Human Gene Module / Chromosome 7 / GIGYF1

GIGYF1GRB10 interacting GYF protein 1

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
4 / 5
Rare Variants / Common Variants
8 / 0
Aliases
GIGYF1, PP3360,  GYF1,  PERQ1
Associated Syndromes
Tourette syndrome
Genetic Category
Rare Single Gene Mutation
Chromosome Band
7q22.1
Associated Disorders
-
Relevance to Autism

Two de novo loss-of-function variants in the GIGYF1 gene have been identified in ASD probands from the Simons Simplex Collection (refs).

Molecular Function

The protein encoded by this gene may act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling and may increase IGF1 receptor phosphorylation under IGF1 stimulation as well as phosphorylation of IRS1 and SHC1 (by similarity).

Reports related to GIGYF1 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
2 Support Excess of rare, inherited truncating mutations in autism. Krumm N , et al. (2015) Yes -
3 Positive Association De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Willsey AJ , et al. (2017) No -
4 Support Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model. Guo H , et al. (2018) Yes -
5 Support Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort. Callaghan DB , et al. (2019) Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2761+2T>C - splice_site_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
c.2688_2689delA - frameshift_variant Unknown - Simplex 31038196 Callaghan DB , et al. (2019)
c.3034C>T p.His1012Tyr missense_variant De novo - Simplex 28472652 Willsey AJ , et al. (2017)
c.242C>T p.Pro81Leu missense_variant Familial Paternal Simplex 30564305 Guo H , et al. (2018)
c.707G>A p.Arg236His missense_variant Familial Maternal Simplex 30564305 Guo H , et al. (2018)
c.1140_1156del p.Gly380fs frameshift_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.163A>G p.Lys55Glu missense_variant Unknown Not maternal Multiplex 30564305 Guo H , et al. (2018)
c.1485_1486insAGATG p.Ala496fs frameshift_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

3

Score Delta: Score remained at 3.3

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

4/1/2017
3
icon
3

Score remained at 3

Description

Two de novo LoF variants in the GIGYF1 gene (both frameshift) were identified in ASD probands from the Simons Simplex Collection (PMID 25363768).

4/1/2015
3
icon
3

Score remained at 3

Description

Two de novo LoF variants in the GIGYF1 gene (both frameshift) were identified in ASD probands from the Simons Simplex Collection (PMID 25363768).

10/1/2014
icon
3

Increased from to 3

Description

Two de novo LoF variants in the GIGYF1 gene (both frameshift) were identified in ASD probands from the Simons Simplex Collection (PMID 25363768).

Krishnan Probability Score

Score 0.44633276596467

Ranking 14840/25841 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 0.97870481168011

Ranking 2177/18225 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 0.018633889054451

Ranking 33/18665 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 12

Ranking 158/461 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 0.36416429410477

Ranking 1858/20870 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.
CNVs associated with GIGYF1(1 CNVs)
7q22.1 21 Deletion-Duplication 37  /  143
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