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

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 (6 variants)
• TELO2-related intellectual disability-neurodevelopmental disorder (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.

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			1	108	13	122
missense	1	1	168	16	16	202
nonsense	3					3
start loss						0
frameshift	3	2	1			6
inframe indel			1			1
splice donor/acceptor (+/-2bp)		3				3
splice region			7	16	2	25
non coding			2	49	18	69
Total	7	6	173	173	47

Highest pathogenic variant AF is 0.0000263

Variants in TELO2

This is a list of pathogenic ClinVar variants found in the TELO2 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-1494288-C-A		Inborn genetic diseases	Uncertain significance (Mar 18, 2021)
16-1494295-C-G		Inborn genetic diseases	Uncertain significance (May 30, 2023)
16-1494300-G-C			Benign (Jan 24, 2020)
16-1494300-GA-AG			Likely benign (Jun 23, 2022)
16-1494300-GA-CG			Benign (Feb 01, 2024)
16-1494301-A-G			Benign (Jan 24, 2020)
16-1494312-G-A		Inborn genetic diseases	Likely benign (Sep 01, 2021)
16-1494312-GC-AA		not specified	Uncertain significance (Jan 24, 2024)
16-1494313-C-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Sep 01, 2021)
16-1494323-AG-A		Inborn genetic diseases	Uncertain significance (Feb 19, 2021)
16-1494331-A-G		Inborn genetic diseases	Uncertain significance (Jun 07, 2024)
16-1494341-G-A			Likely benign (Aug 01, 2024)
16-1494355-G-A			Benign (Nov 27, 2023)
16-1494356-C-T			Benign (Jan 30, 2024)
16-1494358-G-T			Uncertain significance (Nov 02, 2023)
16-1494377-G-A			Likely benign (May 29, 2023)
16-1494381-T-A		Inborn genetic diseases	Uncertain significance (May 30, 2024)
16-1494387-A-G			Uncertain significance (Nov 27, 2023)
16-1494390-C-T			Uncertain significance (Mar 05, 2022)
16-1494399-G-T		Inborn genetic diseases	Uncertain significance (Jun 26, 2023)
16-1494410-G-A			Likely benign (Nov 01, 2022)
16-1494413-T-G			Likely benign (Jul 18, 2022)
16-1494449-G-A			Uncertain significance (Oct 30, 2023)
16-1494475-G-C		TELO2-related intellectual disability-neurodevelopmental disorder	Conflicting classifications of pathogenicity (Sep 20, 2024)
16-1494481-C-A			Uncertain significance (Jul 03, 2022)

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