TRNT1

Chr 3

tRNA nucleotidyl transferase 1

Also known as: CCA1, CGI-47, MtCCA, RPEM, SIFD

NCBI Gene: 51095 ENSG00000072756 UniProt: Q96Q11

The TRNT1 protein is a CCA-adding enzyme that catalyzes the addition of the essential CCA nucleotide sequence to the 3' terminus of tRNA molecules, which is necessary for amino acid attachment and tRNA processing. Mutations cause autosomal recessive disorders including sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay, as well as retinitis pigmentosa with erythrocytic microcytosis. The gene shows low constraint against loss-of-function variants (pLI 0.0002, LOEUF 0.88), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a CCA-adding enzyme which belongs to the tRNA nucleotidyltransferase/poly(A) polymerase family. This essential enzyme functions by catalyzing the addition of the conserved nucleotide triplet CCA to the 3' terminus of tRNA molecules. Mutations in this gene result in sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay

UniProtRetinitis pigmentosa and erythrocytic microcytosis

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome · AR · ClinGen 2022

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

—

LOEUF

LOF

Mechanism· G2P

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GeneReview available — TRNT1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in TRNT1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 90

691 rare PASS variants

Rare truncating (LoF)

1 in 370

147 rare PASS variants

Rare synonymous (reference)

1 in 380

211 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TRNT1; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 360
South Asian	~43k	1 in 85	1 in 510
Remaining (unassigned)	~30k	1 in 93	1 in 590
European (Finnish)	~27k	1 in 150	1 in 420
Admixed American	~22k	1 in 98	1 in 600
African / African American	~21k	1 in 100	1 in 650
East Asian	~20k	1 in 120	1 in 1,200
Ashkenazi Jewish	~13k	1 in 420	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 130	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 6 of 7 coding exons well covered in gnomAD exomes; exon 5 marginal. Genomes: all 7.? see exons ↓