TERF2

telomeric repeat binding factor 2, the group of Myb/SANT domain containing|Shelterin complex

Basic information

Region (hg38): 16:69355566-69408571

Previous symbols: [ "TRBF2" ]

Links

ENSG00000132604 ∙ NCBI:7014 ∙ OMIM:602027 ∙ HGNC:11729 ∙ Uniprot:Q15554 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TERF2 gene.

• not provided (16 variants)
• Inborn genetic diseases (12 variants)
• TERF2-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TERF2 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	1	2
missense			13		2	15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					11	11
Total	0	0	13	1	14

Variants in TERF2

This is a list of pathogenic ClinVar variants found in the TERF2 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-69356678-T-C			Benign (Jun 15, 2019)
16-69356739-G-A			Benign (Jun 14, 2019)
16-69356756-C-T			Benign (Jun 27, 2019)
16-69356799-C-CA			Benign (Aug 15, 2019)
16-69357014-G-C		not specified	Uncertain significance (Oct 06, 2021)
16-69357756-C-A			Benign (Jun 27, 2019)
16-69357811-C-G			Benign (Jun 14, 2019)
16-69361309-G-A			Benign (Jun 15, 2019)
16-69361455-C-T		not specified	Uncertain significance (Dec 08, 2021)
16-69361489-T-C		not specified	Likely benign (Jan 03, 2024)
16-69361531-A-G			Benign (Jun 14, 2019)
16-69366825-G-C		not specified	Uncertain significance (Sep 06, 2022)
16-69366844-C-T		not specified	Uncertain significance (Sep 20, 2023)
16-69366877-C-T		not specified	Uncertain significance (Oct 17, 2023)
16-69366888-T-C		not specified	Uncertain significance (Jan 18, 2023)
16-69366892-G-C			Benign (Apr 04, 2018)
16-69366895-C-G		not specified	Uncertain significance (Oct 27, 2022)
16-69366978-G-A		not specified	Uncertain significance (Dec 08, 2023)
16-69366998-C-T		TERF2-related disorder	Likely benign (May 28, 2019)
16-69367020-T-C		not specified	Uncertain significance (Jul 06, 2021)
16-69367048-C-T		not specified	Uncertain significance (Nov 21, 2022)
16-69367065-G-A		not specified	Likely benign (Feb 12, 2024)
16-69367152-G-A		not specified	Uncertain significance (Mar 02, 2023)
16-69367182-G-T			Benign (Feb 25, 2018)
16-69368349-C-T			Benign (Jun 14, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TERF2	protein_coding	protein_coding	ENST00000603068	10	53011

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.992	0.00763	125743	0	5	125748	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.07	170	265	0.642	0.0000136	3244
Missense in Polyphen		52	105.17	0.49444		1327
Synonymous	1.57	84	104	0.805	0.00000585	992
Loss of Function	4.10	2	23.4	0.0855	0.00000115	282

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000446	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and plays a central role in telomere maintenance and protection against end-to-end fusion of chromosomes. In addition to its telomeric DNA-binding role, required to recruit a number of factors and enzymes required for telomere protection, including the shelterin complex, TERF2IP/RAP1 and DCLRE1B/Apollo. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Together with DCLRE1B/Apollo, plays a key role in telomeric loop (T loop) formation by generating 3' single- stranded overhang at the leading end telomeres: T loops have been proposed to protect chromosome ends from degradation and repair. Required both to recruit DCLRE1B/Apollo to telomeres and activate the exonuclease activity of DCLRE1B/Apollo. Preferentially binds to positive supercoiled DNA. Together with DCLRE1B/Apollo, required to control the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Recruits TERF2IP/RAP1 to telomeres, thereby participating in to repressing homology- directed repair (HDR), which can affect telomere length. {ECO:0000269|PubMed:16166375, ECO:0000269|PubMed:20655466, ECO:0000269|PubMed:9476899}.
• Pathway: Hematopoietic Stem Cell Gene Regulation by GABP alpha-beta Complex;Packaging Of Telomere Ends;Telomere Maintenance;Chromosome Maintenance;Cell Cycle;Regulation of Telomerase;ATM pathway (Consensus)

Recessive Scores

• pRec: 0.190

Intolerance Scores

• loftool: 0.346
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.13

Haploinsufficiency Scores

• pHI: 0.546
• hipred: Y
• hipred_score: 0.771
• ghis: 0.478

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.907

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Terf2
• Phenotype: liver/biliary system 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); cellular phenotype

Gene ontology

• Biological process: telomere maintenance;RNA-dependent DNA biosynthetic process;regulation of transcription by RNA polymerase II;cell cycle;positive regulation of gene expression;negative regulation of gene expression;telomere capping;telomeric loop formation;protection from non-homologous end joining at telomere;regulation of telomere maintenance;negative regulation of telomere maintenance;negative regulation of telomere maintenance via recombination;regulation of telomere maintenance via telomerase;negative regulation of telomere maintenance via telomerase;negative regulation of telomere maintenance via semi-conservative replication;positive regulation of nitric-oxide synthase activity;telomeric D-loop disassembly;protein localization to chromosome, telomeric region;cellular senescence;anterograde axonal transport of messenger ribonucleoprotein complex;negative regulation of beta-galactosidase activity;negative regulation of telomere single strand break repair;negative regulation of telomere capping;negative regulation of telomere maintenance via telomere lengthening;negative regulation of t-circle formation;negative regulation of exonuclease activity;negative regulation of telomeric D-loop disassembly;negative regulation of cellular senescence
• Cellular component: chromosome, telomeric region;nuclear telomere cap complex;nuclear chromosome, telomeric region;nucleus;nucleoplasm;nuclear body;Mre11 complex;shelterin complex;axon cytoplasm
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;double-stranded telomeric DNA binding;telomerase activity;protein binding;protein C-terminus binding;enzyme binding;telomeric DNA binding;protein homodimerization activity;protein-containing complex binding;G-rich strand telomeric DNA binding