Human Gene Module / Chromosome 19 / TSHZ3

TSHZ3teashirt zinc finger homeobox 3

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
5 / 7
Rare Variants / Common Variants
10 / 0
Aliases
TSHZ3, TSH3,  ZNF537
Associated Syndromes
-
Chromosome Band
19
Associated Disorders
-
Relevance to Autism

Caubit et al., 2016 evaluated 7 new patients and 15 previously reported cases with 19q12-q13.11 deletions and determined that TSHZ3 lies within the minimal region of overlap for 19q12-q13.11 deletions found in patients with neurodevelopmental disorders, including ASD. Tshz3 +/- mice display altered corticostriatal synaptic transmission and plasticity and autism-like behavioral defects (Caubit et al., 2016).

Molecular Function

This gene encodes a zinc-finger transcription factor involved in developmental processes.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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Mouse
Entrez GeneMouse Genome Informatics
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to TSHZ3 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior Doan RN , et al. (2016) Yes -
2 Primary TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons Caubit X , et al. (2016) Yes -
3 Support Postnatal Tshz3 Deletion Drives Altered Corticostriatal Function and Autism Spectrum Disorder-like Behavior Chabbert D , et al. (2019) No -
4 Support - Caubit X et al. (2022) Yes -
5 Support - Zhou X et al. (2022) Yes -
6 Support - Axel Schmidt et al. (2024) No -
7 Support - Soo-Whee Kim et al. (2024) Yes -
Rare Variants   (10)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 27668656 Caubit X , et al. (2016)
- - copy_number_loss Unknown - - 27668656 Caubit X , et al. (2016)
C>T - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
- - copy_number_loss Familial Paternal - 27668656 Caubit X , et al. (2016)
- - copy_number_loss Familial Maternal Multiplex 27668656 Caubit X , et al. (2016)
c.2346C>A p.Tyr782Ter stop_gained Unknown - - 39039281 Axel Schmidt et al. (2024)
c.250C>T p.Arg84Ter stop_gained De novo - Multiplex 35982159 Zhou X et al. (2022)
c.2232G>A p.Leu744= synonymous_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.1288G>A p.Val430Ile missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2661C>T p.Pro887= synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
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.

10/1/2019
4
icon
1

Decreased from 4 to 1

New Scoring Scheme
Description

Caubit et al., 2016 evaluated 7 new patients and 15 previously reported cases with 19q12-q13.11 deletions and determined that TSHZ3 lies within the minimal region of overlap for 19q12-q13.11 deletions found in patients with neurodevelopmental disorders, including ASD. Tshz3 +/- mice display altered corticostriatal synaptic transmission and plasticity and autism-like behavioral defects (Caubit et al., 2016).

Reports Added
[New Scoring Scheme]
4/1/2019
4
icon
4

Decreased from 4 to 4

Description

Caubit et al., 2016 evaluated 7 new patients and 15 previously reported cases with 19q12-q13.11 deletions and determined that TSHZ3 lies within the minimal region of overlap for 19q12-q13.11 deletions found in patients with neurodevelopmental disorders, including ASD. Tshz3 +/- mice display altered corticostriatal synaptic transmission and plasticity and autism-like behavioral defects (Caubit et al., 2016).

Reports Added
[Postnatal Tshz3 Deletion Drives Altered Corticostriatal Function and Autism Spectrum Disorder-like Behavior.2019]
10/1/2016
icon
4

Increased from to 4

Description

Caubit et al., 2016 evaluated 7 new patients and 15 previously reported cases with 19q12-q13.11 deletions and determined that TSHZ3 lies within the minimal region of ovelap for 19q12-q13.11 deletions found in patients with neurodevelopmental disorders, including ASD. Tshz3 +/- mice display altered corticostriatal synaptic transmission and plasticity and autism-like behavioral defects (Caubit et al., 2016).

Krishnan Probability Score

Score 0.49300337833163

Ranking 4327/25841 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 0.42564558200728

Ranking 5847/18225 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 0.94464847986306

Ranking 16158/18665 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 0.33376337085124

Ranking 2234/20870 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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