TERC

Summary

TERC (telomerase RNA component, HGNC:11727) is a long non-coding RNA gene on chromosome 3q26.2. It is haploinsufficient (ClinGen: sufficient evidence).

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.

Source: NCBI Gene 7012 — RefSeq curated summary.

At a glance

• Gene type: non-coding (lncRNA) — no protein product; not a drug target. Variant/disease associations are omitted (they would be positional, from an overlapping protein-coding gene).
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11727
Approved symbol	TERC
Name	telomerase RNA component
Location	3q26.2
Locus type	RNA, long non-coding
Status	Approved
Aliases	TR, hTR, TRC3, SCARNA19, TER
Ensembl gene	ENSG00000270141
Ensembl biotype	lncRNA
OMIM	602322
Entrez	7012
RNAcentral	URS00004A7003 — ncRNA, 451 nt, 3 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 lncRNA

ENST00000602385

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000602385 — 1 exons

Exon	Start	End
ENSE00004073671	169764610	169765060

Expression profiles

Bgee: expression breadth ubiquitous, 113 present calls, max score 77.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.1328 / max 769.8765, expressed in 1754 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45529	41.8344	1752
45530	1.2984	406

Top tissues by expression

113 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	77.29	gold quality
colonic epithelium	UBERON:0000397	76.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.39	gold quality
bone marrow	UBERON:0002371	75.01	gold quality
sural nerve	UBERON:0015488	74.01	gold quality
tonsil	UBERON:0002372	69.86	gold quality
liver	UBERON:0002107	67.61	gold quality
ganglionic eminence	UBERON:0004023	67.48	gold quality
skeletal muscle tissue	UBERON:0001134	67.27	silver quality
calcaneal tendon	UBERON:0003701	66.64	gold quality
uterine cervix	UBERON:0000002	65.35	gold quality
blood	UBERON:0000178	64.12	gold quality
urinary bladder	UBERON:0001255	63.40	gold quality
adrenal tissue	UBERON:0018303	63.33	gold quality
granulocyte	CL:0000094	59.82	gold quality
gall bladder	UBERON:0002110	59.21	gold quality
stromal cell of endometrium	CL:0002255	59.12	gold quality
muscle tissue	UBERON:0002385	58.56	gold quality
prefrontal cortex	UBERON:0000451	56.72	gold quality
kidney	UBERON:0002113	56.03	gold quality
right lobe of liver	UBERON:0001114	55.82	gold quality
islet of Langerhans	UBERON:0000006	55.51	gold quality
stomach	UBERON:0000945	55.36	gold quality
pancreas	UBERON:0001264	55.33	gold quality
right coronary artery	UBERON:0001625	54.36	gold quality
adult mammalian kidney	UBERON:0000082	54.04	gold quality
lung	UBERON:0002048	53.61	gold quality
thoracic mammary gland	UBERON:0005200	52.31	gold quality
colon	UBERON:0001155	52.22	gold quality
left uterine tube	UBERON:0001303	51.83	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFYA, PAX8, SP1, SP3

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• This paper describes the role of telomerase in chromosomal repair in mouse. (PMID:10973255)
• allosteric inhibitors of telomerase: oligonucleotide N3’–>P5’ phosphoramidates (PMID:11788719)
• TR expression did not change after cisplatin exposure for 72 hours. (PMID:11942411)
• nucleolar localization of hTERT protein is associated with telomerase function. (PMID:12083802)
• TEP1, hTR, hsp90, p23, and dyskerin remained at high and unchanged levels throughout up- or down regulation of telomerase activity. (PMID:12135483)
• Minimum length requirement of the alignment domain of telomerase RNA to sustain catalytic activity (PMID:12384594)
• hTR was consistently present in all ovarian cancer samples. (PMID:12496479)
• hTERC expression is regulated during carcinogenesis, but this regulation is unlikely to depend on hTERC methylation, cell proliferation rate, telomere length or hTERT expression (PMID:12507925)
• These experiments identify essential residues of the telomerase RNA that regulate telomerase activity and processivity. (PMID:12514136)
• examined the effect of the dyskeratosis congenita mutations on the structure and stability of human telomerase RNA pseudoknot and CR7 domains (PMID:12525685)
• Involvement of NF-Y and Sp1 binding sequences in basal transcription of the human telomerase RNA. (PMID:12586348)
• No association observed between grade of the tumour differentiation and semiquantitative levels of hTR- or hTERT-expression. Telomerase is of limited value for the diagnostic of malignant or benign lesions in prostate. (PMID:12661034)
• Only 3 of 210 patients with aplastic anemia, paroxysmal nocturnal hemoglobinuria, or myelodysplasia showed heterozygous TERC mutations, not supporting the hypothesis that TERC mutations might underlie seemingly acquired forms of bone marrow failure. (PMID:12676774)
• expression of telomerase activity and its subunit level in pancreatic carcinoma significantly correlate with the clinical stage of pancreatic carcinoma (PMID:12918126)
• A comprehensive structure-function analysis of the core domain of hTR was made. (PMID:12972604)
• telomerase is regulated in ovarian tumors by p53 and c-myc (PMID:14532990)
• Results show that in HeLa cancer cells, human telomerase RNA (hTR) accumulates in the nucleoplasmic Cajal bodies (CBs). (PMID:14981093)
• Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC (PMID:15098033)
• Mutations in TERC, encoding the RNA component of telomerase, have been found in autosomal dominant dyskeratosis congenita (DC) and aplastic anemia (AA). (PMID:15319288)
• Variants in TERC are unlikely to be a major risk factor for the most common form of human neural tube defects. (PMID:15329831)
• in vitro PinX1 binds directly to the hTERT protein subunit, primarily to the hTR-binding domain, as well as to the hTR subunit (PMID:15381700)
• hTR expression is increased at the adenoma-carcinoma transition stage, but it is not always associated with hTERT expression. (PMID:15481329)
• Review. The importance of telomerase in humans is highlighted. Its deficiency (through DKC1 & TERC mutations) results in multiple abnormalities including premature ageing, bone marrow failure & cancer. (PMID:15613268)
• telomerase is mutated in autosomal dyskeratosis congenita and is defective in telomere elongation (PMID:15753647)
• detection of 3q gain and amplification of TERC in routinely collected Pap smears can assist in identifying low-grade lesions with a high progression risk and in decreasing false-negative cytological screenings. (PMID:15793301)
• evidence against the previous proposed molecular-switch model of telomerase pseudoknot function, and support for a static pseudoknot structure (PMID:15849264)
• TERC mutations are not found in myelodysplastic syndromes, despite telomere attrition seen in these syndromes (PMID:15921388)
• CtBP is a potential repressor of hTERT and hTERC (PMID:16036112)
• hTERT mRNA partially regulates telomerase activity in normal gastric mucosa and gastric adenocarcinoma. In contrast, hTERT mRNA splicing is not involved in the regulation of enzyme activity. (PMID:16047476)
• hTERT and hTR are subject to similar controls under hypoxia (PMID:16170363)
• The limited amount of active telomerase in TERC RNA haploinsufficiency may not be able to maintain the minimal length of an increasing number of short telomeres. (PMID:16284252)
• In the new families described with TERC mutations, there is further evidence of dyskeratosis congenita anticipation associated with shorter telomeres in the younger generations. (PMID:16332973)
• Here, we provide functional characterization of an additional 8 distinct hTERT sequence variants and 5 hTERC variants that have recently been identified in patients with dyskeratosis congenita (DC) or aplastic anemia (AA). (PMID:16990594)
• A novel telomerase-independent function of human telomerase RNA is uncovered that restrains ataxia telangiectasia and Rad3 related (ATR) checkpoint kinase activity and participates in the recovery of cells from UV radiation. (PMID:17098743)
• The lower telomerase activity for full-length telomerase RNA is not due to putative quadruplex formation in the 5’ terminal region. (PMID:17150759)
• Examination of the binding affinity of the single stranded region (1-17) at the 5’-terminus of hTR to deletion variants of hTR. (PMID:17150918)
• protein composition of catalytically active telomerase; mass spectrometric sequencing of the components & molecular size determination indicate an enzyme composition of two molecules each of telomerase reverse transcriptase, telomerase RNA & dyskerin (PMID:17395830)
• Repression of hTR RNA expression in human mesenchymal stem cells is due to promoter-specific histone hypoacetylation coupled with low Pol II and TFIIB trafficking. (PMID:17465827)
• mutations in the telomerase complex and their connections with dyskeratosis congenita and bone marrow failures [review] (PMID:17625368)
• 4 novel TERC mutations (G178A, C180T, D52-86 and G2C) & a recurrent one(D110-113GACT)were found in aplastic anemia patients with various phenotypes suggestive of dyskeratosis congenita. (PMID:17640862)

Cross-species orthologs

0 orthologs

Protein

Non-coding RNA — no protein product; not a drug target.

Function

No curated pathway, Gene-Ontology, or interaction data.

Disease & clinical

No curated disease, variant, or cancer-driver associations.

Drugs & pharmacology

No drug or pharmacology data — not an established drug target.