TERC

ncRNA

telomerase RNA component

Gene summary

Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme consists of a protein component with reverse transcriptase activity, and an RNA component, encoded by this gene, that serves as a template for the telomere repeat. Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells resulting in progressive shortening of telomeres. Deregulation of telomerase expression in somatic cells may be involved in oncogenesis. Studies in mouse suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks. Mutations in this gene cause autosomal dominant dyskeratosis congenita, and may also be associated with some cases of aplastic anemia. [provided by RefSeq, Jul 2008]

MANE transcript

N/A

Inheritance

ClinVar variants

P:1

Top phenotype

Dyskeratosis congenita, autosomal dominant 1; Aplastic anemia; Pulmonary fibrosis and/or bone marrow failure, telomere-related 2

Max pathogenic AF

—

Genomic locus

chr3:169,764,063-169,765,158

External References & Databases

Ensembl (ENSG00000270141)

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

dyskeratosis congenita, autosomal dominant 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007485

Submitter: PanelApp Australia

dyskeratosis congenita, autosomal dominant 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007485

Submitter: Labcorp Genetics (formerly Invitae)

dyskeratosis congenita, autosomal dominant 1DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007485

Submitter: ClinGen

Telomerase RNA component (*TERC*) variants were first reported in relation to autosomal dominant dyskeratosis congenita in 2001 (Vulliamy et al., PMID 11574891). *TERC* is a nearly ubiquitously expressed, long non-coding RNA (lncRNA) that complexes with telomerase reverse transcriptase (*TERT*) and is the template used by TERT to add TTAGGG nucleotide repeats to the ends of telomeres. Variants in telomere related genes have been reported to lead to a group of diseases referred to as telomere biology disorders (TBD’s) (PMID 39371255). Features of TBD’s like dyskeratosis congenita (DC) can include but are not limited to shortened telomeres with or without the classic DC mucocutaneous features (reticular pigmentation of the skin, oral leukoplakia, and nail dystrophy), pulmonary fibrosis, hepatic fibrosis, or bone marrow failure. At least one variant has been reported in a family with only pulmonary fibrosis as a diagnosis in a 64 year old proband with no reported cytopenias or other phenotypes related to dyskeratosis congenita (PMID 17460043). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism, inheritance pattern or phenotypic variability. Therefore, the following disease entities have been lumped into one disease entity, dyskeratosis congenita AD 1 (OMIM:127550), pulmonary fibrosis and/or bone marrow failure, telomere related 2 (OMIM:614743). Twenty-five variants (17 SNV’s and 9 indels) that have been reported in twenty-five probands in eleven publications (PMIDs 11574891, 26024875, 21436073, 19760749, 17640862, 19936245, 16990594, 34267850, 21931702, 17460043, 17392301) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence has been reached. The mechanism of pathogenicity is known to be loss of function leading to shortened telomeres and early cell death. This gene-disease relationship is also supported by mouse models, pull-down assay, and in vitro functional modification assays performed in non-patient cells (PMIDs 26518879, 27587879, 32150348, 11520856, 9335332). In summary, there is definitive evidence supporting the relationship between *TERC* and autosomal dominant *TERC*-related short telomere syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen ILD GCEP on the meeting date November 12, 2024 (SOP11).

acute myeloid leukemiaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0018874

Submitter: Genomics England PanelApp

dyskeratosis congenita, autosomal dominant 1MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0007485

Submitter: Genomics England PanelApp

dyskeratosis congenita, autosomal dominant 1DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007485

Submitter: Ambry Genetics

dyskeratosis congenita, autosomal dominant 1DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007485

Submitter: G2P

Clinical Genomic Database (CGD)

Dyskeratosis congenita, autosomal dominant 1; Aplastic anemia; Pulmonary fibrosis and/or bone marrow failure, telomere-related 2AD

Manifestation: Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Hematologic; Neurologic; Oncologic; Pulmonary

Intervention: Allergy/Immunology/Infectious; Hematologic; Oncologic; Pulmonary

Rationale: In dyskeratosis congenita, the presentation many not always be classic, and individuals are at high risk for hematologic anomalies (including bone marrow failure) and malignancy, and surveillance and prompt diagnosis and treatment may be beneficial; In Aplastic anemia, surveillance and prompt treatment of aplastic anemia and bone marrow failure may reduce morbidity; For treatment related to pulmonary fibrosis, immunotherapy may be beneficial, though lung transplantation may be indicated in individuals with severe/refractory disease

Comments: The presence of variants has also been reported as increasing risk of malignancy, including melanoma

Refs: 11574891; 12090986; 14630445; 17392301; 18753630; 19760749; 21436073; 22341970; 20301779; 23348503

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TERC variants in ClinVar

11 Conditions Cataloged

Dyskeratosis congenita, autosomal dominant 1Total: 279

not providedTotal: 17

Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 2Total: 15

Aplastic anemiaTotal: 12

Pulmonary fibrosisTotal: 10

not specifiedTotal: 8

Dyskeratosis congenita, autosomal dominant 1;Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 2Total: 4

TERC-related conditionTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript . Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense						0
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	1	0	0	0	0	1

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 0 of 0 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
No transcripts match your selected source or search query.

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gastric cancer - Homo sapiens (human)
Hepatocellular carcinoma - Homo sapiens (human)
Pathways in cancer - Homo sapiens (human)
Lung fibrosis
overview of telomerase rna component gene hterc transcriptional regulation

dbNSFP Gene Annotations

Source: dbNSFP

Essentials

Indispensability pred.: E
Indispensability score: 0.914