TRNT1

Chr 3AR

tRNA nucleotidyl transferase 1

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

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.882 OMIM phenotypes
Clinical SummaryTRNT1
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Gene-Disease Validity (ClinGen)
congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 37 VUS of 100 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — TRNT1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.88LOEUF
pLI 0.000
Z-score 1.95
OE 0.50 (0.300.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.15Z-score
OE missense 1.22 (1.101.34)
273 obs / 224.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.50 (0.300.88)
00.351.4
Missense OE1.22 (1.101.34)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 9 / 17.9Missense obs/exp: 273 / 224.7Syn Z: 0.24
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongTRNT1-related retinitis pigmentosa and erythrocytic microcytosisLOFAR
strongTRNT1-related hypogammaglobulinemia, short stature with microcephaly, cataract, and inner retinal dysfunctionOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.76top 25%
GOF
0.5955th %ile
LOF
0.2873th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic3
VUS37
Likely Benign34
Benign1
Conflicting1
13
Pathogenic
3
Likely Pathogenic
37
VUS
34
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
4
0
13
Likely Pathogenic
2
1
0
0
3
VUS
1
32
3
1
37
Likely Benign
0
1
10
23
34
Benign
0
0
1
0
1
Conflicting
1
Total1234182489

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TRNT1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC