TTI2

TELO2 interacting protein 2, the group of Armadillo like helical domain containing|TTT complex

Basic information

Region (hg38): 8:33473385-33513185

Previous symbols: [ "C8orf41" ]

Links

ENSG00000129696 ∙ NCBI:80185 ∙ OMIM:614426 ∙ HGNC:26262 ∙ Uniprot:Q6NXR4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome (Strong), mode of inheritance: AR
• severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome (Supportive), mode of inheritance: AR
• severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 39	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; Dental; Musculoskeletal; Neurologic	21937992; 23956177

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TTI2 gene.

• not provided (35 variants)
• Inborn genetic diseases (21 variants)
• not specified (16 variants)
• Severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome (12 variants)
• Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TTI2 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				15	2	17
missense			31	6	2	39
nonsense			1			1
start loss						0
frameshift			3			3
inframe indel			1			1
splice donor/acceptor (+/-2bp)			2			2
splice region				1		1
non coding			1	2	1	4
Total	0	0	39	23	5

Variants in TTI2

This is a list of pathogenic ClinVar variants found in the TTI2 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-33485215-G-C			Likely benign (Apr 16, 2018)
8-33488618-A-C		not specified	Uncertain significance (Jul 09, 2021)
8-33488781-C-G		not specified	Uncertain significance (Jul 12, 2023)
8-33490319-C-T		not specified	Uncertain significance (Aug 30, 2022)
8-33496729-T-C			Likely benign (Mar 01, 2023)
8-33497293-T-C		not specified	Uncertain significance (Jan 31, 2022)
8-33498469-A-G		not specified	Uncertain significance (Jan 30, 2024)
8-33498484-C-T		not specified	Uncertain significance (Feb 02, 2024)
8-33498591-C-A		not specified	Uncertain significance (Feb 12, 2024)
8-33498615-G-A		not specified	Uncertain significance (Dec 03, 2021)
8-33499194-G-A		not specified	Likely benign (Apr 01, 2023)
8-33499225-T-C		Inborn genetic diseases	Likely benign (Nov 02, 2023)
8-33499261-A-C		Inborn genetic diseases	Uncertain significance (Mar 04, 2024)
8-33499274-G-C		Inborn genetic diseases	Uncertain significance (Nov 09, 2023)
8-33499277-C-T		Inborn genetic diseases	Uncertain significance (Jun 29, 2023)
8-33500336-G-A		Microcephaly	Uncertain significance (-)
8-33500351-G-A			Uncertain significance (Apr 27, 2023)
8-33500353-T-G		not specified	Uncertain significance (May 04, 2022)
8-33500393-C-T		Inborn genetic diseases	Uncertain significance (Jul 12, 2022)
8-33500399-T-TA		Severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome	Conflicting classifications of pathogenicity (Jun 22, 2022)
8-33500443-A-T		Severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome	Pathogenic (Nov 01, 2013)
8-33500453-A-C		Inborn genetic diseases	Uncertain significance (Feb 23, 2023)
8-33500476-A-C		not specified	Conflicting classifications of pathogenicity (Dec 31, 2019)
8-33500499-A-G			Likely benign (Apr 02, 2018)
8-33503426-T-TA			Uncertain significance (May 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TTI2	protein_coding	protein_coding	ENST00000431156	7	40216

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.61e-7	0.807	125684	0	64	125748	0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.289	284	271	1.05	0.0000142	3243
Missense in Polyphen		82	87.798	0.93396		1103
Synonymous	-0.296	118	114	1.04	0.00000604	1081
Loss of Function	1.41	13	19.8	0.657	9.47e-7	249

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00106	0.00106
Ashkenazi Jewish	0.0000999	0.0000992
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000273	0.000273
Middle Eastern	0.000218	0.000217
South Asian	0.000131	0.000131
Other	0.000163	0.000163

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. {ECO:0000269|PubMed:20801936, ECO:0000269|PubMed:20810650}.
• Disease: DISEASE: Mental retardation, autosomal recessive 39 (MRT39) [MIM:615541]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT39 affected individuals show delayed psychomotor development, severe speech delay, short stature, kyphoscoliosis, and dysmorphic facial features. Behavioral abnormalities include hyperactivity, aggression, and stereotypic movements. {ECO:0000269|PubMed:23956177}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0894

Intolerance Scores

• rvis_EVS: 0.18
• rvis_percentile_EVS: 66.07

Haploinsufficiency Scores

• pHI: 0.122
• hipred: Y
• hipred_score: 0.552
• ghis: 0.490

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tti2

Gene ontology

• Cellular component: nucleoplasm;centrosome;cytosol;ASTRA complex