Likely inborn error of metabolism

Gene: SPATA5

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 12 Mar 2026, 10:16 a.m. | Last Modified: 12 Mar 2026, 10:16 a.m.

Panel Version: 8.94

Comment on list classification: SPATA5 has already been promoted to green rating on Mitochondrial disorders panel (https://panelapp.genomicsengland.co.uk/panels/112/gene/SPATA5/) as detailed in the below reviews copied from that panel.

As there is sufficient evidence available for the gene-disease association, this gene can be promoted to green rating on this panel in the next GMS update.

Created: 10 Jun 2025, 9:17 a.m. | Last Modified: 10 Jun 2025, 9:17 a.m.

Panel Version: 8.48

Added new-gene-name tag, new approved HGNC gene symbol for SPATA5 is AFG2A.

Created: 10 Jun 2025, 9:12 a.m. | Last Modified: 10 Jun 2025, 9:12 a.m.

Panel Version: 8.47

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Comment on list classification: There are sufficient cases to promote this gene to Green at the next GMS panel update. Patients display a phenotype that resembles a mitochondrial disorder and functional studies on patient-derived cells have demonstrated an impact on mitochondrial function, further supporting inclusion of SPATA5 on this panel.

Created: 12 Mar 2024, 4:24 p.m. | Last Modified: 12 Mar 2024, 4:24 p.m.

Panel Version: 4.162

Green List (high evidence)

At least five cases with biallelic variants had a clinical presentation resembling a mitochondrial disorder. Functional assays showed SPATA5-deficient neurons had a significant imbalance in the mitochondrial fusion-fission rate, impaired energy production and short axons.

Created: 23 Mar 2020, 3:44 a.m. | Last Modified: 23 Mar 2020, 3:44 a.m.

Panel Version: 2.5

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy, hearing loss, and mental retardation syndrome MIM#616577

Publications

• 30009132
• 29343804

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

Comment on list classification: This gene is being rated as amber as it has not been reviewed as green by the GMS Mitochondrial specialist test group.

Created: 20 Aug 2019, 3:29 p.m. | Last Modified: 20 Aug 2019, 3:29 p.m.

Panel Version: 1.479

Green List (high evidence)

Greater than 15 families have been identified in multiple publications showing that patients with SPATA5 biallelic variants present with intellectual disability, epilepsy, microcephaly and hearing loss, as well as cortical blindness, spasticity and feeding problems; and prior to the gene being discovered to cause the phenotype in these families patients were often thought to have a mitochondrial disorder.

As per Puusepp et al (PMID: 29343804) functional studies were performed on rat cortical neurons. "SPATA5-deficient neurons had a significant imbalance in the mitochondrial fusion-fission rate, impaired energy production and short axons. In conclusion, SPATA5 protein has an important role in mitochondrial dynamics and axonal growth. Biallelic variants in the SPATA5 gene can affect mitochondria in cortical neurons and should be considered in patients with a neurodegenerative disorder and/or with clinical presentation resembling a mitochondrial disorder."
Sources: Literature

Created: 19 Aug 2019, 3:52 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy, hearing loss, and mental retardation syndrome 616577

Publications

• PMID: 27246907
• 29343804
• 26299366