C19orf12: A Key Player in Neurodegeneration and Mitochondrial Iron Homeostasis
Explore the genomic architecture, clinical significance, and molecular mechanisms of C19orf12, a gene linked to neurodegeneration with brain iron accumulation (NBIA) and mitochondrial dysfunction.
Gene Information Card
| Symbol | C19orf12 |
|---|---|
| Full Name | Chromosome 19 Open Reading Frame 12 |
| Gene Type | Protein-coding |
| Chromosomal Location | 19q13.42 |
| NCBI Gene ID | 83637 ncbi.nlm.nih.gov/gene/83637 |
| Ensembl ID | ENSG00000105696 |
| UniProt ID | Q9NSG2 |
| OMIM ID | 614297 |
| HGNC ID | 25438 |
| Aliases | MPAN, NBIA4, C19orf12, FLJ10858 |
Description
C19orf12 encodes a small mitochondrial membrane protein that is predominantly expressed in the brain and is implicated in mitochondrial function and lipid homeostasis. Mutations in this gene are associated with neurodegeneration with brain iron accumulation type 4 (NBIA4), also known as mitochondrial membrane protein-associated neurodegeneration (MPAN). The protein is localized to the outer mitochondrial membrane and may play a role in fatty acid metabolism and iron regulation, though its exact molecular function remains under investigation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodegeneration with brain iron accumulation type 4 (NBIA4) | Loss-of-function mutations in C19orf12 lead to mitochondrial dysfunction, impaired iron homeostasis, and accumulation of iron in the basal ganglia, resulting in progressive neurodegeneration. | ClinVar and OMIM report pathogenic variants; functional studies show mitochondrial abnormalities in patient-derived cells. |
| Mitochondrial membrane protein-associated neurodegeneration (MPAN) | C19orf12 mutations cause MPAN, characterized by dystonia, parkinsonism, and cognitive decline, with iron deposition in the brain. | Multiple case reports and cohort studies; OMIM entry 614297. |
| Spastic paraplegia (in some cases) | Some C19orf12 mutations present with spastic paraplegia, suggesting phenotypic variability. | Case reports in NCBI PubMed; ClinVar entries. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.3 | Medium |
| Brain (basal ganglia) | 10.8 | Medium |
| Heart | 5.2 | Low |
| Liver | 3.1 | Low |
| Skeletal muscle | 2.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.6 | High expression; used in neuronal studies |
| HEK293 (embryonic kidney) | 8.9 | Moderate expression; common for transfection |
| HeLa (cervical carcinoma) | 6.3 | Low expression |
| HepG2 (hepatocellular carcinoma) | 4.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.204_214del (p.Gly69ArgfsTer14) | Frameshift | Rare (found in MPAN families) | Loss of function; truncated protein |
| c.32C>T (p.Thr11Met) | Missense | Rare | Likely damaging; affects protein stability |
| c.424G>A (p.Gly142Ser) | Missense | Rare | Uncertain significance; reported in NBIA cases |
| c.3G>A (p.Met1?) | Start codon loss | Rare | Loss of translation initiation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations are loss-of-function, leading to reduced protein levels or truncated proteins, impairing mitochondrial function.
Gain of Function (GOF)
No evidence for gain-of-function mutations; all reported variants are loss-of-function or hypomorphic.
Dominant Negative (DN)
Not reported; inheritance is autosomal recessive, so dominant-negative effects are unlikely.
View complete mutation data：
Gene Ontology (GO)
| • Mitochondrial outer membrane | • Protein binding |
| • Metal ion binding (putative) | • Cellular response to iron ion (inferred) |
Pathways
• Mitochondrial iron homeostasis
• Lipid metabolism (putative)
• Neurodegeneration pathways (NBIA)
Protein Summary
The C19orf12 protein is a 141-amino acid mitochondrial membrane protein with a transmembrane domain. It is highly expressed in the brain, particularly in neurons, and is thought to be involved in mitochondrial lipid metabolism and iron handling. Structural predictions suggest a role in membrane organization. Defects in this protein lead to mitochondrial dysfunction and iron accumulation, contributing to neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| C19orf12 Knockout HEK293 Cell Line | EDJ-KQ9875 | Human | 83636 | Details Get a Quote |
| C19orf12 Knockout A-549 Cell Line | EDJ-KQ35548 | Human | 83636 | Details Get a Quote |
| C19orf12 Knockout HCT 116 Cell Line | EDJ-KQ36755 | Human | 83636 | Details Get a Quote |
| C19orf12 Knockout HeLa Cell Line | EDJ-KQ36756 | Human | 83636 | Details Get a Quote |
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