TFDP1

Summary

TFDP1 (transcription factor Dp-1, HGNC:11749) is a protein-coding gene on chromosome 13q34, encoding Transcription factor Dp-1 (Q14186). Can stimulate E2F-dependent transcription. It is a selective cancer dependency (DepMap: 66.8% of cell lines).

This gene encodes a member of a family of transcription factors that heterodimerize with E2F proteins to enhance their DNA-binding activity and promote transcription from E2F target genes. The encoded protein functions as part of this complex to control the transcriptional activity of numerous genes involved in cell cycle progression from G1 to S phase. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 1, 15, and X.

Source: NCBI Gene 7027 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 65 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 66.8% of screened cell lines
• Transcription factor: yes — 33 downstream targets (CollecTRI)
• MANE Select transcript: NM_007111

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11749
Approved symbol	TFDP1
Name	transcription factor Dp-1
Location	13q34
Locus type	gene with protein product
Status	Approved
Aliases	Dp-1, DRTF1, DP1, DILC
Ensembl gene	ENSG00000198176
Ensembl biotype	protein_coding
OMIM	189902
Entrez	7027

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 36 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000375370, ENST00000408980, ENST00000453989, ENST00000464794, ENST00000465174, ENST00000475254, ENST00000494812, ENST00000544902, ENST00000866241, ENST00000866242, ENST00000866243, ENST00000866244, ENST00000866245, ENST00000866246, ENST00000866247, ENST00000866248, ENST00000866249, ENST00000866250, ENST00000866251, ENST00000866252, ENST00000927707, ENST00000927708, ENST00000927709, ENST00000927710, ENST00000927711, ENST00000927712, ENST00000927713, ENST00000927714, ENST00000927715, ENST00000960056, ENST00000960057, ENST00000960058, ENST00000960059, ENST00000960060, ENST00000960061, ENST00000960062, ENST00000960063, ENST00000960064, ENST00000960065, ENST00000960066, ENST00000960067

RefSeq mRNA: 1 — MANE Select: NM_007111 NM_007111

CCDS: CCDS9538

Canonical transcript exons

ENST00000375370 — 12 exons

Exon	Start	End
ENSE00001433161	113640120	113641473
ENSE00001466880	113584753	113584888
ENSE00003586278	113631623	113631744
ENSE00003603744	113585774	113585849
ENSE00003619908	113610996	113611062
ENSE00003620430	113637818	113637896
ENSE00003718448	113634534	113634602
ENSE00003735531	113633890	113634033
ENSE00003747296	113633120	113633285
ENSE00003747963	113623180	113623286
ENSE00003749936	113635977	113636128
ENSE00003753122	113636534	113636700

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 97.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.4502 / max 824.2767, expressed in 1822 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136236	53.9652	1822
136235	0.4718	257
136237	0.0132	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.68	gold quality
trabecular bone tissue	UBERON:0002483	97.51	gold quality
ventricular zone	UBERON:0003053	96.35	gold quality
bone marrow	UBERON:0002371	96.19	gold quality
endometrium epithelium	UBERON:0004811	96.08	gold quality
stromal cell of endometrium	CL:0002255	95.84	gold quality
ganglionic eminence	UBERON:0004023	95.43	gold quality
rectum	UBERON:0001052	95.36	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.13	gold quality
esophagus mucosa	UBERON:0002469	94.82	gold quality
buccal mucosa cell	CL:0002336	94.59	gold quality
esophagus squamous epithelium	UBERON:0006920	94.43	gold quality
monocyte	CL:0000576	94.32	gold quality
embryo	UBERON:0000922	94.13	gold quality
bone marrow cell	CL:0002092	94.09	gold quality
tendon of biceps brachii	UBERON:0008188	93.66	gold quality
mononuclear cell	CL:0000842	93.53	gold quality
leukocyte	CL:0000738	93.28	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.21	gold quality
smooth muscle tissue	UBERON:0001135	93.16	gold quality
epithelium of esophagus	UBERON:0001976	93.16	gold quality
cerebellar hemisphere	UBERON:0002245	92.97	gold quality
cerebellar cortex	UBERON:0002129	92.92	gold quality
oocyte	CL:0000023	92.85	gold quality
vermiform appendix	UBERON:0001154	92.79	gold quality
islet of Langerhans	UBERON:0000006	92.73	gold quality
vagina	UBERON:0000996	92.65	gold quality
mucosa of transverse colon	UBERON:0004991	92.51	gold quality
lymph node	UBERON:0000029	92.50	gold quality
esophagus	UBERON:0001043	92.49	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	143.47
E-CURD-122	yes	18.90
E-ANND-3	yes	10.24

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

33 targets.

Target	Regulation
ACHE
CAT
CAV1	Unknown
CCNA2	Activation
CCNE1	Activation
CD74
CDC16
CDK1	Activation
CDK2
CDK4
CDKN1A	Unknown
DHFR	Activation
E2F1
HMOX1	Activation
MPO
MYBL2	Activation
MYC	Activation
NRIP1	Activation
PCNA	Activation
PTTG1	Activation
RB1	Repression
RBL2
RRM1	Activation
SP1	Activation
STMN1	Unknown
TCF3
TNFRSF11A
TOP2B
TP53	Repression
TP53BP1

JASPAR motifs

Motif	Name	Family
MA1122.1	TFDP1	E2F
MA1122.2	TFDP1	E2F

JASPAR matrix evidence (PMIDs): PMID:9027491

Upstream regulators (CollecTRI, top): ESR2, RB1, RBL1, TP53

miRNA regulators (miRDB)

135 targeting TFDP1, 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-4692	100.00	67.32	2066
HSA-MIR-3163	100.00	77.23	8605
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-340-5P	100.00	72.50	4437
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 66.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 22)

• TFDP1, CUL4A, and CDC16 are probable targets of an amplification mechanism and therefore may be involved, together or separately, in development and/or progression of some hepatocellular carcinomas (PMID:12029633)
• expression of the transcription factor DP-1 and its heterodimeric partner E2F-1 in non-Hodgkin lymphoma (PMID:12607600)
• TFDP1 may have a role in progression of some hepatocellular carcinomas by promoting growth of the tumor cells (PMID:14618416)
• DP-1alpha is a novel isoform of DP-1 that acts as a dominant-negative regulator of cell cycle progression (PMID:15863509)
• DP1 is a critical direct target of ARF. (PMID:16135794)
• SOCS-3 acts as a negative regulator of the cell cycle progression under E2F/DP-1 control by interfering with heterodimer formation between DP-1 and E2F (PMID:18687693)
• 13q34 amplification may be of relevance in tumor progression of breast cancers by inducing overexpression of CUL4A and TFDP1, important in cell cycle regulation. These genes were also overexpressed in non-basal-like tumor samples. (PMID:19995430)
• the DP-1 “Stabilon” domain was a C-terminal acidic motif and was quite important for DP-1 stability. (PMID:20513349)
• The authors demonstrate that adenovirus E1A binds to E2F/DP-1 complexes through a direct interaction with DP-1 and may selectively activate a subset of E2F-regulated cellular genes during infection. (PMID:21715488)
• somatic mutations in DP-1 uncouple normal control of the E2F pathway, and thus define a new mechanism that could contribute to aberrant proliferation in tumor cells (PMID:23934193)
• The TFDP1 indel84 mutation generates a gain-of-function phenotype by increasing cell proliferation, migration, and invasion of colorectal cancer cells. (PMID:25133581)
• Amplification of CUL4A, IRS2, and TFDP1 genes showed a significant difference in disease-free survival by both univariate and multivariate survival analyses in intrahepatic cholangiocarcinoma. (PMID:26684807)
• According to our study results, the gene TFDP1 and the cell cycle pathway are strongly associated with high-grade glioblastoma multiforme (GBM); this result may provide new insights into the pathogenesis of GBM. (PMID:27323154)
• role for E2F1 and TFDP1 in the transcriptional regulation of PITX1 in articular chondrocytes (PMID:27802335)
• Here, the authors show that an acidic region of DP1, whose function has remained elusive, binds to the plekstrin homology (PH) domain of the p62 subunit of TFIIH that contributes to transcriptional activation. (PMID:27825926)
• COMMD9 participates in TFDP1/E2F1 activation and plays a critical role in non-small cell lung cancer. (PMID:27871936)
• DILC may mediate the crosstalk between the cascades of IL6/STAT3 and TNFalpha signaling, indicating that DILC may act as a prognostic biomarker of sepsis, and may serve as a potential therapeutic target for the treatment of sepsis. (PMID:30365067)
• We observed a downregulation of TFDP1 in the endometrium cells of women with deep infiltrating endometriosis when compared to the controls (PMID:30638096)
• It uncovered E2F1 and TFDP1 as transport substrates of KPNA2 being retained in the cytoplasm upon KPNA2 ablation, thereby resulting in reduced STMN1 expression. (PMID:31783876)
• miR-4711-5p regulates cancer stemness and cell cycle progression via KLF5, MDM2 and TFDP1 in colon cancer cells. (PMID:32066912)
• Transcription factor Dp-1 knockdown downregulates thymidine kinase 1 expression to protect against proliferation and epithelial-mesenchymal transition in cervical cancer. (PMID:37715794)
• ZNF146 regulates cell cycle progression via TFDP1 and DEPDC1B in ovarian cancer cells. (PMID:38614125)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tfdp1b	ENSDARG00000016304
danio_rerio	tfdp1a	ENSDARG00000019293
mus_musculus	Tfdp1	ENSMUSG00000038482
rattus_norvegicus	Tfdp1	ENSRNOG00000019222
drosophila_melanogaster	Dp	FBGN0011763
caenorhabditis_elegans		WBGENE00001061

Paralogs (2): TFDP2 (ENSG00000114126), TFDP3 (ENSG00000183434)

Protein

Protein identifiers

Transcription factor Dp-1 — Q14186 (reviewed: Q14186)

Alternative names: DRTF1-polypeptide 1, E2F dimerization partner 1

All UniProt accessions (4): Q14186, F5H452, Q5JSB5, Q5JSB6

UniProt curated annotations — full annotation on UniProt →

Function. Can stimulate E2F-dependent transcription. Binds DNA cooperatively with E2F family members through the E2 recognition site, 5’-TTTC[CG]CGC-3’, found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The E2F1:DP complex appears to mediate both cell proliferation and apoptosis. Blocks adipocyte differentiation by repressing CEBPA binding to its target gene promoters.

Subunit / interactions. Component of the E2F:DP transcription factor complex. Forms heterodimers with E2F family members. The complex can interact with hypophosphorylated retinoblastoma protein RB1 and related proteins (RBL1 and RBL2) that inhibit the E2F transactivation domain. This repression involves recruitment of histone deacetylase (HDAC). During the cell cycle, from mid-to-late G1 phase, RB family members become phosphorylated, detach from the DRTF1/E2F complex to render E2F transcriptionally active. Viral oncoproteins, notably E1A, T-antigen and HPV E7, are capable of sequestering RB protein, thus releasing the active complex. Part of the E2F6.com-1 complex in G0 phase is composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2, MBLR, L3MBTL2 YAF2. Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2. The complex TFDP1:E2F1 interacts with CEBPA; the interaction prevents CEBPA binding to target gene promoters and represses its transcriptional activity.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Highest levels in muscle. Also expressed in brain, placenta, liver and kidney. Lower levels in lung and pancreas. Not detected in heart.

Post-translational modifications. Phosphorylation by E2F1-bound cyclin A-CDK2, in the S phase, inhibits E2F-mediated DNA binding and transactivation. Ubiquitinated by the BCR(KBTBD5) complex, leading to its subsequent degradation.

Induction. Down-regulated during differentiation.

Miscellaneous. E2F/DP transactivation can be mediated by several cofactors including TBP, TFIIH, MDM2 and CBP.

Similarity. Belongs to the E2F/DP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14186-1	1	yes
Q14186-2	2

RefSeq proteins (1): NP_009042* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003316	E2F_WHTH_DNA-bd_dom	Domain
IPR014889	Transc_factor_DP_C	Domain
IPR015648	Transcrpt_fac_DP	Family
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR037241	E2F-DP_heterodim	Homologous_superfamily
IPR038168	TF_DP_C_sf	Homologous_superfamily

Pfam: PF02319, PF08781

UniProt features (31 total): region of interest 7, helix 6, strand 5, compositionally biased region 4, modified residue 2, splice variant 2, chain 1, DNA-binding region 1, sequence variant 1, turn 1, short sequence motif 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5TUU	X-RAY DIFFRACTION	2.25
2AZE	X-RAY DIFFRACTION	2.55
5TUV	X-RAY DIFFRACTION	2.9
5GOW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14186-F1	71.03	0.49

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 (2): 3, 23

Function

Pathways and Gene Ontology

Reactome pathways

48 pathways

ID	Pathway
R-HSA-111448	Activation of NOXA and translocation to mitochondria
R-HSA-113501	Inhibition of replication initiation of damaged DNA by RB1/E2F1
R-HSA-1362277	Transcription of E2F targets under negative control by DREAM complex
R-HSA-1362300	Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1
R-HSA-139915	Activation of PUMA and translocation to mitochondria
R-HSA-1538133	G0 and Early G1
R-HSA-1912408	Pre-NOTCH Transcription and Translation
R-HSA-2173796	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-2559585	Oncogene Induced Senescence
R-HSA-6804114	TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest
R-HSA-69202	Cyclin E associated events during G1/S transition
R-HSA-69205	G1/S-Specific Transcription
R-HSA-69231	Cyclin D associated events in G1
R-HSA-69656	Cyclin A:Cdk2-associated events at S phase entry
R-HSA-8953750	Transcriptional Regulation by E2F6
R-HSA-9616222	Transcriptional regulation of granulopoiesis
R-HSA-9661069	Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)
R-HSA-109581	Apoptosis
R-HSA-109606	Intrinsic Pathway for Apoptosis
R-HSA-113510	E2F mediated regulation of DNA replication
R-HSA-114452	Activation of BH3-only proteins
R-HSA-1266738	Developmental Biology
R-HSA-157118	Signaling by NOTCH
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-170834	Signaling by TGF-beta Receptor Complex
R-HSA-1912422	Pre-NOTCH Expression and Processing
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 445 (showing top): MORF_DNMT1, REACTOME_INHIBITION_OF_REPLICATION_INITIATION_OF_DAMAGED_DNA_BY_RB1_E2F1, REACTOME_SIGNALING_BY_NOTCH, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, WANG_CLIM2_TARGETS_UP, REACTOME_G1_S_SPECIFIC_TRANSCRIPTION, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, MORF_ESPL1, MORF_BUB1, GOBP_CELL_CYCLE_PHASE_TRANSITION, MORF_RRM1, RIZ_ERYTHROID_DIFFERENTIATION_CCNE1, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, KENNY_CTNNB1_TARGETS_UP, MITSIADES_RESPONSE_TO_APLIDIN_DN

GO Biological Process (12): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), epidermis development (GO:0008544), anoikis (GO:0043276), positive regulation of transcription by RNA polymerase II (GO:0045944), obsolete positive regulation of DNA-binding transcription factor activity (GO:0051091), negative regulation of fat cell proliferation (GO:0070345), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), regulation of DNA biosynthetic process (GO:2000278), positive regulation of DNA-templated transcription (GO:0045893), regulation of cell cycle (GO:0051726)

GO Molecular Function (9): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA-binding transcription factor activity (GO:0003700), protein domain specific binding (GO:0019904), DNA-binding transcription factor binding (GO:0140297), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (8): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), Rb-E2F complex (GO:0035189), RNA polymerase II transcription regulator complex (GO:0090575), transcription regulator complex (GO:0005667)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Activation of BH3-only proteins	2
G0 and Early G1	2
Cellular Senescence	2
G1/S Transition	2
E2F mediated regulation of DNA replication	1
Mitotic G1 phase and G1/S transition	1
Pre-NOTCH Expression and Processing	1
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1
TP53 Regulates Transcription of Cell Cycle Genes	1
G1 Phase	1
S Phase	1
Generic Transcription Pathway	1
Developmental Biology	1
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	1
Programmed Cell Death	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA-templated transcription	3
regulation of DNA-templated transcription	3
transcription cis-regulatory region binding	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of gene expression	1
regulation of RNA biosynthetic process	1
tissue development	1
apoptotic process	1
positive regulation of DNA-templated transcription	1
negative regulation of cell population proliferation	1
fat cell proliferation	1
regulation of fat cell proliferation	1
G1/S transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
regulation of macromolecule biosynthetic process	1
regulation of DNA metabolic process	1
DNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
cell cycle	1
regulation of cellular process	1
chromatin	1
DNA-binding transcription factor activity	1
transcription regulator activity	1
protein binding	1
transcription factor binding	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1614 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TFDP1	E2F1	Q01094	994
TFDP1	E2F6	O75461	980
TFDP1	E2F4	Q16254	977
TFDP1	E2F3	O00716	886
TFDP1	CCNL2	Q96S94	875
TFDP1	E2F5	Q15329	849
TFDP1	COMMD9	Q9P000	712
TFDP1	CBX3	Q13185	709
TFDP1	L3MBTL2	Q969R5	663
TFDP1	AGO1	Q9UL18	642
TFDP1	RBL2	Q08999	641
TFDP1	LRRK2	Q5S007	641
TFDP1	PCGF6	Q9BYE7	638
TFDP1	CCNA2	P20248	616
TFDP1	EIF4EBP1	Q13541	590

IntAct

154 interactions, top by confidence:

A	B	Type	Score
E2F1	RB1	psi-mi:“MI:0914”(association)	0.980
E2F1	RB1	psi-mi:“MI:0915”(physical association)	0.980
RB1	E2F1	psi-mi:“MI:0915”(physical association)	0.980
TFDP1	E2F6	psi-mi:“MI:0915”(physical association)	0.950
E2F6	TFDP1	psi-mi:“MI:0915”(physical association)	0.950
E2F1	TFDP1	psi-mi:“MI:0915”(physical association)	0.950
TFDP1	E2F1	psi-mi:“MI:0407”(direct interaction)	0.950
CDK2	CCNE2	psi-mi:“MI:0914”(association)	0.940
AXIN1	CTNNB1	psi-mi:“MI:0914”(association)	0.940
CDK2	CCNB1	psi-mi:“MI:0914”(association)	0.890
CDKN1A	CCNE2	psi-mi:“MI:0914”(association)	0.890
CDK2	CCNB2	psi-mi:“MI:0914”(association)	0.860
RYBP	BMI1	psi-mi:“MI:0914”(association)	0.850
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840

BioGRID (256): TFDP1 (Two-hybrid), CREBBP (Reconstituted Complex), TFDP1 (Affinity Capture-Western), TFDP1 (Affinity Capture-Western), TFDP1 (Affinity Capture-Western), TFDP1 (Affinity Capture-Western), TFDP1 (Affinity Capture-Western), TFDP1 (Affinity Capture-MS), TFDP1 (Affinity Capture-MS), TFDP1 (Affinity Capture-MS), TFDP1 (Affinity Capture-MS), TFDP1 (Affinity Capture-MS), TFDP1 (Two-hybrid), TFDP1 (Affinity Capture-Western), TFDP1 (Affinity Capture-Western)

ESM2 similar proteins: A0A3Q0KHE7, A3KPF2, B0W3L6, B4JXV2, B4KA23, B4LVS8, D9PTN5, G5EFI7, H2KYJ8, M9PD06, O45666, O88898, P10383, P49881, P51592, P79926, Q08639, Q09441, Q14149, Q14186, Q17370, Q174R2, Q18192, Q21006, Q23985, Q24143, Q28CK1, Q3SA46, Q66J63, Q6E3C9, Q6E3D0, Q6GN21, Q7Q2B7, Q84W92, Q86NH1, Q8AXW8, Q8UW76, Q91766, Q94527, Q95YE2

Diamond homologs: Q08639, Q14186, Q14188, Q17QZ4, Q22703, Q24318, Q5H9I0, Q64163, Q9FNY2, Q9FNY3

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
TFDP1	“up-regulates quantity by expression”	CCNE1	“transcriptional regulation”
TFDP1	“up-regulates quantity by expression”	PCNA	“transcriptional regulation”
TFDP1	“up-regulates quantity by expression”	CDK1	“transcriptional regulation”
TFDP1	“up-regulates quantity by expression”	DHFR	“transcriptional regulation”
TFDP1	“up-regulates quantity by expression”	TYMS	“transcriptional regulation”
TFDP1	“up-regulates quantity by expression”	MYBL2	“transcriptional regulation”
TFDP1	“up-regulates activity”	E2F1	binding
TFDP1	“up-regulates quantity by expression”	RRM1	“transcriptional regulation”
E2F1	“up-regulates activity”	TFDP1	binding
E2F2	“up-regulates activity”	TFDP1	binding
E2F3	“up-regulates activity”	TFDP1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 117 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
Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1	11	73.5×	4e-17
G0 and Early G1	14	68.3×	7e-21
Transcription of E2F targets under negative control by DREAM complex	11	66.5×	2e-16
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	8	56.4×	2e-11
Polo-like kinase mediated events	7	49.4×	2e-09
Cyclin E associated events during G1/S transition	14	44.4×	7e-18
G1/S-Specific Transcription	11	43.6×	4e-14
Cyclin A:Cdk2-associated events at S phase entry	14	41.3×	2e-17

GO biological processes:

GO term	Partners	Fold	FDR
G1/S transition of mitotic cell cycle	12	21.7×	8e-11
positive regulation of fibroblast proliferation	7	18.6×	1e-05
negative regulation of cell cycle	6	15.7×	2e-04
chromatin remodeling	18	11.8×	5e-12
heterochromatin formation	5	11.5×	4e-03
regulation of mitotic cell cycle	5	10.8×	5e-03
protein-containing complex assembly	7	7.2×	3e-03
negative regulation of gene expression	11	6.8×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2980 predictions. Top by Δscore:

Variant	Effect	Δscore
13:113585847:GAT:G	donor_gain	1.0000
13:113585850:G:GG	donor_gain	1.0000
13:113610990:CCGCA:C	acceptor_loss	1.0000
13:113610991:CGCA:C	acceptor_loss	1.0000
13:113610992:GCA:G	acceptor_loss	1.0000
13:113610993:CAGGC:C	acceptor_loss	1.0000
13:113610994:A:AG	acceptor_gain	1.0000
13:113610994:A:G	acceptor_loss	1.0000
13:113610994:AGGCC:A	acceptor_gain	1.0000
13:113610995:G:A	acceptor_loss	1.0000
13:113610995:G:GT	acceptor_gain	1.0000
13:113610995:GGCC:G	acceptor_gain	1.0000
13:113610995:GGCCG:G	acceptor_gain	1.0000
13:113623174:TTGCA:T	acceptor_loss	1.0000
13:113623175:TGCA:T	acceptor_loss	1.0000
13:113623176:GCAGG:G	acceptor_loss	1.0000
13:113623177:CAG:C	acceptor_loss	1.0000
13:113623178:A:AG	acceptor_gain	1.0000
13:113623179:G:GA	acceptor_gain	1.0000
13:113623179:GGC:G	acceptor_gain	1.0000
13:113623179:GGCGT:G	acceptor_gain	1.0000
13:113623284:GTG:G	donor_gain	1.0000
13:113633108:T:TA	acceptor_gain	1.0000
13:113633111:A:AG	acceptor_gain	1.0000
13:113633111:ATTTT:A	acceptor_gain	1.0000
13:113633112:T:G	acceptor_gain	1.0000
13:113633115:T:TA	acceptor_gain	1.0000
13:113633115:TGAA:T	acceptor_loss	1.0000
13:113633116:GAA:G	acceptor_loss	1.0000
13:113633117:AAGG:A	acceptor_loss	1.0000

AlphaMissense

2722 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:113633154:G:A	G115S	1.000
13:113633154:G:C	G115R	1.000
13:113633154:G:T	G115C	1.000
13:113633155:G:A	G115D	1.000
13:113633157:C:G	L116V	1.000
13:113633158:T:A	L116Q	1.000
13:113633158:T:C	L116P	1.000
13:113633158:T:G	L116R	1.000
13:113633160:C:G	R117G	1.000
13:113633161:G:A	R117Q	1.000
13:113633161:G:C	R117P	1.000
13:113633163:C:G	H118D	1.000
13:113633166:T:A	F119I	1.000
13:113633166:T:C	F119L	1.000
13:113633166:T:G	F119V	1.000
13:113633167:T:C	F119S	1.000
13:113633167:T:G	F119C	1.000
13:113633168:C:A	F119L	1.000
13:113633168:C:G	F119L	1.000
13:113633169:T:C	S120P	1.000
13:113633170:C:A	S120Y	1.000
13:113633170:C:T	S120F	1.000
13:113633177:G:C	K122N	1.000
13:113633177:G:T	K122N	1.000
13:113633178:G:C	V123L	1.000
13:113633178:G:T	V123F	1.000
13:113633179:T:A	V123D	1.000
13:113633179:T:C	V123A	1.000
13:113633181:T:A	C124S	1.000
13:113633181:T:C	C124R	1.000

dbSNP variants (sampled 300 via entrez): RS1000133715 (13:113627421 C>A,T), RS1000179126 (13:113630488 TG>T,TGG), RS1000212320 (13:113589204 T>C), RS1000236497 (13:113630538 C>A,G), RS1000254296 (13:113626148 T>C), RS1000274663 (13:113620514 C>A,T), RS1000332268 (13:113626349 T>C), RS1000363469 (13:113625987 G>A), RS1000368733 (13:113634905 C>A,G), RS1000396843 (13:113603943 G>A), RS1000582961 (13:113596255 C>G,T), RS1000588523 (13:113630293 G>A), RS1000605884 (13:113616078 C>T), RS1000618792 (13:113634358 GA>G,GAA), RS1000659601 (13:113601558 A>G)

Disease associations

OMIM: gene MIM:189902 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003124_6	Mild influenza (H1N1) infection	1.000000e-09
GCST008839_511	Height	1.000000e-10
GCST90002392_419	Mean corpuscular volume	5.000000e-13
GCST90002397_68	Mean spheric corpuscular volume	6.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523289 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	5
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	4
Acetaminophen	increases expression, decreases expression	3
Cyclosporine	decreases expression	3
Cadmium Chloride	decreases expression	3
bisphenol A	affects expression, decreases methylation	2
cobaltous chloride	decreases expression	2
Temozolomide	decreases expression, affects response to substance	2
Arsenic	decreases expression, increases abundance	2
Caffeine	decreases expression, decreases phosphorylation	2
Copper	affects binding, decreases expression, increases expression	2
Fluorouracil	decreases expression	2
Nicotine	decreases reaction, increases expression, decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
Particulate Matter	decreases expression, increases abundance	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
geraniol	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
benzo(e)pyrene	increases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
MK-886	decreases reaction, increases expression	1
tamibarotene	affects 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
CHEMBL4325384	Binding	Antagonist activity at human DP1 transfected in rat C6 cells assessed as decrease in decrease in BW245C-induced DP1 response by measuring intracellular cAMP incubated for 10 mins followed by BW245C addition and measured after 40 mins by TR-	Potent, Selective, Water Soluble, Brain-Permeable EP2 Receptor Antagonist for Use in Central Nervous System Disease Models. — J Med Chem

Cellosaurus cell lines

10 cell lines: 6 cancer cell line, 3 embryonic stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A7I1	SEES3-1V human TFDP1, clone1	Embryonic stem cell	Male
CVCL_A7I2	SEES3-1V human TFDP1, clone2	Embryonic stem cell	Male
CVCL_A7I3	SEES3-1V human TFDP1, clone3	Embryonic stem cell	Male
CVCL_B7ZW	Abcam Raji TFDP1 KO	Cancer cell line	Male
CVCL_C0AP	Abcam THP-1 TFDP1 KO	Cancer cell line	Male
CVCL_C7CC	Abcam PC-3 TFDP1 KO	Cancer cell line	Male
CVCL_D8WZ	Ubigene HCT 116 TFDP1 KO	Cancer cell line	Male
CVCL_D9U3	Ubigene HEK293 TFDP1 KO	Transformed cell line	Female
CVCL_E0QR	Ubigene HeLa TFDP1 KO	Cancer cell line	Female
CVCL_GZ94	K562 eGFP-TFDP1	Cancer cell line	Female

Clinical trials (associated diseases)

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