Human Gene Module / Chromosome 19 / ZNF536

ZNF536zinc finger protein 536

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
7 / 11
Rare Variants / Common Variants
7 / 1
Aliases
-
Associated Syndromes
-
Chromosome Band
19q12
Associated Disorders
-
Relevance to Autism

A de novo missense variant with a CADD score > 25 was identified in the ZNF536 gene in a Korean ASD proband in Kim et al., 2024; this gene was subsequently classified as an ASD candidate gene in males following a combined TADA analysis consisting of the Korean ASD cohort described in Kim et al., 2024 in addition to the Simons Simplex Collection and the SPARK cohort. De novo loss-of-function variants in ZNF536 had previously been identified in an ASD proband from the Simons Simplex Collection and in an ASD proband from a Brazilian cohort (Krumm et al., 2015; Costa et al., 2023). ZNF536 has also been shown to significantly associate with schizophrenia (Schizophrenia Working Group of the Psychiatric Genomics Consortium 2014). Studies of znf536 in zebrafish have demonstrated a role for this gene in the development of forebrain neurons implicated in social behavior and stress (Thyme et al., 2019), while adult znf536 knockout (KO) zebrafish were subsequently found to display significant reductions in anxiety-like behavior and social interaction, as well as decreased cerebellar volume (Kim et al., 2024).

Molecular Function

The protein encoded by this gene is a highly conserved zinc finger protein. The encoded protein is most abundant in brain, where it negatively regulates neuronal differentiation by repressing retinoic acid-induced gene transcription (Qin et al., 2009).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ZNF536 (11 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Zhen Qin et al. (2009) No -
2 Positive Association Biological insights from 108 schizophrenia-associated genetic loci Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) No -
3 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
4 Support Excess of rare, inherited truncating mutations in autism Krumm N , et al. (2015) Yes -
5 Support - Summer B Thyme et al. (2019) No -
6 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
7 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
8 Support - Zhou X et al. (2022) Yes -
9 Support - Costa CIS et al. (2023) Yes -
10 Support - Tae-Yoon Kim et al. (2024) No -
11 Primary - Soo-Whee Kim et al. (2024) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2655G>A p.Leu885= synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1571G>A p.Trp524Ter stop_gained De novo - Simplex 37280359 Costa CIS et al. (2023)
c.601G>A p.Glu201Lys missense_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.3144G>A p.Ala1048= synonymous_variant De novo - - 31452935 Feliciano P et al. (2019)
c.2898G>A p.Arg966= synonymous_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.3279C>T p.Ser1093= synonymous_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.3180del p.Asn1060LysfsTer9 frameshift_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.2171-38331A>G - intron_variant - - - 25056061 Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014)
SFARI Gene score
3

Suggestive Evidence

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2024
3

Initial score established: 3

Krishnan Probability Score

Score 0.58535800170454

Ranking 527/25841 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 0.96521684160008

Ranking 2448/18225 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 0.94771632331045

Ranking 17389/18665 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 0.12489096167985

Ranking 5636/20870 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
Submit New Gene

Report an Error