TUT4

terminal uridylyl transferase 4, the group of Terminal nucleotidyltransferases|Non-canonical poly(A) polymerases|Zinc fingers CCHC-type

Basic information

Region (hg38): 1:52408282-52553487

Previous symbols: [ "ZCCHC11" ]

Links

ENSG00000134744 ∙ NCBI:23318 ∙ OMIM:613692 ∙ HGNC:28981 ∙ Uniprot:Q5TAX3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TUT4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TUT4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	2	3
missense			71	3	2	76
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	71	4	4

Variants in TUT4

This is a list of pathogenic ClinVar variants found in the TUT4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-52411178-A-C		not specified	Uncertain significance (Aug 04, 2023)
1-52411180-A-C		not specified	Uncertain significance (Feb 28, 2023)
1-52413909-C-T		not specified	Uncertain significance (Mar 23, 2023)
1-52413910-G-A		not specified	Uncertain significance (Nov 07, 2022)
1-52413939-C-G		not specified	Uncertain significance (Jan 24, 2024)
1-52413942-C-T		not specified	Uncertain significance (Oct 24, 2023)
1-52413955-T-C		not specified	Uncertain significance (Jan 03, 2024)
1-52414776-G-A		not specified	Uncertain significance (Dec 21, 2023)
1-52414809-A-G		not specified	Uncertain significance (Jun 29, 2023)
1-52414811-C-T		not specified	Uncertain significance (May 31, 2023)
1-52415362-G-A		not specified	Uncertain significance (Oct 25, 2022)
1-52423946-C-A		not specified	Uncertain significance (Oct 20, 2023)
1-52423972-C-T		not specified	Uncertain significance (Mar 29, 2024)
1-52423975-T-G		not specified	Uncertain significance (Jan 05, 2022)
1-52425366-T-C		not specified	Uncertain significance (Feb 27, 2024)
1-52425372-G-C		not specified	Uncertain significance (Jun 11, 2024)
1-52425385-C-T		not specified	Uncertain significance (Jan 11, 2023)
1-52425402-A-T		not specified	Uncertain significance (Aug 20, 2023)
1-52431054-G-A		not specified	Uncertain significance (Oct 03, 2023)
1-52431055-C-A		not specified	Uncertain significance (May 15, 2024)
1-52431058-C-G		not specified	Uncertain significance (Jan 23, 2023)
1-52431064-G-A		not specified	Uncertain significance (Apr 17, 2024)
1-52431099-G-A		not specified	Uncertain significance (Jun 03, 2022)
1-52431214-G-A		not specified	Uncertain significance (Nov 05, 2021)
1-52431220-G-T		not specified	Uncertain significance (Jun 30, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TUT4	protein_coding	protein_coding	ENST00000257177	29	145206

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.51e-11	125739	0	7	125746	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.76	627	854	0.734	0.0000438	10850
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000141	0.000139
European (Non-Finnish)	0.0000357	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.276
• hipred: Y
• hipred_score: 0.628
• ghis: 0.592

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Tut4
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: tut4
• Affected structure: caudal fin
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: nuclear-transcribed mRNA poly(A) tail shortening;oocyte maturation;negative regulation of transposition, RNA-mediated;miRNA metabolic process;miRNA catabolic process;stem cell population maintenance;pre-miRNA processing;RNA 3'-end processing;histone mRNA catabolic process;RNA 3' uridylation;polyuridylation-dependent mRNA catabolic process
• Cellular component: extracellular space;nucleolus;cytoplasm;cytosol;cytoplasmic ribonucleoprotein granule;extracellular exosome
• Molecular function: RNA binding;protein binding;zinc ion binding;miRNA binding;RNA uridylyltransferase activity