TUT4

Chr 1

terminal uridylyl transferase 4

Also known as: PAPD3, TENT3A, ZCCHC11

The TUT4 protein is a uridylyltransferase that regulates mRNA stability and microRNA biogenesis through terminal uridylation of RNA substrates. Mutations cause autosomal recessive developmental delay, intellectual disability, and microcephaly with onset in infancy. This gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.107), reflecting its essential role in RNA metabolism and early development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.11
Clinical SummaryTUT4
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

LoF intolerant — likely haploinsufficient
LoF Constraint
0.11LOEUF
pLI 1.000
Z-score 8.18
OE 0.05 (0.020.11)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.76Z-score
OE missense 0.73 (0.690.79)
627 obs / 853.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.020.11)
00.351.4
Missense OE0.73 (0.690.79)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 4 / 85.8Missense obs/exp: 627 / 853.7Syn Z: 1.57
DN
0.2898th %ile
GOF
0.2795th %ile
LOF
0.76top 10%

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

LOFprediction above median · LOEUF 0.11

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TUT4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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