Human Gene Module / Chromosome 11 / ZBTB16

ZBTB16Zinc finger and BTB domain containing 16

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
1 / 1
Aliases
ZBTB16, PLZF,  ZNF145
Associated Syndromes
-
Chromosome Band
11q23.2
Associated Disorders
-
Relevance to Autism

A SNP within the ZBTB16 gene showed association in the secondary analyses in a combined AGP GWA sample (Anney et al., 2012). A rare damaging missense variant in ZBTB16 was identified in both affected siblings in a Sardinian multiplex ASD family (Bacchelli et al., 2019). Deletion of Zbtb16 in mice was found to result in social impairment, repetitive behaviors, risk-taking behaviors, and cognitive impairment (Usui et al., 2021).

Molecular Function

This gene is a member of the Krueppel C2H2-type zinc-finger protein family and encodes a zinc finger transcription factor that contains nine Kruppel-type zinc finger domains at the carboxyl terminus. This protein is located in the nucleus, is involved in cell cycle progression, and interacts with a histone deacetylase.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ZBTB16 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Individual common variants exert weak effects on the risk for autism spectrum disorders Anney R , et al. (2012) Yes -
2 Support - Bacchelli E et al. (2019) Yes -
3 Support - Usui N et al. (2021) Yes -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1319G>A p.Arg440Gln missense_variant Unknown - Multiplex 30736458 Bacchelli E et al. (2019)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.1453+15115C>T;c.1454-7218C>T - intron_variant - - - 22843504 Anney R , et al. (2012)
SFARI Gene score
2

Strong Candidate

A SNP within the ZBTB16 gene showed association (P-value: 1.842E07) in the secondary analyses in a combined AGP GWA sample (Diagnosis: Higher IQ; Subgroup: All; Inheritance: Additive) in Anney et al., 2012.

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 SNP within the ZBTB16 gene showed association (P-value: 1.842E07) in the secondary analyses in a combined AGP GWA sample (Diagnosis: Higher IQ; Subgroup: All; Inheritance: Additive) in Anney et al., 2012.

4/1/2021
3
icon
3

Decreased from 3 to 3

Description

A SNP within the ZBTB16 gene showed association (P-value: 1.842E07) in the secondary analyses in a combined AGP GWA sample (Diagnosis: Higher IQ; Subgroup: All; Inheritance: Additive) in Anney et al., 2012.

Reports Added
[Analysis of a Sardinian Multiplex Family with Autism Spectrum Disorder Points to Post-Synaptic Density Gene Variants and Identifies CAPG as a Functionally Relevant Candidate Gene2019] [Zbtb16 regulates social cognitive behaviors and neocortical development2021]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A SNP within the ZBTB16 gene showed association (P-value: 1.842E07) in the secondary analyses in a combined AGP GWA sample (Diagnosis: Higher IQ; Subgroup: All; Inheritance: Additive) in Anney et al., 2012.

Reports Added
[New Scoring Scheme]
7/1/2018
icon
4

Increased from to 4

Description

A SNP within the ZBTB16 gene showed association (P-value: 1.842E07) in the secondary analyses in a combined AGP GWA sample (Diagnosis: Higher IQ; Subgroup: All; Inheritance: Additive) in Anney et al., 2012.

Krishnan Probability Score

Score 0.49377499966069

Ranking 3976/25841 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 0.98008730582571

Ranking 2130/18225 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 0.93966110043455

Ranking 14289/18665 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 3

Ranking 369/461 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 0.0910318712231

Ranking 6311/20870 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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