TELO2

telomere maintenance 2, the group of Armadillo like helical domain containing|TTT complex

Basic information

Region (hg38): 16:1493344-1510457

Links

ENSG00000100726

∙ NCBI:9894 ∙ OMIM:611140 ∙ HGNC:29099 ∙ Uniprot:Q9Y4R8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

TELO2-related intellectual disability-neurodevelopmental disorder (Supportive), mode of inheritance: AR
TELO2-related intellectual disability-neurodevelopmental disorder (Strong), mode of inheritance: AR
TELO2-related intellectual disability-neurodevelopmental disorder (Definitive), mode of inheritance: AR
TELO2-related intellectual disability-neurodevelopmental disorder (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
You-Hoover-Fong syndrome	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	27132593

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TELO2 gene.

not_provided (433 variants)
Inborn_genetic_diseases (173 variants)
TELO2-related_intellectual_disability-neurodevelopmental_disorder (32 variants)
TELO2-related_disorder (18 variants)
not_specified (10 variants)
Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TELO2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016111.4. 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			2 clinvar	147 clinvar	11 clinvar	160
missense	1 clinvar	9 clinvar	228 clinvar	32 clinvar	11 clinvar	281
nonsense	4 clinvar	1 clinvar	1 clinvar			6
start loss		1				1
frameshift	7 clinvar	3 clinvar	1 clinvar			11
splice donor/acceptor (+/-2bp)		7 clinvar	1 clinvar			8
Total	12	21	233	179	22

Highest pathogenic variant AF is 0.000180755

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TELO2	protein_coding	protein_coding	ENST00000262319	20	17114

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.20e-14	0.833	125677	0	68	125745	0.000270

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.367	568	544	1.04	0.0000379	5237
Missense in Polyphen		105	117.32	0.89499		1314
Synonymous	-1.95	294	254	1.16	0.0000184	1838
Loss of Function	1.93	27	40.2	0.672	0.00000209	424

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000426	0.000392
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000981	0.000925
Finnish	0.00	0.00
European (Non-Finnish)	0.000289	0.000273
Middle Eastern	0.000981	0.000925
South Asian	0.000296	0.000294
Other	0.000178	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. 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. May be involved in telomere length regulation. {ECO:0000269|PubMed:12670948, ECO:0000269|PubMed:20810650}.;
Disease: DISEASE: You-Hoover-Fong syndrome (YHFS) [MIM:616954]: A syndrome characterized by severe global developmental delay, intellectual disability, dysmorphic facial features, microcephaly, abnormal movements, congenital heart disease comprising developmental abnormalities of the great vessels, and abnormal auditory and visual function. The transmission pattern is consistent with autosomal recessive inheritance. {ECO:0000269|PubMed:27132593}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Fanconi anemia pathway - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Steatosis AOP (Consensus)

Recessive Scores

pRec: 0.108

Intolerance Scores

loftool: 0.217
rvis_EVS: 0.42
rvis_percentile_EVS: 76.68

Haploinsufficiency Scores

pHI: 0.281
hipred: Y
hipred_score: 0.743
ghis: 0.524

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.643

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Telo2
Phenotype: homeostasis/metabolism phenotype; cellular phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Gene ontology

Biological process: telomere maintenance;regulation of TOR signaling;protein stabilization;positive regulation of protein serine/threonine kinase activity;positive regulation of TORC1 signaling;positive regulation of TORC2 signaling
Cellular component: nuclear chromosome, telomeric region;nucleus;cytoplasm;cytosol;membrane;nuclear body;TORC1 complex;TORC2 complex;nuclear periphery;ASTRA complex
Molecular function: protein binding;protein kinase binding;protein-containing complex scaffold activity;telomeric DNA binding;protein-containing complex binding;Hsp90 protein binding