TENT4B

Chr 16

terminal nucleotidyltransferase 4B

Also known as: PAPD5, TRF4-2, TUT3

NCBI Gene: 64282 ENSG00000121274 UniProt: Q8NDF8

Enables guanylyltransferase activity; poly(A) RNA polymerase activity; and telomerase RNA binding activity. Involved in RNA metabolic process; carbohydrate homeostasis; and regulation of nucleobase-containing compound metabolic process. Located in cytosol; nucleolus; and plasma membrane. Part of TRAMP complex. [provided by Alliance of Genome Resources, Jul 2025]

Active trials

Pathogenic / LP

ClinVar variants

Pubs (1 yr)

3.6

Missense Z· constrained

0.21

LOEUF· LoF intolerant

Clinical Summary— TENT4B

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.21LOEUF

pLI 0.999

Z-score 4.77

OE 0.07 (0.03–0.21)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

3.55Z-score

OE missense 0.46 (0.40–0.52)

154 obs / 337.8 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.07 (0.03–0.21)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.46 (0.40–0.52)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93

0≤1.21.6

LoF obs/exp: 2 / 30.3Missense obs/exp: 154 / 337.8Syn Z: 0.68

0.4091th %ile

GOF

0.3789th %ile

LOF

0.76top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.21

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.