HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TTI1
TELO2 interacting protein 1
Chromosome 20 Β· 20q11.23
NCBI Gene: 9675Ensembl: ENSG00000101407.14HGNC: HGNC:29029UniProt: O43156
67PubMed Papers
21Diseases
0Drugs
10Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein stabilizationprotein bindingkinase bindingprotein-containing complex stabilizing activityneurodevelopmental disorder with microcephaly and movement abnormalitiesSevere intellectual disabilityAbnormal brain morphologyneurodegenerative disease
✦AI Summary

TTI1 (TELO2 interacting protein 1) is a critical component of the conserved Triple T (TTT) complex, which consists of TELO2, TTI1, and TTI2 1. This complex serves as an essential co-chaperone for phosphatidylinositol 3-kinase-related protein kinases (PIKKs), including mTOR, ATM, ATR, DNA-PKcs, SMG-1, and TRRAP 2. TTI1 provides a structural platform where TELO2 binds to its central region and TTI2 to its C-terminal end, forming an elongated helical repeat structure 3. The TTT complex is crucial for PIKK stability, proper folding, and assembly of mTORC1 and mTORC2 complexes 2. It collaborates with the R2TP chaperone complex and HSP90 to facilitate co-translational maturation of PIKKs 4. TTI1 plays vital roles in DNA damage response, with its N- and C-terminal segments recognizing specific domains of ATM 3. Loss of TTI1 function leads to impaired mTOR pathway activity and causes autosomal-recessive neurodevelopmental disorders characterized by intellectual disability, microcephaly, short stature, and movement disorders 1. Additionally, TTI1 contributes to radioresistance in cancer by activating the ATM pathway 5.

Sources cited
1
TTI1 is part of the TTT complex and loss causes neurodevelopmental disorders
PMID: 36724785
2
TTI1 provides structural platform and recognizes ATM domains
PMID: 34838521
3
TTI1 stabilizes PIKKs and is essential for mTORC1/mTORC2 assembly
PMID: 20427287
4
TTT complex collaborates with R2TP chaperone for PIKK maturation
PMID: 34233195
5
TTI1 contributes to radioresistance via ATM pathway activation
PMID: 40514657
Disease Associationsβ“˜21
neurodevelopmental disorder with microcephaly and movement abnormalitiesOpen Targets
0.62Moderate
Severe intellectual disabilityOpen Targets
0.41Moderate
Abnormal brain morphologyOpen Targets
0.27Weak
neurodegenerative diseaseOpen Targets
0.25Weak
genetic disorderOpen Targets
0.19Weak
Back painOpen Targets
0.08Suggestive
response to surgeryOpen Targets
0.08Suggestive
alcohol drinkingOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.07Suggestive
colorectal carcinomaOpen Targets
0.06Suggestive
hepatocellular carcinomaOpen Targets
0.05Suggestive
trigeminal nerve diseaseOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.04Suggestive
autosomal recessive nonsyndromic hearing loss 9Open Targets
0.04Suggestive
deafnessOpen Targets
0.04Suggestive
autosomal dominant nonsyndromic hearing lossOpen Targets
0.03Suggestive
Abnormality of the skeletal systemOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
multiple myelomaOpen Targets
0.01Suggestive
lung adenocarcinomaOpen Targets
0.01Suggestive
Neurodevelopmental disorder with microcephaly and movement abnormalitiesUniProt
Pathogenic Variants10
NM_001303457.2(TTI1):c.106C>T (p.Arg36Ter)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2026β†’ Residue 36
NM_001303457.2(TTI1):c.2011G>A (p.Ala671Thr)Likely pathogenic
Neurodevelopmental disorder with microcephaly and movement abnormalities
β˜…β˜†β˜†β˜†2024β†’ Residue 671
NM_001303457.2(TTI1):c.2513C>T (p.Ser838Leu)Likely pathogenic
Severe intellectual disability
β˜…β˜†β˜†β˜†2023β†’ Residue 838
NM_001303457.2(TTI1):c.2998+2T>CPathogenic
Severe intellectual disability
β˜…β˜†β˜†β˜†2023
NM_001303457.2(TTI1):c.2761G>A (p.Asp921Asn)Likely pathogenic
Abnormal brain morphology|Neurodevelopmental disorder with microcephaly and movement abnormalities
β˜…β˜†β˜†β˜†β†’ Residue 921
NM_001303457.2(TTI1):c.1271A>G (p.His424Arg)Likely pathogenic
Neurodevelopmental disorder with microcephaly and movement abnormalities
β˜†β˜†β˜†β˜†2023β†’ Residue 424
NM_001303457.2(TTI1):c.2300T>C (p.Leu767Ser)Pathogenic
Neurodevelopmental disorder with microcephaly and movement abnormalities
β˜†β˜†β˜†β˜†2023β†’ Residue 767
NM_001303457.2(TTI1):c.2302+1G>TPathogenic
Neurodevelopmental disorder with microcephaly and movement abnormalities
β˜†β˜†β˜†β˜†2023
NM_001303457.2(TTI1):c.2978T>G (p.Leu993Arg)Pathogenic
Neurodevelopmental disorder with microcephaly and movement abnormalities
β˜†β˜†β˜†β˜†2023β†’ Residue 993
NM_001303457.2(TTI1):c.2990T>C (p.Leu997Pro)Likely pathogenic
not provided
β˜†β˜†β˜†β˜†2021β†’ Residue 997
View on ClinVar β†—
Related Genes
MTORProtein interaction100%PIH1D1Protein interaction100%RUVBL2Protein interaction100%MLST8Protein interaction99%HSP90AB1Protein interaction99%RPTORProtein interaction99%
Tissue Expression6 tissues
Brain
100%
Liver
76%
Ovary
71%
Heart
67%
Lung
59%
Bone Marrow
45%
Gene Interaction Network
Click a node to explore
TTI1MTORPIH1D1RUVBL2MLST8HSP90AB1RPTOR
PROTEIN STRUCTURE
Preparing viewer…
PDB7OLE Β· 3.41 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.78LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.62 [0.50–0.78]
RankingsWhere TTI1 stands among ~20K protein-coding genes
  • #7,029of 20,598
    Most Researched67
  • #2,860of 5,498
    Most Pathogenic Variants10
  • #6,386of 17,882
    Most Constrained (LOEUF)0.78
Genes detectedTTI1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Bi-allelic TTI1 variants cause an autosomal-recessive neurodevelopmental disorder with microcephaly.
PMID: 36724785
Am J Hum Genet Β· 2023
1.00
2
Structure of the Human TELO2-TTI1-TTI2 Complex.
PMID: 34838521
J Mol Biol Β· 2022
0.90
3
A susceptibility gene signature for ERBB2-driven mammary tumour development and metastasis in collaborative cross mice.
PMID: 39067134
EBioMedicine Β· 2024
0.80
4
Hippocalcin-Like 1 blunts liver lipid metabolism to suppress tumorigenesis via directly targeting RUVBL1-mTOR signaling.
PMID: 36438486
Theranostics Β· 2022
0.70
5
TTI1 contributes to radioresistance by activating ATM pathway in rectal cancer.
PMID: 40514657
J Transl Med Β· 2025
0.60