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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TTC4
tetratricopeptide repeat domain 4
Chromosome 1 · 1p32.3
NCBI Gene: 7268Ensembl: ENSG00000243725.8HGNC: HGNC:12394UniProt: O95801
77PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindinginnate immune responsedefense response to virusnucleusneurodegenerative diseaseendocarditisanal neoplasmcolonic neoplasm
✦AI Summary

TTC4 (tetratricopeptide repeat domain 4) is a nucleoplasmic co-chaperone protein that recruits molecular chaperones Hsp90 and Hsp70 to nascent polypeptides, facilitating proper protein folding 1. TTC4 interacts directly with Hsp70 and stimulates its activity while also binding client proteins including the replication factor CDC6 1. In vascular endothelial cells, TTC4 promotes Hsp70-dependent signaling that inhibits apoptosis through Akt activation and annexin A7 translocation to lysosomes 2. TTC4 additionally functions as a positive regulator of antiviral innate immunity by interacting with TBK1 and promoting Sendai virus-induced immune responses 3. TTC4 exhibits dynamic subcellular localization dependent on the cell cycle, localizing predominantly to the nucleus during G1/S phases 4. Disease relevance includes tumor suppression, as TTC4 maps to chromosome 1, a region frequently deleted in breast cancer 5. Notably, TTC4 harbors mutations in malignant melanoma samples that disrupt CDC6 interaction, suggesting loss of normal tumor-suppressive function contributes to melanoma progression 61. These findings establish TTC4 as a multifunctional protein linking protein quality control, cell cycle regulation, apoptosis resistance, and antiviral immunity.

Sources cited
1
TTC4 is a nucleoplasmic co-chaperone that interacts with HSP90 and HSP70, binds CDC6, and shows elevated expression in malignant melanoma
PMID: 18320024
2
TTC4 interacts with HSP70 to inhibit vascular endothelial cell apoptosis through Akt activation and annexin A7 lysosomal translocation
PMID: 33000523
3
TTC4 is a TBK1 interactor and positive regulator of Sendai virus-induced innate immune responses
PMID: 29251827
4
TTC4 maps to chromosome 1p31, a region with loss of heterozygosity in up to 50% of breast cancers, suggesting tumor suppressor function
PMID: 9933562
5
TTC4 subcellular localization is cell cycle-dependent, localizing to nucleus during G1/S phases
PMID: 19390865
6
TTC4 harbors mutations in malignant melanoma samples but not in benign naevi, indicating involvement in melanoma pathogenesis
PMID: 11126369
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.53Moderate
endocarditisOpen Targets
0.27Weak
anal neoplasmOpen Targets
0.05Suggestive
colonic neoplasmOpen Targets
0.05Suggestive
rectal neoplasmOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.02Suggestive
immune system diseaseOpen Targets
0.02Suggestive
allergic rhinitisOpen Targets
0.02Suggestive
SepsisOpen Targets
0.02Suggestive
rheumatoid arthritisOpen Targets
0.01Suggestive
breast cancerOpen Targets
0.01Suggestive
melanomaOpen Targets
0.01Suggestive
infectionOpen Targets
0.01Suggestive
gliomaOpen Targets
0.01Suggestive
cutaneous melanomaOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
AutoimmunityOpen Targets
0.00Suggestive
colon carcinomaOpen Targets
0.00Suggestive
lung adenocarcinomaOpen Targets
0.00Suggestive
type 2 diabetes mellitusOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
HSP90AA1Protein interaction100%HSP90AB1Protein interaction100%VPS29Protein interaction100%HGH1Protein interaction99%RPS7Protein interaction80%PPIDProtein interaction76%
Tissue Expression6 tissues
Ovary
100%
Brain
100%
Heart
76%
Liver
64%
Lung
57%
Bone Marrow
40%
Gene Interaction Network
Click a node to explore
TTC4HSP90AA1HSP90AB1VPS29HGH1RPS7PPID
PROTEIN STRUCTURE
Preparing viewer…
PDB6HFO · 1.65 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.85LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.63 [0.47–0.85]
RankingsWhere TTC4 stands among ~20K protein-coding genes
  • #6,223of 20,598
    Most Researched77
  • #7,391of 17,882
    Most Constrained (LOEUF)0.85
Genes detectedTTC4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Genomic structure of the human tetratricopeptide repeat-containing gene, TTC4, from chromosome region 1p31 and mutation analysis in breast cancers.
PMID: 10639601
Int J Mol Med · 2000
1.00
2
TTC4, a novel human gene containing the tetratricopeptide repeat and mapping to the region of chromosome 1p31 that is frequently deleted in sporadic breast cancer.
PMID: 9933562
Genomics · 1999
0.90
3
The human TPR protein TTC4 is a putative Hsp90 co-chaperone which interacts with CDC6 and shows alterations in transformed cells.
PMID: 18320024
PLoS One · 2008
0.80
4
Promoting TTC4 and HSP70 interaction and translocation of annexin A7 to lysosome inhibits apoptosis in vascular endothelial cells.
PMID: 33000523
FASEB J · 2020
0.70
5
MROH7-TTC4 read-through lncRNA suppresses vascular endothelial cell apoptosis and is upregulated by inhibition of ANXA7 GTPase activity.
PMID: 31408583
FEBS J · 2019
0.60