TTC19

Chr 17AR

tetratricopeptide repeat domain 19

Also known as: 2010204O13Rik, MC3DN2

NCBI Gene: 54902ENSG00000011295UniProt: Q6DKK2

This gene encodes a protein with a tetratricopeptide repeat (TPR) domain containing several TPRs of about 34 aa each. These repeats are found in a variety of organisms including bacteria, fungi and plants, and are involved in a variety of functions including protein-protein interactions. This protein is embedded in the inner mitochondrial membrane and is involved in the formation of the mitochondrial respiratory chain III. It has also been suggested that this protein plays a role in cytokinesis. Mutations in this gene cause mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2012]

Primary Disease Associations & Inheritance

Mitochondrial complex III deficiency, nuclear type 2MIM #615157
AR
440
ClinVar variants
54
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TTC19
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
54 Pathogenic / Likely Pathogenic· 208 VUS of 440 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.12LOEUF
pLI 0.000
Z-score 1.16
OE 0.73 (0.48–1.12)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.08Z-score
OE missense 0.98 (0.87–1.11)
176 obs / 179.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.73 (0.48–1.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.87–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.19
0≤1.21.6
LoF obs/exp: 15 / 20.7Missense obs/exp: 176 / 179.1Syn Z: -1.21

ClinVar Variant Classifications

440 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic12
VUS208
Likely Benign116
Benign38
Conflicting24
42
Pathogenic
12
Likely Pathogenic
208
VUS
116
Likely Benign
38
Benign
24
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
37
0
42
Likely Pathogenic
10
1
1
0
12
VUS
3
114
87
4
208
Likely Benign
0
8
64
44
116
Benign
0
0
36
2
38
Conflicting
—24
Total1812322550440

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TTC19 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TTC19-related mitochondrial complex III deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mitochondrial complex III deficiency, nuclear type 2

MIM #615157

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — TTC19
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A TTC19 mutation associated with progressive movement disorders and peripheral neuropathy: Case report and systematic review.
Xuan X et al.·CNS Neurosci Ther
2024Case report
Mutations in TTC19: expanding the molecular, clinical and biochemical phenotype.
Koch J et al.·Orphanet J Rare Dis
2015
Phenotypic variation of TTC19-deficient mitochondrial complex III deficiency: a case report and literature review.
Mordaunt DA et al.·Am J Med Genet A
2015Review
Mitochondrial defects caused by PARL deficiency lead to arrested spermatogenesis and ferroptosis.
Radaelli E et al.·Elife
2023
Expanding the Clinical, Pathological, and Molecular Phenotypes of Tetratricopeptide 19 (TTC19) Gene Mutations: A Case Report from India.
Farsana MK et al.·Neurol India
2025Case report
Motor Neuropathy in a Patient With Mitochondrial Disease and a Novel TTC19 Variant: An Underrecognized Phenotypic Feature.
Mandia D et al.·J Peripher Nerv Syst
2025Case report
Novel TTC19 mutation in a family with severe psychiatric manifestations and complex III deficiency.
Nogueira C et al.·Neurogenetics
2013
Novel Homozygous Variant in TTC19 Causing Mitochondrial Complex III Deficiency with Recurrent Stroke-Like Episodes: Expanding the Phenotype.
Conboy E et al.·Semin Pediatr Neurol
2018Case report
Clinical exome sequencing uncovers a high frequency of Mendelian disorders in infants with stroke: A retrospective analysis.
Kumar RD et al.·Am J Med Genet A
2022
Exploiting pyocyanin to treat mitochondrial disease due to respiratory complex III dysfunction.
Peruzzo R et al.·Nat Commun
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools