Human Gene Module / Chromosome 6 / ZNF292

ZNF292zinc finger protein 292

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
10 / 14
Rare Variants / Common Variants
49 / 0
Aliases
ZNF292, Nbla00365,  ZFP292,  ZN-16,  Zn-15,  bA393I2.3
Associated Syndromes
-
Chromosome Band
6q14.3
Associated Disorders
ADHD, ID
Relevance to Autism

A de novo loss-of-function (LoF) variant in the ZNF292 gene was identified in a female ASD proband with positive family history from the Autism Sequencing Consortium (Neale et al., 2012); a second de novo LoF variant in this gene was identified in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort (Wang et al., 2016).

Molecular Function

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

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ZNF292 (14 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Patterns and rates of exonic de novo mutations in autism spectrum disorders Neale BM , et al. (2012) Yes -
2 Support De novo genic mutations among a Chinese autism spectrum disorder cohort Wang T , et al. (2016) Yes -
3 Support Exome Pool-Seq in neurodevelopmental disorders Popp B , 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 Recent Recommendation De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder Mirzaa GM , et al. (2019) Yes ADHD
6 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes ID
7 Support - Bertoli-Avella AM et al. (2021) No -
8 Support - Tuncay IO et al. (2022) Yes -
9 Support - Woodbury-Smith M et al. (2022) Yes -
10 Support - Brea-Fernández AJ et al. (2022) No -
11 Support - Zhou X et al. (2022) Yes -
12 Support - Omri Bar et al. (2024) Yes OCD, ID
13 Support - Hamid Khan et al. (2024) Yes -
14 Support - Axel Schmidt et al. (2024) No -
Rare Variants   (49)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1567C>T p.Gln523Ter stop_gained De novo - - 33004838 Wang T et al. (2020)
c.1897C>T p.Arg633Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.4315C>T p.Gln1439Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.6823C>T p.Arg2275Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.7261C>T p.Arg2421Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.7220A>G p.Tyr2407Cys missense_variant De novo - - 33004838 Wang T et al. (2020)
c.3014T>G p.Leu1005Ter stop_gained De novo - - 39039281 Axel Schmidt et al. (2024)
c.4353A>G p.Pro1451%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.5460A>G p.Pro1820%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.265C>T p.Arg89Ter stop_gained De novo - Simplex 31723249 Mirzaa GM , et al. (2019)
c.1360C>T p.Arg454Ter stop_gained De novo - Simplex 35190550 Tuncay IO et al. (2022)
c.1360C>T p.Arg454Ter stop_gained De novo - Simplex 31723249 Mirzaa GM , et al. (2019)
c.1567C>T p.Gln523Ter stop_gained De novo - Simplex 31723249 Mirzaa GM , et al. (2019)
c.1625_1628dup p.Tyr543Ter frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.2621C>T p.Ser874Leu missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.3812C>A p.Ser1271Ter stop_gained De novo - Simplex 31723249 Mirzaa GM , et al. (2019)
c.4897A>T p.Lys1633Ter stop_gained De novo - Simplex 31723249 Mirzaa GM , et al. (2019)
c.5185C>T p.Gln1729Ter stop_gained De novo - Simplex 31723249 Mirzaa GM , et al. (2019)
c.6343C>T p.Arg2115Ter stop_gained De novo - Simplex 31723249 Mirzaa GM , et al. (2019)
c.6541C>T p.Arg2181Ter stop_gained De novo - Simplex 31723249 Mirzaa GM , et al. (2019)
c.7016del p.Asn2339IlefsTer3 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.6279dup p.Arg2094ThrfsTer10 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.6542G>T p.Arg2181Leu missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.3437A>G p.Asn1146Ser missense_variant Unknown - Multiplex 38256266 Omri Bar et al. (2024)
c.8132A>G p.Asp2711Gly missense_variant Unknown - Multiplex 38256266 Omri Bar et al. (2024)
c.3709dup p.Thr1237AsnfsTer20 frameshift_variant De novo - - 31723249 Mirzaa GM , et al. (2019)
c.2490_2494dup p.Ser832IlefsTer28 frameshift_variant De novo - - 27824329 Wang T , et al. (2016)
c.4417dup p.Ser1473PhefsTer5 frameshift_variant De novo - Simplex 30564305 Guo H , et al. (2018)
c.5331dup p.Gln1778SerfsTer5 frameshift_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.3066_3069del p.Ser1023GlnfsTer33 frameshift_variant De novo - - 29158550 Popp B , et al. (2017)
c.2814_2821dup p.Val941AlafsTer68 frameshift_variant De novo - - 31723249 Mirzaa GM , et al. (2019)
c.433del p.Ser145AlafsTer7 frameshift_variant De novo - Simplex 31723249 Mirzaa GM , et al. (2019)
c.5288A>G p.Lys1763Arg missense_variant Familial Maternal Multiplex 30564305 Guo H , et al. (2018)
c.6661_6664del p.Leu2221SerfsTer10 frameshift_variant De novo - - 31723249 Mirzaa GM , et al. (2019)
c.2170del p.Cys724AlafsTer9 frameshift_variant De novo - Simplex 31723249 Mirzaa GM , et al. (2019)
c.6279dup p.Arg2094ThrfsTer10 frameshift_variant De novo - Simplex 31723249 Mirzaa GM , et al. (2019)
c.1160del p.Arg387LeufsTer5 frameshift_variant De novo - Multiplex 31723249 Mirzaa GM , et al. (2019)
c.3066_3069del p.Glu1022AspfsTer3 frameshift_variant De novo - Simplex 31723249 Mirzaa GM , et al. (2019)
c.5515_5569del p.Glu1839HisfsTer6 frameshift_variant De novo - Simplex 31723249 Mirzaa GM , et al. (2019)
c.5959_5965dup p.Gly1989AlafsTer9 frameshift_variant De novo - Simplex 31723249 Mirzaa GM , et al. (2019)
c.6142_6145del p.Lys2048ValfsTer11 frameshift_variant De novo - Simplex 31723249 Mirzaa GM , et al. (2019)
c.6160_6161del p.Glu2054LysfsTer14 frameshift_variant De novo - Simplex 31723249 Mirzaa GM , et al. (2019)
c.8026G>A p.Asp2676Asn missense_variant Familial Both parents Multiplex 38649688 Hamid Khan et al. (2024)
c.3460_3463del p.Val1154IlefsTer7 frameshift_variant De novo - Multiplex 31723249 Mirzaa GM , et al. (2019)
c.5672del p.Asn1891IlefsTer6 frameshift_variant De novo - Simplex 33875846 Bertoli-Avella AM et al. (2021)
c.3724del p.Gln1242LysfsTer5 frameshift_variant Familial Maternal Simplex 31723249 Mirzaa GM , et al. (2019)
c.6160_6161del p.Glu2054LysfsTer14 frameshift_variant De novo - - 35322241 Brea-Fernández AJ et al. (2022)
c.265C>T p.Arg89Ter stop_gained De novo - Not simplex (positive family history) 22495311 Neale BM , et al. (2012)
c.5740_5741del p.Glu1914LysfsTer14 frameshift_variant De novo - Simplex 33875846 Bertoli-Avella AM et al. (2021)
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."

4/1/2021
1
icon
1

Score remained at 1

Description

A de novo loss-of-function (LoF) variant in the ZNF292 gene was identified in a female ASD proband with positive family history from the Autism Sequencing Consortium (Neale et al., 2012); a second de novo LoF variant in this gene was identified in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort (Wang et al., 2016). Mirzaa et al., 2019 described a cohort of 28 individuals with putatively pathogenic ZNF292 variants that presented with a neurodevelopmental disorder characterized by developmental delay/intellectual disability (96%), speech delay (93%), and ASD or autistic features (61%); ADHD, tone abnormalities, structural brain abnormalities, dysmorphic features, ocular features, and growth failure were also observed in at least 30% of affected individuals.

Reports Added
[Combining exome/genome sequencing with data repository analysis reveals novel gene-disease associations for a wide range of genetic disorders2021]
10/1/2020
1
icon
1

Score remained at 1

Description

A de novo loss-of-function (LoF) variant in the ZNF292 gene was identified in a female ASD proband with positive family history from the Autism Sequencing Consortium (Neale et al., 2012); a second de novo LoF variant in this gene was identified in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort (Wang et al., 2016). Mirzaa et al., 2019 described a cohort of 28 individuals with putatively pathogenic ZNF292 variants that presented with a neurodevelopmental disorder characterized by developmental delay/intellectual disability (96%), speech delay (93%), and ASD or autistic features (61%); ADHD, tone abnormalities, structural brain abnormalities, dysmorphic features, ocular features, and growth failure were also observed in at least 30% of affected individuals.

Reports Added
[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
10/1/2019
4
icon
1

Decreased from 4 to 1

New Scoring Scheme
Description

A de novo loss-of-function (LoF) variant in the ZNF292 gene was identified in a female ASD proband with positive family history from the Autism Sequencing Consortium (Neale et al., 2012); a second de novo LoF variant in this gene was identified in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort (Wang et al., 2016). Mirzaa et al., 2019 described a cohort of 28 individuals with putatively pathogenic ZNF292 variants that presented with a neurodevelopmental disorder characterized by developmental delay/intellectual disability (96%), speech delay (93%), and ASD or autistic features (61%); ADHD, tone abnormalities, structural brain abnormalities, dysmorphic features, ocular features, and growth failure were also observed in at least 30% of affected individuals.

Reports Added
[De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder.2019] [New Scoring Scheme]
1/1/2019
4
icon
4

Decreased from 4 to 4

Description

A de novo loss-of-function (LoF) variant in the ZNF292 gene was identified in a female ASD proband with positive family history from the Autism Sequencing Consortium (Neale et al., 2012); a second de novo LoF variant in this gene was identified in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort (Wang et al., 2016).

Reports Added
[Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.2018]
10/1/2017
4
icon
4

Decreased from 4 to 4

Description

A de novo loss-of-function (LoF) variant in the ZNF292 gene was identified in a female ASD proband with positive family history from the Autism Sequencing Consortium (Neale et al., 2012); a second de novo LoF variant in this gene was identified in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort (Wang et al., 2016).

Reports Added
[Exome Pool-Seq in neurodevelopmental disorders.2017]
10/1/2016
icon
4

Increased from to 4

Description

A de novo loss-of-function (LoF) variant in the ZNF292 gene was identified in a female ASD proband with positive family history from the Autism Sequencing Consortium (Neale et al., 2012); a second de novo LoF variant in this gene was identified in an ASD proband from the Autism Clinical and Genetic Resources in China (ACGC) cohort (Wang et al., 2016).

Krishnan Probability Score

Score 0.57067867734506

Ranking 885/25841 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 0.99997698413608

Ranking 524/18225 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
Iossifov Probability Score

Score 0.969

Ranking 60/239 scored genes


[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists 239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This probability metric combines the evidence from de novo likely-gene- disrupting and missense mutations and assesses it against the background mutation rate in unaffected individuals from the University of Washington’s Exome Variant Sequence database (evs.gs.washington.edu/EVS/). The list of probability scores can be found here: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/- /DCSupplemental/pnas.1516376112.sd02.xlsx
Original Source
Sanders TADA Score

Score 0.67146936298208

Ranking 996/18665 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 0.64062888495895

Ranking 24/20870 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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