Human Gene Module / Chromosome 9 / ASTN2

ASTN2astrotactin 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
13 / 24
Rare Variants / Common Variants
34 / 3
EAGLE Score
2.5
Limited Learn More
Aliases
ASTN2, RP11-45A16.2,  KIAA0634,  bA67K19.1
Associated Syndromes
-
Chromosome Band
9q33.1
Associated Disorders
DD/NDD, ADHD, ID, EPS, ASD
Genetic Category
Rare Single Gene Mutation, Genetic Association, Functional
Relevance to Autism

Association has been found between the ASTN2 gene and autism. Glessner et al. (2009) identified a rare ASTN2 deletion in an autism case. Another study found a link between rare ASTN2 CNVs and schizophrenia.

Molecular Function

This gene encodes a protein that is expressed in the brain and may function in neuronal migration, based on functional studies of the related astrotactin 1 gene in human and mouse. A deletion at this locus has been associated with schizophrenia.

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 ASTN2 (24 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Recent Recommendation Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies Lesch KP , et al. (2008) No -
2 Recent Recommendation Recurrent CNVs disrupt three candidate genes in schizophrenia patients Vrijenhoek T , et al. (2008) No -
3 Primary Autism genome-wide copy number variation reveals ubiquitin and neuronal genes Glessner JT , et al. (2009) Yes -
4 Recent Recommendation Astn2, a novel member of the astrotactin gene family, regulates the trafficking of ASTN1 during glial-guided neuronal migration Wilson PM , et al. (2010) No -
5 Recent Recommendation Genome-wide association analysis identifies susceptibility loci for migraine without aura Freilinger T , et al. (2012) No -
6 Support A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
7 Support Identification of candidate intergenic risk loci in autism spectrum disorder Walker S and Scherer SW (2013) Yes -
8 Recent Recommendation Disruption of the ASTN2/TRIM32 locus at 9q33.1 is a risk factor in males for autism spectrum disorders, ADHD and other neurodevelopmental phenotypes Lionel AC , et al. (2014) Yes ADHD, DD, ID, epilepsy, OCD
9 Positive Association Novel genetic loci associated with hippocampal volume Hibar DP , et al. (2017) No -
10 Positive Association Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017) Yes -
11 Support Expanding the genetic heterogeneity of intellectual disability Anazi S , et al. (2017) No Dysmorphic features
12 Recent recommendation ASTN2 modulates synaptic strength by trafficking and degradation of surface proteins Behesti H , et al. (2018) No ASD, ID, epilepsy/seizures
13 Support Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use Husson T , et al. (2020) Yes -
14 Support - Hildebrand MS et al. (2020) No DD
15 Highly Cited Astrotactin: a novel neuronal cell surface antigen that mediates neuron-astroglial interactions in cerebellar microcultures Edmondson JC , et al. (1988) No -
16 Support - Bauleo A et al. (2021) Yes -
17 Support - Mitani T et al. (2021) No -
18 Support - Woodbury-Smith M et al. (2022) Yes -
19 Support - Zhou X et al. (2022) Yes -
20 Support - Ito T et al. (2023) Yes -
21 Support - Yu Hayashi et al. (2024) No -
22 Support - Michalina Hanzel et al. (2024) Yes -
23 Support - Soo-Whee Kim et al. (2024) Yes -
24 Support - Ashlesha Gogate et al. (2024) Yes -
Rare Variants   (34)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss - - - 19404257 Glessner JT , et al. (2009)
- - copy_number_gain - - - 18940311 Vrijenhoek T , et al. (2008)
- - copy_number_loss - - - 18940311 Vrijenhoek T , et al. (2008)
- - copy_number_loss De novo - Simplex 34582790 Mitani T et al. (2021)
- - copy_number_loss Unknown - Unknown 23275889 Prasad A , et al. (2013)
- - copy_number_loss De novo - Unknown 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Unknown - Unknown 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Unknown - Simplex 23879678 Walker S and Scherer SW (2013)
- - copy_number_gain Familial Maternal Simplex 34412080 Bauleo A et al. (2021)
- - copy_number_loss Familial Paternal Simplex 34412080 Bauleo A et al. (2021)
c.843C>T p.Gly281= synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_loss Familial Maternal Multiplex 34412080 Bauleo A et al. (2021)
- - copy_number_gain Familial Paternal Simplex 24381304 Lionel AC , et al. (2014)
- - copy_number_gain Familial Maternal Unknown 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Familial Maternal Unknown 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Familial Paternal Unknown 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Familial Maternal Multiplex 32094338 Husson T , et al. (2020)
- - copy_number_gain Familial Maternal Multiplex 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Familial Maternal Multiplex 24381304 Lionel AC , et al. (2014)
- - copy_number_gain Familial Paternal Multiplex 30242134 Behesti H , et al. (2018)
- - copy_number_loss Unknown Not maternal Unknown 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Unknown Not paternal Unknown 24381304 Lionel AC , et al. (2014)
- - copy_number_loss Familial Maternal Simplex 23879678 Walker S and Scherer SW (2013)
c.2166G>A p.Leu722= synonymous_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.3361G>A p.Val1121Met missense_variant Unknown - - 32345733 Hildebrand MS et al. (2020)
c.2601G>A p.Lys867= synonymous_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.892G>C p.Asp298His missense_variant - Both parents Simplex 28940097 Anazi S , et al. (2017)
c.870T>A p.Ser257Thr missense_variant Familial Paternal Unknown 24381304 Lionel AC , et al. (2014)
c.1150C>T p.Ser350Leu missense_variant Familial Paternal Unknown 24381304 Lionel AC , et al. (2014)
c.1476G>T p.Val459Leu missense_variant Familial Maternal Unknown 24381304 Lionel AC , et al. (2014)
c.1638A>T p.Thr513Ser missense_variant Familial Maternal Unknown 24381304 Lionel AC , et al. (2014)
c.3522C>A p.Leu1141Met missense_variant Familial Maternal Unknown 24381304 Lionel AC , et al. (2014)
c.3806G>A p.Arg1269Gln missense_variant Familial Paternal Simplex 39632905 Ashlesha Gogate et al. (2024)
c.3901G>A p.Glu1301Lys missense_variant Familial Maternal Simplex 39632905 Ashlesha Gogate et al. (2024)
Common Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.653+1664C>G;c.3344+1664C>G;c.800+1664C>G;c.3497+1664C>G - intron_variant - - - 28098162 Hibar DP , et al. (2017)
- - intergenic_variant - - - 28540026 Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017)
c.512-46957C>A;c.3203-46957C>A;c.659-46957C>A;c.3356-46957C>A - intron_variant - - - 28540026 Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017)
SFARI Gene score
2

Strong Candidate

The report from Glessner et al. indicates that 6/~2000 cases and 1/~2500 controls have deletions that overlap with the ASTN2 locus, inheritance unknown. Multiple case events are exonic while the only control event is within an intron. Of the 6 variants, 2 were confirmed by Affymetrix arrays but the status of the remainder is unknown. Statistical support is lacking (the p value of 9.5 x 10-3 is for all genes within the GO term ?neuron development?, not ASTN2 alone. ASTN2 CNVs in 2/800 cases versus 0/700 controls were reported in Vrijenhoek T et al., A GWAS provides support for ASTN2 (paper unavailable electronically but nominal support presumed) (Lesch KP et al.).

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.

1/1/2020
2
icon
2

Score remained at 2

Description

The report from Glessner et al. indicates that 6/~2000 cases and 1/~2500 controls have deletions that overlap with the ASTN2 locus, inheritance unknown. Multiple case events are exonic while the only control event is within an intron. Of the 6 variants, 2 were confirmed by Affymetrix arrays but the status of the remainder is unknown. Statistical support is lacking (the p value of 9.5 x 10-3 is for all genes within the GO term ?neuron development?, not ASTN2 alone. ASTN2 CNVs in 2/800 cases versus 0/700 controls were reported in Vrijenhoek T et al., A GWAS provides support for ASTN2 (paper unavailable electronically but nominal support presumed) (Lesch KP et al.).

Reports Added
[Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use.2020]
10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

The report from Glessner et al. indicates that 6/~2000 cases and 1/~2500 controls have deletions that overlap with the ASTN2 locus, inheritance unknown. Multiple case events are exonic while the only control event is within an intron. Of the 6 variants, 2 were confirmed by Affymetrix arrays but the status of the remainder is unknown. Statistical support is lacking (the p value of 9.5 x 10-3 is for all genes within the GO term ?neuron development?, not ASTN2 alone. ASTN2 CNVs in 2/800 cases versus 0/700 controls were reported in Vrijenhoek T et al., A GWAS provides support for ASTN2 (paper unavailable electronically but nominal support presumed) (Lesch KP et al.).

Reports Added
[New Scoring Scheme]
10/1/2018
3
icon
3

Decreased from 3 to 3

Description

The report from Glessner et al. indicates that 6/~2000 cases and 1/~2500 controls have deletions that overlap with the ASTN2 locus, inheritance unknown. Multiple case events are exonic while the only control event is within an intron. Of the 6 variants, 2 were confirmed by Affymetrix arrays but the status of the remainder is unknown. Statistical support is lacking (the p value of 9.5 x 10-3 is for all genes within the GO term ?neuron development?, not ASTN2 alone. ASTN2 CNVs in 2/800 cases versus 0/700 controls were reported in Vrijenhoek T et al., A GWAS provides support for ASTN2 (paper unavailable electronically but nominal support presumed) (Lesch KP et al.).

Reports Added
[ASTN2 modulates synaptic strength by trafficking and degradation of surface proteins.2018]
10/1/2017
3
icon
3

Decreased from 3 to 3

Description

The report from Glessner et al. indicates that 6/~2000 cases and 1/~2500 controls have deletions that overlap with the ASTN2 locus, inheritance unknown. Multiple case events are exonic while the only control event is within an intron. Of the 6 variants, 2 were confirmed by Affymetrix arrays but the status of the remainder is unknown. Statistical support is lacking (the p value of 9.5 x 10-3 is for all genes within the GO term ?neuron development?, not ASTN2 alone. ASTN2 CNVs in 2/800 cases versus 0/700 controls were reported in Vrijenhoek T et al., A GWAS provides support for ASTN2 (paper unavailable electronically but nominal support presumed) (Lesch KP et al.).

Reports Added
[Expanding the genetic heterogeneity of intellectual disability.2017]
4/1/2017
3
icon
3

Decreased from 3 to 3

Description

The report from Glessner et al. indicates that 6/~2000 cases and 1/~2500 controls have deletions that overlap with the ASTN2 locus, inheritance unknown. Multiple case events are exonic while the only control event is within an intron. Of the 6 variants, 2 were confirmed by Affymetrix arrays but the status of the remainder is unknown. Statistical support is lacking (the p value of 9.5 x 10-3 is for all genes within the GO term ?neuron development?, not ASTN2 alone. ASTN2 CNVs in 2/800 cases versus 0/700 controls were reported in Vrijenhoek T et al., A GWAS provides support for ASTN2 (paper unavailable electronically but nominal support presumed) (Lesch KP et al.).

Reports Added
[Autism genome-wide copy number variation reveals ubiquitin and neuronal genes.2009] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Identification of candidate intergenic risk loci in autism spectrum disorder.2013] [Disruption of the ASTN2/TRIM32 locus at 9q33.1 is a risk factor in males for autism spectrum disorders, ADHD and other neurodevelopmental phenotypes.2014] [Recurrent CNVs disrupt three candidate genes in schizophrenia patients.2008] [Astrotactin: a novel neuronal cell surface antigen that mediates neuron-astroglial interactions in cerebellar microcultures.1988] [Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies.2008] [Astn2, a novel member of the astrotactin gene family, regulates the trafficking of ASTN1 during glial-guided neuronal migration.2010] [Genome-wide association analysis identifies susceptibility loci for migraine without aura.2012] [Novel genetic loci associated with hippocampal volume.2017] [Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with ...2017]
1/1/2017
3
icon
3

Decreased from 3 to 3

Description

The report from Glessner et al. indicates that 6/~2000 cases and 1/~2500 controls have deletions that overlap with the ASTN2 locus, inheritance unknown. Multiple case events are exonic while the only control event is within an intron. Of the 6 variants, 2 were confirmed by Affymetrix arrays but the status of the remainder is unknown. Statistical support is lacking (the p value of 9.5 x 10-3 is for all genes within the GO term ?neuron development?, not ASTN2 alone. ASTN2 CNVs in 2/800 cases versus 0/700 controls were reported in Vrijenhoek T et al., A GWAS provides support for ASTN2 (paper unavailable electronically but nominal support presumed) (Lesch KP et al.).

Reports Added
[Novel genetic loci associated with hippocampal volume.2017]
7/1/2014
No data
icon
3

Increased from No data to 3

Description

The report from Glessner et al. indicates that 6/~2000 cases and 1/~2500 controls have deletions that overlap with the ASTN2 locus, inheritance unknown. Multiple case events are exonic while the only control event is within an intron. Of the 6 variants, 2 were confirmed by Affymetrix arrays but the status of the remainder is unknown. Statistical support is lacking (the p value of 9.5 x 10-3 is for all genes within the GO term ?neuron development?, not ASTN2 alone. ASTN2 CNVs in 2/800 cases versus 0/700 controls were reported in Vrijenhoek T et al., A GWAS provides support for ASTN2 (paper unavailable electronically but nominal support presumed) (Lesch KP et al.).

4/1/2014
No data
icon
3

Increased from No data to 3

Description

The report from Glessner et al. indicates that 6/~2000 cases and 1/~2500 controls have deletions that overlap with the ASTN2 locus, inheritance unknown. Multiple case events are exonic while the only control event is within an intron. Of the 6 variants, 2 were confirmed by Affymetrix arrays but the status of the remainder is unknown. Statistical support is lacking (the p value of 9.5 x 10-3 is for all genes within the GO term ?neuron development?, not ASTN2 alone. ASTN2 CNVs in 2/800 cases versus 0/700 controls were reported in Vrijenhoek T et al., A GWAS provides support for ASTN2 (paper unavailable electronically but nominal support presumed) (Lesch KP et al.).

Krishnan Probability Score

Score 0.56772529750509

Ranking 1161/25841 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 0.98917228378034

Ranking 1831/18225 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 0.94907007384497

Ranking 17941/18665 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 21

Ranking 96/461 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 0.23040140503017

Ranking 3770/20870 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
External PIN Data
BioGRIDHuman Protein Reference Database
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
Astn1 astrotactin 1 Mouse Protein Binding 11899 Q61137
Auts2 autism susceptibility candidate 2 Mouse DNA Binding 319974 Q6PED7
CCT4 chaperonin containing TCP1, subunit 4 (delta) Human Protein Binding 10575 P50991
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