RTEL1

regulator of telomere elongation helicase 1, the group of DNA helicases

Basic information

Region (hg38): 20:63657810-63696253

Previous symbols: [ "C20orf41" ]

Links

ENSG00000258366 ∙ NCBI:51750 ∙ OMIM:608833 ∙ HGNC:15888 ∙ Uniprot:Q9NZ71 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dyskeratosis congenita, autosomal recessive 5 (Definitive), mode of inheritance: AR
• acute myeloid leukemia (Moderate), mode of inheritance: AD
• acute myeloid leukemia (Moderate), mode of inheritance: AR
• dyskeratosis congenita (Supportive), mode of inheritance: AD
• Hoyeraal-Hreidarsson syndrome (Supportive), mode of inheritance: AD
• pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (Strong), mode of inheritance: AD
• dyskeratosis congenita, autosomal recessive 5 (Strong), mode of inheritance: AR
• pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pulmonary fibrosis and/or bone marrow failure, telomere-related 3; Dyskeratosis congenita, autosomal dominant 4; Dyskeratosis congenita, autosomal recessive 5	AD/AR	Allergy/Immunology/Infectious; Hematologic; Oncologic; Pulmonary	For Dyskeratosis congenita, affected individuals have been described with a number of hematopoietic manifestations, including anemia and thrombocytopenia, and have frequently been reported as suffering from bone marrow failure; Individuals may be at increased risk of oncologic processes, and awareness may allow early detection and treatment; HSCT has been described; For treatment related to pulmonary fibrosis, immunotherapy may be beneficial, though lung transplantation may be indicated in individuals with severe/refractory disease	Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Neurologic; Oncologic; Pulmonary	19461895; 23329068; 23453664; 23591994; 23959892; 25848748

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RTEL1 gene.

• Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (41 variants)
• Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3;Dyskeratosis congenita, autosomal recessive 5 (36 variants)
• Pulmonary fibrosis (4 variants)
• Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 (4 variants)
• Dyskeratosis congenita (3 variants)
• Dyskeratosis congenita, autosomal recessive 5 (3 variants)
• Interstitial lung disease 2 (3 variants)
• not provided (2 variants)
• Telomere syndrome (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RTEL1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			12	921	13	946
missense	1	5	947	19	8	980
nonsense	37	24	2			63
start loss						0
frameshift	46	38	2			86
inframe indel		1	20	1		22
splice donor/acceptor (+/-2bp)	3	60	1	1		65
splice region	1	1	65	200	5	272
non coding			24	548	85	657
Total	87	128	1008	1490	106

Highest pathogenic variant AF is 0.0000723

Variants in RTEL1

This is a list of pathogenic ClinVar variants found in the RTEL1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-63659310-C-T		not specified	Benign (Jan 24, 2024)
20-63659344-A-C			Benign (Feb 07, 2019)
20-63659394-C-G		not specified	Uncertain significance (Sep 27, 2019)
20-63659405-G-GCCCAAGATAGTCCTGAATGGTGTGACCGTAGACTTCCCTTTCC		Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3	Pathogenic (Apr 02, 2021)
20-63659407-C-A			Uncertain significance (Feb 01, 2024)
20-63659408-C-T		RTEL1-related disorder	Likely benign (Feb 23, 2022)
20-63659410-A-C		Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3;Dyskeratosis congenita, autosomal recessive 5 • Dyskeratosis congenita	Uncertain significance (Sep 02, 2021)
20-63659410-AG-A		Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3	Pathogenic (Mar 29, 2021)
20-63659411-G-A		Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3	Likely benign (Dec 16, 2023)
20-63659414-A-C		Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 • Dyskeratosis congenita • Inborn genetic diseases	Likely benign (Dec 30, 2023)
20-63659418-C-T		Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3;Dyskeratosis congenita, autosomal recessive 5	Likely benign (Sep 11, 2023)
20-63659423-T-C		Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3;Dyskeratosis congenita, autosomal recessive 5	Likely benign (May 30, 2023)
20-63659431-C-T		Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3;Dyskeratosis congenita, autosomal recessive 5	Uncertain significance (Sep 01, 2021)
20-63659432-C-T		Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 • Inborn genetic diseases	Likely benign (May 27, 2023)
20-63659433-G-A		Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3;Dyskeratosis congenita, autosomal recessive 5	Uncertain significance (Nov 18, 2023)
20-63659438-C-T		Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3;Dyskeratosis congenita, autosomal recessive 5	Likely benign (Sep 10, 2022)
20-63659444-T-C		not specified	Uncertain significance (Nov 21, 2017)
20-63659447-C-A		Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3 • Dyskeratosis congenita • RTEL1-related disorder	Uncertain significance (May 01, 2024)
20-63659448-C-T		Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3;Dyskeratosis congenita, autosomal recessive 5	Pathogenic (Feb 26, 2021)
20-63659449-A-G		Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3	Uncertain significance (Jul 29, 2022)
20-63659451-C-T		Dyskeratosis congenita	Likely pathogenic (Oct 11, 2016)
20-63659453-C-T		Dyskeratosis congenita, autosomal recessive 5;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3	Likely benign (Aug 30, 2023)
20-63659456-C-T		Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3;Dyskeratosis congenita, autosomal recessive 5	Likely benign (Jun 23, 2023)
20-63659457-A-G		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
20-63659458-A-G		Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3;Dyskeratosis congenita, autosomal recessive 5	Uncertain significance (Aug 12, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RTEL1	protein_coding	protein_coding	ENST00000508582	34	39254

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.87e-10	1.00	125664	0	84	125748	0.000334

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.15	875	784	1.12	0.0000510	7998
Missense in Polyphen		158	239.38	0.66004		2606
Synonymous	-5.44	475	346	1.37	0.0000249	2546
Loss of Function	4.82	29	73.7	0.394	0.00000401	764

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000478	0.000477
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.000327	0.000326
Finnish	0.000509	0.000508
European (Non-Finnish)	0.000324	0.000316
Middle Eastern	0.000327	0.000326
South Asian	0.000438	0.000425
Other	0.000496	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. {ECO:0000255|HAMAP- Rule:MF_03065, ECO:0000269|PubMed:18957201, ECO:0000269|PubMed:23453664, ECO:0000269|PubMed:24009516}.
• Disease: DISEASE: Dyskeratosis congenita, autosomal recessive, 5 (DKCB5) [MIM:615190]: A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. DKCB5 is characterized by onset of bone marrow failure and immunodeficiency in early childhood. Most patients also have growth and developmental delay and cerebellar hypoplasia, consistent with a clinical diagnosis of Hoyeraal-Hreidarsson syndrome. {ECO:0000269|PubMed:23329068, ECO:0000269|PubMed:23453664, ECO:0000269|PubMed:23591994, ECO:0000269|PubMed:23959892, ECO:0000269|PubMed:24009516}. Note=The disease is caused by mutations affecting the gene represented in this entry. RTEL1 mutations have also been found in patients with a dyskeratosis congenita-like phenotype consisting of one feature of dyskeratosis congenita and short telomeres, in the absence of the typical DKC diagnostic triad (PubMed:23329068). {ECO:0000269|PubMed:23329068}.; DISEASE: Dyskeratosis congenita, autosomal dominant, 4 (DKCA4) [MIM:615190]: A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. {ECO:0000269|PubMed:23329068}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pulmonary fibrosis, and/or bone marrow failure, telomere- related, 3 (PFBMFT3) [MIM:616373]: A disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome and acute myeloid leukemia. Phenotype, age at onset, and severity are determined by telomere length. {ECO:0000269|PubMed:25848748}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lung fibrosis;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;DNA Double-Strand Break Repair;Homology Directed Repair;Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA);Resolution of D-Loop Structures;HDR through Homologous Recombination (HRR) (Consensus)

Recessive Scores

• pRec: 0.169

Intolerance Scores

• loftool: 0.0517
• rvis_EVS: -2.48
• rvis_percentile_EVS: 0.95

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.270
• ghis: 0.485

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.427

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rtel1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); embryo phenotype; neoplasm; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: telomere maintenance;strand displacement;DNA repair;regulation of double-strand break repair via homologous recombination;replication fork processing;positive regulation of telomere maintenance;DNA duplex unwinding;telomere maintenance in response to DNA damage;negative regulation of DNA recombination;telomeric loop disassembly;mitotic telomere maintenance via semi-conservative replication;positive regulation of telomere capping;positive regulation of telomere maintenance via telomere lengthening;negative regulation of t-circle formation;negative regulation of telomere maintenance in response to DNA damage;positive regulation of telomeric loop disassembly
• Cellular component: chromosome, telomeric region;nucleus;nucleoplasm
• Molecular function: DNA binding;ATP-dependent DNA helicase activity;protein binding;ATP binding;metal ion binding;4 iron, 4 sulfur cluster binding;DNA polymerase binding