Alt. symbols: C20orf41 | bK3184A7.3 | NHL | DKFZP434C013 | KIAA1088 | RTEL

Approved name: regulator of telomere elongation helicase 1
Alt. names: chromosome 20 open reading frame 41

Location: 20q13.33: 63657810 - 63696253 (+)
Gene type: protein_coding, 21 transcripts.

Scores: LoFtool: 0.051700 | pLI: 0.77775848 | LOEUF: 0.537

HGNC: 15888

NCBI: 51750, RefSeq: NG_033901.1

Ensembl: ENSG00000258366.12

LRG_1149 | Status: public

OMIM: 608833

Expression | ProteinAtlas

RTEL1 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. 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.

Bi-allelic mutations in RTEL1 cause autosomal recessive dyskeratosis congenita, type 5 [MIM:615190] and myelodysplastic syndrome. In addition, heterozygous mutations in RTEL1, have also been associated with autosomal dominant dyskeratosis congenita, type 4 [MIM:615190]. Patients with mono- or bi-allelic mutations in RTEL1 may also be diagnosed with Hoyeraal-Hreidarsson syndrome (HHS). Bi-allelic mutations were first reported by Walne et al. (2013) in 10 patients from 7 families with severe dyske ratosis congenita (PMID:23453664). The authors identified a total of 11 different mutations. Le Guen et al. (2013) (PMID:23591994) and Ballew et al. (2013) (PMID:23329068) reported patients with HHS and bi-allelic mutations. Ballew et al. (2013) were also the first to report mono-allelic mutations leading to HHS and dyskeratosis congenita. For instance, they identified the E615D mutation in homozygosity in an index patient with HHS and in heterozygosity in his unaffected mother and brother. Both heterozygous carriers had shortened telomeres. The brother also had hypocellular bone marrow and was being followed for development of DKC. Moreover, as observed for other telomere-related genes, mono-allelic mutations in RTEL1 have also been associated with telomere-related pulmonary fibrosis and/or bone marrow failure, type 3 [MIM:616373]. Lamm et al. (2009) and Deng et al. (2013) reported that an individual, who was a relative of a patient with biallelic RTEL1 mutations, was found to carry a heterozygous mutation (M492I) and had died of pulmonary fibrosis at age 58 years. A couple of years later, Stuart et al. (2105) and Cogan et al. (2015) reported a total of 14 different mutations in 14 unrelated families with telomere-related pulmonary fibrosis without bone marrow failure. According to ClinVar, UniProt and VarSome there are more than 90 pathogenic or likely pathogenic variants known today, including frameshift (21), missense (28), nonsense (26), splice-site (20), and UTR (9) mutations. [Load More]