Human Gene Module / Chromosome 19 / ZNF559

ZNF559Zinc finger protein 559

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
9 / 9
Rare Variants / Common Variants
30 / 0
Aliases
ZNF559, NBLA00121
Associated Syndromes
-
Chromosome Band
19p13.2
Associated Disorders
-
Relevance to Autism

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015).

Molecular Function

The protein encoded by this gene may be involved in transcriptional regulation.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ZNF559 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Primary Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci Sanders SJ , et al. (2015) Yes -
4 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
5 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
6 Support Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort Wu H , et al. (2019) Yes Macrocephaly
7 Support - Woodbury-Smith M et al. (2022) Yes -
8 Support - Zhou X et al. (2022) Yes -
9 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (30)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.435+229C>G - intron_variant De novo - - 35982159 Zhou X et al. (2022)
c.427C>T p.Arg143Ter stop_gained De novo - Simplex 35982159 Zhou X et al. (2022)
c.701A>G p.Asn234Ser missense_variant De novo - - 31452935 Feliciano P et al. (2019)
c.1225C>T p.Arg409Ter stop_gained Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1261G>T p.Glu421Ter stop_gained Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1450C>T p.Arg484Ter stop_gained Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1720C>T p.Arg574Ter stop_gained Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.377A>T p.Lys126Ile missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1720C>T p.Arg574Ter stop_gained Familial Paternal - 25363760 De Rubeis S , et al. (2014)
c.393G>A p.Gln131%3D synonymous_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.281T>C p.Leu94Ser missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
c.1148A>G p.His383Arg missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1493A>G p.Glu498Gly missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.950C>T p.Ser317Leu missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
c.1148A>G p.His383Arg missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
c.1256G>A p.Cys419Tyr missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
c.1256G>A p.Cys419Tyr missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
c.1337A>C p.Gln446Pro missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
c.1337A>C p.Gln446Pro missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
c.1446C>A p.Phe482Leu missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
c.1604G>A p.Gly535Glu missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
c.1663C>T p.Arg555Trp missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
c.1450C>T p.Arg484Ter stop_gained Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.1341del p.Cys447Ter frameshift_variant Familial Maternal Simplex 31674007 Wu H , et al. (2019)
c.979_983del p.His327Ter frameshift_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.289del p.Gln97LysfsTer10 frameshift_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1225C>T p.Arg409Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.1468C>T p.Arg490Ter stop_gained Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.137-634T>C - splice_site_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.588dup p.Ile197TyrfsTer9 frameshift_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015).

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

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015).

Reports Added
[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.2019] [New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
10/1/2015
icon
4

Increased from to 4

Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015).

Krishnan Probability Score

Score 0.44691521133327

Ranking 14328/25841 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 7.7178850595175E-9

Ranking 16254/18225 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 0.034574231332022

Ranking 40/18665 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
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