Human Gene Module / Chromosome 15 / ZNF774

ZNF774Zinc finger protein 774

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
15 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
15q26.1
Associated Disorders
-
Relevance to Autism

A de novo missense variant in this gene has been identified in a simplex ASD proband (De Rubeis et al., 2014). Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family (Yuen et al., 2015). This gene was also included in a set of genes strongly enriched for those likely to affect risk (FDR < 0.30) (De Rubeis, et al., 2014).

Molecular Function

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

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ZNF774 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Recent Recommendation Whole-genome sequencing of quartet families with autism spectrum disorder Yuen RK , et al. (2015) Yes -
3 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
4 Support - Zhou X et al. (2022) Yes -
Rare Variants   (15)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.876G>T p.Arg292Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
AC>A - frameshift_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.795C>A p.Cys265Ter stop_gained Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1294C>T p.Arg432Ter stop_gained Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
CTG>C - frameshift_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
CTTAG>C - frameshift_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.424C>T p.Leu142Phe missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1099A>G p.Arg367Gly missense_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.1184G>C p.Arg395Pro missense_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
TGTCCTGAGTGTGGCAA>T - frameshift_variant Unknown - Unknown 25363760 De Rubeis S , et al. (2014)
c.1294C>T p.Arg432Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.1324C>T p.Gln442Ter stop_gained Familial Maternal Multiplex 25363760 De Rubeis S , et al. (2014)
c.1032G>C p.Glu344Asp missense_variant Familial Maternal Simplex 25363760 De Rubeis S , et al. (2014)
TGTCCTGAGTGTGGCAA>T - frameshift_variant Familial Paternal Simplex 25363760 De Rubeis S , et al. (2014)
c.299_314del p.Asp100ValfsTer11 frameshift_variant Familial Maternal Multiplex 25621899 Yuen RK , et al. (2015)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo missense variant that was predicted to be damaging in the ZNF774 gene was identified in a simplex ASD proband in De Rubeis et al., 2014. Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family in Yuen et al., 2015. This gene was also included in a set of genes strongly enriched for those likely to affect ASD risk (FDR < 0.30) (De Rubeis, et al., 2014).

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

A de novo missense variant that was predicted to be damaging in the ZNF774 gene was identified in a simplex ASD proband in De Rubeis et al., 2014. Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family in Yuen et al., 2015. This gene was also included in a set of genes strongly enriched for those likely to affect ASD risk (FDR < 0.30) (De Rubeis, et al., 2014).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo missense variant that was predicted to be damaging in the ZNF774 gene was identified in a simplex ASD proband in De Rubeis et al., 2014. Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family in Yuen et al., 2015. This gene was also included in a set of genes strongly enriched for those likely to affect ASD risk (FDR < 0.30) (De Rubeis, et al., 2014).

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

A de novo missense variant that was predicted to be damaging in the ZNF774 gene was identified in a simplex ASD proband in De Rubeis et al., 2014. Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family in Yuen et al., 2015. This gene was also included in a set of genes strongly enriched for those likely to affect ASD risk (FDR < 0.30) (De Rubeis, et al., 2014).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
10/1/2017
icon
4

Increased from to 4

Description

A de novo missense variant that was predicted to be damaging in the ZNF774 gene was identified in a simplex ASD proband in De Rubeis et al., 2014. Furthermore, an inherited LoF variant in this gene was observed in both affected siblings from a quartet ASD family in Yuen et al., 2015. This gene was also included in a set of genes strongly enriched for those likely to affect ASD risk (FDR < 0.30) (De Rubeis, et al., 2014).

Krishnan Probability Score

Score 0.4350567199951

Ranking 20470/25841 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 1.1014466727918E-10

Ranking 16920/18225 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 0.16758606622629

Ranking 94/18665 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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