Human Gene Module / Chromosome 18 / TSHZ1

TSHZ1teashirt zinc finger homeobox 1

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
5 / 6
Rare Variants / Common Variants
9 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
18q22.3
Associated Disorders
-
Relevance to Autism

A number of de novo variants, including three de novo loss-of-function (LoF) variants, have been identified in ASD probands from the MSSNG cohort, the Autism Sequencing Consortium, the SPARK cohort, and the Simons Simplex Collection (Yuen et al., 2017; Satterstrom et al., 2020; Zhou et al., 2022; Trost et al., 2022). Transmission and de novo association (TADA) analysis of whole-exome and whole-genome sequencing data from the Autism Sequencing Consortium, the MSSNG cohort, and the SPARK cohort in Trost et al., 2022 identified TSHZ1 as an ASD-associated gene with a false discovery rate (FDR) < 0.1.

Molecular Function

This gene encodes a colon cancer antigen that was defined by serological analysis of recombinant cDNA expression libraries. The encoded protein is a member of the teashirt C2H2-type zinc-finger protein family and may be involved in transcriptional regulation of developmental processes. Mutations in this gene are associated with congenital aural atresia (OMIM 607842), an autosomal dominant syndrome characterized by conductive hearing impairment, atresia of the external auditory canal, and hyposmia (Feenstra et al., 2011).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to TSHZ1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Feenstra I et al. (2011) No -
2 Primary Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
3 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
4 Support - Zhou X et al. (2022) Yes -
5 Support - Chen WX et al. (2022) Yes -
6 Recent Recommendation - Trost B et al. (2022) Yes -
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1626C>T p.Asp542%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.798C>T p.Asn266%3D synonymous_variant De novo - - 36368308 Trost B et al. (2022)
c.592G>A p.Asp198Asn missense_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.409A>C p.Lys137Gln missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.1905C>T p.Asn635= synonymous_variant De novo - Simplex 36320054 Chen WX et al. (2022)
c.853del p.Arg285GlyfsTer10 frameshift_variant De novo - - 36368308 Trost B et al. (2022)
c.2301G>A p.Ser767%3D synonymous_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.410del p.Lys137ArgfsTer125 frameshift_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.468_469insCCCCCCCCCCCCCCCC p.Thr157ProfsTer68 frameshift_variant De novo - - 31981491 Satterstrom FK 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.

1/1/2023
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1

Increased from to 1

Krishnan Probability Score

Score 0.49293516962559

Ranking 4351/25841 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 0.93955948023357

Ranking 2839/18225 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 0.94494326109589

Ranking 16274/18665 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 0.10676324295924

Ranking 5985/20870 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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