Human Gene Module / Chromosome 14 / YY1

YY1YY1transcription factor

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
3 / 9
Rare Variants / Common Variants
29 / 0
Aliases
YY1, DELTA,  INO80S,  NF-E1,  UCRBP,  YIN-YANG-1
Associated Syndromes
Gabriele-de Vries syndrome, DD, ID
Chromosome Band
14q32.2
Associated Disorders
ASD
Relevance to Autism

Phenotypic information from 23 individuals with de novo mutations or deletions of the YY1 gene was used to identify an intellectual disability syndrome characterized by behavioral abnormalities, intrauterine growth retardation, feeding problems, recurrent dysmorphic features, and various congenital malformations; two of the ten individuals with de novo YY1 mutations presented with autism or ASD (Gabriele et al., 2017). YY1 had previously been shown to interact with MECP2 (Forlani et al., 2010) and HCFC1 (Huang et al., 2012).

Molecular Function

YY1 is a ubiquitously distributed transcription factor belonging to the GLI-Kruppel class of zinc finger proteins. The protein is involved in repressing and activating a diverse number of promoters. YY1 may direct histone deacetylases and histone acetyltransferases to a promoter in order to activate or repress the promoter, thus implicating histone modification in the function of YY1.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to YY1 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The MeCP2/YY1 interaction regulates ANT1 expression at 4q35: novel hints for Rett syndrome pathogenesis Forlani G , et al. (2010) No -
2 Support A noncoding, regulatory mutation implicates HCFC1 in nonsyndromic intellectual disability Huang L , et al. (2012) No -
3 Primary YY1 Haploinsufficiency Causes an Intellectual Disability Syndrome Featuring Transcriptional and Chromatin Dysfunction Gabriele M , et al. (2017) No ASD
4 Support Both rare and common genetic variants contribute to autism in the Faroe Islands Leblond CS , et al. (2019) Yes -
5 Support Identification of De Novo JAK2 and MAPK7 Mutations Related to Autism Spectrum Disorder Using Whole-Exome Sequencing in a Chinese Child and Adolescent Trio-Based Sample Jiao J , et al. (2019) Yes -
6 Support - Cherik F et al. (2022) No ASD, ADHD, stereotypy
7 Support - Zhou X et al. (2022) Yes -
8 Support - Chaves LD et al. (2023) No -
9 Support - Spataro N et al. (2023) No -
Rare Variants   (29)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 35027293 Cherik F et al. (2022)
- - copy_number_loss De novo - - 28575647 Gabriele M , et al. (2017)
- - copy_number_loss Unknown - - 28575647 Gabriele M , et al. (2017)
- p.His320Arg missense_variant De novo - - 35027293 Cherik F et al. (2022)
- p.Val374Gly missense_variant De novo - - 35027293 Cherik F et al. (2022)
c.1062+1G>A - splice_site_variant De novo - - 36943625 Chaves LD et al. (2023)
c.535A>T p.Lys179Ter stop_gained De novo - - 28575647 Gabriele M , et al. (2017)
c.1135G>A p.Gly379Arg missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1030C>T p.Gln344Ter stop_gained De novo - - 28575647 Gabriele M , et al. (2017)
c.527G>A p.Gly176Asp missense_variant De novo - - 35027293 Cherik F et al. (2022)
c.908G>T p.Cys303Phe missense_variant De novo - - 35027293 Cherik F et al. (2022)
c.1001T>C p.Phe334Ser missense_variant De novo - - 35027293 Cherik F et al. (2022)
c.1007A>G p.Glu336Gly missense_variant De novo - - 35027293 Cherik F et al. (2022)
c.1112G>A p.Arg371His missense_variant De novo - - 35027293 Cherik F et al. (2022)
c.1124G>A p.Arg375Gln missense_variant De novo - - 35027293 Cherik F et al. (2022)
c.1036G>T p.Val346Phe missense_variant Unknown - - 36980980 Spataro N et al. (2023)
c.958C>T p.His320Tyr missense_variant De novo - - 28575647 Gabriele M , et al. (2017)
c.1015A>C p.Lys339Gln missense_variant De novo - - 28575647 Gabriele M , et al. (2017)
c.1096C>G p.Leu366Val missense_variant De novo - - 28575647 Gabriele M , et al. (2017)
c.1097T>C p.Leu366Pro missense_variant De novo - - 28575647 Gabriele M , et al. (2017)
c.1138G>T p.Asp380Tyr missense_variant De novo - - 28575647 Gabriele M , et al. (2017)
c.961G>A p.Gly321Ser missense_variant De novo - Simplex 31838722 Jiao J , et al. (2019)
c.690dup p.Asp231ArgfsTer3 frameshift_variant De novo - - 35027293 Cherik F et al. (2022)
c.1177_1179del p.Lys393del inframe_deletion De novo - - 28575647 Gabriele M , et al. (2017)
c.1067C>T p.Thr356Met missense_variant Familial Paternal - 35027293 Cherik F et al. (2022)
c.385del p.Asp129IlefsTer127 frameshift_variant De novo - - 28575647 Gabriele M , et al. (2017)
c.1173del p.Asn391LysfsTer10 frameshift_variant De novo - - 28575647 Gabriele M , et al. (2017)
c.1151_1154dup p.Pro386ValfsTer7 frameshift_variant De novo - - 35027293 Cherik F et al. (2022)
c.679_679+1insATGAAAAAAAAGATATTGACCATGAGACA p.Val237MetfsTer29 frameshift_variant Familial Maternal Simplex 30675382 Leblond CS , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
1S

High Confidence, Syndromic

Score Delta: Score remained at 1S

criteria met
See SFARI Gene'scoring criteria
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.

S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

1/1/2020
1
icon
1

Score remained at 1

Description

Phenotypic information from 23 individuals with de novo mutations or deletions of the YY1 gene was used to identify an intellectual disability syndrome characterized by behavioral abnormalities, intrauterine growth retardation, feeding problems, recurrent dysmorphic features, and various congenital malformations; two of the ten individuals with de novo YY1 mutations presented with autism or ASD (Gabriele et al., 2017). YY1 had previously been shown to interact with MECP2 (Forlani et al., 2010) and HCFC1 (Huang et al., 2012).

Reports Added
[Identification of De Novo JAK2 and MAPK7 Mutations Related to Autism Spectrum Disorder Using Whole-Exome Sequencing in a Chinese Child and Adolesce...2019]
10/1/2019
S
icon
1

Increased from S to 1

New Scoring Scheme
Description

Phenotypic information from 23 individuals with de novo mutations or deletions of the YY1 gene was used to identify an intellectual disability syndrome characterized by behavioral abnormalities, intrauterine growth retardation, feeding problems, recurrent dysmorphic features, and various congenital malformations; two of the ten individuals with de novo YY1 mutations presented with autism or ASD (Gabriele et al., 2017). YY1 had previously been shown to interact with MECP2 (Forlani et al., 2010) and HCFC1 (Huang et al., 2012).

Reports Added
[New Scoring Scheme]
1/1/2019
S
icon
S

Increased from S to S

Description

Phenotypic information from 23 individuals with de novo mutations or deletions of the YY1 gene was used to identify an intellectual disability syndrome characterized by behavioral abnormalities, intrauterine growth retardation, feeding problems, recurrent dysmorphic features, and various congenital malformations; two of the ten individuals with de novo YY1 mutations presented with autism or ASD (Gabriele et al., 2017). YY1 had previously been shown to interact with MECP2 (Forlani et al., 2010) and HCFC1 (Huang et al., 2012).

Reports Added
[Both rare and common genetic variants contribute to autism in the Faroe Islands.2019]
Krishnan Probability Score

Score 0.51758832611444

Ranking 1729/25841 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 0.96783095492667

Ranking 2404/18225 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 0.93349470412787

Ranking 12286/18665 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
Zhang D Score

Score 0.32825282522028

Ranking 2310/20870 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
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