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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PTCD1
pentatricopeptide repeat domain 1
Chromosome 7 · 7q22.1
NCBI Gene: 26024Ensembl: ENSG00000106246.19HGNC: HGNC:22198UniProt: A4D273
51PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
tRNA bindingRNA bindingprotein bindingtRNA 3'-end processingneurodegenerative diseaseAlzheimer diseaselysosomal storage diseaseParkinson disease
✦AI Summary

PTCD1 (pentatricopeptide repeat domain 1) is a mitochondrial matrix protein essential for proper mitochondrial gene expression and energy metabolism. Functionally, PTCD1 acts as a leucine-specific tRNA-binding protein that negatively regulates mitochondrial leucine tRNA levels and thereby restrains leucine-rich electron transport chain complexes 1. PTCD1 participates in 3'-end processing of mitochondrial tRNAs 2 and is critical for 16S rRNA stability and maturation, which are prerequisites for mitochondrial ribosome assembly and mitochondrial translation 3. Loss of PTCD1 impairs oxidative phosphorylation, forcing cells to depend on glycolysis for ATP production 4. Platelet-specific PTCD1 deletion causes thrombocytopenia and bleeding defects by compromising mitochondrial gene expression required for platelet activation and blood coagulation 5. Clinically, PTCD1 variants show enrichment in Alzheimer's disease (AD) patients, suggesting a genetic link to neurodegeneration 46. Neurons expressing AD-associated PTCD1 variants fail to maintain ATP production during metabolic stress, resulting in reduced neuronal energy homeostasis and impaired synaptic activity 4. These findings establish PTCD1 as a mitochondrial regulator whose dysfunction contributes to both blood disorders and neurodegenerative disease pathogenesis.

Sources cited
1
PTCD1 is a mitochondrial matrix leucine tRNA-binding protein that negatively regulates mitochondrial leucine tRNA levels and acts as a negative regulator of mitochondrial translation
PMID: 19651879
2
PTCD1 affects 3' end processing of mitochondrial tRNAs
PMID: 21857155
3
PTCD1 is essential for 16S rRNA stability, pseudouridylation, and mitochondrial ribosome assembly; loss causes cardiomyopathy
PMID: 29617655
4
PTCD1 is required for mitochondrial rRNA levels, ribosome assembly, and oxidative phosphorylation; AD-linked variants impair ATP production and neuronal energy homeostasis
PMID: 30948477
5
PTCD1 gene variants associate with Alzheimer's disease
PMID: 31421943
6
PTCD1 is essential for mitochondrial gene expression; platelet-specific loss causes thrombocytopenia and bleeding defects
PMID: 37889747
7
PTCD1 protein levels are downregulated during amino acid starvation, allowing increased mitochondrial leucine tRNA stability
PMID: 24710704
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.46Moderate
Alzheimer diseaseOpen Targets
0.27Weak
lysosomal storage diseaseOpen Targets
0.26Weak
multiple sclerosisOpen Targets
0.26Weak
Parkinson diseaseOpen Targets
0.26Weak
Abnormality of the skeletal systemOpen Targets
0.14Weak
bladder transitional cell carcinomaOpen Targets
0.07Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.05Suggestive
glycogen storage disease VIOpen Targets
0.04Suggestive
morbid obesityOpen Targets
0.04Suggestive
obesity due to CEP19 deficiencyOpen Targets
0.04Suggestive
carnitine palmitoyl transferase II deficiency, severe infantile formOpen Targets
0.04Suggestive
African iron overloadOpen Targets
0.04Suggestive
metabolic syndromeOpen Targets
0.04Suggestive
hypoinsulinemic hypoglycemia and body hemihypertrophyOpen Targets
0.03Suggestive
lipodystrophy, congenital generalized, type 5Open Targets
0.03Suggestive
MODYOpen Targets
0.03Suggestive
CIDEC-related familial partial lipodystrophyOpen Targets
0.03Suggestive
smoking behaviorOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DDX28Protein interaction91%NGRNProtein interaction86%TRUB2Protein interaction86%FASTKD2Protein interaction86%FASTKD3Protein interaction86%MTERF3Protein interaction80%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
94%
Ovary
71%
Lung
69%
Brain
60%
Heart
60%
Gene Interaction Network
Click a node to explore
PTCD1DDX28NGRNTRUB2FASTKD2FASTKD3MTERF3
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt O75127
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.10LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.87 [0.70–1.10]
RankingsWhere PTCD1 stands among ~20K protein-coding genes
  • #8,717of 20,598
    Most Researched51
  • #11,279of 17,882
    Most Constrained (LOEUF)1.10
Genes detectedPTCD1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Mitochondrial gene expression is required for platelet function and blood clotting.
PMID: 37889747
Cell Rep · 2023
1.00
2
FOXM1 nuclear transcription factor translocates into mitochondria and inhibits oxidative phosphorylation.
PMID: 32348194
Mol Biol Cell · 2020
0.90
3
PTCD1 Is Required for 16S rRNA Maturation Complex Stability and Mitochondrial Ribosome Assembly.
PMID: 29617655
Cell Rep · 2018
0.80
4
Mitochondrial leucine tRNA level and PTCD1 are regulated in response to leucine starvation.
PMID: 24710704
Amino Acids · 2014
0.70
5
Pentatricopeptide repeat domain protein 1 lowers the levels of mitochondrial leucine tRNAs in cells.
PMID: 19651879
Nucleic Acids Res · 2009
0.60