TTI1

TELO2 interacting protein 1, the group of Armadillo like helical domain containing|TTT complex

Basic information

Region (hg38): 20:37983007-38033461

Previous symbols: [ "KIAA0406" ]

Links

ENSG00000101407 ∙ NCBI:9675 ∙ OMIM:614425 ∙ HGNC:29029 ∙ Uniprot:O43156 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly (Limited), mode of inheritance: AR
• neurodevelopmental disorder with microcephaly and movement abnormalities (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with microcephaly and movement abnormalities	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	36724785

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TTI1 gene.

• Inborn_genetic_diseases (165 variants)
• not_provided (33 variants)
• Neurodevelopmental_disorder_with_microcephaly_and_movement_abnormalities (8 variants)
• not_specified (5 variants)
• Intellectual_disability,_severe (2 variants)
• Abnormal_brain_morphology (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TTI1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001303457.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				10	3	13
missense	3	5	173	7		188
nonsense						0
start loss						0
frameshift			4			4
splice donor/acceptor (+/-2bp)	2					2
Total	5	5	177	17	3

Highest pathogenic variant AF is 0.000078072626

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TTI1	protein_coding	protein_coding	ENST00000373448	7	50462

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.90e-10	0.988	125681	0	67	125748	0.000266

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.220	545	560	0.974	0.0000306	7075
Missense in Polyphen		132	146.41	0.90156		1854
Synonymous	-0.720	236	222	1.06	0.0000118	2223
Loss of Function	2.42	21	36.9	0.570	0.00000185	485

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000264	0.000264
Ashkenazi Jewish	0.00120	0.00119
East Asian	0.000489	0.000489
Finnish	0.0000937	0.0000924
European (Non-Finnish)	0.000231	0.000229
Middle Eastern	0.000489	0.000489
South Asian	0.000229	0.000229
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulator of the DNA damage response (DDR). Part of the TTT complex that is required to stabilize protein levels of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins. The TTT complex is involved in the cellular resistance to DNA damage stresses, like ionizing radiation (IR), ultraviolet (UV) and mitomycin C (MMC). Together with the TTT complex and HSP90 may participate in the proper folding of newly synthesized PIKKs. Promotes assembly, stabilizes and maintains the activity of mTORC1 and mTORC2 complexes, which regulate cell growth and survival in response to nutrient and hormonal signals. {ECO:0000269|PubMed:20427287, ECO:0000269|PubMed:20801936, ECO:0000269|PubMed:20810650}.
• Pathway: mTOR signaling pathway - Homo sapiens (human);Steatosis AOP (Consensus)

Recessive Scores

• pRec: 0.0939

Intolerance Scores

• rvis_EVS: -0.52
• rvis_percentile_EVS: 20.94

Haploinsufficiency Scores

• pHI: 0.187
• hipred: Y
• hipred_score: 0.577
• ghis: 0.586

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tti1

Gene ontology

• Biological process: regulation of TOR signaling
• Cellular component: cytoplasm;TORC1 complex;TORC2 complex
• Molecular function: protein binding