TTI2

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

Basic information

Region (hg38): 8:33473386-33513185

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
severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome (Strong), 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.

Inborn_genetic_diseases (65 variants)
not_provided (39 variants)
Severe_intellectual_disability-short_stature-behavioral_abnormalities-facial_dysmorphism_syndrome (18 variants)
not_specified (17 variants)
TTI2-related_disorder (7 variants)
Microcephaly (2 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. These statistics are base on transcript: NM_001102401.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				19 clinvar	1 clinvar	20
missense	4 clinvar	1 clinvar	68 clinvar	16 clinvar	1 clinvar	90
nonsense			1 clinvar			1
start loss						0
frameshift	2 clinvar	1 clinvar	2 clinvar			5
splice donor/acceptor (+/-2bp)		1 clinvar	3 clinvar		1 clinvar	5
Total	6	3	74	35	3

Highest pathogenic variant AF is 0.000047091133

Loading clinvar variants...

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

loftool
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
Phenotype

Gene ontology

Biological process
Cellular component: nucleoplasm;centrosome;cytosol;ASTRA complex
Molecular function