TERF2IP
protein-codingTERF2 interacting protein, the group of Shelterin complex
Gene summary
Enables G-rich strand telomeric DNA binding activity and phosphatase binding activity. Involved in several processes, including negative regulation of telomere maintenance; protection from non-homologous end joining at telomere; and protein localization to chromosome, telomeric region. Located in chromosome, telomeric region; cytoplasm; and nucleus. Part of shelterin complex. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~114.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TERF2IP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018975.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 284 | 284 | ||||
| missense | 520 | 13 | 533 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 2 | |||
| Total | 0 | 1 | 524 | 297 | 0 | 822 |
Highest pathogenic variant AF is 0.0000050167846
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_061848.2 | 3 | MANE Select | |
| Ensembl | ENSP00000300086.4 | 3 | MANE Select | |
| Ensembl | ENSP00000456092.1 | 3 | Standard | |
| Ensembl | ENSP00000454399.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Splicing factor NOVA regulated synaptic proteins
- Packaging Of Telomere Ends
- Telomere Maintenance
- Chromosome Maintenance
- Cell Cycle
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
Molecular Function
- protein binding
- phosphatase binding
- telomeric DNA binding
- G-rich strand telomeric DNA binding
Cellular Component
- nuclear chromosome
- chromosome, telomeric region
- nuclear telomere cap complex
- nuclear chromosome, telomeric region
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000300086
- Coding exons
- 3
- Length
- 114087
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 125748
- p
- 0.0000915
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0292 | 225 | 224 | 1.01 | 0.0000106 | 2565 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.130
Intolerance Scores
- LoFtool
- 0.462
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.985
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |