TUT4
protein-codingterminal uridylyl transferase 4, the group of Terminal nucleotidyltransferases|Non-canonical poly(A) polymerases|Zinc fingers CCHC-type
Gene summary
Enables RNA uridylyltransferase activity. Involved in RNA metabolic process; stem cell population maintenance; and transposable element silencing by mRNA destabilization. Located in cytoplasmic ribonucleoprotein granule and cytosol. Implicated in liver benign neoplasm. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Jun 2026]
- ZCCHC11
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~145.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TUT4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001009881.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 1 | 2 | 8 | ||
| missense | 193 | 7 | 2 | 202 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 205 | 8 | 4 | 217 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001009881.1 | 29 | MANE Select | |
| Ensembl | ENSP00000257177.4 | 29 | MANE Select | |
| RefSeq | NP_056084.1 | 29 | Standard | |
| Ensembl | ENSP00000348063.4 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tut4 | Danio rerio | Structure: caudal fin Quality: malformed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- nuclear-transcribed mRNA poly(A) tail shortening
- oocyte maturation
- negative regulation of transposition, RNA-mediated
- miRNA metabolic process
- miRNA catabolic process
Molecular Function
- RNA binding
- protein binding
- zinc ion binding
- miRNA binding
- RNA uridylyltransferase activity
Cellular Component
- extracellular space
- nucleolus
- cytoplasm
- cytosol
- cytoplasmic ribonucleoprotein granule
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000257177
- Coding exons
- 29
- Length
- 145206
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125746
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.76 | 627 | 854 | 0.734 | 0.0000438 | 10850 |
| Missense (PolyPhen) | 212 | 333.28 | 0.63611 | 4168 | ||
| Synonymous | 1.57 | 264 | 299 | 0.884 | 0.0000153 | 3036 |
| Loss of Function | 8.18 | 4 | 85.8 | 0.0466 | 0.00000495 | 1087 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:25480299). Essential for both oocyte maturation and fertility. Through 3' terminal uridylation of mRNA, sculpts, with TUT7, the maternal transcriptome by eliminating transcripts during oocyte growth (By similarity). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets. Also functions as an integral regulator of microRNA biogenesiS using 3 different uridylation mechanisms (PubMed:25979828). Acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of some miRNA precursors, including that of let-7 (pre-let-7), miR107, miR-143 and miR-200c. Uridylated miRNAs are not processed by Dicer and undergo degradation. Degradation of pre-let-7 contributes to the maintenance of embryonic stem (ES) cell pluripotency (By similarity). Also catalyzes the 3' uridylation of miR-26A, a miRNA that targets IL6 transcript. This abrogates the silencing of IL6 transcript, hence promoting cytokine expression (PubMed:19703396). In the absence of LIN28A, TUT7 and TUT4 monouridylate group II pre-miRNAs, which includes most of pre-let7 members, that shapes an optimal 3' end overhang for efficient processing (PubMed:25979828). Add oligo-U tails to truncated pre-miRNAS with a 5' overhang which may promote rapid degradation of non-fnctional pre-miRNA species (PubMed:25979828). May also suppress Toll-like receptor-induced NF-kappa-B activation via binding to T2BP (PubMed:16643855). Does not play a role in replication-dependent histone mRNA degradation (PubMed:18172165). Due to functional redundancy between TUT4 and TUT7, the identification of the specific role of each of these proteins is difficult (PubMed:25979828, PubMed:25480299, PubMed:16643855, PubMed:19703396, PubMed:18172165) (By similarity). {ECO:0000250|UniProtKB:B2RX14, ECO:0000269|PubMed:16643855, ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:19703396, ECO:0000269|PubMed:25480299, ECO:0000269|PubMed:25979828}.;
Recessive Scores
- pRec
- 0.0981
Intolerance Scores
- RVIS EVS
- -1.59
- RVIS percentile EVS
- 3.1
Essentials
- Essential (gene trap)
- N