TTC19: Tetratricopeptide Repeat Domain 19
Mitochondrial Complex III Assembly Factor and Neurological Disease Gene
Gene Information Card
| Symbol | TTC19 |
|---|---|
| Full Name | Tetratricopeptide Repeat Domain 19 |
| Gene Type | Protein coding |
| Chromosomal Location | 17p12 |
| NCBI Gene ID | 54902 ncbi.nlm.nih.gov/gene/54902 |
| Ensembl ID | ENSG00000108379 |
| UniProt ID | Q6DKK2 |
| OMIM ID | 613814 |
| HGNC ID | 26006 |
| Aliases | FLJ10330, MGC12972 |
Description
TTC19 encodes a tetratricopeptide repeat (TPR)-containing protein localized to the mitochondrial inner membrane. It is essential for the assembly and stability of mitochondrial respiratory chain complex III (ubiquinol-cytochrome c reductase). Loss-of-function mutations in TTC19 cause mitochondrial complex III deficiency, nuclear type 2 (MC3DN2), a severe neurological disorder characterized by progressive encephalopathy, ataxia, and lactic acidosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial complex III deficiency, nuclear type 2 (MC3DN2) | Impaired assembly of complex III due to TTC19 loss leads to respiratory chain dysfunction and oxidative stress | OMIM #616045; multiple case reports with biallelic TTC19 mutations |
| Leigh syndrome | Secondary complex III deficiency from TTC19 mutations can present with Leigh-like neuropathology | ClinVar; case studies with MRI findings of bilateral basal ganglia lesions |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 9.8 | Medium |
| Liver | 7.2 | Low |
| Kidney | 8.1 | Low |
| Skeletal Muscle | 6.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.3 | Neuronal model |
| HEK293 (embryonic kidney) | 11.0 | Common cell line |
| HepG2 (hepatocellular carcinoma) | 8.5 | Liver model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.337C>T (p.Arg113*) | Nonsense | Rare | Loss of function; premature truncation |
| c.523_524delAG (p.Arg175Glyfs*12) | Frameshift | Rare | Loss of function; protein truncation |
| c.754C>T (p.Arg252Trp) | Missense | Rare | Likely loss of function; impaired protein stability |
Mutation functional classification
Loss of Function (LOF)
Majority of reported TTC19 mutations are loss-of-function (nonsense, frameshift, splice-site), leading to reduced or absent protein and complex III deficiency.
Gain of Function (GOF)
No evidence of gain-of-function mutations in TTC19.
Dominant Negative (DN)
No evidence of dominant-negative effects; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • Mitochondrial inner membrane | • Protein binding |
| • Mitochondrial respiratory chain complex III assembly | • Ubiquinol-cytochrome-c reductase activity |
Pathways
• Mitochondrial complex III assembly
• Respiratory electron transport chain
• Oxidative phosphorylation
Protein Summary
TTC19 is a 37 kDa mitochondrial inner membrane protein containing multiple tetratricopeptide repeats (TPRs) that mediate protein-protein interactions. It acts as a chaperone for the assembly of complex III (cytochrome bc1 complex), specifically facilitating the incorporation of the UQCRFS1 (Rieske iron-sulfur protein) subunit. Loss of TTC19 leads to accumulation of complex III assembly intermediates and severe respiratory chain dysfunction.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TTC19 Knockout HEK293 Cell Line | EDJ-KQ15969 | Human | 54902 | Details Get a Quote |
| TTC19 Knockout A-549 Cell Line | EDJ-KQ47010 | Human | 54902 | Details Get a Quote |
| TTC19 Knockout HCT 116 Cell Line | EDJ-KQ47011 | Human | 54902 | Details Get a Quote |
| TTC19 Knockout HeLa Cell Line | EDJ-KQ47012 | Human | 54902 | Details Get a Quote |
