paradigm: Gtf2i gene expression
Western blot
E14
Not Reported:
Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior
Decreased
View More
Description: Decreased social interaction demonstrated by failure to habituate to social stimuli
Exp Paradigm: Three chamber social interaction test
Three-chamber social approach test
Unreported
Decreased
View More
Description: Decreased social approach demonstrated by lesser habituation
Exp Paradigm: Social preference test in open field
Three-chamber social approach test
Unreported
Object recognition memory1
Decreased
View More
Description: Decreased preference for novelty demonstrating equal amount of time exploring novel vs. familiar object
Exp Paradigm: Two choice paradigm in open field test
Novel object recognition test
Unreported
Decreased
View More
Description: Decreased expression of gtf2i in embryo
Exp Paradigm: Gtf2i gene expression
Western blot
E14
No change
Elevated zero maze test
Unreported
Cued or contextual fear conditioning: memory of context1
No change
Fear conditioning test
Unreported
Spatial reference memory1
No change
Morris water maze test
Unreported
No change
Y-maze test
Unreported
No change
Quantitative pcr (qrt-pcr)
Unreported
General locomotor activity1
No change
Open field test
Unreported
Motor coordination and balance1
No change
Accelerating rotarod test
Unreported
No change
Prepulse inhibition
Unreported
Startle response: acoustic stimulus1
No change
Acoustic startle reflex test
Unreported
Not Reported:
Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Maternal behavior, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure
Cell proliferation: neural precursors1
Increased
View More
Description: Gtf2i heterozygous mice show an increase phospho-Histone H3 (Phh3) in the developing cortex. Phh3 is a marker for proliferating cells expressed just before mitosis.
Exp Paradigm: Phh3, Ki67
Immunohistochemistry
E17.5
Dendritic architecture: dendritic tree complexity1
Decreased
View More
Description: Gtf2i heterozygous mice show altered neuronal morphology compared with wildtype, with fewer dendritic branches and lower number of dendrites.
Fluorescence microscopy
P7.5
No change
Immunohistochemistry
E17.5
Neuronal differentiation1
No change
Immunohistochemistry
E17.5
No change
Fluorescence microscopy
E17.5
Not Reported:
Decreased
View More
Description: Gtf2i heterozygous duplication mutant mice show aberrant neuronal orientation. Neurons were stalled between subventricular zone and intermediate zone, failing to migrate into the cortical plate.
Fluorescence microscopy
E17.5
Cell proliferation: neural precursors1
Increased
View More
Description: Gtf2i heterozygous duplication mutant mice show an increase in Ki67-positive cells in the developing cortex. Ki67 is a marker for cells throughout the entire cell cycle and even expressed in non-actively proliferating cells.
Exp Paradigm: Phh3, Ki67
Immunohistochemistry
E17.5
Neuronal differentiation1
Decreased
View More
Description: Gtf2i heterozygous duplication mutant mice show a decrease in Tbr2-expressing intermediate progenitor neurons in the developing cortex.
Exp Paradigm: Tbr2
Immunohistochemistry
E17.5
Dendritic architecture: dendritic tree complexity1
Decreased
View More
Description: Gtf2i heterozygous duplication mutant mice show altered neuronal morphology compared with wildtype, with fewer dendritic branches and lower number of dendrites.
Fluorescence microscopy
P7.5
Abnormal
View More
Description: Gtf2i heterozygous duplication mutant mice show an increase in cells expressing Bcl11b or Cux1, markers for upper and lower cortical layers, in the developing cortex.
Exp Paradigm: Bcl11b, Cux1
Immunohistochemistry
E17.5
Decreased
View More
Description: Gtf2i heterozygous duplication mutant mice show no preference for a novel social stimulus over a familiar one, unlike wildtype mice.
Three-chamber social approach test
unreported
Decreased
View More
Description: Gtf2i heterozygous duplication mutant mice show no preference for a social stimulus over an object, unlike wildtype mice.
Three-chamber social approach test
unreported
Not Reported:
Summary Statistics:
Total Interactions: 102
Total Publications: 54
Show all nodes
Hide non-ASD
Interactor Symbol
Interactor Name
Interactor Organism
Entrez ID
Uniprot ID
Interaction Type
Evidence
Reference
ADSL
adenylosuccinate lyase
158
P30566
Size-exclusion chromatography (SEC); PCP; SILAC
Kristensen AR , et al. 2012
AP2B1
adaptor-related protein complex 2, beta 1 subunit
163
P63010
Y2H
Corominas R , et al. 2014
AP4S1
adaptor-related protein complex 4, sigma 1 subunit
11154
Q9Y587
Y2H
Wang J , et al. 2011
ATF6
activating transcription factor 6
22926
A8K383
IP/WB; CAT reporter assay; EMSA
Parker R , et al. 2001
BRCA1
breast cancer 1, early onset
672
P38398
IP/WB; Co-localization; Luciferase reporter assay
Tanikawa M , et al. 2011
Btk
Bruton agammaglobulinemia tyrosine kinase
12229
P35991
IP/WB
Sacristn C , et al. 2003
C4BPA
C4b-binding protein alpha chain
722
P04003
Y2H
Wang J , et al. 2011
CALM1
calmodulin 1 (phosphorylase kinase, delta)
617095
P62157
mRNA display; Affinity chromatography
Shen X , et al. 2005
CBX2
chromobox homolog 2
84733
Q14781
TAP; MS
Vandamme J , et al. 2011
CDK2
cyclin-dependent kinase 2
1017
P24941
IP; LC-MS/MS
Neganova I , et al. 2011
CHAF1A
chromatin assembly factor 1, subunit A (p150)
10036
Q13111
IP; MALDI-TOF; MS
Hoek M , et al. 2011
CHD8
chromodomain helicase DNA binding protein 8
57680
Q9HCK8
CHIP-seq
Cotney J , et al. 2015
CTCF
CCCTC-binding factor (zinc finger protein)
10664
B5MC38
IP; LC-MS/MS; IP/WB; Co-localization
Pea-Hernndez R , et al. 2015
CTPS2
CTP synthase 2
56474
Q9NRF8
Size-exclusion chromatography (SEC); PCP; SILAC
Kristensen AR , et al. 2012
CUL3
cullin 3
8452
B7Z600
IP; MS/MS
IP; MS; COMPASS
Bennett EJ , et al. 2010
CYP1A1
Cytochrome P450 1A1
1543
P04798
IP; LC-MS/MS
Huttlin EL , et al. 2015
DNMT3B
DNA (cytosine-5-)-methyltransferase 3 beta
1789
Q9UBC3
IP; LC-MS/MS
Adamo A , et al. 2014
DPY30
dpy-30 homolog (C. elegans)
84661
Q9C005
Y2H
Corominas R , et al. 2014
EED
embryonic ectoderm development
8726
O75530
IP; LC-MS/MS
Cao Q , et al. 2014
EEF1A1
eukaryotic translation elongation factor 1 alpha 1
1915
P68104
LC-MS/MS
Havugimana PC , et al. 2012
FBXO6
F-box only protein 6
26270
Q9NRD1
IP; LC-MS/MS
Liu B , et al. 2012
FMR1
fragile X mental retardation 1
2332
G8JLE9
PAR-CLIP
Ascano M Jr , et al. 2012
FXR1
Fragile X retardation 1
8087
P51114
IP; LC-MS/MS
Adamo A , et al. 2014
GCC1
GRIP and coiled-coil domain containing 1
79571
Q96CN9
Y2H
Corominas R , et al. 2014
GTF2IRD2B
General transcription factor II-I repeat domain-containing protein 2B
389524
Q6EKJ0
IP; LC-MS/MS
Huttlin EL , et al. 2015
HDAC1
histone deacetylase 1
3065
Q13547
IP/WB
Wen YD , et al. 2002
HDAC2
histone deacetylase 2
3066
Q92769
Ion-exchange chromatography; LC-MS/MS; Size-exclusion chromatography (SEC); Affinity chromatography; WB
Hakimi MA , et al. 2002
HDAC2
histone deacetylase 2
3066
Q92769
IP; LC-MS/MS
Adamo A , et al. 2014
HDAC3
Histone deacetylase 3
8841
O15379
Affinity chromatography; LC-MS/MS; IP/WB; GST; Co-localization
Wen YD , et al. 2002
HNRNPH1
heterogeneous nuclear ribonucleoprotein H1 (H)
3187
P31943
LC-MS/MS
Havugimana PC , et al. 2012
INPPL1
inositol polyphosphate phosphatase-like 1
3636
O15357
IP; LC-MS/MS
Brehme M , et al. 2009
Jak2
Janus kinase 2
16452
Q62120
in vitro kinase assay; Luciferase reporter assay
Kim DW and Cochran BH 2001
KDM1A
lysine (K)-specific demethylase 1A
23028
O60341
Ion-exchange chromatography; LC-MS/MS; Size-exclusion chromatography (SEC); Affinity chromatography; WB
Hakimi MA , et al. 2002
KDM1A
lysine (K)-specific demethylase 1A
23028
O60341
IP; LC-MS/MS; IP/WB
Adamo A , et al. 2014
LGALS1
Galectin-1
3956
P09382
IP/WB
Voss PG , et al. 2008
LGALS3
Galectin-3
3958
P17931
IP; LC-MS/MS; WB
Voss PG , et al. 2008
Mad2l2
MAD2 mitotic arrest deficient-like 2
71890
Q9D752
IP; LC-MS/MS
Hutchins JR , et al. 2010
MAGEA1
melanoma antigen family A, 1 (directs expression of antigen MZ2-E)
4100
P43355
IP; LC-MS/MS
Huttlin EL , et al. 2015
MAP3K3
mitogen-activated protein kinase kinase kinase 3
4215
Q99759
Y2H
Wang J , et al. 2011
MAPK12
mitogen-activated protein kinase 12
6300
P53778
Y2H
Wang J , et al. 2011
Mapk3
mitogen-activated protein kinase 3
5595
P27361
IP/WB; in vitro kinase assay
IP/WB; in vitro kinase assay; Luciferase reporter assay
Kim DW and Cochran BH 2000
MEPCE
methylphosphate capping enzyme
56257
Q7L2J0
IP; LC-MS/MS
Jeronimo C , et al. 2007
METTL1
tRNA (guanine-N(7)-)-methyltransferase
4234
Q9UBP6
Size-exclusion chromatography (SEC); PCP; SILAC
Kristensen AR , et al. 2012
MTUS2
microtubule associated tumor suppressor candidate 2
23281
J3KQA9
Y2H
Corominas R , et al. 2014
MYC
v-myc myelocytomatosis viral oncogene homolog (avian)
4609
P01106
IP/WB; EMSA; CAT reporter assay
Roy AL , et al. 1993
NAA38
N(alpha)-acetyltransferase 38, NatC auxiliary subunit
51691
A4D0W0
Y2H
Lehner B and Sanderson CM 2004
NFI1
NA
Y2H
Tussie-Luna MI , et al. 2002
NRF1
nuclear respiratory factor 1
4899
Q16656
ChIP
Satoh J , et al. 2013
NUCB1
nucleobindin 1
4924
A8K7Q1
Size-exclusion chromatography (SEC); PCP; SILAC
Kristensen AR , et al. 2012
OTUB2
OTU domain, ubiquitin aldehyde binding 2
78990
Q96DC9
IP; LC-MS/MS
Sowa ME , et al. 2009
PDHA1
pyruvate dehydrogenase (lipoamide) alpha 1
5160
P08559
LC-MS/MS
Havugimana PC , et al. 2012
PGPEP1
pyroglutamyl-peptidase I
54858
Q9NXJ5
IP; LC-MS/MS
Huttlin EL , et al. 2015
PHF21A
PHD finger protein 21A
51317
Q96BD5
Ion-exchange chromatography; LC-MS/MS
Hakimi MA , et al. 2002
PIAS2
protein inhibitor of activated STAT, 2
9063
O75928
Y2H
Corominas R , et al. 2014
Pias2
protein inhibitor of activated STAT 2
17344
Q8C5D8
Y2H; IP/WB; Co-localization; Luciferase reporter assay
Tussie-Luna MI , et al. 2002
POU2AF1
POU domain class 2-associating factor 1
5450
Q16633
S-tag pull-down assay; LC-MS/MS; IP/WB; GST
Ren X , et al. 2011
PRKDC
protein kinase, DNA-activated, catalytic polypeptide
5591
P78527
Size-exclusion chromatography (SEC); PCP; SILAC
Kristensen AR , et al. 2012
PRKG1
protein kinase, cGMP-dependent, type I
5592
Q13976
Y2H; GST; IP/WB; in vitro kinase assay; Co-localization; Luciferase reporter assay
Casteel DE , et al. 2002
PRPS2
phosphoribosyl pyrophosphate synthetase 2
5634
P11908
Size-exclusion chromatography (SEC); PCP; SILAC
Kristensen AR , et al. 2012
PRRX1
paired related homeobox 1
5396
P54821
IP/WB; Affinity chromatography; CAT reporter assay
Grueneberg DA , et al. 1997
PTP4A3
Protein tyrosine phosphatase type IVA 3
11156
O75365
LC/ESI/MS/MS
Ewing RM , et al. 2007
RAD23B
RAD23 homolog B (S. cerevisiae)
5887
P54727
Size-exclusion chromatography (SEC); PCP; SILAC
Kristensen AR , et al. 2012
RCOR2
REST corepressor 2
283248
Q8IZ40
IP; LC-MS/MS
Adamo A , et al. 2014
RNF2
ring finger protein 2
6045
Q99496
IP; LC-MS/MS
Cao Q , et al. 2014
RPA1
replication protein A1, 70kDa
6117
P27694
Affinity chromatography; LC-MS/MS; in vitro ubiquitination assay
Marchal A , et al. 2013
RPA2
replication protein A2, 32kDa
6118
P15927
Affinity chromatography; LC-MS/MS; in vitro ubiquitination assay
Marchal A , et al. 2013
RPA3
replication protein A3, 14kDa
6119
A4D105
Affinity chromatography; LC-MS/MS; in vitro ubiquitination assay
Marchal A , et al. 2013
RPL28
ribosomal protein L28
6158
P46779
Size-exclusion chromatography (SEC); PCP; SILAC
Kristensen AR , et al. 2012
SIRT7
sirtuin 7
51547
Q9NRC8
IP; LC-MS/MS
Tsai YC , et al. 2012
SLU7
SLU7 splicing factor homolog (S. cerevisiae)
10569
O95391
IP/WB
Voss PG , et al. 2008
SMAD2
103222457
IP/WB; Luciferase reporter assay
Ku M , et al. 2005
SNRPN
small nuclear ribonucleoprotein polypeptide N
6638
P63162
IP/WB
Voss PG , et al. 2008
SOST
Sclerostin
50964
Q9BQB4
IP; LC-MS/MS
Huttlin EL , et al. 2015
SRF
serum response factor (c-fos serum response element-binding transcription factor)
6722
P11831
IP/WB; Affinity chromatography
Grueneberg DA , et al. 1997
SRRM1
serine/arginine repetitive matrix 1
10250
Q8IYB3
IP; LC-MS/MS
McCracken S , et al. 2005
SRRM2
serine/arginine repetitive matrix 2
23524
Q9UQ35
IP; MS
McCracken S , et al. 2005
SRSF9
serine/arginine-rich splicing factor 9
8683
Q13242
LC-MS/MS
Havugimana PC , et al. 2012
Stat1
signal transducer and activator of transcription 1
20846
P42225
IP/WB
Kim DW , et al. 1998
STAT3
signal transducer and activator of transcription 3 (acute-phase response factor)
6774
P40763
IP/WB
Kim DW , et al. 1998
SUMO1
SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae)
7341
P63165
IVEC; WB
Gocke CB , et al. 2004
SUMO2
SMT3 suppressor of mif two 3 homolog 2 (S. cerevisiae)
6613
P61956
SILAC; TAP; LC-MS/MS
Tatham MH , et al. 2011
SUV420H2
suppressor of variegation 4-20 homolog 2 (Drosophila)
84787
Q86Y97
IP; LC-MS/MS
Souza PP , et al. 2009
SUZ12
suppressor of zeste 12 homolog (Drosophila)
23512
A8K1U9
IP/WB
Crusselle-Davis VJ , et al. 2007
TAB2
TGF-beta activated kinase 1/MAP3K7 binding protein 2
23118
B4DIR9
Y2H
Wang J , et al. 2011
TFAP4
transcription factor AP-4 (activating enhancer binding protein 4)
7023
Q01664
DNA affinity precipitation
Ku WC , et al. 2009
TIGD6
tigger transposable element derived 6
81789
Q17RP2
IP; LC-MS/MS
Huttlin EL , et al. 2015
TOP2A
topoisomerase (DNA) II alpha 170kDa
7153
P11388
IP; LC-MS/MS
Adamo A , et al. 2014
TOP3B
topoisomerase (DNA) III beta
8940
O95985
HITS-CLIP
Xu D , et al. 2013
TOPORS
topoisomerase I binding, arginine/serine-rich, E3 ubiquitin protein ligase
10210
Q9NS56
in vitro SUMOylation assay; Affinity chromatography; LC-MS/MS
Pungaliya P , et al. 2007
TRAF6
TNF receptor-associated factor 6, E3 ubiquitin protein ligase
7189
Q9Y4K3
Y2H
Corominas R , et al. 2014
UBC
ubiquitin C
7316
P63279
LC-MS/MS
Danielsen JM , et al. 2010
UBD
ubiquitin D
10537
O15205
IP; LC-MS/MS
Leng L , et al. 2013
USF1
upstream transcription factor 1
NM_207005
P22415
IP/WB
Crusselle-Davis VJ , et al. 2006
USP7
ubiquitin specific peptidase 7 (herpes virus-associated)
7874
Q93009
IP; LC-MS/MS
Sowa ME , et al. 2009
WARS
tryptophanyl-tRNA synthetase
7453
P23381
Size-exclusion chromatography (SEC); PCP; SILAC
Kristensen AR , et al. 2012
ZMYM2
zinc finger, MYM-type 2
7750
Q9UBW7
IP; LC-MS/MS
Adamo A , et al. 2014
ZMYM3
zinc finger, MYM-type 3
9203
Q14202
Y2H
Corominas R , et al. 2014
ZMYM3
zinc finger, MYM-type 3
9203
Q14202
IP; LC-MS/MS
Adamo A , et al. 2014
ZNF428
zinc finger protein 428
126299
I6L9C8
IP; LC-MS/MS
Huttlin EL , et al. 2015
Rbfox1
RNA binding protein, fox-1 homolog (C. elegans) 1
268859
Q9JJ43
HITS-CLIP
Weyn-Vanhentenryck SM , et al. 2014
Stx7
Syntaxin-7
O70439
IP; LC-MS/MS
Wade N , et al. 2001
MIB1
mindbomb E3 ubiquitin protein ligase 1
307594
D3ZUV2
Affinity chromatography; LC-MS/MS
Mertz J , et al. 2015