TUT1

Summary

TUT1 (terminal uridylyl transferase 1, U6 snRNA-specific, HGNC:26184) is a protein-coding gene on chromosome 11q12.3, encoding Speckle targeted PIP5K1A-regulated poly(A) polymerase (Q9H6E5). Poly(A) polymerase that creates the 3’-poly(A) tail of specific pre-mRNAs. It is a common-essential gene (DepMap: required in 99.6% of cancer cell lines).

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.

Source: NCBI Gene 64852 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 174 total — 1 likely-pathogenic
• Cancer dependency (DepMap): dependent in 99.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_022830

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26184
Approved symbol	TUT1
Name	terminal uridylyl transferase 1, U6 snRNA-specific
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22347, FLJ22267, FLJ21850, PAPD2, TUTase, TENT1
Ensembl gene	ENSG00000149016
Ensembl biotype	protein_coding
OMIM	610641
Entrez	64852

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000278279, ENST00000308436, ENST00000463241, ENST00000469480, ENST00000476907, ENST00000478537, ENST00000494385, ENST00000938130

RefSeq mRNA: 2 — MANE Select: NM_022830 NM_001367906, NM_022830

CCDS: CCDS8021

Canonical transcript exons

ENST00000476907 — 9 exons

Exon	Start	End
ENSE00001903063	62575052	62576244
ENSE00001935822	62591404	62591523
ENSE00003535347	62577182	62577291
ENSE00003567115	62578561	62579030
ENSE00003569859	62581106	62581206
ENSE00003594812	62576907	62577017
ENSE00003635097	62581386	62581701
ENSE00003661715	62589031	62589221
ENSE00003673913	62576657	62576749

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 93.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.3538 / max 104.2428, expressed in 1802 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120141	6.8232	1687
120143	2.8217	1526
120142	1.7948	1249
120139	0.4858	173
120140	0.4283	159

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	93.00	silver quality
type B pancreatic cell	CL:0000169	92.70	silver quality
tendon of biceps brachii	UBERON:0008188	92.63	gold quality
tongue squamous epithelium	UBERON:0006919	91.01	silver quality
diaphragm	UBERON:0001103	90.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.71	gold quality
olfactory bulb	UBERON:0002264	90.49	silver quality
buccal mucosa cell	CL:0002336	89.82	silver quality
right lobe of liver	UBERON:0001114	89.81	gold quality
vena cava	UBERON:0004087	89.59	silver quality
right uterine tube	UBERON:0001302	89.36	gold quality
body of pancreas	UBERON:0001150	89.32	gold quality
body of tongue	UBERON:0011876	87.83	silver quality
right lobe of thyroid gland	UBERON:0001119	87.73	gold quality
apex of heart	UBERON:0002098	87.48	gold quality
body of stomach	UBERON:0001161	86.86	gold quality
granulocyte	CL:0000094	86.78	gold quality
cardia of stomach	UBERON:0001162	86.73	silver quality
left lobe of thyroid gland	UBERON:0001120	86.44	gold quality
liver	UBERON:0002107	86.19	gold quality
gastrocnemius	UBERON:0001388	86.09	gold quality
pancreas	UBERON:0001264	85.95	gold quality
spleen	UBERON:0002106	85.91	gold quality
thyroid gland	UBERON:0002046	85.84	gold quality
hair follicle	UBERON:0002073	85.84	gold quality
tongue	UBERON:0001723	85.82	silver quality
pericardium	UBERON:0002407	85.34	silver quality
pylorus	UBERON:0001166	85.27	silver quality
upper arm skin	UBERON:0004263	85.25	silver quality
skin of leg	UBERON:0001511	85.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.59

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 16)

• PIPKIalpha co-localizes at nuclear speckles and interacts with a newly identified non-canonical poly(A) polymerase, Star-PAP; the activity of Star-PAP can be specifically regulated by PtdIns4,5P2 (PMID:18288197)
• These data indicate that CKIalpha, PIPKIalpha, and Star-PAP function together to modulate the production of specific Star-PAP messages. (PMID:18305108)
• The data support a model where Star-PAP binds to the pre-mRNA, recruits the CPSF complex to the 3’-end of pre-mRNA and then defines cleavage by CPSF 73 and subsequent polyadenylation of its target mRNAs. (PMID:21102410)
• PIPKIalpha, PI4,5P(2), and PKCdelta regulate Star-PAP control of BIK expression and induction of apoptosis. (PMID:22244330)
• Star-PAP and its regulatory molecules form a signaling nexus at the 3’-end of target mRNAs to control the expression of select group of genes including the ones involved in stress responses. (Review) (PMID:23306079)
• Star-PAP controls E6 mRNA polyadenylation and expression and modulates wild-type p53 levels. (PMID:23416977)
• The human TUT1 nucleotidyl transferase is a global regulator of microRNA abundance. (PMID:23874977)
• Nucleotidyl transferase TUT1 inhibits lipogenesis in osteosarcoma cells through regulation of microRNA-24 and microRNA-29a. (PMID:25142229)
• Star-PAP recognises a unique nucleotide motif on its target mRNA.CstF-64 and 3’-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding poly A polymerase. (PMID:26496945)
• Star-PAP possesses tumor-suppressing activity. (PMID:28151486)
• Crystallographic and biochemical studies of TUT1 revealed the molecular mechanism underlying the specific oligo-uridylylation of the 3’-end of U6 snRNA by TUT1. (PMID:28589955)
• Star-PAP-specific polyadenylation sites usage regulates the expression of the eukaryotic translation initiation factor EIF4A1, the tumor suppressor gene PTEN and the long non-coding RNA NEAT1. (PMID:28911096)
• KLHL7 is a novel regulator of the nucleolus associated with TUT1 ubiquitination, and pathogenic KLHL7 mutants may provide valuable information to elucidate a mechanism of retinitis pigmentosa etiology. (PMID:29032201)
• Star-PAP RNA Binding Landscape Reveals Novel Role of Star-PAP in mRNA Metabolism That Requires RBM10-RNA Association. (PMID:34576144)
• Mechanism of U6 snRNA oligouridylation by human TUT1. (PMID:37563152)
• Star-PAP controls oncogene expression through primary miRNA 3’-end formation to regulate cellular proliferation and tumour formation. (PMID:38364942)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	tut1	ENSDARG00000057321
mus_musculus	Tut1	ENSMUSG00000071645
rattus_norvegicus	Eef1g	ENSRNOG00000020075
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): TUT7 (ENSG00000083223), MTPAP (ENSG00000107951), TUT4 (ENSG00000134744), TENT2 (ENSG00000164329)

Protein

Protein identifiers

Speckle targeted PIP5K1A-regulated poly(A) polymerase — Q9H6E5 (reviewed: Q9H6E5)

Alternative names: RNA-binding motif protein 21, U6 snRNA-specific terminal uridylyltransferase 1

All UniProt accessions (6): Q9H6E5, A0A0A8K9B1, C9JBX0, F5H0R1, F8WA97, J3KN81

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Associates with the cleavage and polyadenylation specificity factor (CPSF) complex. Interacts with CPSF1 and CPSF3; the interaction is direct. Interacts with PIP5K1A.

Subcellular location. Nucleus. Nucleolus. Nucleus speckle.

Tissue specificity. Widely expressed.

Post-translational modifications. Phosphorylated by CK1 in the proline-rich (Pro-rich) region.

Activity regulation. Adenylyltransferase activity is specifically phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2).

Cofactor. Binds 1 divalent cation per subunit.

Domain organisation. The zinc-finger domain is required for terminal uridylyltransferase activity. Together with the RRM domain, binds the 5’-area of U6 snRNA. The RRM domain is required for terminal uridylyltransferase activity. Together with the zinc-finger domain, binds the 5’-area of U6 snRNA. The proline-rich region is dispensable for terminal uridylyltransferase activity.

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

RefSeq proteins (2): NP_001354835, NP_073741* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR002058	PAP_assoc	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR013087	Znf_C2H2_type	Domain
IPR034388	Star-PAP_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR043519	NT_sf	Homologous_superfamily
IPR054708	MTPAP-like_central	Domain

Pfam: PF00076, PF03828, PF12874, PF22600

Enzyme classification (BRENDA):

• EC 2.7.7.19 — polynucleotide adenylyltransferase (BRENDA: 35 organisms, 181 substrates, 125 inhibitors, 114 Km, 53 kcat entries)

Substrate kinetics (BRENDA)

19 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.028–2.191	54
RNA (A)15	0.51–24.99	23
CTP	0.1036–4.7	7
(A)N	0.0468–0.711	5
OLIGO(A)14	0.0005–0.037	5
(A)15	0.0009–0.0053	3
GTP	0.055–0.062	2
OLIGO(A)18	0.0468–0.0642	2
OLIGO(A)N	0.01–0.3	2
2-AMINOPURINE RIBOSIDE TRIPHOSPHATE	0.0197	1
DATP	0.06	1
OLIGO(A)12	0.0004	1
OLIGO(A)17C	0.0263	1
OLIGOADENYLATE	0.2	1
POLY(A)N	0.0036	1

Catalyzed reactions (Rhea), 2 shown:

• RNA(n) + ATP = RNA(n)-3’-adenine ribonucleotide + diphosphate (RHEA:11332)
• RNA(n) + UTP = RNA(n)-3’-uridine ribonucleotide + diphosphate (RHEA:14785)

UniProt features (92 total): strand 30, helix 25, binding site 10, turn 8, region of interest 5, mutagenesis site 4, domain 2, compositionally biased region 2, sequence conflict 2, chain 1, modified residue 1, sequence variant 1, zinc finger region 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
5WU3	X-RAY DIFFRACTION	2.7
5WU1	X-RAY DIFFRACTION	2.8
5WU4	X-RAY DIFFRACTION	2.8
5WU2	X-RAY DIFFRACTION	2.95
5WU6	X-RAY DIFFRACTION	3.21
9J8P	ELECTRON MICROSCOPY	3.21
5WU5	X-RAY DIFFRACTION	3.4
8IDF	X-RAY DIFFRACTION	3.7
2E5G	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H6E5-F1	76.10	0.53

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 (10): 205; 216; 216; 218; 218; 392; 392; 414; 432; 549

Post-translational modifications (1): 750

Mutagenesis-validated functional residues (4):

Position	Phenotype
216	abolishes adenylyltransferase activity; when associated with a-218.
218	abolishes adenylyltransferase activity; when associated with a-216.
779	reduced terminal uridylyltransferase activity; when associated with a-783.
783	reduced terminal uridylyltransferase activity; when associated with a-779.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9770562	mRNA Polyadenylation

MSigDB gene sets: 179 (showing top): CREL_01, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, NKX61_01, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_MRNA_3_END_PROCESSING, GCM_DDX11, GOBP_HISTONE_MRNA_METABOLIC_PROCESS, GOBP_HISTONE_MRNA_CATABOLIC_PROCESS, GCM_NF2, ACEVEDO_LIVER_CANCER_UP, GOBP_SNRNA_PROCESSING, HOXA4_Q2, REACTOME_METABOLISM_OF_RNA, ZHONG_SECRETOME_OF_LUNG_CANCER_AND_MACROPHAGE

GO Biological Process (7): snRNA processing (GO:0016180), RNA 3’-end processing (GO:0031123), mRNA 3’-end processing (GO:0031124), U6 snRNA 3’-end processing (GO:0034477), regulation of RNA metabolic process (GO:0051252), co-transcriptional mRNA 3’-end processing, cleavage and polyadenylation pathway (GO:0180010), mRNA processing (GO:0006397)

GO Molecular Function (15): RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), ATP binding (GO:0005524), zinc ion binding (GO:0008270), U6 snRNA binding (GO:0017070), enzyme binding (GO:0019899), RNA uridylyltransferase activity (GO:0050265), enzyme-substrate adaptor activity (GO:0140767), poly(A) RNA polymerase activity (GO:1990817), nucleotide binding (GO:0000166), 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 (6): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), mRNA cleavage and polyadenylation specificity factor complex (GO:0005847), nuclear speck (GO:0016607), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
mRNA 3’-end processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	3
binding	2
nuclear lumen	2
cellular anatomical structure	2
snRNA metabolic process	1
mRNA processing	1
RNA 3’-end processing	1
snRNA 3’-end processing	1
RNA metabolic process	1
regulation of nucleobase-containing compound metabolic process	1
regulation of macromolecule metabolic process	1
mRNA 3’-end processing	1
co-transcriptional RNA 3’-end processing, cleavage and polyadenylation pathway	1
mRNA metabolic process	1
nucleic acid binding	1
mRNA binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
snRNA binding	1
protein binding	1
uridylyltransferase activity	1
catalytic activity, acting on RNA	1
protein-macromolecule adaptor activity	1
adenylyltransferase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
cation binding	1
intracellular membraneless organelle	1
cytoplasm	1
mRNA cleavage factor complex	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1342 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TUT1	PAPOLA	P51003	951
TUT1	PAPOLG	Q9BWT3	937
TUT1	PAPOLB	Q9NRJ5	913
TUT1	LIN28A	Q9H9Z2	865
TUT1	PIP4K2A	P48426	822
TUT1	DIS3L2	Q8IYB7	763
TUT1	TENT4B	Q8NDF8	741
TUT1	HMOX1	P09601	700
TUT1	LIN28B	Q6ZN17	691
TUT1	XRN2	Q9H0D6	653
TUT1	TUT4	Q5TAX3	623
TUT1	PIP5K1A	Q99755	595
TUT1	USB1	Q9BQ65	593
TUT1	PI4K2A	Q9BTU6	586
TUT1	DICER1	Q9UPY3	566

IntAct

100 interactions, top by confidence:

A	B	Type	Score
LSM3	LSM1	psi-mi:“MI:0914”(association)	0.950
PRPF4	PPIH	psi-mi:“MI:0914”(association)	0.910
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
MED17	MED19	psi-mi:“MI:0914”(association)	0.840
LSM6	LSM1	psi-mi:“MI:0914”(association)	0.840
SART3	PRPF3	psi-mi:“MI:0914”(association)	0.790
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
SART3	PRPF4	psi-mi:“MI:0914”(association)	0.730
PRPF3	PRPF4	psi-mi:“MI:0914”(association)	0.730
YTHDF1	YTHDF3	psi-mi:“MI:0914”(association)	0.720
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
YWHAZ	HSPB1	psi-mi:“MI:0914”(association)	0.680
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670
LSM5	LSM1	psi-mi:“MI:0914”(association)	0.640
PRPF31	PRPF4	psi-mi:“MI:0914”(association)	0.640
SNRPB	SART1	psi-mi:“MI:0914”(association)	0.640
TUT1	PIP5K1A	psi-mi:“MI:0915”(physical association)	0.560
TUT1	PIP5K1A	psi-mi:“MI:0914”(association)	0.560
KATNBL1	TUT1	psi-mi:“MI:0915”(physical association)	0.560
TUT1	PIP5K1A	psi-mi:“MI:0915”(physical association)	0.530

BioGRID (86): TUT1 (Affinity Capture-MS), TUT1 (Two-hybrid), TUT1 (Affinity Capture-MS), TUT1 (Affinity Capture-MS), TUT1 (Affinity Capture-MS), TUT1 (Affinity Capture-MS), TUT1 (Affinity Capture-MS), TUT1 (Affinity Capture-MS), TUT1 (Affinity Capture-MS), TUT1 (Affinity Capture-MS), TUT1 (Affinity Capture-MS), TUT1 (Affinity Capture-MS), TUT1 (Affinity Capture-MS), TUT1 (Affinity Capture-MS), TUT1 (Affinity Capture-MS)

ESM2 similar proteins: A0A061IR73, A0A1B0GUU1, A6H687, A8MYJ7, B1WC39, D3ZVB0, E1BD59, G3MY25, G3MZC5, O75064, P07199, P27790, P29597, P48988, P52333, P52824, Q08DF2, Q0VCE3, Q13608, Q1JPD6, Q2VPB7, Q3TAP4, Q3U1Y4, Q3ZBE0, Q499M4, Q53EQ6, Q5JZY3, Q62137, Q63272, Q6B0B8, Q6DI92, Q6ZPS2, Q6ZS72, Q7TM95, Q80VI1, Q86UT6, Q8BYG9, Q8N9M5, Q8R5G7, Q8TE96

Diamond homologs: A9JTS5, D2HS90, O13833, Q1JPD6, Q3MHT4, Q4KMD7, Q641A1, Q8R3F9, Q9D0D3, Q9H6E5, Q9NVV4, Q9UT49, B2RX14, O17087, O64642, Q0VFA3, Q2HJ44, Q503I9, Q5BLK4, Q5TAX3, Q5U315, Q5VYS8, Q6DFA8, Q6PIY7, Q91YI6, Q9VD44, O13798, O74326, Q9VYS4, Q5XET5, O46102, P07909, P51989, P51990, Q96EP5, Q98SJ2, Q9JII5, Q8WQX5, Q8WQX6, Q7KVS9

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
KLHL7	“down-regulates quantity by destabilization”	TUT1	binding
“Cullin 3-RBX1-Skp1”	“down-regulates quantity by destabilization”	TUT1	polyubiquitination
TUT1	up-regulates	mRNA_polyadenylation
CSNK1A1	“up-regulates activity”	TUT1	phosphorylation
CHKA	“up-regulates activity”	TUT1	phosphorylation
PRKCD	“up-regulates activity”	TUT1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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
mRNA decay by 5’ to 3’ exoribonuclease	6	78.8×	2e-09
Metabolism of non-coding RNA	7	76.6×	8e-11
Processing of Intronless Pre-mRNAs	5	49.2×	7e-07
RNA Polymerase II Transcription Termination	11	41.6×	8e-14
SARS-CoV-2 modulates host translation machinery	8	30.9×	4e-09
snRNP Assembly	8	29.2×	6e-09
mRNA Splicing	15	28.4×	2e-16
mRNA Splicing - Minor Pathway	7	27.0×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	11	87.6×	3e-17
U2-type prespliceosome assembly	6	51.3×	1e-07
RNA splicing, via transesterification reactions	5	42.8×	6e-06
mRNA splicing, via spliceosome	22	27.6×	1e-23
RNA splicing	16	19.3×	1e-14
mRNA processing	9	9.7×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	145
Likely benign	11
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
402172	NM_022830.3(TUT1):c.1297G>A (p.Ala433Thr)	Likely pathogenic

SpliceAI

1465 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62575071:ATTGC:A	donor_gain	1.0000
11:62576607:A:AC	donor_gain	1.0000
11:62576608:C:CC	donor_gain	1.0000
11:62576655:A:AC	donor_gain	1.0000
11:62576656:C:CC	donor_gain	1.0000
11:62576747:CTC:C	acceptor_gain	1.0000
11:62577287:CCAGC:C	acceptor_gain	1.0000
11:62577288:CAGCC:C	acceptor_gain	1.0000
11:62578775:C:A	donor_gain	1.0000
11:62581215:C:CT	acceptor_gain	1.0000
11:62581216:G:T	acceptor_gain	1.0000
11:62581219:C:CT	acceptor_gain	1.0000
11:62581220:A:T	acceptor_gain	1.0000
11:62581382:TTA:T	donor_loss	1.0000
11:62581383:TAC:T	donor_loss	1.0000
11:62581384:A:AC	donor_gain	1.0000
11:62581384:A:T	donor_loss	1.0000
11:62581384:ACCAG:A	donor_loss	1.0000
11:62581385:C:CC	donor_gain	1.0000
11:62581385:C:CG	donor_loss	1.0000
11:62581385:CCA:C	donor_gain	1.0000
11:62589026:TTTA:T	donor_loss	1.0000
11:62589027:TTA:T	donor_loss	1.0000
11:62589028:TAC:T	donor_loss	1.0000
11:62589029:A:AG	donor_loss	1.0000
11:62589029:A:AT	donor_loss	1.0000
11:62589030:C:CA	donor_loss	1.0000
11:62591398:GCTTA:G	donor_loss	1.0000
11:62591400:TTACG:T	donor_loss	1.0000
11:62591402:A:AC	donor_gain	1.0000

AlphaMissense

5568 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62589125:A:T	V60D	0.999
11:62578615:A:T	V369D	0.998
11:62581693:A:C	F94L	0.998
11:62581693:A:T	F94L	0.998
11:62581695:A:G	F94L	0.998
11:62578609:A:G	F371S	0.997
11:62581607:A:T	V123D	0.997
11:62581691:G:T	A95D	0.997
11:62575396:A:G	W775R	0.996
11:62575396:A:T	W775R	0.996
11:62576069:A:C	N550K	0.996
11:62576069:A:T	N550K	0.996
11:62578608:G:C	F371L	0.996
11:62578608:G:T	F371L	0.996
11:62578610:A:G	F371L	0.996
11:62589127:A:C	F59L	0.996
11:62589127:A:T	F59L	0.996
11:62589129:A:G	F59L	0.996
11:62577206:A:G	W416R	0.994
11:62577206:A:T	W416R	0.994
11:62576963:A:G	L442P	0.993
11:62577268:A:G	F395S	0.993
11:62578576:A:T	V382D	0.993
11:62581688:A:T	I96N	0.993
11:62575394:C:A	W775C	0.992
11:62575394:C:G	W775C	0.992
11:62575999:A:G	C574R	0.992
11:62576031:A:G	L563P	0.992
11:62576965:A:C	F441L	0.992
11:62576965:A:T	F441L	0.992

dbSNP variants (sampled 300 via entrez): RS1000018459 (11:62575950 C>T), RS1000435982 (11:62588095 G>C), RS1000851743 (11:62584130 T>A,C), RS1000929517 (11:62579391 G>C), RS1001134790 (11:62577201 A>G), RS1001249054 (11:62576264 G>A,C,T), RS1001480939 (11:62577557 C>G), RS1001733560 (11:62583020 A>T), RS1001844123 (11:62591672 G>A,T), RS1002219539 (11:62585005 G>A), RS1002300117 (11:62577735 T>C), RS1002553315 (11:62583376 T>C), RS1002563234 (11:62590387 G>A,C), RS1002652621 (11:62577976 G>A,T), RS1002682481 (11:62584891 G>A)

Disease associations

OMIM: gene MIM:610641 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST003262_568	Post bronchodilator FEV1	3.000000e-06
GCST003262_569	Post bronchodilator FEV1	2.000000e-06
GCST003262_632	Post bronchodilator FEV1	1.000000e-06
GCST003264_948	Post bronchodilator FEV1/FVC ratio	5.000000e-06
GCST005956_12	Waist-to-hip ratio adjusted for BMI	2.000000e-06
GCST005956_2	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST005962_37	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	5.000000e-07
GCST005962_51	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-07
GCST010145_9	Cerebrospinal fluid immune biomarker levels	5.000000e-08
GCST90020024_381	A body shape index	2.000000e-10
GCST90020029_313	Waist circumference adjusted for body mass index	1.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol A	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Diazinon	increases methylation	1
Valproic Acid	increases methylation	1
Zinc	affects cotreatment, increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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