Ataxia and cerebellar anomalies - narrow panel

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 hypoplasia of the cerebellar vermis on MRI. Ataxia was diagnosed in 1 patient (walking with support at 17yo), while 2 other individuals were nonambulant. Based on available evidence, this gene should be promoted to Green on Ataxia and cerebellar anomalies - narrow panel.

Created: 1 Apr 2026, 11:39 a.m. | Last Modified: 1 Apr 2026, 11:40 a.m.

Panel Version: 8.74

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: 8.74

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