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chromosome 19 open reading frame 12

Recent Research Progress

The C19orf12 gene encodes a protein that is located in the mitochondria and endoplasmic reticulum. The mutation in C19orf12 was first described in a homogenous cohort from Poland, where most cases carried the initial mutation with 11bp deletion. In subsequent large multinational studies, mutations in the C19orf12 gene were found to be associated with a wide range of phenotypes, usually including motor neuropathy, cognitive decline and neuropsychiatric disorders. To date, C19orf12 mutations have been reported to be associated with a variety of diseases, for example Neurodegeneration with brain iron accumulation (NBIA), palliative pyramidal syndrome, hereditary spastic paraplegia (HSPs), etc.

The mutation of C19orf12 gene is related to NIBA

NIBA comprises heterogeneous group of progressive neurodegenerative disorders that present with a progressive extrapyramidal syndrome and excessive iron deposition in the basal ganglia showed by brain magnetic resonance imaging (MRI). Mutations in C19orf12 have recently been found in patients with NBIA. Currently, nine different subtypes of NBIA have been found to correspond to their genes. PANK2, PLA2G6 and C19orf12 are hot genes, with C19orf12 accounting alone for up to 30% of cases. The autosomal recessive form of NBIA is caused by mutations in C19orf12, called mitochondrial membrane protein-associated neurodegeneration (MPAN). It is reported that the P.Thr11Met mutation in C19orf12 is common in adult Turkish MPAN patients. Besides, the results of Anne Tschentscher et al. showed that the previously described homozygous C19orf12 mutation (4.3%) was found in 3/69 patients with NBIA, and the C19orf12 mutation was confirmed in the heterogeneous NBIA cohort.

C19orf12 mutations can cause palliative pyramidal syndrome

Palliative pyramidal syndrome with or without dystonia, with or without Parkinson's disease and spasm, is part of a mixed neurodegenerative disorder. Some disease-causing genes have been shown to cause palliative pyramidal syndrome, including FBXO7, ATP13A2, PLA2G6, PRKN and SPG11. Mutations in C19orf12 have been shown to cause phenotypes similar to PLA2G6 mutations. Michael C et al. reported the C19orf12 mutation in a multipath, homologous Saudi relative with a clinical characteristic of palliative cone syndrome. The results showed that patients with C19orf12 mutations typically had brain iron deposits in the white globule and the black matter, unlike those with FBXO7, SPG11 and PRKN mutations, and similar to those with many plaque 2g6 mutations. Consequently, C19orf12 should be considered in PLA2G6-negative palliative pyramidal syndrome.

Mutational analysis of C19orf12 genes in autosomal recessive HSPs

HSPs include a group of neurodegenerative disorders with inherited inhomogeneity. So far, 60 HSPs subtypes have been described. Some scholars analyzed the mutation of C19orf12 gene (causative for the subtypes SPG5A, SPG39 and SPG43, respectively) in HSPs. The results showed that two new homogenous mutations (one transcoding mutation and one missense mutation) were detected in SPG5A, while no disease mutations were found in SPG39 and SPG43. SPG5A appears to be one of the ‘more frequent’ forms of rare recessive HSPs. The mutation of C19orf12 in HSPs patients needs further study and analysis.

In conclusion, C19orf12 is a hot gene, especially in the study of NIBA. In addition, studies have confirmed that NIBA patients often have Parkinson's disease, but whether it is related to the mutation of C19orf12 needs further study. It is believed that further research and analysis of C19orf12 will have great clinical significance and practical value.


  1. Tschentscher A, et al. Analysis of the C19orf12 and WDR45 genes in patients with neurodegeneration with brain iron accumulation. Journal of the Neurological Sciences, 2015, 349:105–109.
  2. Michael C, et al. C19orf12 mutation leads to a pallido-pyramidal syndrome. Gene, 2014, 537: 352–356.
  3. Sarah F, et al. Mutational analysis of the CYP7B1, PNPLA6 and C19orf12 genes in autosomal recessive hereditary spastic paraplegia. Molecular and Cellular Probes, 2016, 30:53e55.
  4. Gagliardi M, et al. C19orf12 gene mutations in patients with neurodegeneration with brain iron accumulation. Parkisonism & Related Disorders, 2015, 21(7):813-816.
  5. Olgiati S, et al. The p.Thr11Met mutation in c19orf12 is frequent among adult Turkish patients with MPAN. Parkinsonism and Related Disorders, 2017, 39:64-70.
  6. Nabil Al Macki, et al. A Novel Deletion Mutation of Exon 2 of the C19orf12 Gene in an Omani Family with Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN). Oman Medical Journal, 2017, 1: 66–68.
  7. Iuso A, et al. Impairment of Drosophila Orthologs of the Human Orphan Protein C19orf12 Induces Bang Sensitivity and Neurodegeneration. Plos One, 2014, 9(2): e89439.

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