TOB1

Summary

TOB1 (transducer of ERBB2, 1, HGNC:11979) is a protein-coding gene on chromosome 17q21.33, encoding Protein Tob1 (P50616). Anti-proliferative protein; the function is mediated by association with deadenylase subunits of the CCR4-NOT complex.

This gene encodes a member of the transducer of erbB-2 /B-cell translocation gene protein family. Members of this family are anti-proliferative factors that have the potential to regulate cell growth. The encoded protein may function as a tumor suppressor. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 10140 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_005749

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11979
Approved symbol	TOB1
Name	transducer of ERBB2, 1
Location	17q21.33
Locus type	gene with protein product
Status	Approved
Aliases	TOB, TROB, APRO5
Ensembl gene	ENSG00000141232
Ensembl biotype	protein_coding
OMIM	605523
Entrez	10140

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000268957, ENST00000499247, ENST00000509385, ENST00000851192, ENST00000851193, ENST00000851194, ENST00000851195, ENST00000932427, ENST00000947299

RefSeq mRNA: 3 — MANE Select: NM_005749 NM_001243877, NM_001243885, NM_005749

CCDS: CCDS11576

Canonical transcript exons

ENST00000499247 — 2 exons

Exon	Start	End
ENSE00001962440	50862223	50864163
ENSE00002049853	50866058	50866354

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 99.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.7663 / max 1224.8194, expressed in 1818 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167001	51.7432	1816
167000	8.0232	1468

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	99.59	gold quality
germinal epithelium of ovary	UBERON:0001304	99.17	gold quality
upper leg skin	UBERON:0004262	99.17	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.14	gold quality
seminal vesicle	UBERON:0000998	99.11	gold quality
choroid plexus epithelium	UBERON:0003911	99.03	gold quality
trachea	UBERON:0003126	98.93	gold quality
biceps brachii	UBERON:0001507	98.92	gold quality
vastus lateralis	UBERON:0001379	98.91	gold quality
cardia of stomach	UBERON:0001162	98.90	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.85	gold quality
quadriceps femoris	UBERON:0001377	98.73	gold quality
cauda epididymis	UBERON:0004360	98.68	gold quality
penis	UBERON:0000989	98.66	gold quality
amniotic fluid	UBERON:0000173	98.62	gold quality
urethra	UBERON:0000057	98.61	gold quality
triceps brachii	UBERON:0001509	98.58	gold quality
blood vessel layer	UBERON:0004797	98.36	gold quality
jejunum	UBERON:0002115	98.34	gold quality
bronchial epithelial cell	CL:0002328	98.27	gold quality
body of tongue	UBERON:0011876	98.26	gold quality
skeletal muscle tissue	UBERON:0001134	98.10	gold quality
skin of hip	UBERON:0001554	98.10	gold quality
jejunal mucosa	UBERON:0000399	98.04	gold quality
palpebral conjunctiva	UBERON:0001812	98.02	gold quality
superficial temporal artery	UBERON:0001614	97.91	gold quality
pharyngeal mucosa	UBERON:0000355	97.89	gold quality
cervix squamous epithelium	UBERON:0006922	97.84	gold quality
caput epididymis	UBERON:0004358	97.83	gold quality
gluteal muscle	UBERON:0002000	97.81	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-GEOD-111727	yes	10075.43
E-GEOD-89232	yes	2626.12
E-MTAB-7051	yes	2049.08
E-HCAD-4	yes	34.67
E-MTAB-10287	yes	32.01
E-CURD-114	yes	27.15
E-GEOD-135922	yes	23.42
E-HCAD-10	yes	18.74
E-GEOD-81608	yes	16.17
E-MTAB-9801	yes	4.31
E-MTAB-6379	no	5406.95
E-CURD-97	no	5057.65
E-MTAB-6058	no	1401.53
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
IL2	Repression

Upstream regulators (CollecTRI, top): GLI2, NANOG, RORC

miRNA regulators (miRDB)

150 targeting TOB1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-371A-3P	99.99	66.77	91
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960

Literature-anchored findings (GeneRIF, showing 40)

• functions as lateral signal transmitter (PMID:11904957)
• Antiproliferative proteins of the BTG/Tob family are degraded by the ubiquitin-proteasome system. the C-terminal regions are necessary and sufficient to control the stabilities of BTG1, BTG2, Tob, and Tob2 proteins. (PMID:12135500)
• identified as a MAPK substrate (PMID:12151396)
• Decreased expression or phosphorylation status of tob protein is associated with lung cancer (PMID:14643028)
• N-terminal region of TOB is a functional nuclear export signal. (PMID:15051490)
• Tob is involved in the translational suppression of IL-2 mRNA in anergic T cells through its interaction with iPABP. (PMID:15676026)
• Tob1 is a novel target for degradation by the SCF-Skp2 ubiquitin ligase in a cell line. (PMID:16951159)
• Reverse-transcription polymerase chain reaction confirmed increased expression of GADD45A, BTG2, PDE4B, and CEBPD and downregulation of TOB1 in skeletal muscle intradialysis. (PMID:16997058)
• Subtractive hybridization identified Twisted gastrulation (Tsg) as one of the genes suppressed by Tob. (PMID:17164348)
• Data show that TOB enhances mRNA deadenylation in vivo, and that interaction with PABPC1 is necessary for TOB’s deadenylation-enhancing effect. (PMID:17785442)
• antiproliferative region of human Tob (residues 1-138) and intact hCaf1 were co-expressed in Escherichia coli, purified and successfully cocrystallized (PMID:18084094)
• Tob associates with the CCR4-NOT complex. (PMID:18377426)
• positive correlation of TOB1 phosphorylation status with proliferation marker Ki67 suggests that elevated TOB1 phosphorylation might abrogate the antiproliferative effect of TOB1 in breast cancer (PMID:19491269)
• Down-regulation of TOB is associated with breast cancer tumorigenesis. (PMID:19569230)
• Tob interactions with Caf1 and a C-terminal domain of PABPC1 (PMID:20595394)
• Together, these results indicate that Tob mediates the recruitment of Caf1 to the target of CPEB3 and elicits deadenylation and decay of the mRNA. (PMID:21336257)
• Silencing of HIC1 and TOB1 expression is a common occurrence in gastric cancer and may contribute to the development and progression of the disease. (PMID:21533545)
• Longer survival was associated with hypomethylation at specific CpG sites (e.g. GREB1, TGIF and TOB1) and hypermethylation in other genes (e.g. TMCO5, PTPRN and GUCY2C). (PMID:21577013)
• TOB1 overexpression not only increased the expression of the phosphatase and tensin homolog (PTEN), an important tumor suppressor, but also regulated the downstream effectors in the PI3K/PTEN signaling pathway, including Akt, ERK1/2, etc. (PMID:22158108)
• The antiproliferative and the mRNA deadenylation/decay-promoting effects of TOB1 and TOB2 proteins are linked. (PMID:22252318)
• study demonstrates that the overexpression of Tob1 inhibits gastric cancer progression by activating Smad4- and inhibiting betacatenin-mediated signaling pathways (PMID:22710759)
• Cdc7 phosphorylates and interacts with Tob to inhibit the Cul4-DDB1(Cdt2)-dependent Tob degradation. (PMID:23066029)
• Tob is a key factor in the regulation of c-myc gene expression, which is essential for cell growth. (PMID:23178487)
• TOB1 modulates the radiosensitivity of lung cancer cells via the MAPK/ERK signaling pathway. (PMID:23589165)
• TOB1 demonstrated a radioprotective function in the immortalized normal human bronchial epithelial cell line. (PMID:23756562)
• miR-25 promotes GC progression by directly downregulating TOB1 expression, and may be a noninvasive biomarker for the prognosis of GC patients. (PMID:25043310)
• arsenite-induced oxidative stress inhibits deadenylation of mRNA primarily through downregulation of Tob and Pan3, both of which mediate the recruitment of deadenylases to mRNA (PMID:25446091)
• Reduced TOB1 expression in gastric adenocarcinoma is associated with the extent of differentiation and the TNM stage of gastric cancer. (PMID:25760308)
• A novel role for TOB1 in mediating survival of estrogen-independent breast cancers. (PMID:26165839)
• The dual-luciferase reporter assay also confirmed that miR-25 harbored the A allele which caused an incapacitation of binding at the TOB1. In conclusion, rs41274221 in miR-25 was a subgroup which may protect the patients from further growth and metastasis of gastric cancer and might serve as a novel biomarker for the disease (PMID:26572149)
• MiR-590 targets Tob1 that is significantly decreased in patients with multiple sclerosis. (PMID:28947212)
• Our findings provide important insights into a previously unrecognized oncogenic role of Tob1 in colon cancer and suggest that Tob1 is an adverse prognostic factor and therapeutic target for colon cancer. (PMID:30447686)
• TOB1 was found to be directly targeted by miR-371a-3p, in which TOB1 was down-regulated by miR-371a-3p in gastric cancer (GC). Most importantly, results showed that TOB1 plays a tumor-suppressive role in GC cells, and it is required for the miR-371a-3p’s oncogenic activities in GC cells. (PMID:30529155)
• The downregulation of DAL-1 and TOB1 expression is associated with shorter survival of gastric cancer patients and may be considered potential novel markers for predicting the outcomes of patients with gastric cancer (PMID:30962003)
• TOB1 suppresses proliferation in K-Ras wild-type pancreatic cancer. (PMID:31891232)
• LncRNA WEE2-AS1 promotes proliferation and inhibits apoptosis in triple negative breast cancer cells via regulating miR-32-5p/TOB1 axis. (PMID:32307083)
• Identification of miR253p as a tumor biomarker: Regulation of cellular functions via TOB1 in breast cancer. (PMID:33786619)
• Involvement of TOB1 on autophagy in gastric cancer AGS cells via decreasing the activation of AKT/mTOR signaling pathway. (PMID:35186488)
• Methylation Mediated Downregulation of TOB1-AS1 and TOB1 Correlates with Malignant Progression and Poor Prognosis of Esophageal Squamous Cell Carcinoma. (PMID:36002674)
• TOB1 modulates neutrophil phenotypes to influence gastric cancer progression and immunotherapy efficacy. (PMID:38617839)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	tob1b	ENSDARG00000021372
danio_rerio	tob1a	ENSDARG00000032619
mus_musculus	Tob1	ENSMUSG00000037573
rattus_norvegicus	Tob1	ENSRNOG00000002828
drosophila_melanogaster	Tob	FBGN0028397
caenorhabditis_elegans	fog-3	WBGENE00001483
caenorhabditis_elegans	T09B4.6	WBGENE00020380

Paralogs (1): TOB2 (ENSG00000183864)

Protein

Protein identifiers

Protein Tob1 — P50616 (reviewed: P50616)

Alternative names: Transducer of erbB-2 1

All UniProt accessions (1): P50616

UniProt curated annotations — full annotation on UniProt →

Function. Anti-proliferative protein; the function is mediated by association with deadenylase subunits of the CCR4-NOT complex. Mediates CPEB3-accelerated mRNA deadenylation by binding to CPEB3 and recruiting CNOT7 which leads to target mRNA deadenylation and decay.

Subunit / interactions. Interacts with ERBB2. Interacts with CNOT7. Interacts with CPEB3 (via C-terminal RNA-binding region); recruits CNOT7 to CPEB3 to form a ternary complex required for mRNA deadenylation and decay. Interacts with CNOT8. Interacts with CPEB4.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated on Ser and Thr residues.

Similarity. Belongs to the BTG family.

RefSeq proteins (3): NP_001230806, NP_001230814, NP_005740* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002087	Anti_prolifrtn	Domain
IPR015676	Tob1/2	Family
IPR036054	BTG-like_sf	Homologous_superfamily

Pfam: PF07742

UniProt features (29 total): mutagenesis site 5, helix 5, region of interest 4, strand 4, turn 3, compositionally biased region 3, short sequence motif 2, chain 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2Z15	X-RAY DIFFRACTION	2.3
5CI9	X-RAY DIFFRACTION	2.3
5CI8	X-RAY DIFFRACTION	2.33
2D5R	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50616-F1	67.03	0.35

Functional residue map

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

Post-translational modifications (1): 204

Mutagenesis-validated functional residues (5):

Position	Phenotype
45	impairs interaction with cnot7 and cnot8.
55	impairs interaction with cnot7 and cnot8.
65	impairs interaction with cnot7 and cnot8.
93	impairs interaction with cnot7 and cnot8.
95	impairs interaction with cnot7 and cnot8.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 522 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, FREAC2_01, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, HNF3ALPHA_Q6, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, ENK_UV_RESPONSE_KERATINOCYTE_UP, SHEPARD_CRASH_AND_BURN_MUTANT_UP, SP3_Q3, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GCAAGGA_MIR502, GOBP_OSTEOBLAST_DIFFERENTIATION

GO Biological Process (10): negative regulation of cell population proliferation (GO:0008285), regulation of gene expression (GO:0010468), negative regulation of translation (GO:0017148), negative regulation of BMP signaling pathway (GO:0030514), negative regulation of osteoblast differentiation (GO:0045668), negative regulation of nuclear-transcribed mRNA poly(A) tail shortening (GO:0060212), positive regulation of nuclear-transcribed mRNA poly(A) tail shortening (GO:0060213), regulation of SMAD protein signal transduction (GO:0060390), positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:1900153), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (4): transcription corepressor activity (GO:0003714), receptor tyrosine kinase binding (GO:0030971), SMAD binding (GO:0046332), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), CCR4-NOT complex (GO:0030014)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear-transcribed mRNA poly(A) tail shortening	2
regulation of nuclear-transcribed mRNA poly(A) tail shortening	2
positive regulation of mRNA catabolic process	2
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
osteoblast differentiation	1
negative regulation of cell differentiation	1
regulation of osteoblast differentiation	1
negative regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
SMAD protein signal transduction	1
regulation of intracellular signal transduction	1
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
signaling receptor binding	1
protein tyrosine kinase binding	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular protein-containing complex	1

Protein interactions and networks

STRING

592 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOB1	ERBB2	P04626	853
TOB1	CNOT7	Q9UIV1	735
TOB1	CNOT8	Q9UFF9	676
TOB1	PABPC1	P11940	668
TOB1	FZD2	Q14332	668
TOB1	SMAD4	Q13485	665
TOB1	EIF3A	Q14152	590
TOB1	TBX2	Q13207	543
TOB1	CPEB3	Q8NE35	514
TOB1	MAPK1	P28482	485
TOB1	PABPC4	Q13310	483
TOB1	BTBD2	Q9BX70	482
TOB1	SMAD2	Q15796	446
TOB1	SMAD3	P84022	436
TOB1	CPEB4	Q17RY0	428

IntAct

73 interactions, top by confidence:

A	B	Type	Score
CNOT7	TOB1	psi-mi:“MI:0914”(association)	0.930
TOB1	CNOT7	psi-mi:“MI:0915”(physical association)	0.930
CNOT7	TOB1	psi-mi:“MI:0915”(physical association)	0.930
CNOT7	TOB1	psi-mi:“MI:0407”(direct interaction)	0.930
TOB1	CNOT7	psi-mi:“MI:0407”(direct interaction)	0.930
CNOT7	CNOT1	psi-mi:“MI:0914”(association)	0.880
CNOT3	TOB1	psi-mi:“MI:0914”(association)	0.710
CNOT6L	TOB1	psi-mi:“MI:0914”(association)	0.710
TOB1	CNOT1	psi-mi:“MI:0914”(association)	0.710
CNOT3	TOB1	psi-mi:“MI:0915”(physical association)	0.710
TOB1	CNOT6L	psi-mi:“MI:0915”(physical association)	0.710
TOB1	CNOT1	psi-mi:“MI:0915”(physical association)	0.710
TOB1	TARDBP	psi-mi:“MI:0914”(association)	0.670
TOB1	TARDBP	psi-mi:“MI:0915”(physical association)	0.670
CPEB3	TOB1	psi-mi:“MI:0914”(association)	0.650
CPEB3	TOB1	psi-mi:“MI:0915”(physical association)	0.650
TOB1	CPEB3	psi-mi:“MI:0915”(physical association)	0.650
TOB1	CPEB3	psi-mi:“MI:0407”(direct interaction)	0.650

BioGRID (83): TOB1 (Affinity Capture-Western), CORO7 (Two-hybrid), TOB1 (Biochemical Activity), TOB1 (Affinity Capture-RNA), TOB1 (Affinity Capture-MS), TOB1 (Affinity Capture-MS), CNOT6 (Affinity Capture-MS), CNOT6L (Affinity Capture-MS), CNOT2 (Affinity Capture-MS), TNKS1BP1 (Affinity Capture-MS), TOB1 (Affinity Capture-MS), CNOT3 (Affinity Capture-MS), RQCD1 (Affinity Capture-MS), CNOT11 (Affinity Capture-MS), CNOT8 (Affinity Capture-MS)

ESM2 similar proteins: A3LTE2, A3LZ57, A4R227, A5DBE7, A6ZL53, A6ZVF4, B0XXN8, B0XYE0, B3LN45, C7GUK6, D3UEK1, G4NDR3, G5EEG1, G5EGU9, O13858, O61708, P20134, P34758, P36041, P38266, P39523, P40473, P46582, P50616, P53035, Q03063, Q09446, Q09801, Q10108, Q10134, Q10475, Q10655, Q20870, Q4IL82, Q4WX78, Q4WXY0, Q61471, Q6BJD4, Q6BMF7, Q6CK58

Diamond homologs: A4UTQ2, O70552, O88677, P27049, P34743, P40744, P40745, P50615, P50616, P53348, P62324, P62325, P78543, Q04211, Q14106, Q14201, Q54NU5, Q61471, Q63073, Q8R5K6, Q9JM55, Q9NY30

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
Gbeta	down-regulates	TOB1	phosphorylation
ERK1/2	down-regulates	TOB1	phosphorylation
TOB1	“down-regulates activity”	“CCR4-NOT complex”	binding
MAPK1	down-regulates	TOB1	phosphorylation
MAPK3	down-regulates	TOB1	phosphorylation
MAPK9	down-regulates	TOB1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	7	173.0×	1e-13
Deadenylation of mRNA	8	167.3×	3e-15
M-decay: degradation of maternal mRNAs by maternally stored factors	8	124.3×	2e-14
mRNA Polyadenylation	6	25.1×	2e-06
Processing of Capped Intron-Containing Pre-mRNA	5	19.6×	5e-05
mRNA Splicing - Major Pathway	6	15.6×	2e-05
Dengue Virus-Host Interactions	6	13.1×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
nuclear-transcribed mRNA poly(A) tail shortening	7	216.1×	2e-13
regulatory ncRNA-mediated gene silencing	7	181.5×	4e-13
negative regulation of translation	6	45.2×	2e-07
regulation of RNA splicing	5	42.1×	3e-06
mRNA splicing, via spliceosome	7	24.7×	3e-07
mRNA processing	5	15.1×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

362 predictions. Top by Δscore:

Variant	Effect	Δscore
17:50863965:T:TC	acceptor_gain	1.0000
17:50866054:TTA:T	donor_loss	1.0000
17:50866055:TA:T	donor_loss	1.0000
17:50866056:A:AC	donor_gain	1.0000
17:50866056:ACG:A	donor_loss	1.0000
17:50866056:ACGGG:A	donor_gain	1.0000
17:50866057:C:CA	donor_gain	1.0000
17:50866057:CG:C	donor_gain	1.0000
17:50866057:CGG:C	donor_gain	1.0000
17:50866057:CGGG:C	donor_gain	1.0000
17:50866057:CGGGC:C	donor_gain	1.0000
17:50863962:T:C	acceptor_gain	0.9900
17:50863962:T:TC	acceptor_gain	0.9800
17:50864056:C:CT	acceptor_gain	0.9800
17:50864057:A:T	acceptor_gain	0.9800
17:50863967:G:C	acceptor_gain	0.9700
17:50864165:T:C	acceptor_gain	0.9700
17:50865267:T:A	donor_gain	0.9700
17:50866052:A:AC	donor_gain	0.9700
17:50866053:C:CC	donor_gain	0.9700
17:50863967:G:GC	acceptor_gain	0.9600
17:50866050:ATACT:A	donor_loss	0.9300
17:50866051:TACTT:T	donor_loss	0.9300
17:50865894:C:A	donor_gain	0.9200
17:50863961:C:CC	acceptor_gain	0.9100
17:50864053:C:CT	acceptor_gain	0.9100
17:50863965:T:C	acceptor_gain	0.9000
17:50864165:T:TC	acceptor_gain	0.9000
17:50864163:CCT:C	acceptor_gain	0.8900
17:50864053:C:T	acceptor_gain	0.8500

AlphaMissense

2310 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:50863455:C:A	G188V	1.000
17:50863455:C:T	G188D	1.000
17:50863456:C:G	G188R	1.000
17:50863457:G:C	F187L	1.000
17:50863457:G:T	F187L	1.000
17:50863458:A:C	F187C	1.000
17:50863458:A:G	F187S	1.000
17:50863459:A:C	F187V	1.000
17:50863459:A:G	F187L	1.000
17:50863459:A:T	F187I	1.000
17:50863460:C:A	K186N	1.000
17:50863460:C:G	K186N	1.000
17:50863462:T:C	K186E	1.000
17:50863464:G:A	T185I	1.000
17:50863470:G:T	A183D	1.000
17:50863472:A:C	F182L	1.000
17:50863472:A:T	F182L	1.000
17:50863473:A:C	F182C	1.000
17:50863473:A:G	F182S	1.000
17:50863474:A:G	F182L	1.000
17:50863485:G:A	T178I	1.000
17:50863487:A:C	F177L	1.000
17:50863487:A:T	F177L	1.000
17:50863489:A:G	F177L	1.000
17:50863683:A:G	L112P	1.000
17:50863683:A:T	L112H	1.000
17:50863713:T:G	Q102P	1.000
17:50863717:A:C	Y101D	1.000
17:50863720:A:G	S100P	1.000
17:50863722:A:T	V99D	1.000

dbSNP variants (sampled 300 via entrez): RS1000010245 (17:50866349 C>T), RS1000062799 (17:50866419 G>A), RS1000306595 (17:50865808 A>G), RS1001745085 (17:50865176 C>G,T), RS1002183547 (17:50865876 G>A), RS1002300659 (17:50865714 C>A), RS1002642675 (17:50866203 C>A), RS1002930840 (17:50864428 A>G), RS1003303764 (17:50868565 G>T), RS1003356130 (17:50868894 G>A), RS1003701337 (17:50868414 A>G), RS1003903434 (17:50866475 C>T), RS1003954422 (17:50866625 A>G), RS1004161523 (17:50868005 T>G), RS1005579751 (17:50865569 C>T)

Disease associations

OMIM: gene MIM:605523 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression, increases expression	4
Benzo(a)pyrene	increases methylation, increases expression	4
Valproic Acid	affects expression, decreases expression, increases expression	4
Cisplatin	increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Formaldehyde	increases expression	2
Tamoxifen	affects expression, affects cotreatment, decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
arsenite	increases degradation	1
cobaltous chloride	increases expression	1
zinc chromate	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
cupric chloride	decreases expression	1
nickel sulfate	increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
octa-2,4,6-trienoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
torcetrapib	increases expression	1
abrine	decreases expression	1
LG 100815	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2J9	Abcam HeLa TOB1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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