Human Gene Module / Chromosome 1 / ASTN1

ASTN1astrotactin 1

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
4 / 6
Rare Variants / Common Variants
20 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
1q25.2
Associated Disorders
-
Relevance to Autism

Levine et al., 2026 described eighteen individuals from twelve unrelated families with biallelic, ultra-rare, predicted damaging variants in ASTN1 and one individual with heterozygous variants in both ASTN1 and ASTN2 presenting with a variable neurodevelopmental disorder characterized by mild to profound developmental delay or intellectual disability, autism or autistic features, ADHD, epilepsy, dysmorphic facial features, hypotonia, spasticity, ataxia, and structural brain abnormalities. A homozygous missense variant in the ASTN1 gene was previously identified in an ASD proband born to consanguineous Middle Eastern parents in Tuncay et al., 2022, while additional de novo heterozygous variants in the ASTN1 gene, including a de novo loss-of-function variant and several de novo missense variants, have been reported in ASD probands from the iHART cohort, the SPARK cohort, and a Chinese ASD cohort (Ruzzo et al., 2019; Zhou et al., 2022; Yuan et al., 2023).

Molecular Function

Astrotactin is a neuronal adhesion molecule required for glial-guided migration of young postmitotic neuroblasts in cortical regions of developing brain, including cerebrum, hippocampus, cerebellum, and olfactory bulb.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
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Reports related to ASTN1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
2 Support - Tuncay IO et al. (2022) Yes ADHD, DD, ID
3 Support - Zhou X et al. (2022) Yes -
4 Support - Yuan B et al. (2023) Yes -
5 Support - Akif Ayaz et al. (2025) No -
6 Primary - Jesse M Levine et al. (2026) No ASD or autistic features, ADHD
Rare Variants   (20)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1599-14G>A - intron_variant Unknown - Simplex 41544630 Jesse M Levine et al. (2026)
c.177del p.Ser60ArgfsTer90 frameshift_variant De novo - - 36881370 Yuan B et al. (2023)
c.1245T>C p.His415= synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.3299C>T p.Pro1100Leu missense_variant De novo - Unknown 35982159 Zhou X et al. (2022)
c.1270+1G>A - splice_site_variant Unknown - Simplex 41544630 Jesse M Levine et al. (2026)
c.2773A>G p.Met925Val missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.1446C>G p.Cys482Trp missense_variant De novo - Multiplex 31398340 Ruzzo EK , et al. (2019)
c.1549C>T p.Arg517Ter stop_gained Familial Both parents Simplex 39667727 Akif Ayaz et al. (2025)
c.1523+1G>T - splice_site_variant Familial Both parents Simplex 41544630 Jesse M Levine et al. (2026)
c.1736+5G>A - splice_site_variant Familial Both parents Simplex 41544630 Jesse M Levine et al. (2026)
c.2770C>T p.His924Tyr missense_variant Familial Maternal Simplex 41544630 Jesse M Levine et al. (2026)
c.2773A>G p.Met925Val missense_variant Familial Paternal Simplex 41544630 Jesse M Levine et al. (2026)
c.3283A>C p.Met1095Leu missense_variant Familial Both parents Simplex 35190550 Tuncay IO et al. (2022)
c.3283A>C p.Met1095Leu missense_variant Familial Paternal Simplex 41544630 Jesse M Levine et al. (2026)
c.1132C>T p.Arg378Ter stop_gained Familial Both parents Multiplex 41544630 Jesse M Levine et al. (2026)
c.838_839delGA p.Glu280LysfsTer11 frameshift_variant Unknown - Simplex 41544630 Jesse M Levine et al. (2026)
c.2224G>C p.Gly742Arg missense_variant Familial Both parents Multiplex 41544630 Jesse M Levine et al. (2026)
c.3334C>T p.Arg1112Ter stop_gained Familial Both parents Extended multiplex 41544630 Jesse M Levine et al. (2026)
c.3125delAinsGACCACAAGTG p.Glu1042GlyfsTer28 frameshift_variant Unknown - Simplex 41544630 Jesse M Levine et al. (2026)
c.3159_3160del p.Gln1053HisfsTer13 frameshift_variant Familial Both parents Multiplex 41544630 Jesse M Levine et al. (2026)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

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.

4/1/2026
1

Initial score established: 1

Krishnan Probability Score

Score 0.60709699525995

Ranking 306/25841 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 0.99941599729198

Ranking 967/18225 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 0.94799583271868

Ranking 17503/18665 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 0.24305475333907

Ranking 3572/20870 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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