RTEL1
Chr 20ADARregulator of telomere elongation helicase 1
Also known as: C20orf41, DKCA4, DKCB5, NHL, PFBMFT3, RTEL
This gene encodes an ATP-dependent DNA helicase that regulates telomere length, prevents toxic DNA recombination, and maintains genomic stability by disassembling problematic DNA structures including telomeric loops and G-quadruplexes. Mutations cause dyskeratosis congenita and pulmonary fibrosis and/or bone marrow failure syndrome with telomere-related pathology, affecting multiple systems including skin, nails, mucous membranes, lungs, and hematopoietic system. The gene shows both autosomal dominant and autosomal recessive inheritance patterns and is highly intolerant to loss-of-function variants.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 11 | 0 | 1 | 0 | 12 |
Likely Pathogenic | 24 | 3 | 0 | 0 | 27 |
VUS | 1 | 263 | 12 | 2 | 278 |
Likely Benign | 0 | 7 | 73 | 98 | 178 |
Benign | 0 | 1 | 0 | 0 | 1 |
Conflicting | — | 3 | |||
| Total | 36 | 274 | 86 | 100 | 499 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RTEL1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History
NOT YET RECRUITINGA Study of Pembrolizumab and Olaparib for People With Metastatic Pancreatic Ductal Adenocarcinoma and Homologous Recombination Deficiency or Exceptional Treatment Response to Platinum-Based Therapy
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools