TPT1

Summary

TPT1 (tumor protein, translationally-controlled 1, HGNC:12022) is a protein-coding gene on chromosome 13q14.13, encoding Translationally-controlled tumor protein (P13693). Involved in calcium binding and microtubule stabilization. It is a common-essential gene (DepMap: required in 96.5% of cancer cell lines).

This gene encodes a protein that is a regulator of cellular growth and proliferation. Its mRNA is highly structured and contains an oligopyrimidine tract (5’-TOP) in its 5’ untranslated region that functions to repress its translation under quiescent conditions. The encoded protein is involved in a variety of cellular pathways, including apoptosis, protein synthesis and cell division. It binds to and stabilizes microtubules, and removal of this protein through phosphorylation is required for progression through mitotic and meiotic cell divisions. This gene is known to play a role in carcinogenesis, and is upregulated in some cancer cells. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 7178 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 14 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 96.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_003295

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12022
Approved symbol	TPT1
Name	tumor protein, translationally-controlled 1
Location	13q14.13
Locus type	gene with protein product
Status	Approved
Aliases	TCTP, fortilin
Ensembl gene	ENSG00000133112
Ensembl biotype	protein_coding
OMIM	600763
Entrez	7178

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 21 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000309246, ENST00000379055, ENST00000379056, ENST00000379060, ENST00000442760, ENST00000484604, ENST00000490277, ENST00000527226, ENST00000528619, ENST00000529421, ENST00000530245, ENST00000530705, ENST00000533567, ENST00000616577, ENST00000887578, ENST00000887579, ENST00000887580, ENST00000929562, ENST00000929563, ENST00000929564, ENST00000929565, ENST00000929566, ENST00000929567, ENST00000929568, ENST00000929569, ENST00000929570

RefSeq mRNA: 3 — MANE Select: NM_003295 NM_001286272, NM_001286273, NM_003295

CCDS: CCDS66538, CCDS73566, CCDS9397

Canonical transcript exons

ENST00000530705 — 6 exons

Exon	Start	End
ENSE00001534177	45333471	45337388
ENSE00002153770	45341042	45341183
ENSE00003458609	45340712	45340785
ENSE00003536559	45338660	45338776
ENSE00003594311	45339497	45339602
ENSE00003755227	45339994	45340184

Expression profiles

Bgee: expression breadth ubiquitous, 310 present calls, max score 100.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2089.2180 / max 21981.9717, expressed in 1828 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137091	2068.7365	1828
137090	9.9982	1732
137085	8.3064	1628
137087	0.9807	484
137086	0.9053	582
137088	0.2614	77
137089	0.0295	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
urethra	UBERON:0000057	100.00	gold quality
ileal mucosa	UBERON:0000331	100.00	gold quality
mucosa of urinary bladder	UBERON:0001259	100.00	gold quality
tibialis anterior	UBERON:0001385	100.00	gold quality
skin of hip	UBERON:0001554	100.00	gold quality
vena cava	UBERON:0004087	100.00	gold quality
upper leg skin	UBERON:0004262	100.00	gold quality
body of tongue	UBERON:0011876	100.00	gold quality
epithelial cell of pancreas	CL:0000083	99.99	gold quality
type B pancreatic cell	CL:0000169	99.99	gold quality
colonic mucosa	UBERON:0000317	99.99	gold quality
pharyngeal mucosa	UBERON:0000355	99.99	gold quality
renal medulla	UBERON:0000362	99.99	gold quality
cranial nerve II	UBERON:0000941	99.99	gold quality
pleura	UBERON:0000977	99.99	gold quality
penis	UBERON:0000989	99.99	gold quality
mammalian vulva	UBERON:0000997	99.99	gold quality
diaphragm	UBERON:0001103	99.99	gold quality
cardia of stomach	UBERON:0001162	99.99	gold quality
pylorus	UBERON:0001166	99.99	gold quality
deltoid	UBERON:0001476	99.99	gold quality
superficial temporal artery	UBERON:0001614	99.99	gold quality
trigeminal ganglion	UBERON:0001675	99.99	gold quality
tongue	UBERON:0001723	99.99	gold quality
mammary duct	UBERON:0001765	99.99	gold quality
parotid gland	UBERON:0001831	99.99	gold quality
epithelium of nasopharynx	UBERON:0001951	99.99	gold quality
nipple	UBERON:0002030	99.99	gold quality
parietal pleura	UBERON:0002400	99.99	gold quality
visceral pleura	UBERON:0002401	99.99	gold quality

Single-cell (SCXA)

Detected in 53 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	12770.04
E-MTAB-9543	yes	10573.31
E-GEOD-137537	yes	8406.54
E-HCAD-31	yes	4655.43
E-GEOD-84465	yes	2112.62
E-MTAB-7316	yes	19.49
E-MTAB-10042	yes	17.19
E-HCAD-35	yes	8.77
E-CURD-112	no	22375.12
E-HCAD-15	no	15323.00
E-MTAB-9841	no	15201.21
E-MTAB-10662	no	14847.64
E-CURD-46	no	12539.50
E-GEOD-149689	no	12129.40
E-MTAB-10885	no	11720.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, TP53, VDR

miRNA regulators (miRDB)

122 targeting TPT1, 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-3064-3P	100.00	70.09	1254
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-338-5P	99.92	72.34	2951

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• The mRNA of the translationally controlled tumor protein P23/TCTP is a highly structured RNA, which activates the dsRNA-dependent protein kinase PKR (TCTP PROTEIN) (PMID:11991642)
• Physical and functional interaction between myeloid cell leukemia 1 protein (MCL1) and this protein (PMID:12149273)
• Human TCTP was identified as a putative Plk-interacting clone by a two-hybrid screen. Plk phosphorylates TCTP on two serine residues in vitro and cofractionates with the majority of kinase activity toward TCTP in mitotic cell lysates. (PMID:12167714)
• genetic regulation in tumor reversion (PMID:12399545)
• results do not support the hypothesis that IgE(mn+) induces a late allergic reaction (LAR), but do not exclude the alternative hypothesis that HRFs are released during a LAR and contribute to asthma severity (PMID:12487227)
• Patients with Multiple drug allergy syndrome and more than 1/3 with hypersensitivity to a single antibacterial drug showed the presence of circulating histamine-releasing factors. Such factors might play a role in drug-induced adverse reactions. (PMID:12876410)
• HRF p23 can stimulate nonimmune epithelium such as bronchial epithelium (PMID:12948934)
• Human recombinant histamine-releasing factor can partially inhibit the secretion of IL-2 and IL-13 protein in a dose-dependent manner from both purified peripheral blood T cells and Jurkat T cells. (PMID:14500674)
• TCTP preferentially stabilized the GDP form of eEF1A, and, furthermore, impaired the GDP exchange reaction promoted by eEF1Bbeta. (PMID:14623968)
• Interaction between HrHRF and EF-1delta taken with some of the recently published information concerning the TCTP (HrHRF) mentioned above suggest a possible intracellular role for TCTP/HrHRF. (PMID:15062873)
• the fortilin-MCL1 interaction increases cellular resistance to apoptosis by allowing MCL1, an independently antiapoptotic protein, to stabilize another independently antiapoptotic protein, fortilin (PMID:15262975)
• role for TSAP6 in the export of TCTP and indicate that this multipass membrane protein could have a general role in the regulation of vesicular trafficking and secretion. (PMID:15319436)
• the expression of TPT1 in the human placenta and a direct role of the protein in placental calcium transport (PMID:15958728)
• TPT1 is regulated by CREB transcription factors. (PMID:16859841)
• PAI-1 downregulates TCTP in LnCAP prostatic cancer. (PMID:17549383)
• Cross-inhibition assays showed that the patients’ IgEs recognize common epitopes on both the human and C. herbarum proteins. (PMID:17645945)
• analysis of of the weak calcium-binding site of human translationally controlled tumor protein by NMR (PMID:17897616)
• Priming of basophils for histamine release induced by TCTP differs from that induced by interleukin-3. (PMID:18042794)
• study found a structural similarity between the H2-H3 helices of TCTP and the H5-H6 helices of Bax; TCTP antagonizes apoptosis by inserting into the mitochondrial membrane and inhibiting Bax dimerization (PMID:18274553)
• interaction between fortilin and TSC-22 prevents apoptosis via the destabilization of TSC-22 in ovarian carcinoma cells (PMID:18325344)
• Data show that histamine-releasing factor is found in pannus from rheumatoid arthritis patients, and suggest that it plays a role in the pathogenesis of RA. (PMID:18345488)
• The Chfr-TCTP interaction was stable throughout the cell cycle, but it could be diminished by the complete depolymerization of the microtubules. (PMID:18504434)
• neither TCTP nor FKBP38 regulates mTORC1 signaling. (PMID:18676370)
• Data describe the ultrastructure of the choroid plexus, the number of mast cells that may infiltrate it, and the immunodistribution of histamine receptors H4 and histamine-releasing factor. (PMID:19271148)
• A potential therapeutic application for prostate cancer by targeting TCTP gene using an siRNA approach. (PMID:19360337)
• Proton pump inhibitors exert anti-allergic effects by reducing TCTP secretion (PMID:19484128)
• These findings suggest that TCTP may belong to a novel small molecular weight heat shock protein. (PMID:19523440)
• TCTP interacts with hRheb and accelerates its GDP release in vitro. (PMID:19570981)
• In contrast to the very modest phenotype observed in the thymus, a significant reduction of mature T cells is observed in the peripheral lymphoid organs of two conditional null TCTP mutant mice. (PMID:19605695)
• Knockdown of TCTP inhibited proliferation, migration, and invasion activities of LoVo cells in vitro and in vivo. (PMID:19621893)
• Data suggest a kind of feedback regulation between TCTP and VDR to regulate a variety of (Ca(2+) dependent) cellular effects and in this way further underscore the physiological relevance of the observed physical interaction beteen TCTP and VDR. (PMID:19815065)
• These results identify TCTP-bearing nanovesicles as a novel component of the paracrine apoptotic program of potential importance in vascular repair. (PMID:20966960)
• Results clearly indicate that the interaction between TCTP and p53 prevents apoptosis by destabilizing p53. (PMID:21081126)
• fortilin is a novel p53-interacting molecule and p53 inhibitor (PMID:21795694)
• The TCTP is a survival factor that protects cancer cells from oxidative stress-induced cell-death. (PMID:21801721)
• CHD1L/TCTP/Cdc25C/Cdk1 molecular pathway causes the malignant transformation of hepatocytes with the phenotypes of accelerated mitotic progression and the production of aneuploidy (PMID:21953552)
• P53 binds to a P53 responsive element that is present in the promoter of TCTP, leading to the transcriptional repression of TCTP (PMID:22157679)
• Results imply that TCTP might be a mediator of PRL-3-promoted proliferation, migration and invasion of human colon cancer cells. (PMID:22340241)
• Data suggest that TCTP may play a critical role in maintaining genomic integrity in response to DNA-damaging agents. (PMID:22451927)
• Demonstrate the presence of TCTP in human cornea, and suggest a potential role in the pathogenesis of herpes virus keratitis. (PMID:22853445)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tpt1	ENSDARG00000092693
drosophila_melanogaster	Tctp	FBGN0037874
caenorhabditis_elegans	tct-1	WBGENE00009122

Protein

Protein identifiers

Translationally-controlled tumor protein — P13693 (reviewed: P13693)

Alternative names: Fortilin, Histamine-releasing factor, p23

All UniProt accessions (7): A0A0B4J2C3, A0A0P1J1R0, E9PJF7, P13693, H0YCX0, J3KPG2, Q5W0H4

UniProt curated annotations — full annotation on UniProt →

Function. Involved in calcium binding and microtubule stabilization. Acts as a negative regulator of TSC22D1-mediated apoptosis, via interaction with and destabilization of TSC22D1 protein.

Subunit / interactions. Homodimer. Interacts with STEAP3. Interacts with TSC22D1; interaction results in the destabilization of TSC22D1 protein.

Subcellular location. Cytoplasm.

Tissue specificity. Found in several healthy and tumoral cells including erythrocytes, hepatocytes, macrophages, platelets, keratinocytes, erythroleukemia cells, gliomas, melanomas, hepatoblastomas, and lymphomas. It cannot be detected in kidney and renal cell carcinoma (RCC). Expressed in placenta and prostate.

Induction. Down-regulated in response to enterovirus 71 (EV71) infection.

Similarity. Belongs to the TCTP family.

Isoforms (2)

UniProt ID	Names	Canonical?
P13693-1	1	yes
P13693-2	2

RefSeq proteins (3): NP_001273201, NP_001273202, NP_003286* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011057	Mss4-like_sf	Homologous_superfamily
IPR011323	Mss4/transl-control_tumour	Homologous_superfamily
IPR018103	Translation_control_tumour_CS	Conserved_site
IPR018105	Translational_control_tumour_p	Family
IPR034737	TCTP	Domain

Pfam: PF00838

UniProt features (31 total): strand 11, helix 7, turn 3, modified residue 3, sequence conflict 2, chain 1, domain 1, region of interest 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
5O9M	X-RAY DIFFRACTION	1.4
5O9L	X-RAY DIFFRACTION	1.75
6IZB	X-RAY DIFFRACTION	1.9
1YZ1	X-RAY DIFFRACTION	2
4Z9V	X-RAY DIFFRACTION	2.1
6IZE	X-RAY DIFFRACTION	2.29
3EBM	X-RAY DIFFRACTION	2.6
2HR9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13693-F1	91.78	0.85

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 (3): 46, 53, 64

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 276 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, GNF2_TPT1, GCM_NPM1, CGGAARNGGCNG_UNKNOWN, MATTIOLI_MGUS_VS_PCL, HSIAO_HOUSEKEEPING_GENES, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_ECTODERM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_APOPTOTIC_SIGNALING_PATHWAY, KOYAMA_SEMA3B_TARGETS_UP, DOANE_RESPONSE_TO_ANDROGEN_DN, PID_PLK1_PATHWAY

GO Biological Process (8): calcium ion transport (GO:0006816), intracellular calcium ion homeostasis (GO:0006874), response to virus (GO:0009615), stem cell population maintenance (GO:0019827), regulation of apoptotic process (GO:0042981), negative regulation of apoptotic process (GO:0043066), negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage (GO:1902230), negative regulation of ectoderm development (GO:2000384)

GO Molecular Function (4): RNA binding (GO:0003723), calcium ion binding (GO:0005509), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515)

GO Cellular Component (9): spindle pole (GO:0000922), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), multivesicular body (GO:0005771), cytosol (GO:0005829), cytoplasmic microtubule (GO:0005881), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
apoptotic process	2
cytoplasm	2
metal ion transport	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
response to other organism	1
multicellular organismal process	1
maintenance of cell number	1
regulation of programmed cell death	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
intrinsic apoptotic signaling pathway in response to DNA damage	1
regulation of intrinsic apoptotic signaling pathway in response to DNA damage	1
negative regulation of intrinsic apoptotic signaling pathway	1
ectoderm development	1
negative regulation of developmental process	1
regulation of ectoderm development	1
nucleic acid binding	1
metal ion binding	1
transcription factor binding	1
binding	1
spindle	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
late endosome	1
microtubule	1
extracellular vesicle	1

Protein interactions and networks

STRING

2808 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPT1	STEAP3	Q658P3	891
TPT1	RHEB	Q15382	841
TPT1	PKMYT1	Q99640	796
TPT1	RPS6KB2	Q9UBS0	786
TPT1	MCL1	Q07820	777
TPT1	BNIP3L	O60238	684
TPT1	RABIF	P47224	668
TPT1	EEF1A1	P04719	667
TPT1	TSC1	Q92574	659
TPT1	FNTA	P49354	642
TPT1	TP53	P04637	617
TPT1	CASP3	P42574	592
TPT1	PLK1	P53350	590
TPT1	BCL2L1	Q07817	589
TPT1	RPS6KB1	P23443	566

IntAct

113 interactions, top by confidence:

A	B	Type	Score
XRCC6	XRCC5	psi-mi:“MI:0914”(association)	0.970
XRCC5	XRCC6	psi-mi:“MI:0914”(association)	0.970
TPT1	TP53	psi-mi:“MI:0915”(physical association)	0.710
TPT1	XRCC6	psi-mi:“MI:0915”(physical association)	0.710
TPT1	XRCC6	psi-mi:“MI:0914”(association)	0.710
TP53	TPT1	psi-mi:“MI:0915”(physical association)	0.710
TSC22D1	TPT1	psi-mi:“MI:0407”(direct interaction)	0.590
TPT1	TSC22D1	psi-mi:“MI:0915”(physical association)	0.590
TSC22D1	TPT1	psi-mi:“MI:0915”(physical association)	0.590
TPT1	ACTB	psi-mi:“MI:0915”(physical association)	0.570
TPT1	YBX1	psi-mi:“MI:0915”(physical association)	0.570
TPT1	PRDX1	psi-mi:“MI:0915”(physical association)	0.570
TPT1	HSPA9	psi-mi:“MI:0915”(physical association)	0.570
TPT1	TUBA1C	psi-mi:“MI:0915”(physical association)	0.570

BioGRID (343): TPT1 (Reconstituted Complex), TPT1 (Affinity Capture-Western), BCL2L1 (Affinity Capture-Western), MCL1 (Affinity Capture-Western), TUBB2A (Protein-peptide), BCL2L1 (Protein-peptide), TPT1 (Protein-peptide), TPT1 (Reconstituted Complex), TPT1 (Affinity Capture-Western), VHL (Affinity Capture-Western), TPT1 (Two-hybrid), TRIP13 (Two-hybrid), TPT1 (Reconstituted Complex), TPT1 (Two-hybrid), TPT1 (Affinity Capture-Western)

ESM2 similar proteins: A3PAL2, A4SG83, A5A6K2, A5FMN0, A7GT88, A9VIN2, B8I3F5, G3LU44, J3SFJ3, M5B4R7, O18477, O66413, O67064, P0CR82, P0CR83, P13693, P43347, P43348, P54173, P61288, P63028, P63029, P84152, P91800, Q03545, Q10344, Q1HR79, Q2UR29, Q4PLZ3, Q5A860, Q5E984, Q5MGM6, Q5MIP6, Q60FS1, Q622B7, Q6AS26, Q6BP09, Q6C4G1, Q6CTH3, Q6FKB6

Diamond homologs: A1KXP4, A5A6K2, D0MQ50, G3LU44, J3SFJ3, M5B4R7, O03992, O18477, P0CR82, P0CR83, P13693, P28014, P31265, P35681, P35691, P43347, P43348, P43349, P50906, P61288, P63028, P63029, P84152, P90697, P91800, Q10344, Q1HR79, Q202I6, Q293Y0, Q2L875, Q2PS27, Q2UR29, Q4IJT5, Q4N938, Q4PF30, Q4PLZ3, Q4UGL5, Q4WRB8, Q54RX6, Q56UQ5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PLK1	down-regulates	TPT1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 70 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.

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair	5	17.8×	2e-03
DNA damage response	9	8.4×	9e-04
negative regulation of apoptotic process	9	5.5×	6e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

769 predictions. Top by Δscore:

Variant	Effect	Δscore
13:45337307:AAGT:A	donor_gain	1.0000
13:45337389:C:CC	acceptor_gain	1.0000
13:45338647:T:TA	donor_gain	1.0000
13:45338651:TGTAC:T	donor_loss	1.0000
13:45338652:GTAC:G	donor_loss	1.0000
13:45338653:TAC:T	donor_loss	1.0000
13:45338654:ACTTA:A	donor_loss	1.0000
13:45338655:CT:C	donor_loss	1.0000
13:45338656:TTAC:T	donor_loss	1.0000
13:45338657:TACAC:T	donor_loss	1.0000
13:45338658:A:AC	donor_gain	1.0000
13:45338658:A:T	donor_loss	1.0000
13:45338659:C:CA	donor_gain	1.0000
13:45338659:CA:C	donor_gain	1.0000
13:45338659:CACA:C	donor_gain	1.0000
13:45338659:CACAT:C	donor_gain	1.0000
13:45338682:T:TA	donor_gain	1.0000
13:45338772:AAGAA:A	acceptor_gain	1.0000
13:45338773:AGAA:A	acceptor_gain	1.0000
13:45338774:GAA:G	acceptor_gain	1.0000
13:45338775:AA:A	acceptor_gain	1.0000
13:45338775:AAC:A	acceptor_loss	1.0000
13:45338777:C:CC	acceptor_gain	1.0000
13:45338777:C:CG	acceptor_loss	1.0000
13:45338778:T:C	acceptor_gain	1.0000
13:45338778:T:TC	acceptor_gain	1.0000
13:45338786:C:CT	acceptor_gain	1.0000
13:45339603:C:CC	acceptor_gain	1.0000
13:45339988:ACTT:A	donor_loss	1.0000
13:45339990:TTAC:T	donor_loss	1.0000

AlphaMissense

1169 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:45338736:G:T	A147D	1.000
13:45340054:A:G	L78P	1.000
13:45340717:C:A	G33W	1.000
13:45338676:A:G	L167S	0.999
13:45338679:C:A	G166V	0.999
13:45338679:C:T	G166D	0.999
13:45338680:C:G	G166R	0.999
13:45338703:G:T	P158Q	0.999
13:45338716:C:G	D154H	0.999
13:45338733:A:T	L148Q	0.999
13:45338739:A:T	V146D	0.999
13:45338745:C:A	G144V	0.999
13:45338745:C:T	G144D	0.999
13:45338746:C:G	G144R	0.999
13:45338766:C:A	G137V	0.999
13:45338766:C:T	G137D	0.999
13:45338767:C:G	G137R	0.999
13:45338774:G:C	F134L	0.999
13:45338774:G:T	F134L	0.999
13:45338775:A:G	F134S	0.999
13:45338776:A:G	F134L	0.999
13:45339543:G:T	A118D	0.999
13:45339554:A:C	F114L	0.999
13:45339554:A:T	F114L	0.999
13:45339555:A:G	F114S	0.999
13:45339556:A:G	F114L	0.999
13:45339588:A:G	L103P	0.999
13:45340008:T:A	K93N	0.999
13:45340008:T:G	K93N	0.999
13:45340010:T:C	K93E	0.999

dbSNP variants (sampled 300 via entrez): RS1000473099 (13:45335426 G>A,C), RS1000835272 (13:45340908 C>A,T), RS1000947155 (13:45334441 A>G), RS1001064935 (13:45336306 T>G), RS1001130814 (13:45341378 A>C,G,T), RS1001169423 (13:45339160 A>G), RS1001373559 (13:45339347 C>A,T), RS1001447102 (13:45334901 G>A), RS1001659633 (13:45339104 A>G), RS1001707542 (13:45342936 C>G,T), RS1002257586 (13:45340298 A>C), RS1002432190 (13:45335760 T>A), RS1002809705 (13:45342490 A>C,G), RS1002842283 (13:45342714 A>T), RS1002918566 (13:45338060 T>C)

Disease associations

OMIM: gene MIM:600763 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002806_10	Type 2 diabetes	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066956 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.09	Kd	821.2	nM	CHEMBL5653589
6.09	ED50	821.2	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149649: Binding affinity to human TPT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.8212	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	decreases expression, increases expression	3
Tobacco Smoke Pollution	affects expression, increases expression, increases methylation	3
Cadmium Chloride	decreases expression, increases methylation, increases expression	3
bisphenol A	affects expression, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
perfluorooctanoic acid	decreases expression	2
Resveratrol	decreases expression, increases expression	2
Artesunate	affects binding, decreases expression, decreases reaction, affects response to substance	2
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases expression	2
Doxorubicin	increases expression, affects expression	2
Smoke	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
chlorophyllin	increases expression	1
deoxynivalenol	increases expression	1
trichostatin A	affects cotreatment, decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
bufalin	decreases expression	1
zinc chromate	increases abundance, increases expression	1
ochratoxin A	increases expression	1
butylidenephthalide	decreases expression	1
phenanthrene	decreases expression	1
puerarin	increases expression	1
perfluorodecanoic acid	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
diallyl trisulfide	decreases expression	1
chromium hexavalent ion	increases abundance, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652691	Binding	Binding affinity to human TPT1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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