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 / 8
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
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome Informatics
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to TSHZ3 (8 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 -
8 Support - Patricia R Nano et al. (2025) No -
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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