TERF2IP

TERF2 interacting protein, the group of Shelterin complex

Basic information

Region (hg38): 16:75647772-75761872

Links

ENSG00000166848 ∙ NCBI:54386 ∙ OMIM:605061 ∙ HGNC:19246 ∙ Uniprot:Q9NYB0 ∙ 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 TERF2IP gene.

• Inborn genetic diseases (579 variants)
• not provided (59 variants)
• not specified (35 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TERF2IP 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				226		226
missense			363	7	1	371
nonsense			1			1
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			1	3		4
non coding			1	7	9	17
Total	0	1	366	240	10

Variants in TERF2IP

This is a list of pathogenic ClinVar variants found in the TERF2IP region.

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

Position	Type	Phenotype	Significance	ClinVar
16-75647801-G-T			Benign (Jun 15, 2019)
16-75647845-C-G			Benign (Jun 14, 2019)
16-75647848-G-A		not specified	Likely benign (Aug 15, 2023)
16-75647858-C-A		not specified	Benign (Aug 15, 2023)
16-75647858-C-T		not specified	Likely benign (Aug 15, 2023)
16-75647882-C-T		not specified	Uncertain significance (Aug 15, 2023)
16-75647888-G-A		not specified	Likely benign (Nov 22, 2023)
16-75647894-G-A		not specified	Likely benign (Jan 20, 2023)
16-75647896-T-C		not specified	Uncertain significance (Jul 28, 2021)
16-75647898-G-T		not specified	Uncertain significance (Dec 05, 2023)
16-75647902-T-C		not specified	Uncertain significance (Mar 16, 2022)
16-75647912-C-T		not specified	Likely benign (Nov 11, 2019)
16-75647915-C-T		not specified	Likely benign (Mar 14, 2022)
16-75647920-G-A		not specified	Uncertain significance (Jul 27, 2023)
16-75647921-G-A		not specified	Likely benign (Apr 22, 2021)
16-75647922-C-T		not specified	Uncertain significance (Oct 17, 2023)
16-75647923-C-A		not specified	Uncertain significance (Aug 20, 2021)
16-75647924-C-T		not specified	Likely benign (Aug 08, 2023)
16-75647925-A-C		not specified	Uncertain significance (Dec 17, 2022)
16-75647926-C-T		not specified	Uncertain significance (Oct 03, 2022)
16-75647927-C-G		not specified	Likely benign (Aug 11, 2021)
16-75647928-C-T		not specified	Uncertain significance (Sep 28, 2023)
16-75647929-A-G		not specified	Uncertain significance (Sep 05, 2023)
16-75647930-T-C		not specified	Likely benign (Sep 07, 2023)
16-75647931-T-C		not specified	Uncertain significance (Mar 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TERF2IP	protein_coding	protein_coding	ENST00000300086	3	114087

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000267	0.781	125725	0	23	125748	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0292	225	224	1.01	0.0000106	2565
Missense in Polyphen		44	51.579	0.85305		599
Synonymous	-1.18	107	92.6	1.16	0.00000453	794
Loss of Function	1.18	9	13.7	0.655	6.73e-7	166

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000399	0.000398
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000110	0.000105
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts both as a regulator of telomere function and as a transcription regulator. Involved in the regulation of telomere length and protection as a component of the shelterin complex (telosome). In contrast to other components of the shelterin complex, it is dispensible for telomere capping and does not participate in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair. Instead, it is required to negatively regulate telomere recombination and is essential for repressing homology-directed repair (HDR), which can affect telomere length. Does not bind DNA directly: recruited to telomeric double-stranded 5'-TTAGGG-3' repeats via its interaction with TERF2. Independently of its function in telomeres, also acts as a transcription regulator: recruited to extratelomeric 5'- TTAGGG-3' sites via its association with TERF2 or other factors, and regulates gene expression. When cytoplasmic, associates with the I-kappa-B-kinase (IKK) complex and acts as a regulator of the NF-kappa-B signaling by promoting IKK-mediated phosphorylation of RELA/p65, leading to activate expression of NF-kappa-B target genes. {ECO:0000269|PubMed:16166375, ECO:0000269|PubMed:19763083}.
• Pathway: Splicing factor NOVA regulated synaptic proteins;Packaging Of Telomere Ends;Telomere Maintenance;Chromosome Maintenance;Cell Cycle;Regulation of Telomerase (Consensus)

Recessive Scores

• pRec: 0.130

Intolerance Scores

• loftool: 0.462
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.64

Haploinsufficiency Scores

• pHI: 0.550
• hipred: Y
• hipred_score: 0.739
• ghis: 0.623

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Terf2ip
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; pigmentation 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); liver/biliary system phenotype; immune system phenotype

Gene ontology

• Biological process: telomere maintenance;negative regulation of protein phosphorylation;regulation of transcription, DNA-templated;telomere maintenance via telomerase;regulation of double-strand break repair via homologous recombination;telomere maintenance via telomere lengthening;telomere capping;protection from non-homologous end joining at telomere;regulation of telomere maintenance;negative regulation of telomere maintenance;positive regulation of peptidyl-serine phosphorylation;positive regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of DNA recombination at telomere;positive regulation of NF-kappaB transcription factor activity;protein localization to chromosome, telomeric region;positive regulation of NIK/NF-kappaB signaling;positive regulation of protein acetylation
• Cellular component: nuclear chromosome;chromosome, telomeric region;nuclear telomere cap complex;nuclear chromosome, telomeric region;nucleus;nuclear envelope;nucleoplasm;cytoplasm;cytosol;nuclear body;Mre11 complex;shelterin complex
• Molecular function: protein binding;phosphatase binding;telomeric DNA binding;G-rich strand telomeric DNA binding