Human Gene Module / Chromosome 7 / GTF2I

GTF2Igeneral transcription factor IIi

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 11
Rare Variants / Common Variants
3 / 2
Aliases
GTF2I, WBS,  DIWS,  SPIN,  IB291,  BAP135,  BTKAP1,  TFII-I,  WBSCR6,  GTFII-I,  FLJ38776
Associated Syndromes
Williams syndrome, Williams-Beuren syndrome, 7q11.23 duplication synd, ASD, chromosome 7q11.23 duplication syndrome, Williams-Beuren syndrome
Chromosome Band
7q11.23
Associated Disorders
-
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.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to GTF2I (11 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Williams syndrome deficits in visual spatial processing linked to GTF2IRD1 and GTF2I on chromosome 7q11.23 Hirota H , et al. (2003) No -
2 Highly Cited GTF2I hemizygosity implicated in mental retardation in Williams syndrome: genotype-phenotype analysis of five families with deletions in the Williams syndrome region Morris CA , et al. (2003) No -
3 Recent Recommendation Expression of the transcription factor, TFII-I, during post-implantation mouse embryonic development Fijalkowska I , et al. (2010) No -
4 Recent Recommendation An SNP in an ultraconserved regulatory element affects Dlx5/Dlx6 regulation in the forebrain Poitras L , et al. (2010) No -
5 Primary Association of GTF2i in the Williams-Beuren syndrome critical region with autism spectrum disorders Malenfant P , et al. (2011) Yes -
6 Support Autism risk in offspring can be assessed through quantification of male sperm mosaicism Breuss MW , et al. (2019) Yes -
7 Support - Yuan B et al. (2023) Yes -
8 Support - Wang J et al. (2023) Yes -
9 Support - Emma Strong et al. (2023) No -
10 Support - Alejandro López-Tobón et al. (2023) Yes -
11 Support - Jason W Adams et al. (2024) No -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.508C>T p.Leu170%3D missense_variant De novo - - 36881370 Yuan B et al. (2023)
c.557+2T>G - splice_site_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.427C>T p.Arg143Ter stop_gained De novo - Simplex 31873310 Breuss MW , et al. (2019)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.-6+14101A>G;c.-6+14101G>A;c.10+13152A>G A/G intron_variant - - - 22048961 Malenfant P , et al. (2011)
c.-5-8738G>T;c.-5-8738T>G;c.11-8738G>T;c.-6+1165G>T - intron_variant - - - 22048961 Malenfant P , et al. (2011)
SFARI Gene score
2

Strong Candidate

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).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 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
3
icon
2

Decreased from 3 to 2

Description

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).

1/1/2020
3
icon
3

Decreased from 3 to 3

Description

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).

Reports Added
[Autism risk in offspring can be assessed through quantification of male sperm mosaicism.2019]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

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).

Reports Added
[New Scoring Scheme]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

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).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

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).

Krishnan Probability Score

Score 0.49343047536835

Ranking 4159/25841 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.
Original Source
ExAC Score

Score 0.99934868993106

Ranking 986/18225 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
Original Source
Sanders TADA Score

Score 0.9418698504808

Ranking 15093/18665 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).
Original Source
Larsen Cumulative Evidence Score

Score 2

Ranking 390/461 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.
Original Source
Zhang D Score

Score 0.029761750774249

Ranking 7790/20870 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.
Original Source
CNVs associated with GTF2I(1 CNVs)
Sort By:
7q11.23 86 Deletion-Duplication 116  /  461
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
CYP1A1 Cytochrome P450 1A1 Human Protein Binding 1543 P04798
DPY30 dpy-30 homolog (C. elegans) Human Protein Binding 84661 Q9C005
FBXO6 F-box only protein 6 Human Protein Binding 26270 Q9NRD1
GTF2IRD2B General transcription factor II-I repeat domain-containing protein 2B Human Protein Binding 389524 Q6EKJ0
LGALS3 Galectin-3 Human Protein Binding 3958 P17931
MAGEA1 melanoma antigen family A, 1 (directs expression of antigen MZ2-E) Human Protein Binding 4100 P43355
METTL1 tRNA (guanine-N(7)-)-methyltransferase Human Protein Binding 4234 Q9UBP6
NFI1 Baker's yeast Protein Binding NA
POU2AF1 POU domain class 2-associating factor 1 Human Protein Binding 5450 Q16633
PTP4A3 Protein tyrosine phosphatase type IVA 3 Human Protein Binding 11156 O75365
SOST Sclerostin Human Protein Binding 50964 Q9BQB4
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