Malformations of cortical development

Gene: ATG12

Green List (high evidence)

Comment on list classification: There are 5 unrelated families reported in literature with individuals harbouring biallelic ATG12 variants and presenting with corpus callosum hypoplasia and hypoplasia of the cerebellar vermis on brain MRI, along with other less consistent cortical findings. Hence, this gene should be upgraded to Green for Malformations of cortical development.

Created: 1 Apr 2026, 11:44 a.m. | Last Modified: 1 Apr 2026, 11:44 a.m.

Panel Version: 7.46

PMID: 41895291 Lambton et al, 2026
Homozygous and compound heterozygous variants in ATG12 reported in 6 individuals from five unrelated families with neurodevelopmental disorder with hypotonia, seizures (all 6 individuals with variable severity), ataxia, developmental delay and / or intellectual disability (seen in all 5 families), corpus callosum hypoplasia (4/5 individuals) and hypoplasia of the cerebellar vermis (5/5 individuals assessed). Other less consistent MRI findings: reduced white and gray matter, polymicrogyria, cerebellocerebral atrophy, thinning of pons, brainstem hypomyelination, and more. 4/6 individuals died before age 5 years.

Family 1: 2 sibs with ATG12 variants c.359A>C, p.Tyr120Ser and c.363+3A>T (demonstrated to cause exon 3 skipping)
Family 2: proband with a homozygous variant c.413C>T, p.Ala138Val
Family 3 : proband with a homozygous variant c.359A>C p.Tyr.120Ser
Family 4: proband S5 comp het for ATG12 variants c.235C>T (p.Arg79∗) & c.359A>C p.Tyr.120Ser
Family 5: proband with homozygous missense variant c.324T>G (p.Phe108Leu)

Functional: Loss of atg12 function in zebrafish causes developmental delay, impaired brain function, and pre-adult lethality.

This gene has no disease association in OMIM (accessed 1st Apr 2026).
Sources: Literature

Created: 1 Apr 2026, 11:32 a.m. | Last Modified: 1 Apr 2026, 11:44 a.m.

Panel Version: 7.46

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder, MONDO:0700092; Hypoplasia of the corpus callosum, HP:0002079; Cerebellar hypoplasia, HP:0001321

Publications

• 41895291