Human Gene Module / Chromosome 17 / ZNF18

ZNF18zinc finger protein 18

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
7 / 0
Aliases
ZNF18, HDSG1,  KOX11,  ZKSCAN6,  ZNF535,  Zfp535
Associated Syndromes
-
Chromosome Band
17p12
Associated Disorders
-
Relevance to Autism

A homozygous mutation in the ZNF18 gene was found to segregate perfectly with disease in a multiplex ASD family. No homozygotes for this mutation were observed in 1340 control chromosomes. An additional homozygous mutation, as well as a compound heterozygous mutation, in the ZNF18 gene were identified in two ASD cases from the replication cohort that were not observed in 371 controls (Chahrour et al., 2012).

Molecular Function

May be involved in transcriptional regulation.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to ZNF18 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism Chahrour MH , et al. (2012) Yes -
2 Support - Zhou X et al. (2022) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.647T>A p.Leu216Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.216A>G p.Pro72%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.440C>T p.Pro147Leu missense_variant Familial - - 22511880 Chahrour MH , et al. (2012)
c.1299G>C p.Glu433Asp missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1313G>A p.Cys438Tyr missense_variant Familial - - 22511880 Chahrour MH , et al. (2012)
c.440C>T p.Pro147Leu missense_variant Familial Both parents - 22511880 Chahrour MH , et al. (2012)
c.1129C>A p.Pro377Thr missense_variant Familial Both parents Multiplex 22511880 Chahrour MH , et al. (2012)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A homozygous missense mutation in the ZNF18 gene was found to segregate perfectly with disease in a multiplex ASD family. No homozygotes for this mutation were observed in 1340 control chromosomes. An additional homozygous mutation, as well as a compound heterozygous mutation, in the ZNF18 gene were identified in two ASD cases from the replication cohort that were not observed in 371 controls (Chahrour 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 homozygous missense mutation in the ZNF18 gene was found to segregate perfectly with disease in a multiplex ASD family. No homozygotes for this mutation were observed in 1340 control chromosomes. An additional homozygous mutation, as well as a compound heterozygous mutation, in the ZNF18 gene were identified in two ASD cases from the replication cohort that were not observed in 371 controls (Chahrour et al., 2012).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A homozygous missense mutation in the ZNF18 gene was found to segregate perfectly with disease in a multiplex ASD family. No homozygotes for this mutation were observed in 1340 control chromosomes. An additional homozygous mutation, as well as a compound heterozygous mutation, in the ZNF18 gene were identified in two ASD cases from the replication cohort that were not observed in 371 controls (Chahrour et al., 2012).

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

Increased from to 4

Description

A homozygous missense mutation in the ZNF18 gene was found to segregate perfectly with disease in a multiplex ASD family. No homozygotes for this mutation were observed in 1340 control chromosomes. An additional homozygous mutation, as well as a compound heterozygous mutation, in the ZNF18 gene were identified in two ASD cases from the replication cohort that were not observed in 371 controls (Chahrour et al., 2012).

Krishnan Probability Score

Score 0.41235338841517

Ranking 22128/25841 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 0.0002382024779816

Ranking 12611/18225 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 0.61076662454465

Ranking 745/18665 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 7

Ranking 247/461 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 0.51175346477331

Ranking 430/20870 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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