RTEL1 — regulator of telomere elongation helicase 1

15 sources retrieved · Most recent: April 2026 · Index updated 3 months ago

119PubMed Papers

#3,974 · top 20% of 19K genes

23Diseases

top 2%

0Drugs

287Pathogenic Variants

top 4%

OMIM Disease GeneDNA RepairVariant-RichExperimental GO EvidenceSwiss-Prot Reviewed

protein bindingnegative regulation of t-circle formationnucleusnucleoplasmdyskeratosis congenita, autosomal recessive 5dyskeratosis congenitapulmonary fibrosis and/or bone marrow failure, Telomere-related, 3idiopathic pulmonary fibrosis

AI Summary

RTEL1 is an ATP-dependent DNA helicase essential for maintaining telomere integrity and genomic stability 1. Primary functions include disassembling telomeric loop (T-loop) structures and resolving G4-DNA/R-loop complexes to prevent telomere fragility 2. RTEL1 acts as an anti-recombinase during meiosis, promoting noncrossover DNA repair through strand displacement and D-loop disassembly, thereby regulating crossover homeostasis 3. Beyond telomeres, RTEL1 resolves R-loops genome-wide to prevent transcription-replication collisions (TRCs), which are critical for maintaining global transcriptional and replicative fidelity 2. RTEL1 dysfunction associates with telomeropathies including dyskeratosis congenita (autosomal dominant and recessive forms) and telomere-related pulmonary fibrosis/bone marrow failure 4. Rare genetic variants in RTEL1 influence telomere length in the general population and associate with multiple malignancies including lung cancer 5 6, neuroblastoma 7, and familial breast cancer 8. The clinical significance of RTEL1 extends beyond inherited telomere disorders to understanding cancer predisposition and aging-associated pathologies, making it a potential target for therapeutic intervention in telomere biology diseases 1.

Sources cited

RTEL1 is a DNA helicase important for telomeres and genome integrity with diverse cellular functions

PMID: 37532653

RTEL1 unwinds G4-DNA/R-loops to prevent transcription-replication collisions and maintains global replication fidelity

PMID: 33357438

RTEL1 is a helicase that resolves R-loops and plays roles in telomere maintenance and DNA repair

PMID: 37778731

RTEL1 mutations cause telomeropathies including dyskeratosis congenita and bone marrow failure

PMID: 29146883

Rare RTEL1 variants are significantly associated with telomere length in large population studies

PMID: 39192095

RTEL1 is identified as a telomere-related gene associated with lung cancer susceptibility

PMID: 28604730

RTEL1 SNPs confer increased neuroblastoma risk in a gender- and site-specific manner

PMID: 38001404

RTEL1 variants are associated with familial breast cancer susceptibility

PMID: 30303537

Disease Associations23

dyskeratosis congenita, autosomal recessive 5Open Targets

0.84Strong

dyskeratosis congenitaOpen Targets

0.81Strong

pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3Open Targets

0.81Strong

idiopathic pulmonary fibrosisOpen Targets

0.73Strong

pulmonary fibrosisOpen Targets

0.55Moderate

pulmonary fibrosis and/or bone marrow failure, telomere-relatedOpen Targets

0.50Moderate

Hoyeraal-Hreidarsson syndromeOpen Targets

0.46Moderate

minimally differentiated acute myeloblastic leukemiaOpen Targets

0.46Moderate

telomere syndromeOpen Targets

0.45Moderate

dyskeratosis congenita, X-linkedOpen Targets

0.42Moderate

acute myeloid leukemiaOpen Targets

0.34Weak

genetic disorderOpen Targets

0.34Weak

Abnormality of blood and blood-forming tissuesOpen Targets

0.34Weak

Adams-Oliver syndromeOpen Targets

0.34Weak

dyskeratosis congenita, autosomal recessive 1Open Targets

0.30Weak

gliomaOpen Targets

0.29Weak

neurodegenerative diseaseOpen Targets

0.28Weak

action myoclonus-renal failure syndromeOpen Targets

0.27Weak

Combined oxidative phosphorylation defect type 24Open Targets

0.27Weak

mitochondrial oxidative phosphorylation disorderOpen Targets

0.27Weak

Dyskeratosis congenita, autosomal dominant, 4UniProt

Dyskeratosis congenita, autosomal recessive, 5UniProt

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

Pathogenic Variants287

NM_001283009.1(RTEL1):c.3791G>A (p.Arg1264His)Pathogenic

★★☆☆2026→ Residue 1264

NM_001283009.2(RTEL1):c.2260C>T (p.Arg754Ter)Pathogenic

Dyskeratosis congenita, autosomal recessive 5|Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3

★★☆☆2026→ Residue 754

NM_001283009.2(RTEL1):c.2920C>T (p.Arg974Ter)Pathogenic

Dyskeratosis congenita, autosomal recessive 5|Interstitial lung disease 2|Dyskeratosis congenita|Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3|not provided|Pulmonary fibrosis|Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3

★★☆☆2026→ Residue 974

NM_001283009.2(RTEL1):c.2635del (p.Arg879fs)Pathogenic

Dyskeratosis congenita, autosomal recessive 5|Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3|Dyskeratosis congenita

★★☆☆2026→ Residue 879

NM_001283009.2(RTEL1):c.3610C>T (p.Gln1204Ter)Pathogenic

Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3|Dyskeratosis congenita

★★☆☆2026→ Residue 1204

NM_001283009.2(RTEL1):c.1476G>T (p.Met492Ile)Pathogenic

Dyskeratosis congenita, autosomal recessive 5|Dyskeratosis congenita|Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3|not provided

★★☆☆2026→ Residue 492

NM_001283009.2(RTEL1):c.396-26C>TPathogenic

not provided|Dyskeratosis congenita, autosomal recessive 5|Dyskeratosis congenita|Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3

★★☆☆2025

NM_001283009.2(RTEL1):c.102+2T>CPathogenic

Dyskeratosis congenita

★★☆☆2025

NM_001283009.2(RTEL1):c.190C>T (p.Arg64Ter)Pathogenic

not provided|Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3;Dyskeratosis congenita, autosomal recessive 5|Dyskeratosis congenita

★★☆☆2025→ Residue 64

NM_001283009.2(RTEL1):c.3040C>T (p.Gln1014Ter)Pathogenic

Dyskeratosis congenita, autosomal recessive 5|Dyskeratosis congenita

★★☆☆2025→ Residue 1014

NM_001283009.2(RTEL1):c.478-2A>GLikely pathogenic

Dyskeratosis congenita, autosomal recessive 5|Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3

★★☆☆2025

NM_001283009.2(RTEL1):c.3109+1G>CPathogenic

not provided|Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3;Dyskeratosis congenita, autosomal recessive 5

★★☆☆2025

NM_001283009.2(RTEL1):c.3110-2A>TPathogenic

Dyskeratosis congenita, autosomal recessive 5|Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3|Dyskeratosis congenita

★★☆☆2025

NM_001283009.2(RTEL1):c.2940_2956del (p.Glu981fs)Pathogenic

Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3;Dyskeratosis congenita, autosomal recessive 5|not provided

★★☆☆2025→ Residue 981

NM_001283009.2(RTEL1):c.2956C>T (p.Arg986Ter)Pathogenic

★★☆☆2025→ Residue 986

NM_001283009.2(RTEL1):c.2614C>T (p.Arg872Ter)Pathogenic

Dyskeratosis congenita, autosomal recessive 5|Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3|RTEL1-related disorder|Dyskeratosis congenita

★★☆☆2025→ Residue 872

NM_001283009.2(RTEL1):c.1135+1G>APathogenic

Dyskeratosis congenita|Acute myeloid leukemia|Pulmonary fibrosis|Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3

★★☆☆2025

NM_001283009.2(RTEL1):c.1482-1G>APathogenic

Interstitial lung disease 2|Dyskeratosis congenita|Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3

★★☆☆2025

NM_001283009.2(RTEL1):c.1037+1G>TLikely pathogenic

Dyskeratosis congenita, autosomal recessive 5|Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3|Dyskeratosis congenita

★★☆☆2025

NM_001283009.2(RTEL1):c.320del (p.Pro107fs)Likely pathogenic

Dyskeratosis congenita|not provided

★★☆☆2025→ Residue 107

Tissue Expression6 tissues

Bone Marrow

100%

Ovary

63%

Lung

50%

Heart

34%

Liver

29%

Brain

23%

Gene Interaction Network6 neighbors

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Structure3 PDB hits

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PDB7WU8 · 1.60 Å · X-ray

View on RCSB

ConstraintgnomAD v4.1

LOEUFⓘ

0.66LoF Tolerant

pLIⓘ

0.00Tolerant

Observed/Expected LoF0.55 [0.47–0.66]

Rankings3 dim

Where RTEL1 stands among ~20K protein-coding genes

#3,973of 20,598
Most Researched119 · top quartile
#217of 5,509
Most Pathogenic Variants287 · top 5%
#4,838of 17,882
Most Constrained (LOEUF)0.66