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

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.

• Intellectual disability, severe (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6	3	9
missense		2	74	4		80
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region						0
non coding				1	1	2
Total	1	2	74	11	4

Variants in TTI1

This is a list of pathogenic ClinVar variants found in the TTI1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-37983482-G-A			Uncertain significance (Jan 25, 2024)
20-37983493-G-A		Inborn genetic diseases	Uncertain significance (May 01, 2022)
20-37983512-C-T		Inborn genetic diseases	Uncertain significance (Nov 20, 2023)
20-37983518-C-T		Inborn genetic diseases	Uncertain significance (Nov 09, 2023)
20-37983551-G-T			Uncertain significance (Feb 07, 2024)
20-37983624-C-G		Inborn genetic diseases	Uncertain significance (Sep 26, 2023)
20-37983632-G-A		Inborn genetic diseases	Uncertain significance (May 27, 2022)
20-37996435-T-G		Inborn genetic diseases	Uncertain significance (Dec 28, 2023)
20-37996747-A-G		Intellectual disability, severe	Pathogenic (Apr 20, 2023)
20-37996757-A-G			Likely pathogenic (Dec 04, 2021)
20-37996769-A-C		Neurodevelopmental disorder with microcephaly and movement abnormalities	Pathogenic (Jul 21, 2023)
20-37996823-G-C		Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
20-37996829-A-G		Inborn genetic diseases	Uncertain significance (Aug 21, 2023)
20-37996869-G-T		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
20-37996875-C-T		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
20-37996884-T-C		Inborn genetic diseases	Uncertain significance (Jun 02, 2023)
20-37996946-C-T		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)
20-37996947-G-A		Inborn genetic diseases	Uncertain significance (May 10, 2024)
20-37996947-G-T		Inborn genetic diseases	Uncertain significance (Dec 13, 2023)
20-37999179-G-A			Benign (Jun 27, 2018)
20-37999191-G-C		Inborn genetic diseases	Uncertain significance (Jan 10, 2023)
20-37999220-C-T		Abnormal brain morphology • Neurodevelopmental disorder with microcephaly and movement abnormalities	Likely pathogenic (-)
20-37999223-G-A		Inborn genetic diseases	Uncertain significance (Jul 13, 2021)
20-37999231-C-T		Inborn genetic diseases	Uncertain significance (Nov 21, 2023)
20-37999238-C-T			Uncertain significance (Dec 09, 2023)

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