White matter disorders and cerebral calcification - narrow panel

Gene: ATP11A

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 12 Mar 2026, 9:56 a.m. | Last Modified: 12 Mar 2026, 9:56 a.m.

Panel Version: 7.15

Green List (high evidence)

Comment on publications: PMID: 39432785 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques

Created: 25 Feb 2025, 4:46 p.m. | Last Modified: 25 Feb 2025, 4:46 p.m.

Panel Version: 6.6

Three heterozygous ATP11A variants have been associated with Leukodystrophy, hypomyelinating, 24 (OMIM:619851), in four unrelated cases with varying severity of neurological disorders (PMID: 34403372;39432785). It would appear that these variants interfere with the normal translocation of phosphatidylserine and phosphatidylethanolamine from the outer leaflet to the inner leaflet, resulting in an increased sphingomyelin (SM) levels on the cell surface, resulting in a greater susceptibility to SM phosphodiesterase-mediated cell lysis. Experiments in mice also support the role of ATP11A variants in neurological disorders (PMID: 34403372;39432785).

Created: 25 Feb 2025, 4:45 p.m. | Last Modified: 25 Feb 2025, 4:45 p.m.

Panel Version: 6.5

Phenotypes
Leukodystrophy, hypomyelinating, 24, OMIM:619851; leukodystrophy, hypomyelinating, 24 MONDO:0859242

Publications

• 34403372
• 39432785

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. There is currently only 1 case and a mouse model which showed neurological deficit phenotypes (including tremors, abnormal gait, hind limb clasping and reduction in brain size. The patient was a 26 yo male born to healthy non-consanguineous Japanese parents. At birth his length was -3.3. SD and OFC was -1.3 SD. Developed epilepsy at 2 weeks followed by global developmental delay and mild hypothyroidism and cataracts.He suffered gradual lost of developmental milestones. At 18 yo, height was -4.6 SD and OFC was -4.0 SD.

As there is currently not enough evidence to support a gene-disease association, this gene has been given an Amber rating.

Created: 13 Oct 2021, 12:10 p.m. | Last Modified: 13 Oct 2021, 12:10 p.m.

Panel Version: 3.1353

I don't know

PMID: 34403372:
- Single de novo missense variant reported in a patient with developmental delay and neurological deterioration.
- Patient MRI showed severe cerebral atrophy, ventriculomegaly, hypomyelination leukodystrophy, thinned corpus callosum. Axonal neuropathy suggested.
- K/I heterozygous mice died perinatally.
- Functional studies on missense variant show plasma membrane lipid content impairment, reduced ATPase activity etc.

gnomAD: some NMD PTCs present, good quality variants found with 4-5 hets.
Sources: Literature

Created: 11 Oct 2021, 9:24 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder

Publications

• 34403372