E2F3

Summary

E2F3 (E2F transcription factor 3, HGNC:3115) is a protein-coding gene on chromosome 6p22.3, encoding Transcription factor E2F3 (O00716). Transcription activator that binds DNA cooperatively with DP proteins 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. It is a selective cancer dependency (DepMap: 26.4% of cell lines).

This gene encodes a member of a small family of transcription factors that function through binding of DP interaction partner proteins. The encoded protein recognizes a specific sequence motif in DNA and interacts directly with the retinoblastoma protein (pRB) to regulate the expression of genes involved in the cell cycle. Altered copy number and activity of this gene have been observed in a number of human cancers. There are pseudogenes for this gene on chromosomes 2 and 17. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1871 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 54 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 26.4% of screened cell lines
• Transcription factor: yes — 72 downstream targets (CollecTRI)
• MANE Select transcript: NM_001949

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3115
Approved symbol	E2F3
Name	E2F transcription factor 3
Location	6p22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000112242
Ensembl biotype	protein_coding
OMIM	600427
Entrez	1871

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000346618, ENST00000535432, ENST00000938961

RefSeq mRNA: 2 — MANE Select: NM_001949 NM_001243076, NM_001949

CCDS: CCDS4545, CCDS58999

Canonical transcript exons

ENST00000346618 — 7 exons

Exon	Start	End
ENSE00000689096	20481206	20481425
ENSE00000689160	20482762	20482920
ENSE00000689263	20488113	20488248
ENSE00001083306	20486689	20486803
ENSE00001148453	20401879	20402625
ENSE00001984976	20479846	20479957
ENSE00002241451	20490168	20493714

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 96.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6743 / max 350.7578, expressed in 1766 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66247	15.9354	1367
66251	4.8688	1594
66246	0.3433	154
66252	0.1860	49
66248	0.1856	76
66253	0.1552	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.63	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.86	gold quality
middle temporal gyrus	UBERON:0002771	92.17	gold quality
endothelial cell	CL:0000115	91.05	gold quality
tendon of biceps brachii	UBERON:0008188	88.82	silver quality
gingival epithelium	UBERON:0001949	87.36	silver quality
tibia	UBERON:0000979	87.19	gold quality
cartilage tissue	UBERON:0002418	86.79	gold quality
bone marrow	UBERON:0002371	86.61	gold quality
visceral pleura	UBERON:0002401	86.61	gold quality
monocyte	CL:0000576	86.54	gold quality
embryo	UBERON:0000922	86.40	gold quality
trabecular bone tissue	UBERON:0002483	86.37	gold quality
mononuclear cell	CL:0000842	86.30	gold quality
leukocyte	CL:0000738	86.26	gold quality
blood	UBERON:0000178	85.84	gold quality
medial globus pallidus	UBERON:0002477	85.83	gold quality
ganglionic eminence	UBERON:0004023	85.72	gold quality
ventricular zone	UBERON:0003053	85.61	gold quality
sperm	CL:0000019	84.90	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.44	gold quality
amniotic fluid	UBERON:0000173	84.01	gold quality
gingiva	UBERON:0001828	83.66	silver quality
pericardium	UBERON:0002407	83.53	gold quality
germinal epithelium of ovary	UBERON:0001304	83.36	gold quality
globus pallidus	UBERON:0001875	83.31	gold quality
epithelium of nasopharynx	UBERON:0001951	83.10	gold quality
pleura	UBERON:0000977	82.73	gold quality
stromal cell of endometrium	CL:0002255	82.64	gold quality
saphenous vein	UBERON:0007318	82.64	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-75367	yes	364.99
E-ANND-3	yes	5.47

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

72 targets.

Target	Regulation
ASF1B	Activation
ATM	Activation
AURKA	Activation
BIRC5	Activation
BRCA1
CCNA2	Unknown
CCNB1	Unknown
CCND3	Activation
CCNE1	Activation
CDC6	Unknown
CDCA4	Activation
CDCA7	Activation
CDK1	Unknown
CDK2
CDKN1A	Activation
CDKN2A	Activation
CDT1	Activation
CITED2
CUX1	Unknown
DDB2
DIRAS3
DLST
E2F1	Activation
ERICD	Repression
FBN2	Activation
FBXO43	Activation
FBXO5	Activation
FGF2	Activation
FGFR2	Activation
FOXO1	Activation

JASPAR motifs

Motif	Name	Family
MA0469.2	E2F3	E2F
MA0469.3	E2F3	E2F
MA0469.4	E2F3	E2F

JASPAR matrix evidence (PMIDs): PMID:18836037

Upstream regulators (CollecTRI, top): BRD7, CEBPA, E2F1, E2F4, HIF1A, KLF5, MYC, NKX2-1, POU5F1, RB1, REL, TFDP3, TP53, TRIM28

miRNA regulators (miRDB)

251 targeting E2F3, 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-8485	100.00	77.57	4731
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4668-3P	100.00	68.74	2635
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-4283	100.00	66.42	2097
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-499A-5P	99.98	70.79	1323
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

DepMap (CRISPR cell-line fitness): dependent in 26.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• determination of interaction with RYBP and YY1 (PMID:12411495)
• Data suggest that the physical interaction of TFE3 and E2F3 facilitates transcriptional activation of the p68 gene and provides strong evidence for the specificity of E2F function. (PMID:12748276)
• In bladder cancer, the E2F3 gene is associated with overexpression of its encoded mRNA transcripts and high levels of E2F3 expression. (PMID:14716298)
• We conclude that E2F3 is frequently amplified and overexpressed in invasively growing bladder cancer (stage pT1-4). E2F3 expression appears to provide a growth advantage to tumor cells by activating cell proliferation in a subset of bladder tumors. (PMID:15122326)
• results suggest that DEK and E2F3 are potential targets of 6p gains in retinoblastoma (PMID:16007192)
• E2F3 mRNA and protein are overexpressed in retinoblastoma. (PMID:16180235)
• E2F3 levels have a critical role in modifying cellular proliferation rate in human bladder and prostate cancer. (PMID:16909110)
• E2F3 is overexpressed in 55-70% of squamous cell carcinomas and 79% of adenocarcinomas of the lung. In addition very high level expression of nuclear E2F3 is found in almost all small cell lung cancers analysed. (PMID:16938365)
• E2F1, E2F2, and E2F3 directly bind the promoter of the mir-17-92 cluster, activating its transcription. miR-20a from the mir-17-92 cluster in turn modulates the translation of E2F2 and E2F3, suggesting an autoregulatory feedback loop. (PMID:17135249)
• Study demonstrates the strength of E2F3 as a potential marker for discriminating benign and malignant disease, addressing the current limitations of serum PSA measurements. (PMID:17701752)
• requirement of E2F3 for BCR/ABL leukemogenesis (PMID:17925491)
• Inactivation of the retinoblastoma pathway occurs in bladder tumors with 6p22 amplification. (PMID:18037967)
• E2F3 contributes to ataxia telangiectasia mutated (ATM) kinase-dependent p53 phosphorylation and apoptosis in cells expressing E1A. (PMID:18235226)
• Genes involved in the E2F3 pathway are associated with chemotherapy sensitivity among ER- tumors. The mutant p53 signature and expression of ER-related genes were associated with lower sensitivity to chemotherapy in ER+ breast tumors only. (PMID:18445275)
• A significant elevation in expression of E2F3 in oral squamous cell carcinoma cells was seen in carbon and neon-irradiated cells. (PMID:18514338)
• Expression of E2F3 was lowest in early-stage tumors and highest in metastatic tissue. Expression profiling of miRNAs in WT showed that expression of each measured member of the Oncomir-1 family was highest in WT relative to other kidney tumor subtypes (PMID:18519660)
• E2F3 gain is associated with the late stage of retinoblastoma. (PMID:18785023)
• miR-128 can inhibit proliferation of glioma cells through one of its targets, E2F3a. (PMID:18810376)
• report confirms significant mRNA overexpression of KIF14 and E2F3 together in a large cohort of retinoblastoma tumors (PMID:19190782)
• these data reveal the novel ability of E2f3 to function as a master regulator of the DNA damage response. (PMID:19917728)
• the hypoxia component of ischemia may limit wound re-epithelialization by stabilizing HIF-1alpha, which induces miR-210 expression, resulting in the down-regulation of the cell-cycle regulatory protein E2F3 (PMID:20308562)
• E2F3a induces apoptosis in HepG2 cells and plays important roles in regulating transcription (PMID:20803551)
• Data report that ANCCA directly interacts with E2F1 to E2F3 in its complex with MLL and that its N terminus interacts with both the N and C termini of E2F1. (PMID:20855524)
• miR-34a targeting the Sirt1 and E2F3 genes could negatively regulate the resistance to 5-FU in human colorectal cancer DLD-1 cells. (PMID:21067862)
• Data show that E2F is likely a central coordinator of multiple responses that culminate in regulation of EBP1 gene expression, and which may vary depending on cell type and context. (PMID:21085677)
• Our results suggest that down-regulation of miR-200b could lead to E2F3 overexpression and in turn contribute to chemoresistance of lung adenocarcinoma cells to docetaxel. (PMID:22139708)
• just as E2F3, HELLS is overexpressed in human tumours including prostate cancer, indicating that either factor may contribute to the malignant progression of tumours (PMID:22157815)
• human Pumilio homologs Pum 1 and Pum 2 repress the translation of E2F3 by binding to the E2F3 3’ untranslated region (UTR) and also enhance the activity of multiple E2F3 targeting microRNAs (miRNAs) (PMID:22345517)
• miR-203 induced cellular senescence by targeting E2F3 in human melanoma Mewo and A2058 cells (PMID:22354972)
• E2F3 controls the ubiquitination of PCNA through the transcriptional regulation of Rad18. (PMID:22391204)
• Data suggest that microRNA/mRNA pairs in hsa-miR-140-3p/RAD51AP1/, hsa-miR-145/E2F3, hsa-miR-139-5p/TOP2A, and hsa-miR-133a/GCLC were correlated with ovarian tumorigenesis. (PMID:22452920)
• Studied E2F3 and its two isoforms E2F3a and E2F3b in wild-type ovarian carcinomas and ovarian carcinomas associated with germline BRCA1 and BRCA2 mutations. (PMID:22887716)
• findings authenticate the efficiency of siRNA (E2F3) to fight against breast cancer; hence, the siRNA mediated E2F3 gene silencing knockdown the E2F3 (PMID:22960857)
• A homology model of DNA-binding domain of transcription factor E2F3 was generated for the design of selective ligands. (PMID:23009996)
• Trim28 regulates cell proliferation by bridging HDAC1 and E2F3 and E2F4 interactions. (PMID:23060449)
• down-regulation of E2f3 with age helps drive the dramatic decline in Igf2 expression in postnatal organs, and E2F3 overexpression in cancer induces IGF2 overexpression (PMID:23530192)
• The correlation between CCND1, E2F3 and miR-449b showed that miR-449b could downregulate CCND1 and E2F3 expression. This, in turn, reduced the proliferative ability of colon cancer stem cells. (PMID:23674142)
• Overexpression of E2F3 promotes proliferation of functional human beta cells without induction of apoptosis. (PMID:23907129)
• Studies show that a large fraction of E2F3 target genes are synergistically coregulated by aberrant ETS proteins. (PMID:23940108)
• two cell cycle-related molecules, cyclin D3 and E2F3, were identified as the direct miR-503 targets. (PMID:23967867)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	e2f3	ENSDARG00000070463
mus_musculus	E2f3	ENSMUSG00000016477
rattus_norvegicus	E2f3	ENSRNOG00000029273

Paralogs (7): E2F2 (ENSG00000007968), E2F1 (ENSG00000101412), E2F8 (ENSG00000129173), E2F5 (ENSG00000133740), E2F7 (ENSG00000165891), E2F6 (ENSG00000169016), E2F4 (ENSG00000205250)

Protein

Protein identifiers

Transcription factor E2F3 — O00716 (reviewed: O00716)

All UniProt accessions (1): O00716

UniProt curated annotations — full annotation on UniProt →

Function. Transcription activator that binds DNA cooperatively with DP proteins 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 DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase. E2F3 binds specifically to RB1 in a cell-cycle dependent manner. Inhibits adipogenesis, probably through the repression of CEBPA binding to its target gene promoters.

Subunit / interactions. Component of the DRTF1/E2F transcription factor complex. Binds cooperatively with TFDP1/Dp-1 to E2F sites. Interacts with retinoblastoma protein RB1 and related proteins (such as RBL1) that inhibit the E2F transactivation domain. Binds EAPP.

Subcellular location. Nucleus.

Similarity. Belongs to the E2F/DP family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00716-1	1	yes
O00716-2	2

RefSeq proteins (2): NP_001230005, NP_001940* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003316	E2F_WHTH_DNA-bd_dom	Domain
IPR015633	E2F	Family
IPR032198	E2F_CC-MB	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR037241	E2F-DP_heterodim	Homologous_superfamily

Pfam: PF02319, PF16421

UniProt features (19 total): region of interest 7, compositionally biased region 4, splice variant 3, sequence variant 2, 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-O00716-F1	61.16	0.25

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1912408	Pre-NOTCH Transcription and Translation
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-2559585	Oncogene Induced Senescence
R-HSA-68911	G2 Phase
R-HSA-69231	Cyclin D associated events in G1
R-HSA-9661069	Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)

MSigDB gene sets: 437 (showing top): RNGTGGGC_UNKNOWN, E2F_Q4, CREL_01, REACTOME_SIGNALING_BY_NOTCH, MODULE_52, E2F_Q4_01, FREAC2_01, E2F4DP1_01, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, CMYB_01, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, KONG_E2F3_TARGETS, CAGCTG_AP4_Q5

GO Biological Process (10): G1/S transition of mitotic cell cycle (GO:0000082), regulation of transcription by RNA polymerase II (GO:0006357), transcription initiation at RNA polymerase II promoter (GO:0006367), protein import into nucleus (GO:0006606), positive regulation of cell population proliferation (GO:0008284), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of fat cell proliferation (GO:0070345), positive regulation of vascular associated smooth muscle cell apoptotic process (GO:1905461), regulation of DNA-templated transcription (GO:0006355), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (12): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA-binding transcription activator activity (GO:0001216), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), sequence-specific DNA binding (GO:0043565), protein dimerization activity (GO:0046983), sequence-specific double-stranded DNA binding (GO:1990837), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), RNA polymerase II transcription regulator complex (GO:0090575), transcription regulator complex (GO:0005667)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Cellular Senescence	2
Pre-NOTCH Expression and Processing	1
Mitotic G2-G2/M phases	1
G1 Phase	1
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription cis-regulatory region binding	4
regulation of DNA-templated transcription	3
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
positive regulation of DNA-templated transcription	2
DNA-templated transcription	2
DNA-binding transcription factor activity	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
DNA-templated transcription initiation	1
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
negative regulation of cell population proliferation	1
fat cell proliferation	1
regulation of fat cell proliferation	1
positive regulation of smooth muscle cell apoptotic process	1
vascular associated smooth muscle cell apoptotic process	1
regulation of vascular associated smooth muscle cell apoptotic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	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
transcription regulator activity	1
DNA binding	1
protein binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1

Protein interactions and networks

STRING

1958 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
E2F3	RB1	P06400	897
E2F3	TFDP1	Q14186	886
E2F3	TFE3	P19532	839
E2F3	CCND1	P24385	764
E2F3	MYCN	P04198	728
E2F3	CDK2	P24941	722
E2F3	MYC	P01106	721
E2F3	TP53	P04637	707
E2F3	RBL2	Q08999	706
E2F3	CDKN2A	P42771	666
E2F3	SIRT1	Q96EB6	657
E2F3	CCNE2	O96020	651
E2F3	CDK6	Q00534	651
E2F3	TFDP2	Q14188	641
E2F3	TFDP3	Q5H9I0	634

IntAct

51 interactions, top by confidence:

A	B	Type	Score
RB1	E2F3	psi-mi:“MI:0915”(physical association)	0.820
L3MBTL3	E2F3	psi-mi:“MI:0915”(physical association)	0.560
TFDP2	E2F3	psi-mi:“MI:0914”(association)	0.530
TFDP3	E2F3	psi-mi:“MI:0914”(association)	0.530
TFDP1	E2F3	psi-mi:“MI:0914”(association)	0.530
HELLS	E2F3	psi-mi:“MI:0915”(physical association)	0.500
E2F3	MSH2	psi-mi:“MI:2364”(proximity)	0.480
Sp1	E2F3	psi-mi:“MI:0915”(physical association)	0.400
E2F3	L3MBTL2	psi-mi:“MI:0915”(physical association)	0.400
BRD8	E2F3	psi-mi:“MI:0915”(physical association)	0.400
E2F3	VPS72	psi-mi:“MI:0915”(physical association)	0.400
DEK	E2F3	psi-mi:“MI:0915”(physical association)	0.400
E2F3	SSR3	psi-mi:“MI:0915”(physical association)	0.400
MYBL2	E2F3	psi-mi:“MI:0915”(physical association)	0.400
E2F3	E7	psi-mi:“MI:0915”(physical association)	0.400
E7	E2F3	psi-mi:“MI:0915”(physical association)	0.400
CCL1	E2F3	psi-mi:“MI:0915”(physical association)	0.370
	E2F3	psi-mi:“MI:0914”(association)	0.350
	KPNA4	psi-mi:“MI:0914”(association)	0.350
RB1	KPNA3	psi-mi:“MI:0914”(association)	0.350
TFDP2	MCIDAS	psi-mi:“MI:0914”(association)	0.350
E2F3	MYO1C	psi-mi:“MI:0914”(association)	0.350

BioGRID (105): E2F3 (Affinity Capture-MS), E2F3 (Affinity Capture-MS), E2F3 (Co-localization), E2F3 (Reconstituted Complex), UCHL5 (Reconstituted Complex), E2F3 (Affinity Capture-MS), E2F3 (Affinity Capture-MS), E2F3 (Affinity Capture-RNA), E2F3 (Affinity Capture-RNA), E2F3 (Affinity Capture-MS), E2F3 (Affinity Capture-RNA), E2F3 (Co-localization), E2F3 (Co-localization), E2F3 (Co-localization), E2F3 (Biochemical Activity)

ESM2 similar proteins: A0JMD2, A5D7E9, A6NMN3, A7XW16, F1QDF8, F1RDM5, O00716, O09139, O35261, O35668, O42367, O43151, O54968, P14607, P59054, P59598, P97691, Q00175, Q01094, Q08050, Q14209, Q14494, Q16254, Q4V8F1, Q5DU28, Q5NUA6, Q5RA25, Q5W1J6, Q5ZL67, Q60664, Q60795, Q61321, Q61501, Q61985, Q63449, Q66IG8, Q6DJE5, Q6JPI3, Q76N89, Q7TS75

Diamond homologs: A0AVK6, A5HWA8, D4A4D7, E1BE02, E1BKK0, F1LMN3, F1QZ88, F6YVB9, F7EA39, O00716, O35261, O54917, O75461, P56931, Q01094, Q08DY6, Q14209, Q15329, Q16254, Q20619, Q27368, Q58FA4, Q5RIX9, Q61501, Q61502, Q62814, Q6DE14, Q6S7F2, Q8LSZ4, Q8R0K9, Q8RWL0, Q90977, Q96AV8, Q9FNY0, Q9FV70, Q9FV71, Q9LFQ9, O09139, O77051

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CHEK1	up-regulates	E2F3	phosphorylation
E2F3	“up-regulates activity”	TFDP1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 34 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
Cyclin E associated events during G1/S transition	5	52.9×	6e-06
Cyclin A:Cdk2-associated events at S phase entry	5	49.2×	6e-06
Transcriptional Regulation by TP53	5	11.5×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of cell cycle	5	11.7×	3e-03
transcription by RNA polymerase II	5	11.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1903 predictions. Top by Δscore:

Variant	Effect	Δscore
6:20479954:AAAA:A	donor_gain	1.0000
6:20479956:AA:A	donor_gain	1.0000
6:20479956:AAGTA:A	donor_loss	1.0000
6:20479957:AGTAA:A	donor_loss	1.0000
6:20479958:G:GG	donor_gain	1.0000
6:20479958:GTAAG:G	donor_loss	1.0000
6:20479959:T:A	donor_loss	1.0000
6:20481422:GGAT:G	donor_gain	1.0000
6:20481423:GAT:G	donor_gain	1.0000
6:20481423:GATG:G	donor_gain	1.0000
6:20481426:G:GG	donor_gain	1.0000
6:20488112:GA:G	acceptor_gain	1.0000
6:20490164:TCA:T	acceptor_loss	1.0000
6:20490166:A:AG	acceptor_gain	1.0000
6:20490166:A:AT	acceptor_loss	1.0000
6:20490167:G:GG	acceptor_gain	1.0000
6:20490167:GACTT:G	acceptor_gain	1.0000
6:20402624:CGG:C	donor_loss	0.9900
6:20402626:GT:G	donor_loss	0.9900
6:20402627:T:G	donor_loss	0.9900
6:20404139:T:G	donor_gain	0.9900
6:20440047:G:GG	donor_gain	0.9900
6:20479955:AAA:A	donor_gain	0.9900
6:20481203:A:AG	acceptor_gain	0.9900
6:20481204:A:G	acceptor_gain	0.9900
6:20481421:TGGAT:T	donor_gain	0.9900
6:20481422:GGATG:G	donor_gain	0.9900
6:20481424:ATG:A	donor_loss	0.9900
6:20481425:TGTG:T	donor_loss	0.9900
6:20481426:GT:G	donor_loss	0.9900

AlphaMissense

2992 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:20481232:C:G	R178G	1.000
6:20481245:C:A	S182Y	1.000
6:20481245:C:T	S182F	1.000
6:20481247:C:T	L183F	1.000
6:20481248:T:A	L183H	1.000
6:20481248:T:C	L183P	1.000
6:20481250:G:C	G184R	1.000
6:20481251:G:A	G184D	1.000
6:20481254:T:C	L185P	1.000
6:20481256:C:T	L186F	1.000
6:20481257:T:A	L186H	1.000
6:20481257:T:C	L186P	1.000
6:20481260:C:A	T187N	1.000
6:20481260:C:T	T187I	1.000
6:20481268:T:C	F190L	1.000
6:20481269:T:C	F190S	1.000
6:20481270:C:A	F190L	1.000
6:20481270:C:G	F190L	1.000
6:20481278:T:C	L193P	1.000
6:20481308:A:G	D203G	1.000
6:20481311:T:C	L204S	1.000
6:20481311:T:G	L204W	1.000
6:20481312:G:C	L204F	1.000
6:20481312:G:T	L204F	1.000
6:20481322:G:C	A208P	1.000
6:20481332:T:A	L211Q	1.000
6:20481332:T:C	L211P	1.000
6:20481337:G:A	V213M	1.000
6:20481337:G:C	V213L	1.000
6:20481337:G:T	V213L	1.000

dbSNP variants (sampled 300 via entrez): RS1000005443 (6:20441713 C>A,G), RS1000018432 (6:20481528 T>A), RS1000094049 (6:20401257 C>A), RS1000127947 (6:20419376 T>G), RS1000131797 (6:20436404 G>A), RS1000181066 (6:20460624 A>C,G), RS1000229792 (6:20412618 G>C), RS1000231240 (6:20429672 A>C), RS1000242618 (6:20419012 T>C), RS1000262319 (6:20429985 C>T), RS1000277852 (6:20401001 A>G), RS1000298724 (6:20474758 T>C), RS1000360342 (6:20454353 A>G), RS1000372348 (6:20461289 C>T), RS1000386625 (6:20406767 G>A)

Disease associations

OMIM: gene MIM:600427 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001762_854	Obesity-related traits	4.000000e-06
GCST002937_5	Molybdenum levels	1.000000e-06
GCST008745_54	Estimated glomerular filtration rate in non-diabetics	1.000000e-08
GCST009391_1581	Metabolite levels	5.000000e-06
GCST009391_2144	Metabolite levels	5.000000e-06
GCST010244_129	Triglyceride levels	2.000000e-13
GCST010988_352	Adult body size	2.000000e-09
GCST011122_55	Walking pace	5.000000e-09
GCST90011898_137	Alanine aminotransferase levels	7.000000e-10
GCST90013405_45	Liver enzyme levels (alanine transaminase)	8.000000e-13
GCST90020025_991	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020026_311	Hip index	8.000000e-09
GCST90020026_312	Hip index	7.000000e-13
GCST90020027_748	Waist-hip index	4.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0003940	physical activity
EFO:0010349	cholesteryl ester 20:5 measurement
EFO:0010551	xanthurenate measurement
EFO:0004530	triglyceride measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630726 (PROTEIN FAMILY)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases reaction, affects expression, affects cotreatment, increases expression	5
bisphenol A	affects cotreatment, decreases expression, increases expression	3
sodium arsenite	decreases reaction, increases expression, decreases expression	3
Arsenic Trioxide	increases expression, increases response to substance	2
Arsenic	increases abundance, increases expression	2
Doxorubicin	decreases expression, affects cotreatment, affects response to substance	2
Formaldehyde	decreases expression, increases expression	2
Quercetin	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
UF010 compound	decreases activity	1
geldanamycin	increases expression	1
testosterone enanthate	affects expression	1
lasiocarpine	decreases expression, increases metabolic processing	1
naringenin	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
propylparaben	affects expression	1
sodium arsenate	increases abundance, increases expression	1
kojic acid	increases expression	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
methylparaben	increases expression	1
sulforaphane	increases methylation	1
ochratoxin A	decreases expression	1
butylparaben	affects expression	1
leptomycin B	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
polyhexamethyleneguanidine	increases expression	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A1C1	SEES3-1V human E2F3, clone1	Embryonic stem cell	Male
CVCL_A1C2	SEES3-1V human E2F3, clone2	Embryonic stem cell	Male
CVCL_A1C3	SEES3-1V human E2F3, clone3	Embryonic stem cell	Male
CVCL_B1QM	Abcam HeLa E2F3 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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