Human Gene Module / Chromosome 6 / PTK7

PTK7Protein tyrosine kinase 7 (inactive)

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
7 / 8
Rare Variants / Common Variants
9 / 0
Aliases
PTK7, CCK-4,  CCK4
Associated Syndromes
-
Chromosome Band
6p21.1
Associated Disorders
-
Relevance to Autism

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

Molecular Function

This gene encodes a member of the receptor protein tyrosine kinase family of proteins that transduce extracellular signals across the cell membrane. The encoded protein lacks detectable catalytic tyrosine kinase activity, is involved in the Wnt signaling pathway and plays a role in multiple cellular processes including polarity and adhesion.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PTK7 (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Primary Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci Sanders SJ , et al. (2015) Yes -
4 Support Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases Stessman HA , et al. (2017) No -
5 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
6 Support - Woodbury-Smith M et al. (2022) Yes -
7 Support - Zhou X et al. (2022) Yes -
8 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.34T>A p.Ser12Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1708C>T p.Arg570Ter stop_gained De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1545A>C p.Pro515= synonymous_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.55G>A p.Ala19Thr missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.507A>G p.Gln169%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.851G>A p.Arg284His missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1709G>A p.Arg570Gln missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.1386_1387delGAinsA p.Asn463MetfsTer20 frameshift_variant De novo - - 28191889 Stessman HA , et al. (2017)
c.785del p.Pro262ArgfsTer35 stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
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.

4/1/2022
2
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1

Decreased from 2 to 1

1/1/2020
2
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2

Decreased from 2 to 2

Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of < 0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

Reports Added
[Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism2020]
10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of < 0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

Reports Added
[New Scoring Scheme]
10/1/2015
icon
3

Increased from to 3

Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

Krishnan Probability Score

Score 0.43093659742988

Ranking 20787/25841 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 0.9758794810162

Ranking 2231/18225 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 0.096863782899724

Ranking 64/18665 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 -0.21023282244281

Ranking 15646/20870 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
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
WNT1 wingless-type MMTV integration site family member 1 Human Protein Binding 7471 P04628
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