| C12orf65 Gene | |
|---|---|
| Symbol | C12orf65 |
| Full Name | Chromosome 12 Open Reading Frame 65 |
| Location | 12q24.31 |
| NCBI Gene ID | [84879](https://www.ncbi.nlm.nih.gov/gene/84879) |
| OMIM | [613541](https://www.omim.org/entry/613541) |
| Ensembl | [ENSG00000178732](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000178732) |
| UniProt | [Q5R390](https://www.uniprot.org/uniprot/Q5R390) |
| Associated Diseases | Leigh syndrome, Spastic paraplegia, Optic atrophy |
Paraplegin is a human gene whose product c12orf65 (also known as mitochondrial release factor) is a mitochondrial matrix protein that functions as a peptide release factor in mitochondrial translation termination. It recognizes stop codons (UAA, UAG) in mitochondrial mRNA and catalyzes the release of newly synthesized polypeptides from the ribosome, a critical step in mitochondrial protein synthesis [1]. Variants in Paraplegin have been implicated in Combined Oxidative Phosphorylation Deficiency 7 (COXPD7), Leigh Syndrome Spectrum, Hereditary Spastic Paraplegia. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
C12orf65 (also known as mitochondrial release factor) is a mitochondrial matrix protein that functions as a peptide release factor in mitochondrial translation termination. It recognizes stop codons (UAA, UAG) in mitochondrial mRNA and catalyzes the release of newly synthesized polypeptides from the ribosome, a critical step in mitochondrial protein synthesis [1].
C12orf65 is essential for the production of mitochondrial-encoded subunits of the electron transport chain, particularly those of Complex IV (cytochrome c oxidase) and Complex V (ATP synthase). Loss of C12orf65 function leads to impaired oxidative phosphorylation and cellular energy deficiency, especially in high-energy-demand tissues like neurons [2].
Key functions include:
Biallelic C12orf65 mutations cause COXPD7, a severe mitochondrial disorder characterized by:
C12orf65-related disorders frequently present with Leigh syndrome features, including bilateral symmetric brainstem and basal ganglia lesions on MRI, reflecting the vulnerability of these regions to mitochondrial dysfunction [4].
Some C12orf65 variants present primarily as a complicated hereditary spastic paraplegia with:
C12orf65 is ubiquitously expressed, with highest levels in:
The protein localizes exclusively to mitochondria, consistent with its role in mitochondrial translation [5].
Current management includes:
Physical therapy for spasticity management
Visual aids for optic atrophy
Nutritional support
Respiratory monitoring
SURF1: Cytochrome c oxidase assembly - Leigh syndrome
SPG7: Paraplegin - HSP
OPA1: Optic atrophy 1 - mitochondrial dynamics