TUT7

Summary

TUT7 (terminal uridylyl transferase 7, HGNC:25817) is a protein-coding gene on chromosome 9q21.33, encoding Terminal uridylyltransferase 7 (Q5VYS8). Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay.

Enables RNA uridylyltransferase activity and miRNA binding activity. Involved in RNA metabolic process and transposable element silencing by mRNA destabilization. Located in cytosol and nucleoplasm.

Source: NCBI Gene 79670 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 181 total
• MANE Select transcript: NM_024617

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25817
Approved symbol	TUT7
Name	terminal uridylyl transferase 7
Location	9q21.33
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1711, FLJ13409, PAPD6, TENT3B
Ensembl gene	ENSG00000083223
Ensembl biotype	protein_coding
OMIM	613467
Entrez	79670

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000277141, ENST00000375947, ENST00000375948, ENST00000375957, ENST00000375960, ENST00000375963, ENST00000469004, ENST00000896498, ENST00000896499, ENST00000896500, ENST00000971594, ENST00000971595

RefSeq mRNA: 4 — MANE Select: NM_024617 NM_001185059, NM_001185074, NM_001330718, NM_024617

CCDS: CCDS35057, CCDS55323, CCDS83383

Canonical transcript exons

ENST00000375963 — 27 exons

Exon	Start	End
ENSE00000710308	86303086	86303201
ENSE00000710328	86309928	86310017
ENSE00000804106	86308429	86308606
ENSE00000804107	86309212	86309289
ENSE00000983022	86322325	86322475
ENSE00000983026	86309463	86309576
ENSE00001171510	86301276	86301601
ENSE00001171516	86304856	86304947
ENSE00001171520	86305192	86305239
ENSE00001171525	86310706	86310809
ENSE00001171584	86319584	86319670
ENSE00001196766	86317219	86317276
ENSE00001468980	86354271	86354410
ENSE00001468986	86287733	86288744
ENSE00003469085	86318958	86319058
ENSE00003490207	86337419	86337538
ENSE00003509385	86346299	86346480
ENSE00003567650	86328340	86328492
ENSE00003579339	86343075	86343163
ENSE00003614941	86344977	86345154
ENSE00003617516	86352680	86353230
ENSE00003657640	86340036	86340105
ENSE00003659755	86345669	86345785
ENSE00003670290	86338823	86338949
ENSE00003690587	86322873	86323960
ENSE00003692157	86325334	86325514
ENSE00003756548	86341002	86341053

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 97.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.6386 / max 1187.4778, expressed in 1793 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101218	10.3299	1653
101217	10.0716	1702
101214	0.7374	398
101216	0.6767	249
101213	0.2566	65
101215	0.2048	77
101212	0.1872	83
101210	0.1644	80
101211	0.0101	3

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	97.99	gold quality
cervix squamous epithelium	UBERON:0006922	95.60	gold quality
tongue squamous epithelium	UBERON:0006919	95.55	gold quality
blood	UBERON:0000178	94.61	gold quality
buccal mucosa cell	CL:0002336	94.29	gold quality
tendon	UBERON:0000043	94.08	gold quality
oviduct epithelium	UBERON:0004804	93.39	gold quality
periodontal ligament	UBERON:0008266	92.87	gold quality
cervix epithelium	UBERON:0004801	92.72	gold quality
calcaneal tendon	UBERON:0003701	92.67	gold quality
upper leg skin	UBERON:0004262	92.62	gold quality
monocyte	CL:0000576	92.55	gold quality
squamous epithelium	UBERON:0006914	92.55	gold quality
lower esophagus mucosa	UBERON:0035834	92.45	gold quality
mononuclear cell	CL:0000842	92.42	gold quality
epithelium of nasopharynx	UBERON:0001951	92.41	gold quality
nasopharynx	UBERON:0001728	92.39	gold quality
leukocyte	CL:0000738	92.33	gold quality
bone marrow cell	CL:0002092	92.28	gold quality
skin of leg	UBERON:0001511	92.20	gold quality
oral cavity	UBERON:0000167	92.14	gold quality
esophagus squamous epithelium	UBERON:0006920	92.05	gold quality
skin of abdomen	UBERON:0001416	92.04	gold quality
zone of skin	UBERON:0000014	91.90	gold quality
penis	UBERON:0000989	91.89	gold quality
palpebral conjunctiva	UBERON:0001812	91.45	gold quality
tonsil	UBERON:0002372	91.29	gold quality
sperm	CL:0000019	91.26	gold quality
tibia	UBERON:0000979	91.00	gold quality
mucosa of urinary bladder	UBERON:0001259	90.93	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

109 targeting TUT7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489

Literature-anchored findings (GeneRIF, showing 15)

• Lin28 uses two different TUTases to control let-7 expression . (PMID:22898984)
• Study identified TUT7, TUT4, and TUT2 as novel components of the miRNA biogenesis pathway. (PMID:23063654)
• Study identified TUT4 and TUT7 as uridylyl transferases for poly(A)+ mRNAs in humans and delineated in detail the action mechanism and molecular function of uridylation in the mRNA decay pathway. (PMID:25480299)
• TUT7 generates an oligo-U tail in microRNAs that leads to degradation. (PMID:25979828)
• Results from a study on gene expression variability markers in early-stage human embryos shows that TUT7 (ZCCHC6) is a putative expression variability marker for the 3-day, 8-cell embryo stage. (PMID:26288249)
• Knockdown of 3’hExo also altered the uridylation of histone mRNAs, suggesting that TUT7 and 3’hExo function together in trimming and uridylating histone mRNAs (PMID:27609902)
• Following an intratracheal challenge with S. pneumoniae, Zcchc6 deficiency led to a modest but significant increase in the expression of select cytokines including IL-6, CXCL1, and CXCL5. These findings were recapitulated in vitro whereby Zcchc6-deficient macrophages exhibited similar increases in cytokine expression due to bacterial stimulation (PMID:28665939)
• The authors found that TUT4(7) utilize two multidomain functional modules during the switch from either promoting expression of let-7 microRNA (monoU) or marking it for degradation (oligoU). (PMID:28671666)
• Uridine residues added by TUT7 in the cytoplasm inhibit initiation of reverse transcription of LINE-1 mRNAs once they are reimported to the nucleus. (PMID:30122351)
• ZCCHC6 (TUT7) was markedly up-regulated in damaged cartilage from human osteoarthritis (OA) patients and from wild-type mice with surgically induced OA. (PMID:30302948)
• This tail-U-mediated repression (TUMR) is abolished in cells lacking the uridylation enzymes TUT4 and TUT7, indicating that uridylation alters miRNA function by modulating target recognition. We identified a set of non-canonical targets in human cells that are specifically regulated by uridylated miR-27a. (PMID:31178353)
• High ZCCHC6 expression is associated with head and neck squamous cell carcinoma. (PMID:32526260)
• RNA uridyl transferases TUT4/7 differentially regulate miRNA variants depending on the cancer cell type. (PMID:34949722)
• TENT2, TUT4, and TUT7 selectively regulate miRNA sequence and abundance. (PMID:36071058)
• Terminal Uridylyltransferases TUT4/7 Regulate microRNA and mRNA Homeostasis. (PMID:36497000)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000074645
mus_musculus	Tut7	ENSMUSG00000035248
rattus_norvegicus	Tut7	ENSRNOG00000016629
caenorhabditis_elegans	gld-2	WBGENE00001596
caenorhabditis_elegans		WBGENE00011131
caenorhabditis_elegans		WBGENE00019628
caenorhabditis_elegans		WBGENE00019629
caenorhabditis_elegans	T08B2.4	WBGENE00020345
caenorhabditis_elegans		WBGENE00021338
caenorhabditis_elegans		WBGENE00194706

Paralogs (4): MTPAP (ENSG00000107951), TUT4 (ENSG00000134744), TUT1 (ENSG00000149016), TENT2 (ENSG00000164329)

Protein

Protein identifiers

Terminal uridylyltransferase 7 — Q5VYS8 (reviewed: Q5VYS8)

Alternative names: Zinc finger CCHC domain-containing protein 6

All UniProt accessions (5): Q5VYS8, A0A0C4DFW3, Q5VYS9, Q5VYT0, X6R3Q3

UniProt curated annotations — full annotation on UniProt →

Function. Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay. 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. 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. Acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of some miRNA precursors, including that of let-7 (pre-let-7). Uridylated pre-let-7 RNA is not processed by Dicer and undergo degradation. Pre-let-7 uridylation is strongly enhanced in the presence of LIN28A. 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. Add oligo-U tails to truncated pre-miRNAS with a 5’ overhang which may promote rapid degradation of non-functional pre-miRNA species. Does not play a role in replication-dependent histone mRNA degradation. Due to functional redundancy between TUT4 and TUT7, the identification of the specific role of each of these proteins is difficult. TUT4 and TUT7 restrict retrotransposition of long interspersed element-1 (LINE-1) in cooperation with MOV10 counteracting the RNA chaperonne activity of L1RE1. TUT7 uridylates LINE-1 mRNAs in the cytoplasm which inhibits initiation of reverse transcription once in the nucleus, whereas uridylation by TUT4 destabilizes mRNAs in cytoplasmic ribonucleoprotein granules.

Subunit / interactions. Interacts with MOV10; the interaction is RNA-dependent.

Subcellular location. Cytoplasm.

Domain organisation. Utilizes two multidomain functional modules during the switch from monouridylation to oligouridylation. The catalytic module (containing the 3 CCHC-type Zinc finger domains) is essential for both activities while the Lin28-interacting module (LIM) at the N-terminal part is indispensable for oligouridylation.

Similarity. Belongs to the DNA polymerase type-B-like family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q5VYS8-1	1	yes
Q5VYS8-2	2
Q5VYS8-3	3
Q5VYS8-4	4
Q5VYS8-5	5
Q5VYS8-6	6

RefSeq proteins (4): NP_001171988, NP_001172003, NP_001317647, NP_078893* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001878	Znf_CCHC	Domain
IPR002058	PAP_assoc	Domain
IPR003604	Matrin/U1-like-C_Znf_C2H2	Domain
IPR036875	Znf_CCHC_sf	Homologous_superfamily
IPR043519	NT_sf	Homologous_superfamily
IPR045100	TUT4/7_NTP_transf	Domain
IPR054708	MTPAP-like_central	Domain

Pfam: PF00098, PF03828, PF16631, PF19088, PF22600

Enzyme classification (BRENDA):

• EC 2.7.7.52 — RNA uridylyltransferase (BRENDA: 12 organisms, 81 substrates, 9 inhibitors, 35 Km, 33 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UTP	0.0004–0.3084	20
RNAN	0.0002–0.132	7
RNAN CONTAINING A TERMINAL U RESIDUE	0.0126–0.0208	2
ATP	0.0002	1
CTP	0.055	1
GTP	0.23	1
U6 SNRNAN	0.0001	1
RNA	—	0

Catalyzed reactions (Rhea), 1 shown:

• RNA(n) + UTP = RNA(n)-3’-uridine ribonucleotide + diphosphate (RHEA:14785)

UniProt features (100 total): helix 18, strand 13, compositionally biased region 11, region of interest 9, splice variant 9, binding site 8, modified residue 8, sequence conflict 8, turn 6, zinc finger region 4, domain 2, mutagenesis site 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
5W0M	X-RAY DIFFRACTION	2.3
5W0O	X-RAY DIFFRACTION	2.49
5W0N	X-RAY DIFFRACTION	2.5
5W0B	X-RAY DIFFRACTION	2.61
8OPT	ELECTRON MICROSCOPY	3.65
8OPP	ELECTRON MICROSCOPY	3.76
8OPS	ELECTRON MICROSCOPY	3.82
8OEF	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VYS8-F1	66.41	0.41

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 1047–1050; 1057–1060; 1058; 1060; 1130; 1152; 1170–1174; 1286

Post-translational modifications (8): 57, 64, 132, 172, 600, 844, 893, 939

Mutagenesis-validated functional residues (2):

Position	Phenotype
1060	abolishes inhibition of lire1 retrotransposition.
1097–1099	abolishes monouridylation activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-429947	Deadenylation of mRNA
R-HSA-9819196	Zygotic genome activation (ZGA)
R-HSA-9820865	Z-decay: degradation of maternal mRNAs by zygotically expressed factors

MSigDB gene sets: 228 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GNF2_MSN, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_OOGENESIS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_ANATOMICAL_STRUCTURE_MATURATION, FOSTER_TOLERANT_MACROPHAGE_UP, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GNF2_ICAM3, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS

GO Biological Process (6): oocyte maturation (GO:0001556), miRNA metabolic process (GO:0010586), pre-miRNA processing (GO:0031054), RNA 3’-end processing (GO:0031123), transposable element silencing by mRNA destabilization (GO:0141008), polyuridylation-dependent mRNA catabolic process (GO:1990074)

GO Molecular Function (10): RNA binding (GO:0003723), zinc ion binding (GO:0008270), miRNA binding (GO:0035198), RNA uridylyltransferase activity (GO:0050265), uridylyltransferase activity (GO:0070569), nucleic acid binding (GO:0003676), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Maternal to zygotic transition (MZT)	2
Deadenylation-dependent mRNA decay	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
mRNA destabilization	2
binding	2
developmental process involved in reproduction	1
cell maturation	1
oocyte development	1
RNA metabolic process	1
miRNA processing	1
RNA processing	1
transposable element silencing	1
mRNA catabolic process	1
modification-dependent macromolecule catabolic process	1
nucleic acid binding	1
transition metal ion binding	1
regulatory RNA binding	1
uridylyltransferase activity	1
catalytic activity, acting on RNA	1
nucleotidyltransferase activity	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
cation binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TUT7	LIN28A	Q9H9Z2	966
TUT7	DIS3L2	Q8IYB7	814
TUT7	DICER1	Q9UPY3	646
TUT7	PAPOLG	Q9BWT3	625
TUT7	LIN28B	Q6ZN17	607
TUT7	PAPOLA	P51003	595
TUT7	PAPOLB	Q9NRJ5	570
TUT7	DROSHA	Q9NRR4	568
TUT7	DIS3L	Q8TF46	559
TUT7	DIS3	Q9Y2L1	529
TUT7	XRN1	Q8IZH2	519
TUT7	MOV10	Q9HCE1	507
TUT7	ERI1	Q8IV48	492
TUT7	LSM1	O15116	485
TUT7	PARN	O95453	473

IntAct

113 interactions, top by confidence:

A	B	Type	Score
PLK1	EVI5	psi-mi:“MI:0914”(association)	0.660
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
ZNF574	THAP12	psi-mi:“MI:0914”(association)	0.620
N	NOP56	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
FGF3	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNF512	ZNF724	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
CCDC59	GAPDHS	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
LIN28B	ELAVL2	psi-mi:“MI:0914”(association)	0.530
RPL13	RRP8	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
Cep152	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
Tor1aip1	PEX10	psi-mi:“MI:0914”(association)	0.350
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
Kif13b	TCF3	psi-mi:“MI:0914”(association)	0.350
Iqgap3	SRGAP3	psi-mi:“MI:0914”(association)	0.350
Ccn1	SRGAP3	psi-mi:“MI:0914”(association)	0.350
PCIF1	POLR2A	psi-mi:“MI:0914”(association)	0.350
ATL3	SNX14	psi-mi:“MI:0914”(association)	0.350
PCDH7	RNF113A	psi-mi:“MI:0914”(association)	0.350
TIMM13	OARD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (148): ZCCHC6 (Two-hybrid), ZCCHC6 (Affinity Capture-MS), ZCCHC6 (Affinity Capture-MS), ZCCHC6 (Affinity Capture-MS), ZCCHC6 (Affinity Capture-MS), ZCCHC6 (Affinity Capture-MS), ZCCHC6 (Affinity Capture-MS), ZCCHC6 (Affinity Capture-MS), ZCCHC6 (Affinity Capture-MS), ZCCHC6 (Affinity Capture-MS), ZCCHC6 (Affinity Capture-MS), ZCCHC6 (Affinity Capture-MS), ZCCHC6 (Affinity Capture-MS), ZCCHC6 (Affinity Capture-MS), ZCCHC6 (Affinity Capture-MS)

ESM2 similar proteins: A0A5K7RLP0, A1YEX3, A7YWH3, B1WBU4, O15151, O35618, O43298, O88850, P24278, P97303, Q01954, Q0V8G8, Q15916, Q17RG1, Q562E2, Q5RC05, Q5RDQ6, Q5SXH7, Q5TC79, Q5VYS8, Q5W0Q7, Q5XIN1, Q6ZPY5, Q6ZSB9, Q6ZU67, Q7ZUW7, Q7ZYI3, Q8BLK9, Q8BSV3, Q8IW35, Q8K088, Q8N680, Q8N7W2, Q8TCN5, Q8VHI4, Q8WW38, Q90W33, Q96BR9, Q96S38, Q99ME3

Diamond homologs: B2RX14, D2HS90, O13833, O17087, O64642, Q0VFA3, Q1JPD6, Q2HJ44, Q3MHT4, Q503I9, Q5BLK4, Q5TAX3, Q5U315, Q5VYS8, Q641A1, Q6DFA8, Q6PIY7, Q8R3F9, Q91YI6, Q9H6E5, Q9UT49, Q9VD44, A9JTS5, O13798, Q4KMD7, Q9VYS4, O74326, Q5XET5, Q8WQX6, Q9UTN3, Q8WQX5, Q9NVV4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TUT7	down-regulates	mRNA_polyadenylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 129 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Peptide chain elongation	18	30.9×	1e-20
Viral mRNA Translation	18	30.9×	1e-20
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	18	30.5×	1e-20
Selenocysteine synthesis	18	29.2×	1e-20
Eukaryotic Translation Termination	18	29.2×	1e-20
Formation of a pool of free 40S subunits	19	28.8×	5e-21
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	18	28.6×	2e-20
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	18	28.6×	2e-20

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	19	31.7×	4e-21
ribosomal large subunit biogenesis	5	20.0×	4e-04
ribosomal small subunit biogenesis	9	18.5×	2e-07
translation	17	15.7×	1e-13
negative regulation of translation	8	14.1×	1e-05
rRNA processing	10	12.8×	8e-07
RNA processing	6	11.8×	8e-04
mRNA processing	9	6.4×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

181 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	144
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3973 predictions. Top by Δscore:

Variant	Effect	Δscore
9:86301597:TTACT:T	acceptor_gain	1.0000
9:86301599:ACT:A	acceptor_gain	1.0000
9:86301600:CT:C	acceptor_gain	1.0000
9:86301600:CTC:C	acceptor_gain	1.0000
9:86301601:TCT:T	acceptor_gain	1.0000
9:86301602:C:CC	acceptor_gain	1.0000
9:86303080:A:AC	donor_gain	1.0000
9:86303081:C:CC	donor_gain	1.0000
9:86303081:CTTA:C	donor_gain	1.0000
9:86303084:A:AC	donor_gain	1.0000
9:86303084:ACTT:A	donor_loss	1.0000
9:86303084:ACTTT:A	donor_gain	1.0000
9:86303085:C:CA	donor_gain	1.0000
9:86303085:C:T	donor_loss	1.0000
9:86303085:CT:C	donor_gain	1.0000
9:86303085:CTT:C	donor_gain	1.0000
9:86303085:CTTT:C	donor_gain	1.0000
9:86303085:CTTTC:C	donor_gain	1.0000
9:86303197:TATTC:T	acceptor_gain	1.0000
9:86303198:ATTC:A	acceptor_gain	1.0000
9:86303199:TTC:T	acceptor_gain	1.0000
9:86303200:TC:T	acceptor_gain	1.0000
9:86303201:CC:C	acceptor_gain	1.0000
9:86303202:C:CC	acceptor_gain	1.0000
9:86303203:T:G	acceptor_loss	1.0000
9:86304948:C:CC	acceptor_gain	1.0000
9:86305190:A:AC	donor_gain	1.0000
9:86305191:C:CC	donor_gain	1.0000
9:86308603:TAGG:T	acceptor_gain	1.0000
9:86308605:GG:G	acceptor_gain	1.0000

AlphaMissense

9938 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:86301300:A:G	C1466R	1.000
9:86301339:A:G	C1453R	1.000
9:86303100:A:C	C1360W	1.000
9:86303101:C:A	C1360F	1.000
9:86303101:C:G	C1360S	1.000
9:86303101:C:T	C1360Y	1.000
9:86303102:A:G	C1360R	1.000
9:86303102:A:T	C1360S	1.000
9:86303115:G:C	H1355Q	1.000
9:86303115:G:T	H1355Q	1.000
9:86303119:C:T	G1354E	1.000
9:86303130:A:C	C1350W	1.000
9:86303131:C:A	C1350F	1.000
9:86303131:C:G	C1350S	1.000
9:86303131:C:T	C1350Y	1.000
9:86303132:A:G	C1350R	1.000
9:86303132:A:T	C1350S	1.000
9:86303139:A:C	C1347W	1.000
9:86303140:C:A	C1347F	1.000
9:86303140:C:G	C1347S	1.000
9:86303140:C:T	C1347Y	1.000
9:86303141:A:G	C1347R	1.000
9:86303141:A:T	C1347S	1.000
9:86303145:T:A	R1345S	1.000
9:86303145:T:G	R1345S	1.000
9:86303146:C:G	R1345T	1.000
9:86304935:A:T	I1300K	1.000
9:86304947:A:C	M1296R	1.000
9:86305206:C:T	G1291E	1.000
9:86305212:C:T	G1289E	1.000

dbSNP variants (sampled 300 via entrez): RS1000064801 (9:86336013 A>C,G,T), RS1000075016 (9:86342883 T>G), RS1000076465 (9:86351099 A>C), RS1000086092 (9:86295550 A>G), RS1000117655 (9:86352708 G>A), RS1000118303 (9:86335724 G>A), RS1000133188 (9:86287466 C>T), RS1000185091 (9:86287817 T>C), RS1000192237 (9:86302095 A>C), RS1000225062 (9:86342723 G>A), RS1000237254 (9:86288207 A>G), RS1000274866 (9:86342339 T>C), RS1000279982 (9:86346844 A>G,T), RS1000332350 (9:86349731 G>A,T), RS1000381661 (9:86294615 A>C,G,T)

Disease associations

OMIM: gene MIM:613467 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000817_39	Height	3.000000e-12
GCST002875_55	Diisocyanate-induced asthma	5.000000e-06
GCST008660_6	Lung function in never smokers (high FEV1 vs average FEV1)	3.000000e-07
GCST009462_100	Optic disc size	2.000000e-14
GCST009723_79	Vertical cup-disc ratio (adjusted for vertical disc diameter)	8.000000e-07
GCST009724_18	Vertical cup-disc ratio (multi-trait analysis)	9.000000e-10
GCST012227_455	Hip circumference adjusted for BMI	4.000000e-09
GCST90002387_338	Immature fraction of reticulocytes	4.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0004314	forced expiratory volume
EFO:0006939	cup-to-disc ratio measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17461620	TUT7		0.00	0

CTD chemical–gene interactions

43 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	increases expression	2
FR900359	affects phosphorylation	1
methylmercuric chloride	increases expression	1
methylparaben	increases expression	1
sodium arsenite	increases expression	1
16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione	increases expression	1
cupric chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
torcetrapib	increases expression	1
ICG 001	decreases expression	1
thifluzamide	decreases expression	1
pyrachlostrobin	decreases expression	1
jinfukang	decreases expression	1
picoxystrobin	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Antimycin A	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases mutagenesis	1
Clorgyline	increases expression	1
Diethylstilbestrol	affects expression	1
Ketoconazole	increases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Progesterone	increases expression	1
Rotenone	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.