TFDP3

Summary

TFDP3 (transcription factor Dp family member 3, HGNC:24603) is a protein-coding gene on chromosome Xq26.2, encoding Transcription factor Dp family member 3 (Q5H9I0). Competitive inhibitor of E2F-mediated transactivation activity.

This gene encodes a member of the DP family of transcription factors. These factors heterodimerize with E2F proteins to enhance their DNA-binding activity and promote transcription from E2F target genes. This protein functions as a negative regulator and inhibits the DNA binding and transcriptional activities of E2F factors.

Source: NCBI Gene 51270 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_016521

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24603
Approved symbol	TFDP3
Name	transcription factor Dp family member 3
Location	Xq26.2
Locus type	gene with protein product
Status	Approved
Aliases	HCA661, E2F-like, CT30
Ensembl gene	ENSG00000183434
Ensembl biotype	protein_coding
OMIM	300772
Entrez	51270

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000310125

RefSeq mRNA: 1 — MANE Select: NM_016521 NM_016521

CCDS: CCDS14636

Canonical transcript exons

ENST00000310125 — 1 exons

Exon	Start	End
ENSE00001330593	133216662	133218354

Expression profiles

Bgee: expression breadth broad, 11 present calls, max score 81.24.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0174 / max 13.0815, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200550	0.0174	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.24	gold quality
buccal mucosa cell	CL:0002336	76.52	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.58	gold quality
diaphragm	UBERON:0001103	71.34	gold quality
hair follicle	UBERON:0002073	67.76	gold quality
right testis	UBERON:0004534	66.40	gold quality
testis	UBERON:0000473	65.01	gold quality
left testis	UBERON:0004533	64.69	gold quality
superficial temporal artery	UBERON:0001614	63.94	gold quality
mucosa of paranasal sinus	UBERON:0005030	63.37	gold quality
mucosa of urinary bladder	UBERON:0001259	63.05	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	62.63	gold quality
olfactory bulb	UBERON:0002264	62.21	gold quality
type B pancreatic cell	CL:0000169	62.04	gold quality
tongue squamous epithelium	UBERON:0006919	60.15	gold quality
epithelium of nasopharynx	UBERON:0001951	59.06	gold quality
male germ cell	CL:0000015	59.04	gold quality
gluteal muscle	UBERON:0002000	58.85	gold quality
sperm	CL:0000019	58.39	gold quality
triceps brachii	UBERON:0001509	58.22	gold quality
lower lobe of lung	UBERON:0008949	58.13	silver quality
myocardium	UBERON:0002349	54.89	gold quality
left ventricle myocardium	UBERON:0006566	54.71	gold quality
jejunal mucosa	UBERON:0000399	53.20	gold quality
endothelial cell	CL:0000115	53.05	gold quality
vastus lateralis	UBERON:0001379	53.01	gold quality
quadriceps femoris	UBERON:0001377	52.80	gold quality
thymus	UBERON:0002370	51.35	gold quality
Brodmann (1909) area 46	UBERON:0006483	51.34	gold quality
upper arm skin	UBERON:0004263	50.49	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.81

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
ARHGEF15
E2F1	Unknown
E2F3	Repression
E2F4	Repression
E2F5	Repression
MAP1LC3B	Activation

miRNA regulators (miRDB)

59 targeting TFDP3, 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-186-5P	99.99	70.83	3707
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514

Literature-anchored findings (GeneRIF, showing 8)

• TFDP3, a novel DP protein, inhibits DNA binding and transactivation by E2F (PMID:17062573)
• DP-4 downregulating E2F-1 activity and contributes to a new pRb-independent mechanism for regulating cell cycle progression. (PMID:20559320)
• Data show that TFDP3 upregulates the expression of autophagy gene LC3B and inhibits E2F1-induced apoptosis, and may play an important role in prostate cancer. (PMID:22482402)
• Data gathered from cell lines, tumorigenicity studies, and primary hepatocellular carcinoma samples demonstrate a negative role of HIF-2alpha in tumors, which is mediated by the TFDP3/E2F1 pathway. (PMID:23212661)
• TFDP3 was highly expressed in cancer tissues including prostate cancer tissues.TFDP3 was expressed in coordination with E2F1 in most prostate cancer tissues. (PMID:24406621)
• Authors established a preclinical model of resistance to induction therapy to examine the functional relevance of TFDP3 to chemoresistance in MRD derived from Jurkat/E6-1. (PMID:27902457)
• data highlight that TFDP3 is expressed in breast cancer, that it is a member of the cancer-testis antigen family and that it functions as a regulator in epithelial-mesenchymal transition (PMID:28114432)
• TFDP3 can bind to E2F1 molecule to form E2F/TFDP3 complex; and the localizations of TFDP3 and E2F1 molecules and the co-localization were different in different phases of cell cycle in the nucleus and cytoplasm, which indicated that the E2F/TFDP3 complex involved in the process of regulating the cell cycle. (PMID:28797103)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	Dp	FBGN0011763
caenorhabditis_elegans		WBGENE00001061

Paralogs (2): TFDP2 (ENSG00000114126), TFDP1 (ENSG00000198176)

Protein

Protein identifiers

Transcription factor Dp family member 3 — Q5H9I0 (reviewed: Q5H9I0)

Alternative names: Cancer/testis antigen 30, Hepatocellular carcinoma-associated antigen 661

All UniProt accessions (1): Q5H9I0

UniProt curated annotations — full annotation on UniProt →

Function. Competitive inhibitor of E2F-mediated transactivation activity. Impairs E2F-mediated cell-cycle progression from G(1) to S phase.

Subunit / interactions. Heterodimer: with E2F family members. TFDP3/E2F heterodimers do not bind DNA and repress E2F-dependent transcriptional activity.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Predominantly expressed in testis. Low level of expression in pancreas. Highly expressed in ovarian and colon cancer cell lines.

Domain organisation. The potential DNA-binding domain differs in sequence from that of other DP family members and cannot bind DNA.

Induction. In response to DNA damage.

Similarity. Belongs to the E2F/DP family.

RefSeq proteins (1): NP_057605* (*=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 (22 total): mutagenesis site 7, region of interest 5, site 4, compositionally biased region 3, chain 1, DNA-binding region 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5H9I0-F1	68.99	0.46

Functional residue map

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

Catalytic / active sites (4): 121 (critical for repression of e2f activity); 130 (critical for repression of e2f activity); 131 (critical for repression of e2f activity); 140 (critical for repression of e2f activity)

Mutagenesis-validated functional residues (7):

Position	Phenotype
112	no effect on down-regulation of e2f transcriptional activity; when associated with or without r-161 or with v-164.
121	restores enhanced e2f-mediated transcriptional activity; when associated with y-130; n-131 and e-145.
130	restores enhanced e2f-mediated transcriptional activity; when associated with k-121; n-131 and e-145.
131	restores enhanced e2f-mediated transcriptional activity; when associated with k-121; y-130 and e-145.
140	restores enhanced e2f-mediated transcriptional activity; when associated with k-121; y-130 and n-131.
161	no effect on down-regulation of e2f transcriptional activity; when associated with or without r-112.
164	no effect on down-regulation of e2f transcriptional activity; when associated r-112.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 80 (showing top): GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_NEGATIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_DNA_DAMAGE_RESPONSE, GOBP_MITOTIC_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_REGULATION_OF_CELL_CYCLE_PHASE_TRANSITION, GOBP_REGULATION_OF_CELL_CYCLE_PROCESS, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN

GO Biological Process (6): regulation of transcription by RNA polymerase II (GO:0006357), DNA damage response (GO:0006974), obsolete negative regulation of DNA-binding transcription factor activity (GO:0043433), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134), regulation of DNA-templated transcription (GO:0006355), regulation of cell cycle (GO:0051726)

GO Molecular Function (4): DNA binding (GO:0003677), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), DNA-binding transcription factor binding (GO:0140297), transcription regulator inhibitor activity (GO:0140416)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of gene expression	2
cellular anatomical structure	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
cellular response to stress	1
G1/S transition of mitotic cell cycle	1
negative regulation of mitotic cell cycle phase transition	1
negative regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
cell cycle	1
regulation of cellular process	1
nucleic acid binding	1
DNA-binding transcription factor binding	1
transcription factor binding	1
transcription regulator activity	1
molecular function inhibitor activity	1
chromosome	1
intracellular membrane-bounded organelle	1
protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

716 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TFDP3	HRK	O00198	916
TFDP3	E2F8	A0AVK6	881
TFDP3	APC	P25054	881
TFDP3	E2F7	Q96AV8	872
TFDP3	DPP8	Q6V1X1	849
TFDP3	E2F5	Q15329	841
TFDP3	E2F4	Q16254	812
TFDP3	E2F6	O75461	780
TFDP3	DPP9	Q86TI2	777
TFDP3	E2F1	Q01094	749
TFDP3	CTAG1A	P78358	679
TFDP3	E2F2	Q14209	673
TFDP3	HLA-DPB1	P01916	668
TFDP3	E2F3	O00716	634
TFDP3	EEF2	P13639	572

IntAct

16 interactions, top by confidence:

A	B	Type	Score
TFDP3	E2F3	psi-mi:“MI:0914”(association)	0.530
HSP90AB1	TFDP3	psi-mi:“MI:0915”(physical association)	0.400
TFDP3	MLF1	psi-mi:“MI:0915”(physical association)	0.400
TFDP3	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
HSF2	TFDP3	psi-mi:“MI:0915”(physical association)	0.400
TFDP3	NUDC	psi-mi:“MI:0915”(physical association)	0.400
TFDP3	NUDCD3	psi-mi:“MI:0915”(physical association)	0.400
TFDP3	SGTA	psi-mi:“MI:0915”(physical association)	0.400
	TFDP3	psi-mi:“MI:0915”(physical association)	0.400
TFDP3	STUB1	psi-mi:“MI:0915”(physical association)	0.400
TFDP3	CACYBP	psi-mi:“MI:0915”(physical association)	0.400
TFDP3	AARSD1	psi-mi:“MI:0915”(physical association)	0.400
TFDP3	rep	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (66): ACTA2 (Affinity Capture-MS), ERCC6L (Affinity Capture-MS), UBR4 (Affinity Capture-MS), AKAP11 (Affinity Capture-MS), E2F4 (Affinity Capture-MS), PLEC (Affinity Capture-MS), KANK2 (Affinity Capture-MS), PHLDB3 (Affinity Capture-MS), KIF11 (Affinity Capture-MS), RB1 (Affinity Capture-MS), E2F3 (Affinity Capture-MS), BRCC3 (Affinity Capture-MS), ALMS1 (Affinity Capture-MS), POLA1 (Affinity Capture-MS), SSFA2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IWI1, A5ABV9, B7ZRI2, B7ZRJ4, O08791, O08792, O13987, O73673, O73742, O74412, O74954, O93375, P06536, P06537, P49843, P49844, P56721, Q00858, Q03414, Q03571, Q07802, Q08DL5, Q10902, Q13761, Q13950, Q20937, Q23238, Q5H9I0, Q61X54, Q63398, Q64131, Q6E3C9, Q6E3D0, Q6E3D4, Q6E3D5, Q6P4K7, Q6PF39, Q700C2, Q8BYR2, Q8K4J2

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

94 predictions. Top by Δscore:

Variant	Effect	Δscore
X:133218081:CCAA:C	donor_gain	0.6700
X:133217279:CGG:C	donor_gain	0.6600
X:133217278:A:AC	donor_gain	0.6100
X:133217279:C:CC	donor_gain	0.6100
X:133217293:TTGGG:T	donor_gain	0.4800
X:133217063:A:AC	donor_gain	0.4700
X:133217064:C:CC	donor_gain	0.4700
X:133217279:CGGCT:C	donor_gain	0.4700
X:133217011:T:TA	donor_gain	0.4500
X:133218084:A:C	donor_gain	0.4500
X:133217193:C:CC	acceptor_gain	0.4300
X:133217221:TGGA:T	donor_gain	0.4300
X:133217276:G:T	donor_gain	0.4300
X:133217049:T:TA	donor_gain	0.4000
X:133217229:G:A	donor_gain	0.3900
X:133218082:CAAT:C	donor_gain	0.3800
X:133217241:A:T	donor_gain	0.3600
X:133217246:T:TA	donor_gain	0.3600
X:133216948:C:CT	acceptor_gain	0.3500
X:133217059:T:A	donor_gain	0.3500
X:133217256:C:A	donor_gain	0.3500
X:133218088:C:CT	donor_gain	0.3500
X:133217280:G:GT	donor_gain	0.3400
X:133217534:G:T	donor_gain	0.3400
X:133218089:CACT:C	donor_gain	0.3400
X:133217382:T:TA	donor_gain	0.3300
X:133217551:A:AC	donor_gain	0.3300
X:133217552:C:CC	donor_gain	0.3300
X:133217584:TTTG:T	acceptor_gain	0.3100
X:133217243:ACCTC:A	acceptor_gain	0.3000

AlphaMissense

2697 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:133217607:A:G	L218P	0.980
X:133217598:A:G	L221P	0.976
X:133217310:G:T	A317D	0.971
X:133217298:A:T	V321D	0.970
X:133217568:A:G	L231P	0.968
X:133217492:G:C	F256L	0.965
X:133217492:G:T	F256L	0.965
X:133217494:A:G	F256L	0.965
X:133217704:A:G	W186R	0.964
X:133217704:A:T	W186R	0.964
X:133217581:C:G	A227P	0.958
X:133217311:C:G	A317P	0.956
X:133217286:A:G	L325P	0.948
X:133217319:A:G	L314P	0.945
X:133217618:T:A	K214N	0.943
X:133217618:T:G	K214N	0.943
X:133217402:A:C	F286L	0.942
X:133217402:A:T	F286L	0.942
X:133217404:A:G	F286L	0.942
X:133217274:A:T	V329E	0.940
X:133217421:A:G	F280S	0.940
X:133217586:T:G	Q225P	0.938
X:133217414:A:C	F282L	0.934
X:133217414:A:T	F282L	0.934
X:133217416:A:G	F282L	0.934
X:133217616:T:G	Q215P	0.931
X:133217743:C:G	A173P	0.928
X:133217349:A:G	L304P	0.922
X:133217477:A:C	S261R	0.920
X:133217477:A:T	S261R	0.920

dbSNP variants (sampled 300 via entrez): RS1001551006 (X:133216625 C>T), RS1001919174 (X:133218304 A>G), RS1002268076 (X:133218541 C>T), RS1003998125 (X:133220014 T>G), RS1005119239 (X:133219567 A>G), RS1006009427 (X:133218449 G>A), RS1007672774 (X:133219930 G>A,C), RS1007725177 (X:133219436 T>C), RS1008284996 (X:133219229 A>G), RS1010637067 (X:133216677 G>A), RS1012200373 (X:133220160 G>A), RS1013936848 (X:133218455 G>A), RS1014798326 (X:133218392 C>G,T), RS1015519749 (X:133216241 T>C), RS1015573895 (X:133218766 C>G)

Disease associations

OMIM: gene MIM:300772 | 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

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects cotreatment, increases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1

Clinical trials (associated diseases)

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