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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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TTC19
tetratricopeptide repeat domain 19
Chromosome 17 Β· 17p12
NCBI Gene: 54902Ensembl: ENSG00000011295.17HGNC: HGNC:26006UniProt: Q6DKK2
47PubMed Papers
21Diseases
0Drugs
28Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingmitochondrial respiratory chain complex III assemblymitochondrial inner membranemitochondrionIsolated CoQ-cytochrome C reductase deficiencymitochondrial complex III deficiencymitochondrial diseasegenetic disorder
✦AI Summary

TTC19 (tetratricopeptide repeat domain 19) is a mitochondrial protein essential for maintaining the structural and functional integrity of respiratory complex III 12. It facilitates physiological turnover of the Rieske iron-sulfur protein UQCRFS1 and clears N-terminal fragments generated during UQCRFS1 incorporation into complex III; these fragments impair catalytic activity if not removed 2. TTC19 functions as a complex III assembly factor 3. Biallelic TTC19 mutations cause mitochondrial complex III deficiency, nuclear type 2 (CIII deficiency type 2), an autosomal recessive disorder 4. All reported TTC19 mutations are nonsense or frameshift variants 3. Clinical manifestations include progressive neurodegeneration with Leigh-like brain MRI abnormalities, cerebellar ataxia, spastic paraplegia, cognitive dysfunction, and developmental delay, with variable age of onset and disease progression 356. Emerging phenotypes include palatal tremor, hypertrophic olivary degeneration, and axonal neuropathy 6. Genetically predicted lower TTC19 expression is associated with increased Parkinson's disease risk 78. Disease severity does not correlate with residual complex III enzyme activity 3, suggesting variable expressivity among patients with similar mutations.

Sources cited
1
TTC19 is required for preservation of complex III structural and functional integrity through UQCRFS1 turnover
PMID: 21278747
2
TTC19 allows physiological turnover of UQCRFS1 and clears detrimental N-terminal fragments
PMID: 28673544
3
TTC19 mutations cause autosomal recessive mitochondrial complex III deficiency with limb weakness and movement disorders
PMID: 37927170
4
TTC19 is a complex III assembly factor; all reported mutations are nonsense; consistent features include progressive neurodegeneration with Leigh-like MRI findings
PMID: 25899669
5
TTC19 mutations present with cerebellar ataxia, spastic paraparesis, and sensory impairment with variable disease severity
PMID: 25652355
6
TTC19 variants present with palatal tremor, hypertrophic olivary degeneration, and axonal neuropathy as emerging manifestations
PMID: 40652486
7
Lower TTC19 expression is associated with increased Parkinson's disease risk through mitochondrial dysfunction
PMID: 39838927
8
TTC19 shows significant associations with Parkinson's disease at both proteome-wide and transcriptome-wide levels
PMID: 38240717
Disease Associationsβ“˜21
Isolated CoQ-cytochrome C reductase deficiencyOpen Targets
0.79Strong
mitochondrial complex III deficiencyOpen Targets
0.70Moderate
mitochondrial diseaseOpen Targets
0.64Moderate
genetic disorderOpen Targets
0.45Moderate
mitochondrial complex III deficiency nuclear type 1Open Targets
0.42Moderate
Leigh syndromeOpen Targets
0.37Weak
Renal tubulopathy - encephalopathy - liver failureOpen Targets
0.37Weak
asthmaOpen Targets
0.34Weak
chronic rhinosinusitisOpen Targets
0.33Weak
neurodegenerative diseaseOpen Targets
0.27Weak
obesityOpen Targets
0.13Weak
autismOpen Targets
0.11Weak
triple-negative breast cancerOpen Targets
0.07Suggestive
ovarian neoplasmOpen Targets
0.06Suggestive
response to stimulusOpen Targets
0.04Suggestive
intellectual developmental disorder, X-linked 110Open Targets
0.04Suggestive
Parkinson diseaseOpen Targets
0.02Suggestive
hyperinsulinemic hypoglycemia, familial, 4Open Targets
0.02Suggestive
cancerOpen Targets
0.01Suggestive
cerebellar ataxiaOpen Targets
0.01Suggestive
Mitochondrial complex III deficiency, nuclear type 2UniProt
Pathogenic Variants28
NM_017775.4(TTC19):c.601_604del (p.Gly201fs)Pathogenic
Mitochondrial complex III deficiency nuclear type 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 201
NM_017775.4(TTC19):c.656T>G (p.Leu219Ter)Pathogenic
Mitochondrial complex III deficiency nuclear type 2|not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 219
NM_017775.4(TTC19):c.554T>C (p.Leu185Pro)Pathogenic
Mitochondrial complex III deficiency nuclear type 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 185
NM_017775.4(TTC19):c.194G>A (p.Trp65Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 65
NM_017775.4(TTC19):c.583C>T (p.Gln195Ter)Pathogenic
Mitochondrial complex III deficiency nuclear type 2|not provided|Autism
β˜…β˜…β˜†β˜†2024β†’ Residue 195
NM_017775.4(TTC19):c.296dup (p.Leu100fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 100
NM_017775.4(TTC19):c.423+1G>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_017775.4(TTC19):c.72C>A (p.Cys24Ter)Pathogenic
Mitochondrial complex III deficiency nuclear type 2
β˜…β˜†β˜†β˜†2025β†’ Residue 24
NM_017775.4(TTC19):c.93dup (p.Leu32fs)Likely pathogenic
Mitochondrial complex III deficiency nuclear type 2
β˜…β˜†β˜†β˜†2024β†’ Residue 32
NM_017775.4(TTC19):c.581+1G>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_017775.4(TTC19):c.646_647del (p.Glu216fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 216
NM_017775.4(TTC19):c.184+1G>ALikely pathogenic
Mitochondrial complex III deficiency nuclear type 2
β˜…β˜†β˜†β˜†2024
NM_017775.4(TTC19):c.793C>T (p.Gln265Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 265
NM_017775.4(TTC19):c.519+2T>ALikely pathogenic
Mitochondrial complex III deficiency nuclear type 2
β˜…β˜†β˜†β˜†2024
GRCh38/hg38 17p12(chr17:16018139-16028011)x0Pathogenic
Mitochondrial complex III deficiency nuclear type 2
β˜…β˜†β˜†β˜†2023
NM_017775.4(TTC19):c.463-1G>CLikely pathogenic
Mitochondrial complex III deficiency nuclear type 2
β˜…β˜†β˜†β˜†2023
NM_017775.4(TTC19):c.451C>T (p.Gln151Ter)Pathogenic
Mitochondrial disease
β˜…β˜†β˜†β˜†2023β†’ Residue 151
NM_017775.4(TTC19):c.903dup (p.Met302fs)Likely pathogenic
Mitochondrial complex III deficiency nuclear type 2
β˜…β˜†β˜†β˜†2022β†’ Residue 302
NM_017775.4(TTC19):c.520-2A>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
NM_017775.4(TTC19):c.424-1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
View on ClinVar β†—
Related Genes
ZFYVE26Protein interaction87%BCS1LProtein interaction78%LYRM7Protein interaction60%UQCC4Shared pathway50%UQCC1Shared pathway50%CKAP2Shared pathway33%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
80%
Liver
69%
Heart
68%
Ovary
50%
Lung
46%
Gene Interaction Network
Click a node to explore
TTC19ZFYVE26BCS1LLYRM7UQCC4UQCC1CKAP2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q6DKK2
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.05LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.78 [0.59–1.05]
RankingsWhere TTC19 stands among ~20K protein-coding genes
  • #9,285of 20,598
    Most Researched47
  • #1,876of 5,498
    Most Pathogenic Variants28
  • #10,489of 17,882
    Most Constrained (LOEUF)1.05
Genes detectedTTC19
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
A TTC19 mutation associated with progressive movement disorders and peripheral neuropathy: Case report and systematic review.
PMID: 37927170
CNS Neurosci Ther Β· 2024
1.00
2
Mitochondria-Related Genome-Wide Mendelian Randomization Identifies Putatively Causal Genes for Neurodegenerative Diseases.
PMID: 39838927
Mov Disord Β· 2025
0.90
3
Phenotypic variation of TTC19-deficient mitochondrial complex III deficiency: a case report and literature review.
PMID: 25899669
Am J Med Genet A Β· 2015
0.80
4
Joint analysis of proteome, transcriptome, and multi-trait analysis to identify novel Parkinson's disease risk genes.
PMID: 38240717
Aging (Albany NY) Β· 2024
0.70
5
A Japanese case of cerebellar ataxia, spastic paraparesis and deep sensory impairment associated with a novel homozygous TTC19 mutation.
PMID: 25652355
J Hum Genet Β· 2015
0.60