TUT1
protein-codingterminal uridylyl transferase 1, U6 snRNA-specific, the group of RNA binding motif containing|Terminal nucleotidyltransferases|Non-canonical poly(A) polymerases
Gene summary
This gene encodes a nucleotidyl transferase that functions as both a terminal uridylyltransferase and a nuclear poly(A) polymerase. The encoded enzyme specifically adds and removes nucleotides from the 3' end of small nuclear RNAs and select mRNAs and may function in controlling gene expression and cell proliferation.[provided by RefSeq, Apr 2009]
- RBM21
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.6 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 TUT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022830.3. 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 | 1 | 3 | 2 | 6 | ||
| missense | 1 | 134 | 7 | 2 | 144 | |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 1 | 136 | 10 | 4 | 151 |
Highest pathogenic variant AF is 0.00002044777
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_073741.3 | 9 | MANE Select | |
| Ensembl | ENSP00000419607.1 | 9 | MANE Select | |
| RefSeq | NP_001354835.1 | 9 | Standard | |
| Ensembl | ENSP00000278279.3 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pyrimidine metabolism
Biological Process
- mRNA polyadenylation
- snRNA processing
- histone mRNA catabolic process
- pre-mRNA cleavage required for polyadenylation
Molecular Function
- RNA binding
- mRNA 3'-UTR binding
- polynucleotide adenylyltransferase activity
- protein binding
- ATP binding
Cellular Component
- nucleus
- nucleolus
- cytosol
- mRNA cleavage and polyadenylation specificity factor complex
- nuclear speck
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000308436
- Coding exons
- 9
- Length
- 17133
- Individuals with no LoFs
- 125674
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 74
- Defined
- 125748
- p
- 0.000294
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.422 | 504 | 531 | 0.948 | 0.0000313 | 5774 |
| Missense (PolyPhen) | 164 | 191.26 | 0.85746 | 2011 | ||
| Synonymous | -0.613 | 230 | 218 | 1.05 | 0.0000121 | 2026 |
| Loss of Function | 2.41 | 23 | 39.3 | 0.585 | 0.00000236 | 382 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0011 | 0.00080 | notable |
| Latino/Admixed American | 0.00030 | 0.00029 | rare |
| Ashkenazi Jewish | 0.00021 | 0.00020 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00015 | 0.00014 | rare |
| European (Non-Finnish) | 0.00026 | 0.00025 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Poly(A) polymerase that creates the 3'-poly(A) tail of specific pre-mRNAs. Localizes to nuclear speckles together with PIP5K1A and mediates polyadenylation of a select set of mRNAs, such as HMOX1. In addition to polyadenylation, it is also required for the 3'-end cleavage of pre-mRNAs: binds to the 3'UTR of targeted pre-mRNAs and promotes the recruitment and assembly of the CPSF complex on the 3'UTR of pre-mRNAs. In addition to adenylyltransferase activity, also has uridylyltransferase activity. However, the ATP ratio is higher than UTP in cells, suggesting that it functions primarily as a poly(A) polymerase. Acts as a specific terminal uridylyltransferase for U6 snRNA in vitro: responsible for a controlled elongation reaction that results in the restoration of the four 3'-terminal UMP-residues found in newly transcribed U6 snRNA. Not involved in replication- dependent histone mRNA degradation. {ECO:0000269|PubMed:16790842, ECO:0000269|PubMed:18288197, ECO:0000269|PubMed:21102410}.;
Recessive Scores
- pRec
- 0.0704
Intolerance Scores
- LoFtool
- 0.847
- RVIS EVS
- -0.84
- RVIS percentile EVS
- 11.45
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.881
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |