Early onset or syndromic epilepsy

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 to have seizures and/or epileptiform activity on EEG (PMIDs: 29706646; 41544630). Based on available evidence, this gene should be promoted to Green for Early onset or syndromic epilepsy.

Created: 10 Feb 2026, 3:27 p.m. | Last Modified: 10 Feb 2026, 3:28 p.m.

Panel Version: 8.111

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).

Created: 10 Feb 2026, 3:25 p.m. | Last Modified: 10 Feb 2026, 3:25 p.m.

Panel Version: 8.108

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

• 41544630

Red List (low evidence)

Comment on list classification: Epilepsy only reported in a single patient. Further cases required to ascertain the contribution of ASTN1 variants to this phenotype.

Created: 24 Jul 2020, 10:23 a.m. | Last Modified: 24 Jul 2020, 10:23 a.m.

Panel Version: 2.127

Not associated with any phenotype in OMIM or G2P. Homozygous ASTN1 variants identified in three families, all as part of large screening studies of ID and related disorders.

PMID: 26539891 (2015) - Two affected sibs with ID and partial corpus callosum agenesis, born to consanguineous Turkish parents (second-degree cousins). The ASTN1 variant (c.G2224C; p.G742R) segregated with the phenotype (but testing in a third, unaffected sib was not performed).

PMID - 27431290 (2016) - Large screening study of patients with ID/DD. Authors state that likely causal variants were identified in ASTN1, supporting candidacy on the basis of the previous report. However, it was not possible to map this finding to a specific case/variant based on the published data.

PMID - 29706646 (2018) - Compound heterozygous variants ([c.3283A>C, p.Met1095Leu];[c.2770C>T, p.His924Tyr]) identified in a Polish patient with diffuse polymicrogyria, spastic tetraplegia, epilepsy and DD.

Created: 24 Jul 2020, 10:15 a.m. | Last Modified: 24 Jul 2020, 10:15 a.m.

Panel Version: 2.126

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability

Publications

• 26539891
• 27431290
• 29706646

Green List (high evidence)

Three families reported as part of large cohorts albeit proposing multiple novel candidate genes with minimal detail and no functional validation.
Sources: Expert list

Created: 7 Jan 2020, 8 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability; epilepsy; cortical malformations

Publications

• 29706646
• 27431290
• 26539891

Variants in this GENE are reported as part of current diagnostic practice