TERF1
protein-codingtelomeric repeat binding factor 1, the group of Shelterin complex|Myb/SANT domain containing
Gene summary
This gene encodes a telomere specific protein which is a component of the telomere nucleoprotein complex. This protein is present at telomeres throughout the cell cycle and functions as an inhibitor of telomerase, acting in cis to limit the elongation of individual chromosome ends. The protein structure contains a C-terminal Myb motif, a dimerization domain near its N-terminus and an acidic N-terminus. Multiple transcripts of this gene are alternatively spliced products. [provided by RefSeq, Aug 2022]
- TRBF1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~39.3 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 TERF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017489.3. 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 | 1 | 3 | 3 | 7 | ||
| missense | 38 | 1 | 39 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 42 | 4 | 3 | 49 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_059523.2 | 10 | MANE Select | |
| Ensembl | ENSP00000276603.5 | 10 | MANE Select | |
| RefSeq | NP_001397857.1 | 10 | Standard | |
| RefSeq | NP_001400293.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- telomeres telomerase cellular aging and immortality
- Packaging Of Telomere Ends
- Telomere Maintenance
- Chromosome Maintenance
- Cell Cycle
Biological Process
- telomere maintenance
- regulation of transcription by RNA polymerase II
- telomere maintenance via telomerase
- negative regulation of DNA replication
- telomere capping
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- double-stranded telomeric DNA binding
- telomerase activity
- protein binding
Cellular Component
- nuclear telomere cap complex
- nuclear chromosome, telomeric region
- fibrillar center
- nucleus
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000276603
- Coding exons
- 10
- Length
- 39259
- Individuals with no LoFs
- 125712
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 14
- Defined
- 125726
- p
- 0.0000557
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.372 | 202 | 217 | 0.929 | 0.0000101 | 2905 |
| Missense (PolyPhen) | 43 | 68.424 | 0.62843 | 937 | ||
| Synonymous | -1.49 | 92 | 75.5 | 1.22 | 0.00000376 | 761 |
| Loss of Function | 3.62 | 3 | 20.9 | 0.144 | 9.71e-7 | 290 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000071 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.000083 | 0.000079 | rare |
| South Asian | 0.000072 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and negatively regulates telomere length. Involved in the regulation of the mitotic spindle. 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. {ECO:0000269|PubMed:16166375}.;
Recessive Scores
- pRec
- 0.281
Intolerance Scores
- LoFtool
- 0.166
- RVIS EVS
- -0.6
- RVIS percentile EVS
- 17.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.687
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |