Human Gene Module / Chromosome 13 / SETDB2

SETDB2SET domain, bifurcated 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 3
Rare Variants / Common Variants
11 / 0
Aliases
SETDB2, C13orf4,  CLLD8,  CLLL8,  KMT1F
Associated Syndromes
-
Chromosome Band
13q14.2
Associated Disorders
ASD, EPS
Relevance to Autism

A total of nine ASD-specific variants, three of which were non-synonymous, in the SETDB2 gene were identified in cases but not controls (Cukier et al., 2012).

Molecular Function

Histone methyltransferase involved in left-right axis specification in early development and mitosis. Plays a role in chromosome condensation and segregation during mitosis.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SETDB2 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study Rauch A , et al. (2012) No Epilepsy, ASD
2 Primary The expanding role of MBD genes in autism: identification of a MECP2 duplication and novel alterations in MBD5, MBD6, and SETDB1 Cukier HN , et al. (2012) Yes -
3 Support - Zhou X et al. (2022) Yes -
Rare Variants   (11)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.829T>C p.Phe277Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.209-8C>A - intron_variant Unknown Unknown Unknown 23055267 Cukier HN , et al. (2012)
c.143-52G>C - intron_variant Unknown Unknown Unknown 23055267 Cukier HN , et al. (2012)
c.869+49C>T - intron_variant Unknown Unknown Unknown 23055267 Cukier HN , et al. (2012)
c.869+86A>G - intron_variant Unknown Unknown Unknown 23055267 Cukier HN , et al. (2012)
c.986+35A>G - intron_variant Unknown Unknown Unknown 23055267 Cukier HN , et al. (2012)
c.1156+42C>T - intron_variant Unknown Unknown Unknown 23055267 Cukier HN , et al. (2012)
c.1444dup p.Ser482PhefsTer26 frameshift_variant De novo - Simplex 23020937 Rauch A , et al. (2012)
c.1274T>C p.Ile425Thr missense_variant Familial Maternal Simplex 23055267 Cukier HN , et al. (2012)
c.1424C>T p.Thr475Met missense_variant Familial Maternal Simplex 23055267 Cukier HN , et al. (2012)
c.1607C>G p.Ala536Gly missense_variant Familial Paternal Simplex 23055267 Cukier HN , et al. (2012)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A total of nine ASD-specific variants, three of which were non-synonymous, in the SETDB2 gene were identified in cases but not controls (Cukier et al., 2012); however, the three non-synonymous variants were not predicted to be deleterious. A de novo frameshift insertion in the SETDB2 gene was identified in a patient with intellectual disability in PMID 23020937).

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 total of nine ASD-specific variants, three of which were non-synonymous, in the SETDB2 gene were identified in cases but not controls (Cukier et al., 2012); however, the three non-synonymous variants were not predicted to be deleterious. A de novo frameshift insertion in the SETDB2 gene was identified in a patient with intellectual disability in PMID 23020937).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A total of nine ASD-specific variants, three of which were non-synonymous, in the SETDB2 gene were identified in cases but not controls (Cukier et al., 2012); however, the three non-synonymous variants were not predicted to be deleterious. A de novo frameshift insertion in the SETDB2 gene was identified in a patient with intellectual disability in PMID 23020937).

Reports Added
[New Scoring Scheme]
7/1/2015
icon
4

Increased from to 4

Description

A total of nine ASD-specific variants, three of which were non-synonymous, in the SETDB2 gene were identified in cases but not controls (Cukier et al., 2012); however, the three non-synonymous variants were not predicted to be deleterious. A de novo frameshift insertion in the SETDB2 gene was identified in a patient with intellectual disability in PMID 23020937).

Krishnan Probability Score

Score 0.41141721327378

Ranking 22446/25841 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 0.043730109197382

Ranking 8692/18225 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 0.84508636560882

Ranking 3294/18665 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
Larsen Cumulative Evidence Score

Score 20

Ranking 105/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score 0.19369762661487

Ranking 4361/20870 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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