RTEL1

Chr 20ADAR

regulator of telomere elongation helicase 1

ENSG00000258366 UniProt: Q9NZ71 OMIM: 608833

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

A probable ATP-dependent DNA helicase implicated in telomere-length regulation, DNA repair and the maintenance of genomic stability. Acts as an anti-recombinase to counteract toxic recombination and limit crossover during meiosis. Regulates meiotic recombination and crossover homeostasis by physically dissociating strand invasion events and thereby promotes noncrossover repair by meiotic synthesis dependent strand annealing (SDSA) as well as disassembly of D loop recombination intermediates. Also disassembles T loops and prevents telomere fragility by counteracting telomeric G4-DNA structures, which together ensure the dynamics and stability of the telomere

OMIM ResearchGenerating clinical summary…

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

Clinical highlights

Gene-disease validity (ClinGen)

pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 · SDDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.54

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

-1.15Z-score

OE missense 1.12 (1.05–1.18)

875 obs / 784.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.39 (0.29–0.54)

0≤0.351.4

Missense OE?1.12 (1.05–1.18)

0≤0.61.4

Synonymous OE?1.37

0≤1.21.6

LoF obs/exp: 29 / 73.7Missense obs/exp: 875 / 784.3Syn Z: -5.44

ClinVar

No ClinVar data available.

Protein Context — Lollipop Plot

RTEL1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

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

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

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

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