RTEL1

Chr 20ADAR

regulator of telomere elongation helicase 1

Also known as: C20orf41, DKCA4, DKCB5, NHL, PFBMFT3, RTEL

NCBI Gene: 51750ENSG00000258366UniProt: Q9NZ71

This gene encodes a DNA helicase which functions in the stability, protection and elongation of telomeres and interacts with proteins in the shelterin complex known to protect telomeres during DNA replication. Mutations in this gene have been associated with dyskeratosis congenita and Hoyerall-Hreidarsson syndrome. Read-through transcription of this gene into the neighboring downstream gene, which encodes tumor necrosis factor receptor superfamily, member 6b, generates a non-coding transcript. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

Primary Disease Associations & Inheritance

Dyskeratosis congenita, autosomal dominant 4MIM #615190
ADAR
Dyskeratosis congenita, autosomal recessive 5MIM #615190
ADAR
Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 3MIM #616373
AD
599
ClinVar variants
23
Pathogenic / LP
0.00
pLI score
3
Active trials
Clinical Summary— RTEL1
🧬
Gene-Disease Validity (ClinGen)
pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 428 VUS of 599 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.54LOEUF
pLI 0.000
Z-score 4.82
OE 0.39 (0.29–0.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.15Z-score
OE missense 1.12 (1.05–1.18)
875 obs / 784.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.39 (0.29–0.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.12 (1.05–1.18)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.37
0≤1.21.6
LoF obs/exp: 29 / 73.7Missense obs/exp: 875 / 784.3Syn Z: -5.44

ClinVar Variant Classifications

599 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic13
VUS428
Likely Benign141
Benign1
Conflicting6
10
Pathogenic
13
Likely Pathogenic
428
VUS
141
Likely Benign
1
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
6
0
10
Likely Pathogenic
8
1
4
0
13
VUS
2
412
12
2
428
Likely Benign
0
15
31
95
141
Benign
0
1
0
0
1
Conflicting
—6
Total144295397599

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.

Gene2Phenotype Curations

RTEL1-related dyskeratosis congenita

limited
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersSkinCancer
G2P ↗

RTEL1-related dyskeratosis congenita

definitive
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersSkinCancer
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Dyskeratosis congenita, autosomal dominant 4

MIM #615190

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Dyskeratosis congenita, autosomal recessive 5

MIM #615190

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 3

MIM #616373

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — RTEL1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic architecture of telomere length in 462,666 UK Biobank whole-genome sequences.
Burren OS et al.·Nat Genet
2024
A landscape of germ line mutations in a cohort of inherited bone marrow failure patients.
Bluteau O et al.·Blood
2018Cohort
Familial breast cancer and DNA repair genes: Insights into known and novel susceptibility genes from the GENESIS study, and implications for multigene panel testing.
Girard E et al.·Int J Cancer
2019
Helicases FANCJ, RTEL1 and BLM Act on Guanine Quadruplex DNA in Vivo.
Lansdorp P et al.·Genes (Basel)
2019Review
RecQ helicase expression in patients with telomeropathies.
Silva JPL et al.·Mol Biol Rep
2024Cohort
Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants.
Peljto AL et al.·Am J Respir Crit Care Med
2023
Molecular mechanisms of telomere biology disorders.
Grill S et al.·J Biol Chem
2021Review
Germline RTEL1 Variants in Telomere Biology Disorders.
Thompson AS et al.·Am J Med Genet A
2025
NRDE2 deficiency impairs homologous recombination repair and sensitizes hepatocellular carcinoma to PARP inhibitors.
Wang Y et al.·Cell Genom
2024
Heterozygous RTEL1 variants in bone marrow failure and myeloid neoplasms.
Marsh JCW et al.·Blood Adv
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING
NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21
NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies
Metastatic Pancreatic Ductal AdenocarcinomaHomologous Recombination Deficiency (HRD)

A 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 RECRUITING
NCT04666740Phase PHASE2Memorial Sloan Kettering Cancer CenterStarted 2020-12-18
PembrolizumabOlaparib
Idiopathic Interstitial Pneumopathy/Pneumopathy Interstitial DiffusePaediatric and Adult Patients

RaDiCo PID Cohort (RaDiCo-ILD Cohort in English)

RECRUITING
NCT04238871Institut National de la Santé Et de la Recherche Médicale, FranceStarted 2017-06-21

External Resources

Links to major genomics databases and tools