Malformations of cortical development

Gene: ASTN1

Green List (high evidence)

Comment on list classification: Comment on list classification: There are more than 3 unrelated individuals reported with biallelic ASTN1 variants and a neurodevelopmental disorder. 11 patients were reported have abnormal brain MRI results, including callosal dysgenesis (7) and dysgenesis of the cerebellum (5). Based on available evidence, this gene should be promoted to Green for Malformations of cortical development.

Created: 16 Feb 2026, 3:30 p.m. | Last Modified: 16 Feb 2026, 3:30 p.m.

Panel Version: 7.23

PMID: 41544630 Levine et al., 2026
Report of 18 individuals from 12 unrelated families with biallelic ASTN1 variants and a neurodevelopmental disorder, plus one individual with digenic inheritance with heterozygous variants in ASTN1 and ASTN2. Of these, 6 families are previously unreported (F1-6). Method: exome seq. Phenotypic spectrum: ID/DD (18/18 - mild to severe), seizures and/or epileptiform activity on EEG (10/18), subtle dysmorphic features (11/18), hypotonia (10/18), ataxia (4/18), hyperreflexia (5/18), and other less common findings.
Brain MRI was abnormal in 11/15 tested individuals, with callosal dysgenesis (7/15) and dysgenesis of the cerebellum (5/15) being most common findings.
Variants included missense, nonsense, and splice type. 2 patients had other candidate variants reported:
P1 - KDM3A:c.1639C>T, (p.Arg547Ter) de novo, heterozygous
P4 - TRAK2:c.1675C>T, (p.Gln559Ter) homozygous
Neither of these genes is linked to disease in OMIM.

ASTN1 is not yet associated with disease in OMIM, ClinGen, or Gene2Phenotype (resources accessed 10th Feb 2026).
Sources: Literature

Created: 16 Feb 2026, 3:29 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

• 41544630