Likely inborn error of metabolism

Gene: C2orf69

Green List (high evidence)

Comment on list classification: This gene should be added with green rating to this panel as this gene has already been promoted to green rating on Mitochondrial disorders panel (https://panelapp.genomicsengland.co.uk/panels/112/gene/C2orf69/)

Created: 6 Jun 2025, 3:26 p.m. | Last Modified: 6 Jun 2025, 3:26 p.m.

Panel Version: 8.15

The OMIM entry for this gene is OMIM:619219, which has been cross-checked with both Ensembl and HGNC. Hence, gene-checked tag has been added.

Created: 16 Oct 2023, 6:59 p.m. | Last Modified: 16 Oct 2023, 7:07 p.m.

Panel Version: 4.99

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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: 11 Oct 2023, 9:52 a.m. | Last Modified: 11 Oct 2023, 9:52 a.m.

Panel Version: 4.95

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Comment on list classification: New gene added to this panel by Zornitza Stark (Australian Genomics). Associated with a relevant phenotype in OMIM (MIM# 619423) but is not yet listed in G2P. At least 13 unrelated families reported in literature (PMIDs: 33945503; 34038740). Sufficient cases plus zebrafish model to promote this gene to green at the next GMS panel update.

Created: 18 Apr 2023, 11:06 a.m. | Last Modified: 18 Apr 2023, 11:06 a.m.

Panel Version: 4.27

Green List (high evidence)

PMID 34038740: 20 affected children from 8 unrelated families reported, presenting with fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. Endogenous C2ORF69 was found to be (1) loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. Zebrafish model.

PMID 33945503: 8 individuals from 5 families reported with muscle hypotonia, developmental delay, progressive microcephaly, and brain MRI abnormalities. Age at onset ranged from birth to 6 months of age. Six patients had vision impairment, liver abnormalities, inflammation/inflammatory arthritis, and 5 patients had seizures.
Sources: Literature

Created: 7 Aug 2021, 1:46 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Combined oxidative phosphorylation deficiency-53 (COXPD53), MIM#619423

Publications

• 34038740
• 33945503

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