TFDP2

Summary

TFDP2 (transcription factor Dp-2, HGNC:11751) is a protein-coding gene on chromosome 3q23, encoding Transcription factor Dp-2 (Q14188). Can stimulate E2F-dependent transcription.

The gene is a member of the transcription factor DP family. The encoded protein forms heterodimers with the E2F transcription factors resulting in transcriptional activation of cell cycle regulated genes. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 7029 — RefSeq curated summary.

At a glance

• GWAS associations: 33 (top 4% of genes corpus-wide)
• Clinical variants (ClinVar): 62 total — 1 pathogenic
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈6% of expected missense variation)
• GTEx eGene: eQTL in 12 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.44 (moderately constrained)
• MANE Select transcript: NM_001178139
• Notable: 62 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11751
Approved symbol	TFDP2
Name	transcription factor Dp-2
Location	3q23
Locus type	gene with protein product
Status	Approved
Aliases	Dp-2
Ensembl gene	ENSG00000114126
Ensembl biotype	protein_coding
OMIM	602160
Entrez	7029

Gene structure

Transcript identifiers

Ensembl transcripts: 51 — 29 protein_coding, 15 nonsense_mediated_decay, 4 retained_intron, 3 protein_coding_CDS_not_defined

MANE Select: ENST00000489671

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 6, TSL 2: 6, TSL 3: 3, TSL 4: 4, TSL 5: 5

ENST00000489671, ENST00000464782, ENST00000467072, ENST00000467634, ENST00000467667, ENST00000471095, ENST00000474279, ENST00000475734, ENST00000476617, ENST00000477292, ENST00000478006, ENST00000479040, ENST00000486111, ENST00000487734, ENST00000488107, ENST00000491667, ENST00000492919, ENST00000493204, ENST00000494358, ENST00000494656, ENST00000495095, ENST00000495310, ENST00000497579, ENST00000499676, ENST00000874024, ENST00000874025, ENST00000931342, ENST00000944546, ENST00000997106, ENST00000997107, ENST00000997108, ENST00000997109, ENST00000997110, ENST00000997111, ENST00000997112, ENST00000997113, ENST00000997114, ENST00000997115, ENST00000997116, ENST00001041829, ENST00001041830, ENST00001041831, ENST00001041832, ENST00001041833, ENST00001041834, ENST00001041835, ENST00001041836, ENST00001041837, ENST00001115943, ENST00001117254, ENST00001138976

RefSeq mRNA: 14 — MANE Select: NM_001178139 NM_001178138, NM_001178139, NM_001178140, NM_001178141, NM_001178142, NM_001375756, NM_001375773, NM_001375774, NM_001375775, NM_001375776, NM_001375778, NM_001375779, NM_001375780, NM_006286

CCDS: CCDS43159, CCDS54647, CCDS54648, CCDS54649, CCDS54650, CCDS93401

Canonical transcript exons

ENST00000489671 — 13 exons

Exon	Start	End
ENSE00001829733	142149183	142149544
ENSE00003351069	141944428	141952696
ENSE00003494551	142005441	142005544
ENSE00003618195	142093061	142093127
ENSE00003680631	142101735	142101841
ENSE00003760788	141952911	141953016
ENSE00003762738	141963812	141963963
ENSE00003762781	141974048	141974191
ENSE00003764619	141995020	141995141
ENSE00003767374	141993538	141993585
ENSE00003769425	141978520	141978682
ENSE00003774745	141970073	141970141
ENSE00003775216	141959674	141959840

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 97.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.6334 / max 828.2257, expressed in 1807 samples.

Highest expression (Bgee): calcaneal tendon, testis, adrenal tissue, ventricular zone, bone marrow cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TFDP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	5.9e-44	-1.58	3:141993284:A:C
Cells Cultured fibroblasts	eqtl	2.0e-12	+0.31	3:142149569:A:T
Liver	eqtl	1.1e-08	+0.40	3:142173578:G:T
Skin Sun Exposed Lower leg	eqtl	1.2e-07	+0.14	3:141971511:C:T
Esophagus Mucosa	eqtl	2.7e-04	+0.18	3:141993866:G:A
Heart Left Ventricle	eqtl	5.6e-03	-0.12	3:141972296:G:A
Colon Sigmoid	eqtl	7.7e-03	+0.38	3:143115985:C:T
Nerve Tibial	eqtl	1.4e-02	+0.10	3:142244111:GTTAACA:G
Stomach	eqtl	2.0e-02	+0.11	3:142223018:C:T
Skin Not Sun Exposed Suprapubic	eqtl	2.5e-02	-0.13	3:142052413:T:C
Colon Transverse	eqtl	2.6e-02	+0.30	3:142074179:C:T
Pancreas	eqtl	3.1e-02	-0.24	3:141853697:G:A
Thyroid	sqtl	3.6e-02	+0.45	3:141682378:G:A
Whole Blood	eqtl	4.9e-02	+0.10	3:142136919:C:T

FANTOM5 promoters

showing 10 of 11 alternative TSS:

Promoter ID	TPM avg	Samples expressed
44828	13.9347	1674
44836	8.9812	1707
44837	5.9877	1635
44827	1.3024	471
44832	1.0160	553
44835	0.4494	253
44830	0.3094	45
44829	0.2961	88
44833	0.1822	65
44834	0.0938	25

Top tissues by expression

showing 100 of 293 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.16	gold quality
left testis	UBERON:0004533	95.78	gold quality
right testis	UBERON:0004534	95.73	gold quality
testis	UBERON:0000473	94.90	gold quality
adrenal tissue	UBERON:0018303	94.39	gold quality
ventricular zone	UBERON:0003053	93.61	gold quality
bone marrow cell	CL:0002092	93.08	gold quality
bone marrow	UBERON:0002371	92.76	gold quality
thymus	UBERON:0002370	92.70	gold quality
ganglionic eminence	UBERON:0004023	92.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.46	gold quality
colonic epithelium	UBERON:0000397	92.29	gold quality
tendon	UBERON:0000043	92.26	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.99	gold quality
sperm	CL:0000019	91.86	gold quality
male germ cell	CL:0000015	91.47	gold quality
embryo	UBERON:0000922	90.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.56	gold quality
trabecular bone tissue	UBERON:0002483	90.02	gold quality
adult organism	UBERON:0007023	89.57	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.47	gold quality
gall bladder	UBERON:0002110	89.08	gold quality
sural nerve	UBERON:0015488	88.57	gold quality
placenta	UBERON:0001987	88.09	gold quality
muscle of leg	UBERON:0001383	88.08	gold quality
renal medulla	UBERON:0000362	87.56	gold quality
gastrocnemius	UBERON:0001388	87.51	gold quality
stromal cell of endometrium	CL:0002255	87.40	gold quality
myocardium	UBERON:0002349	87.39	gold quality
heart left ventricle	UBERON:0002084	87.10	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.05	gold quality
cardiac ventricle	UBERON:0002082	87.00	gold quality
nasal cavity mucosa	UBERON:0001826	86.91	gold quality
left ventricle myocardium	UBERON:0006566	86.83	gold quality
heart	UBERON:0000948	86.81	gold quality
muscle organ	UBERON:0001630	86.81	gold quality
right atrium auricular region	UBERON:0006631	86.78	gold quality
mucosa of stomach	UBERON:0001199	86.71	gold quality
cardiac atrium	UBERON:0002081	86.67	gold quality
adult mammalian kidney	UBERON:0000082	86.63	gold quality
ovary	UBERON:0000992	86.61	gold quality
duodenum	UBERON:0002114	86.48	gold quality
kidney	UBERON:0002113	86.33	gold quality
left ovary	UBERON:0002119	86.22	gold quality
triceps brachii	UBERON:0001509	86.05	gold quality
prostate gland	UBERON:0002367	86.00	gold quality
biceps brachii	UBERON:0001507	85.96	gold quality
skeletal muscle tissue	UBERON:0001134	85.90	gold quality
adrenal gland	UBERON:0002369	85.87	gold quality
muscle tissue	UBERON:0002385	85.79	gold quality
nipple	UBERON:0002030	85.65	gold quality
caput epididymis	UBERON:0004358	85.65	gold quality
cortical plate	UBERON:0005343	85.65	gold quality
corpus epididymis	UBERON:0004359	85.59	gold quality
connective tissue	UBERON:0002384	85.56	gold quality
rectum	UBERON:0001052	85.53	gold quality
heart right ventricle	UBERON:0002080	85.42	gold quality
apex of heart	UBERON:0002098	85.41	gold quality
adipose tissue	UBERON:0001013	85.39	gold quality
urethra	UBERON:0000057	85.37	gold quality
gluteal muscle	UBERON:0002000	85.29	gold quality
nasal cavity epithelium	UBERON:0005384	85.27	gold quality
cardiac muscle of right atrium	UBERON:0003379	85.26	gold quality
metanephros cortex	UBERON:0010533	85.11	gold quality
smooth muscle tissue	UBERON:0001135	85.00	gold quality
left adrenal gland	UBERON:0001234	84.94	gold quality
popliteal artery	UBERON:0002250	84.92	gold quality
tibial artery	UBERON:0007610	84.92	gold quality
right adrenal gland cortex	UBERON:0035827	84.85	gold quality
right adrenal gland	UBERON:0001233	84.83	gold quality
descending thoracic aorta	UBERON:0002345	84.76	gold quality
endometrium	UBERON:0001295	84.74	gold quality
right ovary	UBERON:0002118	84.64	gold quality
left adrenal gland cortex	UBERON:0035825	84.62	gold quality
adrenal cortex	UBERON:0001235	84.60	gold quality
urinary bladder	UBERON:0001255	84.57	gold quality
subcutaneous adipose tissue	UBERON:0002190	84.51	gold quality
tonsil	UBERON:0002372	84.45	gold quality
aorta	UBERON:0000947	84.40	gold quality
deltoid	UBERON:0001476	84.39	silver quality
female reproductive system	UBERON:0000474	84.33	gold quality
corpus callosum	UBERON:0002336	84.22	gold quality
cauda epididymis	UBERON:0004360	84.21	gold quality
thyroid gland	UBERON:0002046	84.13	gold quality
small intestine	UBERON:0002108	84.09	gold quality
ectocervix	UBERON:0012249	84.03	gold quality
tibial nerve	UBERON:0001323	84.02	gold quality
mucosa of transverse colon	UBERON:0004991	83.98	gold quality
left lobe of thyroid gland	UBERON:0001120	83.92	gold quality
endocervix	UBERON:0000458	83.86	gold quality
adipose tissue of abdominal region	UBERON:0007808	83.80	gold quality
thoracic aorta	UBERON:0001515	83.74	gold quality
stomach	UBERON:0000945	83.71	gold quality
ascending aorta	UBERON:0001496	83.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	83.67	gold quality
right lobe of thyroid gland	UBERON:0001119	83.66	gold quality
uterine cervix	UBERON:0000002	83.59	gold quality
muscle layer of sigmoid colon	UBERON:0035805	83.59	gold quality
skin of leg	UBERON:0001511	83.56	gold quality
uterus	UBERON:0000995	83.54	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	507.41
E-GEOD-93593	yes	482.82
E-CURD-112	yes	39.20
E-MTAB-8271	yes	10.51
E-ANND-3	yes	10.03
E-CURD-122	yes	5.59
E-GEOD-75367	no	704.65
E-HCAD-6	no	30.10

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	157.9
Testis	tissue	65.2	high
Postcentral gyrus	tissue	58.3
Nucleus accumbens	tissue	49.7
Choroid plexus	tissue	48.6
Hippocampus	tissue	47.6	high
Bone marrow	tissue	47.3	medium
Locus coeruleus	tissue	46.2
Spinal cord	tissue	31.9
Olfactory bulb	tissue	31.2
Cerebellum	tissue	30.2	high
Kidney	tissue	27.5	high
Skeletal muscle	tissue	26.7	medium
Placenta	tissue	26.6	high
Hippocampal formation	tissue	25.2
Corpus callosum	tissue	25.0
Putamen	tissue	24.8
Substantia nigra	tissue	24.5
Heart muscle	tissue	24.3	medium
Midbrain	tissue	23.7
Medulla oblongata	tissue	23.5
Thalamus	tissue	22.1
Pons	tissue	21.6
Superior colliculi	tissue	21.5
Duodenum	tissue	21.4	high
Ventral forebrain	tissue	20.9
Septum	tissue	20.5
Ovary	tissue	20.3	high
Thyroid gland	tissue	20.2	high
Small intestine	tissue	20.1	high
Tongue	tissue	19.9
Periaqueductal gray	tissue	19.8
Basal ganglia	tissue	19.1	high
Cerebral cortex	tissue	19.0	high
Hypothalamus	tissue	19.0
Entorhinal cortex	tissue	19.0
Occipital cortex	tissue	19.0
Somatosensory cortex	tissue	18.8
Temporal cortex	tissue	18.5
Amygdala	tissue	18.4
Motor cortex	tissue	18.3
Gallbladder	tissue	18.2	high
Prostate	tissue	18.2	medium
Prefrontal cortex	tissue	18.1
Breast	tissue	17.7	high
Adipose tissue	tissue	17.6	medium
Caudate putamen	tissue	17.2
Insular cortex	tissue	17.2
Retrosplenial and cingulate cortex	tissue	16.4
Liver	tissue	16.2	medium
Retrosplenial cortex	tissue	15.9
Parathyroid gland	tissue	15.7	high
Epididymis	tissue	15.0	high
Endometrium 1	tissue	14.3	medium
Adrenal gland	tissue	14.2	high
Colon	tissue	13.9	high
Fallopian tube	tissue	13.9	high
Smooth muscle	tissue	13.4	medium
Rectum	tissue	13.2	high
Seminal vesicle	tissue	12.9	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Flocculonodular lobe (76.3), Cerebellar cortex (75.6), Vermis (70.7), Anterior cochlear nucleus, ventral (58.2), Nucleus raphe magnus (58.2).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

8 targets:

Target	Regulation
ADAM2
HMOX1	Activation
HRK
MIR122
MYC	Unknown
PCNA	Activation
RFC3	Activation
TFDP2

Upstream regulators (CollecTRI, top): AHR, TFDP2

miRNA regulators (miRDB)

Targeting TFDP2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 329 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819

Functional genomics

gnomAD constraint: pLI 0.999, LOEUF 0.443, missense Z 2.34 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000489671 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈6% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
3:141,952,516–141,974,112	223 / 292.5	0.76	no
3:141,974,113–141,974,185	6 / 29.4	0.20	yes (p 1.6e-05)
3:141,974,186–142,101,749	162 / 206.8	0.78	no

Literature-anchored findings (GeneRIF, showing 3)

• DP2 is expressed by the bronchial epithelium, and its activation drives epithelial differentiation, suggesting that in addition to its well-characterized role in inflammatory cell migration, DP2 might contribute to airway remodeling in asthmatic patients. (PMID:25312757)
• GAB2, GSPT1, TFDP2 and ZFPM1 are four new susceptibility loci for testicular germ cell tumor. (PMID:26503584)
• This study demonstrates translation from an internal methionine. (PMID:8755520)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tfdp2	ENSDARG00000042835
mus_musculus	Tfdp2	ENSMUSG00000032411
rattus_norvegicus	Tfdp2	ENSRNOG00000011241
drosophila_melanogaster	Dp	FBGN0011763
caenorhabditis_elegans		WBGENE00001061

Paralogs (2): TFDP3 (ENSG00000183434), TFDP1 (ENSG00000198176)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q17QZ4	92.9%	Diamond
Arabidopsis thaliana	Q9FNY2	53.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GK5	protein-coding	256356
ATP1B3	protein-coding	483
XRN1	protein-coding	54464
ATR	protein-coding	545

Protein

Protein identifiers

Transcription factor Dp-2 — Q14188 (reviewed: Q14188)

Alternative names: E2F dimerization partner 2

All UniProt accessions (11): C9J461, C9J5D5, C9J872, C9J977, C9JCY5, C9JNB6, Q14188, C9JTZ9, F8WAY9, H7C5C2, R4GN09

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 TFDP2:E2F complex functions in the control of cell-cycle progression from G1 to S phase. 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 DRTF1/E2F 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. During the cell cycle, RB becomes phosphorylated in mid-to-late G1 phase, detaches from the DRTF1/E2F complex rendering E2F transcriptionally active. Viral oncoproteins, notably E1A, T-antigen and HPV E7, are capable of sequestering RB protein, thus releasing the active complex. Interacts with GMCL. 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 TFDP2:E2F1 interacts with CEBPA; the interaction prevents CEBPA binding to target genes promoters and represses its transcriptional activity.

Subcellular location. Nucleus.

Tissue specificity. High levels in heart and skeletal muscle. Also found in placenta, kidney, brain, lung and liver. The presence as well as the abundance of the different transcripts appear to vary significantly in different tissues and cell lines.

Post-translational modifications. Ser-24 is probably phosphorylated by CDK2.

Similarity. Belongs to the E2F/DP family.

Isoforms (8)

UniProt ID	Names	Canonical?
Q14188-1	Alpha, 49 kDa	yes
Q14188-2	Beta, 43 kDa
Q14188-3	Gamma
Q14188-4	Delta, 48 kDa
Q14188-5	Epsilon
Q14188-6	6
Q14188-7	7
Q14188-8	8

RefSeq proteins (14): NP_001171609, NP_001171610, NP_001171611, NP_001171612, NP_001171613, NP_001362685, NP_001362702, NP_001362703, NP_001362704, NP_001362705, NP_001362707, NP_001362708, NP_001362709, NP_006277 (=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): splice variant 7, region of interest 5, helix 4, modified residue 3, compositionally biased region 2, sequence variant 2, strand 2, short sequence motif 2, initiator methionine 1, chain 1, DNA-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
1CF7	STRUCTURAL BASIS OF DNA RECOGNITION BY THE HETERODIMERIC CELL CYCLE TRANSCRIPTION FACTOR …	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14188-F1	66.53	0.41

Human Protein Atlas

Protein class: Predicted intracellular proteins, Transcription factors, Helix-turn-helix domains, Cancer-related genes, Candidate cancer biomarkers

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; mitotic spindle; vesicles

Antibody reliability (HPA): IH supported · IF supported

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)

Type	Positions
N-acetylthreonine	2
Phosphoserine	24, 122

Function

Pathways and Gene Ontology

Reactome pathways

12 curated (TAS) of 48; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

48 pathways:

ID	Pathway	Evidence
R-HSA-9661069	Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) ⚕	curated
R-HSA-111448	Activation of NOXA and translocation to mitochondria	curated
R-HSA-139915	Activation of PUMA and translocation to mitochondria	curated
R-HSA-69656	Cyclin A:Cdk2-associated events at S phase entry	curated
R-HSA-69231	Cyclin D associated events in G1	curated
R-HSA-69202	Cyclin E associated events during G1/S transition	curated
R-HSA-1538133	G0 and Early G1	curated
R-HSA-2559585	Oncogene Induced Senescence	curated
R-HSA-2559580	Oxidative Stress Induced Senescence	curated
R-HSA-2173796	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	curated
R-HSA-6804114	TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest	curated
R-HSA-8953750	Transcriptional Regulation by E2F6	curated
R-HSA-9659787	Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects ⚕	—
R-HSA-9687139	Aberrant regulation of mitotic cell cycle due to RB1 defects ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-9675126	Diseases of mitotic cell cycle ⚕	—
R-HSA-114452	Activation of BH3-only proteins	—
R-HSA-109581	Apoptosis	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-2559583	Cellular Senescence	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-1266738	Developmental Biology	—
R-HSA-113510	E2F mediated regulation of DNA replication	—
R-HSA-69236	G1 Phase	—
R-HSA-69206	G1/S Transition	—
R-HSA-69205	G1/S-Specific Transcription	electronic
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-113501	Inhibition of replication initiation of damaged DNA by RB1/E2F1	electronic
R-HSA-109606	Intrinsic Pathway for Apoptosis	—
R-HSA-453279	Mitotic G1 phase and G1/S transition	—
R-HSA-1912422	Pre-NOTCH Expression and Processing	—
R-HSA-1912408	Pre-NOTCH Transcription and Translation	electronic
R-HSA-5357801	Programmed Cell Death	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-69242	S Phase	—
R-HSA-162582	Signal Transduction	—
R-HSA-157118	Signaling by NOTCH	—
R-HSA-170834	Signaling by TGF-beta Receptor Complex	—
R-HSA-9006936	Signaling by TGFB family members	—
R-HSA-6791312	TP53 Regulates Transcription of Cell Cycle Genes	—
R-HSA-1362277	Transcription of E2F targets under negative control by DREAM complex	electronic
R-HSA-1362300	Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1	electronic
R-HSA-3700989	Transcriptional Regulation by TP53	—
R-HSA-2173793	Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	—
R-HSA-9616222	Transcriptional regulation of granulopoiesis	electronic

MSigDB gene sets: 384 (showing top): REACTOME_INHIBITION_OF_REPLICATION_INITIATION_OF_DAMAGED_DNA_BY_RB1_E2F1, REACTOME_SIGNALING_BY_NOTCH, MULLIGHAN_NPM1_SIGNATURE_3_UP, MORF_FLT1, REACTOME_G1_S_SPECIFIC_TRANSCRIPTION, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, HNF3ALPHA_Q6, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_MSH3, CHIARETTI_T_ALL_REFRACTORY_TO_THERAPY, HOFMANN_CELL_LYMPHOMA_UP, MORF_BRCA1, IVANOVA_HEMATOPOIESIS_MATURE_CELL, TAL1ALPHAE47_01, MORF_ESR1

GO Biological Process (6): DNA-templated transcription (GO:0006351), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of cell cycle (GO:0051726)

GO Molecular Function (7): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), transcription factor binding (GO:0008134), protein domain specific binding (GO:0019904), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), RNA polymerase II transcription regulator complex (GO:0090575), transcription regulator complex (GO:0005667)

Reactome top-level categories

16 top-level categories:

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
Apoptosis	1

GO top-level categories

29 GO namespaces:

Category	Terms
DNA-templated transcription	2
regulation of DNA-templated transcription	2
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
protein binding	2
cellular anatomical structure	2
gene expression	1
RNA biosynthetic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
cell cycle	1
regulation of cellular process	1
chromatin	1
DNA-binding transcription factor activity	1
nucleic acid binding	1
transcription cis-regulatory region 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
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
transcription regulator complex	1
nuclear protein-containing complex	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of DNA-templated transcription	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	direct assay
RNA polymerase II transcription regulator complex	CC	direct assay
nucleoplasm	CC	direct assay
protein domain specific binding	MF	physical interaction
transcription factor binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 868 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TFDP2	E2F1	Q01094	666
TFDP2	E2F5	Q15329	632
TFDP2	E2F4	Q16254	490
TFDP2	ZSCAN2	Q7Z7L9	425
TFDP2	E2F3	O00716	411
TFDP2	E2F2	Q14209	407
TFDP2	RNF7	Q9UBF6	399
TFDP2	SOX1	O00570	389
TFDP2	E2F8	A0AVK6	382
TFDP2	HIKESHI	Q53FT3	370
TFDP2	MAPRE1	Q15691	370
TFDP2	E2F7	Q96AV8	362
TFDP2	GAS6	Q14393	360
TFDP2	IQGAP1	P46940	359
TFDP2	CCNE2	O96020	359

IntAct

Human interaction partners of TFDP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

9 partners by confidence:

Partner	Interaction type	MIscore	Records
E2F6	physical association	0.910	7
E2F4	direct interaction	0.770	1
RB1	physical association	0.740	1
E7	physical association	0.560	1
E2F3	association	0.530	2
YWHAE	physical association	0.400	1
E6	physical association	0.370	8
IL31	physical association	0.370	1
MCIDAS	association	0.350	1

BioGRID (109 interactions; top human partners by supporting records): E2F6 (Two-hybrid; 13 records), E2F1 (Affinity Capture-MS; 7 records), E2F4 (Affinity Capture-MS; 6 records), RB1 (Affinity Capture-MS; 5 records), L3MBTL2 (Affinity Capture-MS; 4 records), PCGF6 (Affinity Capture-MS; 4 records), E2F2 (Affinity Capture-MS; 3 records), E2F3 (Affinity Capture-MS; 3 records), E2F5 (Affinity Capture-MS; 3 records), COMMD8 (Affinity Capture-MS; 2 records), LIN37 (Affinity Capture-MS; 2 records), LIN54 (Affinity Capture-MS; 2 records), LIN9 (Affinity Capture-MS; 2 records), RBL1 (Affinity Capture-Western; 2 records), RBL2 (Affinity Capture-MS; 2 records)

Disease & clinical

Genetic variants

Variant evidence for TFDP2: 62 ClinVar records (1 pathogenic / likely pathogenic); 33 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	40
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2671581	Single allele	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore TFDP2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 45 predictions of 1,301):

Position(s)	Effect	Δscore	Sites
3:141959672–141959673	donor_loss	1.0000	4
3:141959841–141959842	acceptor_loss	1.0000	5
3:141959848	acceptor_gain	1.0000
3:141963810–141963811	donor_loss	1.0000	5
3:141963964–141963965	acceptor_loss	1.0000	4
3:141974046–141974047	donor_loss	1.0000	5
3:141978518–141978519	donor_loss	1.0000	5
3:141978683–141978684	acceptor_loss	1.0000	6
3:141995018–141995019	donor_loss	1.0000	6
3:142005545–142005546	acceptor_loss	1.0000	4

AlphaMissense

1,145 missense substitutions predicted likely pathogenic (of 2,919 scored), across 256 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M192	9	0.984	1.000
M194	9	0.943	0.999
M137	9	0.907	0.995
D186	8	1.000	1.000
N179	8	0.999	1.000
N189	8	0.999	1.000
F135	8	0.996	1.000
F302	8	0.993	0.999
D311	8	0.987	0.997
N255	8	0.986	0.997
F300	8	0.985	0.999
F306	8	0.983	1.000
H134	8	0.980	0.997
D176	8	0.978	0.994
D294	8	0.978	0.998
D310	8	0.978	0.995
D288	8	0.977	0.995
N152	8	0.971	0.999
F276	8	0.968	0.999
D156	8	0.964	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	8.44e-06
Rectum Adenocarcinoma (TCGA)	favorable	0.000193
Glioblastoma Multiforme (validation)	favorable	0.000507
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000585

Disease associations

OMIM: gene MIM:602160 | disease phenotypes:

GWAS associations

showing 30 of 33 associations:

Study	Trait	p-value
GCST008058_31	Estimated glomerular filtration rate	1e-44
GCST008059_23	Estimated glomerular filtration rate	2e-40
GCST008747_74	Estimated glomerular filtration rate	4e-26
GCST90002396_327	Mean reticulocyte volume	2e-25
GCST90002392_339	Mean corpuscular volume	9e-23
GCST007876_133	Estimated glomerular filtration rate	1e-20
GCST008747_4	Estimated glomerular filtration rate	2e-20
GCST90002390_607	Mean corpuscular hemoglobin	8e-20
GCST90002397_674	Mean spheric corpuscular volume	9e-20
GCST007344_66	Estimated glomerular filtration rate	3e-17
GCST003401_25	Glomerular filtration rate in non diabetics (creatinine)	2e-14
GCST003372_38	Glomerular filtration rate (creatinine)	9e-14
GCST90002393_497	Monocyte count	5e-13
GCST004602_87	Mean corpuscular volume	1e-12
GCST000649_6	Chronic kidney disease	3e-11
GCST004292_37	Glomerular filtration rate (creatinine)	5e-11
GCST010703_50	Brain morphology (MOSTest)	1e-10
GCST007344_101	Estimated glomerular filtration rate	4e-10
GCST008972_201	Urate levels	5e-10
GCST010699_49	Brain morphology (min-P)	6e-10
GCST003246_1	Testicular germ cell tumor	2e-9
GCST006871_2	Total hippocampal volume	3e-9
GCST010701_108	Cortical surface area (MOSTest)	4e-9
GCST004630_131	Mean corpuscular hemoglobin	6e-9
GCST007344_57	Estimated glomerular filtration rate	1e-8
GCST010702_69	Subcortical volume (MOSTest)	1e-8
GCST003790_26	Glomerular filtration rate	4e-8
GCST010226_1	Cortical surface area (global PC1)	4e-8
GCST011986_2	Congenital left-sided heart lesions	5e-8
GCST008971_135	Urate levels	8e-8

EFO canonical traits (from GWAS)

7 canonical traits:

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0005035	hippocampal volume
EFO:0004531	urate measurement
EFO:0008381	total cortical area measurement
EFO:0004346	neuroimaging measurement
EFO:0005091	monocyte count
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105986 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4082745	EC50	8 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.75	IC50	1800	nM	CHEMBL4082745

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
5-[[6-chloro-5-(4-phenylphenyl)-1H-benzimidazol-2-yl]oxy]-2-methylbenzoic acid	1471632: Binding affinity to DP2 receptor (unknown origin)	ic50	1.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
Tretinoin	decreases expression	3
Valproic Acid	affects expression, decreases expression	3
trichostatin A	affects cotreatment, decreases expression	2
cobaltous chloride	decreases expression, increases expression	2
entinostat	decreases expression, affects cotreatment	2
Air Pollutants	decreases expression, affects expression, increases abundance	2
Nickel	decreases expression	2
Ozone	affects expression, increases abundance, affects cotreatment, increases oxidation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cadmium Chloride	increases expression	2
p-Chloromercuribenzoic Acid	decreases expression, affects cotreatment	2
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
N(6)-(delta(2)-isopentenyl)adenine	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
testosterone undecanoate	decreases expression	1
ochratoxin A	decreases acetylation, decreases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
aflatoxin B2	decreases methylation	1
cupric chloride	affects expression	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
cotylenin A	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4026676	Binding	Binding affinity to DP2 receptor (unknown origin)	Hit-to-Lead Optimization and Discovery of 5-((5-([1,1’-Biphenyl]-4-yl)-6-chloro-1H-benzo[d]imidazol-2-yl)oxy)-2-methylbenzoic Acid (MK-3903): A Novel Class of Benzimidazole-Based Activators of AMP-Activated Protein Kinase. — *J Med Chem*

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3J7	Abcam HEK293T TFDP2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TFDP2 across ~30M SureChEMBL compounds — explore on Sugi Predict.