Human Gene Module / Chromosome 1 / CASZ1

CASZ1castor zinc finger 1

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
4 / 7
Rare Variants / Common Variants
43 / 0
EAGLE Score
9.55
Moderate Learn More
Aliases
CASZ1, CAS11,  CST,  SRG,  ZNF693,  dJ734G22.1
Associated Syndromes
-
Chromosome Band
1p36.22
Associated Disorders
ID
Genetic Category
Rare Single Gene Mutation
Relevance to Autism

De novo likely gene-disruptive (LGD) variants in the CASZ1 gene have been identified in two ASD-affected siblings from a multiplex family (Yuen et al., 2017), one proband with intellectual disability (Lelieveld et al., 2016), and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified CASZ1 as a gene with an excess of LGD variants (false discovery rata < 5%, count >1) (Coe et al., 2018).

Molecular Function

The protein encoded by this gene is a zinc finger transcription factor and may function as a tumor suppressor.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CASZ1 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability Lelieveld SH et al. (2016) No -
2 Support Prevalence and architecture of de novo mutations in developmental disorders et al. (2017) No -
3 Primary Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
4 Recent Recommendation Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity Coe BP , et al. (2018) No -
5 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes ID
6 Support - Zhou X et al. (2022) Yes -
7 Support - Yuan B et al. (2023) Yes -
Rare Variants   (43)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2689C>T p.Gln897Ter stop_gained De novo - - 28135719 et al. (2017)
c.1738-2A>G p.? splice_site_variant Unknown - - 33004838 Wang T et al. (2020)
c.512C>G p.Ala171Gly missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.644C>T p.Pro215Leu missense_variant De novo - - 36881370 Yuan B et al. (2023)
c.1841G>A p.Arg614His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2290G>A p.Ala764Thr missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.3782G>A p.Trp1261Ter missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.4219G>A p.Glu1407Lys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.92del p.Leu31ArgfsTer8 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.163del p.Glu55ArgfsTer33 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.575C>G XP_005263536.1:p.Ser192Ter stop_gained De novo - - 33004838 Wang T et al. (2020)
c.4953del p.Asp1653ThrfsTer190 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.178G>A XP_005263536.1:p.Ala60Thr missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.352G>A XP_005263536.1:p.Gly118Arg missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.596G>A XP_005263536.1:p.Arg199Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1183G>T XP_005263536.1:p.Gly395Trp missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1693G>A XP_005263536.1:p.Gly565Ser missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1849G>A XP_005263536.1:p.Glu617Lys missense_variant De novo - - 33004838 Wang T et al. (2020)
c.1918G>A XP_005263536.1:p.Gly640Ser missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2165G>A XP_005263536.1:p.Arg722His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2242G>A XP_005263536.1:p.Asp748Asn missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2893G>A XP_005263536.1:p.Glu965Lys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2717del p.Pro906ArgfsTer4 frameshift_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.3509C>T XP_005263536.1:p.Thr1170Met missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.3809G>A XP_005263536.1:p.Arg1270His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.3818G>T XP_005263536.1:p.Cys1273Phe missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.3884G>A XP_005263536.1:p.Arg1295Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.3884G>C XP_005263536.1:p.Arg1295Pro missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.3983G>A XP_005263536.1:p.Arg1328Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.4123G>A XP_005263536.1:p.Asp1375Asn missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.4207C>T XP_005263536.1:p.Pro1403Ser missense_variant De novo - - 33004838 Wang T et al. (2020)
c.4210G>A XP_005263536.1:p.Val1404Met missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.4213G>T XP_005263536.1:p.Gly1405Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.4328C>T XP_005263536.1:p.Ala1443Val missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.4337G>A XP_005263536.1:p.Arg1446Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.4672C>A XP_005263536.1:p.Arg1558Ser missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.4613del p.Gly1538AlafsTer5 frameshift_variant De novo - Simplex 27479843 Lelieveld SH et al. (2016)
c.820G>A XP_005263536.1:p.Glu274Lys missense_variant Familial Maternal - 33004838 Wang T et al. (2020)
c.3983G>A XP_005263536.1:p.Arg1328Gln missense_variant Unknown - Simplex 33004838 Wang T et al. (2020)
c.4403dup p.Cys1469LeufsTer358 frameshift_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.1693G>A XP_005263536.1:p.Gly565Ser missense_variant Familial Maternal - 33004838 Wang T et al. (2020)
c.3424G>A XP_005263536.1:p.Ala1142Thr missense_variant Familial Maternal - 33004838 Wang T et al. (2020)
c.3428G>C XP_005263536.1:p.Trp1143Ser missense_variant Familial Maternal - 33004838 Wang T et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

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.

10/1/2020
1
icon
1

Score remained at 1

Description

De novo likely gene-disruptive (LGD) variants in the CASZ1 gene have been identified in two ASD-affected siblings from a multiplex family (Yuen et al., 2017), one proband with intellectual disability (Lelieveld et al., 2016), and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified CASZ1 as a gene with an excess of LGD variants (false discovery rata < 5%, count >1) (Coe et al., 2018).

Reports Added
[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
10/1/2019
3
icon
1

Decreased from 3 to 1

New Scoring Scheme
Description

De novo likely gene-disruptive (LGD) variants in the CASZ1 gene have been identified in two ASD-affected siblings from a multiplex family (Yuen et al., 2017), one proband with intellectual disability (Lelieveld et al., 2016), and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified CASZ1 as a gene with an excess of LGD variants (false discovery rata < 5%, count >1) (Coe et al., 2018).

Reports Added
[New Scoring Scheme]
1/1/2019
icon
3

Increased from to 3

Description

De novo likely gene-disruptive (LGD) variants in the CASZ1 gene have been identified in two ASD-affected siblings from a multiplex family (Yuen et al., 2017), one proband with intellectual disability (Lelieveld et al., 2016), and one proband with an unspecified developmental disorder (Deciphering Developmental Disorders Study 2017). An integrated meta-analysis of de novo mutation data from a combined dataset of 10,927 individuals with neurodevelopmental disorders identified CASZ1 as a gene with an excess of LGD variants (false discovery rata < 5%, count >1) (Coe et al., 2018).

Krishnan Probability Score

Score 0.4085263468816

Ranking 22930/25841 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 0.99993847632778

Ranking 607/18225 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 0.9465492065483

Ranking 16915/18665 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 -0.00584111679281

Ranking 8867/20870 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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