Alt. symbols: MtCCA | CGI-47 | CCA1

Approved name: tRNA nucleotidyl transferase 1
Alt. names: tRNA nucleotidyl transferase, CCA-adding, 1, tRNA CCA nucleotidyl transferase 1 | ATP(CTP):tRNA nucleotidyltransferase, CCA-adding enzyme

Location: 3p26.2: 3126933 - 3153435 (+)
Gene type: protein_coding, 31 transcripts.

Scores: LoFtool: 0.899000 | pLI: 0.00000246 | LOEUF: 0.876

HGNC: 17341

NCBI: 51095, RefSeq: NG_041800.2

Ensembl: ENSG00000072756.18

LRG_1314 | Status: public

OMIM: 612907

Expression | ProteinAtlas

TRNT1 encodes an essential enzyme that catalyzes CCA terminus addition to the 3’ end of cytoplasmic and mitochondrial tRNA precursors, a fundamental prerequisite for mature tRNAs to become aminoacylated and participate in protein biosynthesis.

Biallelic LOF mutations in TRNT1, resulting in aberrant tRNA processing, have been associated with related AR syndromes - Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) [MIM:616084] on the more severe end of the disease spectrum, and Retinitis pigmentosa and erythrocytic microcytosis [MIM:616959] on the milder end. The latter stems from compound heterozygosity for insertion, deletion and splice site mutations that cause less reduced protein lev els than in SIFD, resulting in disease limited almost entirely to the retina (PMID: 26494905). On the other hand, SIFD is an autoinflammatory syndrome of congenital sideroblastic anemia, predominantly B cell immunodeficiency, periodic fevers and developmental delay, along with more variable features of sensorineural hearing loss, retinitis pigmentosa, nephrocalcinosis, and cardiomyopathy (PMID: 25652405, 29170023, 32181284). TRNT1-deficient patient cells fail to upregulate protein clearance pathways in response to stress and show evidence of increased TNF-dependent cell death (PMID: 30758723). High levels of inflammatory cytokines such as IL-6, IL-12, IL-18, IFN-γ and IFN-induced cytokines were elevated in patient sera, while TNF and IL-1beta were present in tissue biopsies of patients with active inflammatory disease (PMID: 29358286). [Load More]