E2F2

Summary

E2F2 (E2F transcription factor 2, HGNC:3114) is a protein-coding gene on chromosome 1p36.12, encoding Transcription factor E2F2 (Q14209). 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 protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein and another 2 members, E2F1 and E2F3, have an additional cyclin binding domain. This protein binds specifically to retinoblastoma protein pRB in a cell-cycle dependent manner, and it exhibits overall 46% amino acid identity to E2F1.

Source: NCBI Gene 1870 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 66 total — 1 pathogenic
• Druggable target: yes
• Transcription factor: yes — 51 downstream targets (CollecTRI)
• MANE Select transcript: NM_004091

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3114
Approved symbol	E2F2
Name	E2F transcription factor 2
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Aliases	E2F-2
Ensembl gene	ENSG00000007968
Ensembl biotype	protein_coding
OMIM	600426
Entrez	1870

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000361729, ENST00000487237, ENST00000915331

RefSeq mRNA: 1 — MANE Select: NM_004091 NM_004091

CCDS: CCDS236

Canonical transcript exons

ENST00000361729 — 7 exons

Exon	Start	End
ENSE00000758550	23524383	23524488
ENSE00000758551	23521837	23522056
ENSE00000758555	23516335	23516527
ENSE00000859746	23506438	23510148
ENSE00000859749	23530542	23531233
ENSE00001435321	23519016	23519130
ENSE00001436167	23520913	23521071

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 88.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.1777 / max 332.5391, expressed in 920 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10989	4.2353	800
10986	1.3304	390
10988	0.2391	82
10985	0.1556	72
10984	0.1260	22
10983	0.0667	21
10987	0.0246	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow	UBERON:0002371	88.27	gold quality
bone marrow cell	CL:0002092	85.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.50	gold quality
blood	UBERON:0000178	81.63	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.56	gold quality
mucosa of transverse colon	UBERON:0004991	80.83	gold quality
lower esophagus mucosa	UBERON:0035834	80.20	gold quality
ganglionic eminence	UBERON:0004023	80.05	gold quality
ventricular zone	UBERON:0003053	78.03	gold quality
monocyte	CL:0000576	77.62	gold quality
leukocyte	CL:0000738	77.42	gold quality
esophagus mucosa	UBERON:0002469	76.62	gold quality
granulocyte	CL:0000094	75.64	gold quality
lymph node	UBERON:0000029	73.57	gold quality
rectum	UBERON:0001052	72.31	gold quality
vermiform appendix	UBERON:0001154	71.48	gold quality
duodenum	UBERON:0002114	70.78	gold quality
spleen	UBERON:0002106	68.64	gold quality
placenta	UBERON:0001987	68.43	gold quality
skin of leg	UBERON:0001511	67.87	gold quality
zone of skin	UBERON:0000014	67.82	gold quality
skin of abdomen	UBERON:0001416	67.55	gold quality
stromal cell of endometrium	CL:0002255	66.18	gold quality
testis	UBERON:0000473	66.09	gold quality
transverse colon	UBERON:0001157	65.99	gold quality
tonsil	UBERON:0002372	65.94	gold quality
right testis	UBERON:0004534	65.11	gold quality
left testis	UBERON:0004533	65.01	gold quality
small intestine	UBERON:0002108	60.61	gold quality
smooth muscle tissue	UBERON:0001135	60.24	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	16.11
E-GEOD-75367	no	167.65
E-CURD-11	no	90.71
E-ENAD-27	no	3.86
E-ANND-3	no	2.01

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

51 targets.

Target	Regulation
AHR	Activation
ARNT	Activation
ASF1B	Activation
BAX	Activation
BIRC5	Activation
BRCA1
CCND3	Activation
CCNE1	Activation
CDC6	Activation
CDCA4	Activation
CDCA7	Activation
CDK1	Activation
CDKN1A	Activation
CDKN2A	Activation
CDT1	Activation
CHEK1	Repression
CUX1	Unknown
DIRAS3	Repression
E2F1	Activation
ECE1	Unknown
FBN2	Activation
FBXO43	Activation
FBXO5	Activation
FGFR2	Activation
FOXO1	Activation
GMNN	Activation
MAP3K5	Unknown
MCM10	Activation
MCM2	Activation
MCM5	Activation

JASPAR motifs

Motif	Name	Family
MA0864.1	E2F2	E2F
MA0864.2	E2F2	E2F
MA0864.3	E2F2	E2F

JASPAR matrix evidence (PMIDs): PMID:9372931, PMID:18836037

Upstream regulators (CollecTRI, top): CEBPA, E2F4, E2F7, GTF2I, KLF1, RB1, SMAD3

miRNA regulators (miRDB)

215 targeting E2F2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-302E	99.96	70.74	2669
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520

Literature-anchored findings (GeneRIF, showing 40)

• determination of interaction with RYBP and YY1 (PMID:12411495)
• E2F2 has a role in blood pressure regulation via a component of the endothelin system (PMID:12566389)
• 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)
• Proliferation-promoting E2F transcription factor E2F-2 plays a pivotal role in the tumor biology of ovarian cancer. (PMID:17341621)
• Up-regulation of E2F2 was detected in a set of 54 astrocytomas of different grades and significantly associated with malignancy. (PMID:17588684)
• identify a novel E2F-binding site in the survivin promoter and show that mutation of either the p53- or E2F-binding sites is sufficient to increase promoter activity (PMID:17916908)
• Myc is required to allow the interaction of the E2F1 protein with the E2F gene promoters. (PMID:18345030)
• Decreased expression of E2F2 is associated with Increased expression of HER2 in breast tumors. (PMID:19142864)
• miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to “seedless” 3’UTR microRNA recognition elements. (PMID:19748357)
• Microarray expression analysis indicated that E2F1 and E2F2 are downstream genes in the KDM5B pathway. (PMID:20226085)
• the 3’UTR of E2F2 and CCND2 were directly bound to let-7a and let-7a down-regulated the expression of E2F2 and CCND2, suppressing prostate cancer cell proliferation in culture (PMID:20418948)
• 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)
• Findings suggest that the deregulated activity of E2F in cancer cells causes increased activation of the Kpnbeta1 and Kpnalpha2 promoters, leading to elevated levels of these proteins, and ultimately impacting the cancer phenotype. (PMID:22125623)
• E2F1 and E2F2 genetic variants may jointly play important roles in head and neck squamous cell carcinoma (PMID:22344756)
• Overexpression of E2F transcription factor 2 is associated with nonepithelial ovarian cancer. (PMID:22531302)
• Low expression of E2F2 may reflect functional redundancy between members of the E2F family, in this case between E2F1 and E2F2. (PMID:22688350)
• miR-125b plays important roles in regulating the proliferation of cancer stem cells by directly targeting E2F2. (PMID:22999819)
• ALY is a novel E2F2-interacting protein and a relevant modulator of E2F-responsive gene expression. (PMID:23297349)
• these results indicate that LXR ligands target gene networks, including those regulated by E2F family members, are critical for tumor biology and disease progression and merit further consideration as potential agents (PMID:23809258)
• Data suggest that the uniquely increased expression of CD38 and E2F2 in rheumatoid arthritis (RA) synovial tissues contribute to the immunoactivation of the disease. (PMID:24397353)
• E2F2 knockdown can inhibit hESC proliferation and tumorigenicity without significantly harming stemness. (PMID:24446828)
• Overall, miR-155 plays an important role in colorectal carcinoma tumorigenesis by negative regulation of its targets including E2F2. (PMID:24793496)
• miR-31 regulated the proliferation of colon cancer cells by targeting E2F2. (PMID:25362258)
• Results show evidence that let-7a expression in osteosarcoma (OS) cells is significantly reduced and inversely correlated with E2F2 expression levels and that let-7a plays an important role in OS cell proliferation and tumorigenesis by targeting E2F2. (PMID:25647078)
• miR218 and miR520a are crucial in the development of hepatocellular carcinoma via the inhibition of cell proliferation and cycle progression by downregulating E2F2. (PMID:25816091)
• Elevated E2F2 expression in glioblastoma cells weakens the effect of elevated levels of miR-218. (PMID:26012781)
• cell cycle-dependent transcription of the TRAIP gene by E2F1, E2F2, and E2F4 and rapid protein degradation leads to cell cycle-dependent expression with a maximum in G2/M (PMID:26369285)
• E2F2 loss results in increased lung metastasis in breast cancer, potentially functioning through a PTPRD dependent mechanism. (PMID:26474282)
• Data indicate that microRNA miR-214 has tumor-suppressive activity in hepatocellular carcinoma (HCC) through inhibition of E2F2 transcription factor (E2F2), cyclin-dependent kinases CDK3 and CDK6. (PMID:26498144)
• we validated for the first time that E2F2 acts as a tumor activator in non-small cell lung carcinoma. (PMID:26617764)
• Low E2F2 expression is associated with invasion in clear cell renal cell carcinoma. (PMID:26967247)
• Data indicate E2F transcription factor 2 protein (E2F2) as the direct target of miR-31 in gastric cancer cells. (PMID:27174918)
• Using iterative experimental and computational analyses, the authors show physical and functional interactions between NF-kappaB and the E2 Factor 1 (E2F-1) and E2 Factor 4 (E2F-4) cell cycle regulators. (PMID:27185527)
• Let-7b inhibits the malignant behavior of glioma cells and glioma stem-like cells via downregulation of E2F2. (PMID:27520092)
• In NSCLC patients, E2F2 expression was found to be significantly correlated with sex and tumor size. E2F1 and E2F2 overexpression showed a significant association with poor prognosis. (PMID:27655285)
• Compared with patients with variant genotypes of E2F2-rs2742976 and E2F2-rs3218123, patients with common homozygous genotypes had better disease-free survival (both log-rank, P < 0.001) and lower squamous cell carcinoma of the oropharynx recurrence risk (HR, 0.4, 95% CI, 0.3-0.6 and HR, 0.3, 95% CI, 0.2-0.5, respectively) after multivariable adjustment. (PMID:27864908)
• Accordingly, our results demonstrated that NAMPT is a prognostic marker in melanoma, and the identificationofNAMPT-E2F2-SIRT1 pathway establishes another link between NAMPT and apoptosis events in melanoma, with therapeutic implications for this deadly cancer. (PMID:28919418)
• These results suggest that miR-125a acts as a tumor suppressor via regulation of E2F2 expression in osteosarcoma progression, and miR-125a may represent a novel therapeutic target for the treatment of osteosarcoma. (PMID:28950256)
• miR-99a reveals two novel targets E2F2 and EMR2 that play a key role in lung tumourigenesis. By inhibiting E2F2 and EMR2, miR-99a represses in vivo the transition of epithelial cells through an EMT process concomitantly with the inhibition of stemness features and consequently decreasing the CSC population. (PMID:29072692)
• these findings indicate that E2F2 may play an important role in pathogenesis of rheumatoid arthritis. (PMID:29422529)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	E2f2	ENSMUSG00000018983
rattus_norvegicus	E2f2	ENSRNOG00000047741
drosophila_melanogaster	E2f1	FBGN0011766
drosophila_melanogaster	E2f2	FBGN0024371
caenorhabditis_elegans		WBGENE00001161
caenorhabditis_elegans		WBGENE00001162
caenorhabditis_elegans		WBGENE00009899

Paralogs (7): E2F1 (ENSG00000101412), E2F3 (ENSG00000112242), E2F8 (ENSG00000129173), E2F5 (ENSG00000133740), E2F7 (ENSG00000165891), E2F6 (ENSG00000169016), E2F4 (ENSG00000205250)

Protein

Protein identifiers

Transcription factor E2F2 — Q14209 (reviewed: Q14209)

All UniProt accessions (1): Q14209

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. E2F2 binds specifically to RB1 in a cell-cycle dependent manner.

Subunit / interactions. Component of the DRTF1/E2F transcription factor complex. Forms heterodimers with DP family members. The E2F2 complex binds specifically hypophosphorylated retinoblastoma protein RB1. During the cell cycle, RB1 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 RB1, thus releasing the active complex. Binds EAPP.

Subcellular location. Nucleus.

Tissue specificity. Highest level of expression is found in placenta, low levels are found in lung. Found as well in many immortalized cell lines derived from tumor samples.

Post-translational modifications. Phosphorylated by CDK2 and cyclin A-CDK2 in the S-phase.

Similarity. Belongs to the E2F/DP family.

RefSeq proteins (1): NP_004082* (*=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 (14 total): region of interest 6, compositionally biased region 2, sequence variant 2, chain 1, DNA-binding region 1, helix 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1N4M	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14209-F1	64.42	0.32

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-2559585	Oncogene Induced Senescence
R-HSA-69231	Cyclin D associated events in G1
R-HSA-9661069	Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)

MSigDB gene sets: 301 (showing top): WANG_CLIM2_TARGETS_UP, FISCHER_G1_S_CELL_CYCLE, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GENTILE_RESPONSE_CLUSTER_D3, PATIL_LIVER_CANCER, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_SPROUTING_ANGIOGENESIS, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_SPROUTING_ANGIOGENESIS, KEGG_PATHWAYS_IN_CANCER, GOBP_REGULATION_OF_CELL_CYCLE, KEGG_PROSTATE_CANCER, GOBP_BLOOD_VESSEL_MORPHOGENESIS, MODULE_99, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN

GO Biological Process (8): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), transcription initiation at RNA polymerase II promoter (GO:0006367), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of cell cycle (GO:0051726), intrinsic apoptotic signaling pathway by p53 class mediator (GO:0072332), negative regulation of sprouting angiogenesis (GO:1903671), lens fiber cell apoptotic process (GO:1990086)

GO Molecular Function (11): 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, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), 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), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleoplasm (GO:0005654), Rb-E2F complex (GO:0035189), RNA polymerase II transcription regulator complex (GO:0090575), nucleus (GO:0005634), transcription regulator complex (GO:0005667)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cellular Senescence	2
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 by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription cis-regulatory region binding	3
regulation of DNA-templated transcription	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
DNA-templated transcription initiation	1
positive regulation of DNA-templated transcription	1
cell cycle	1
regulation of cellular process	1
signal transduction by p53 class mediator	1
intrinsic apoptotic signaling pathway	1
sprouting angiogenesis	1
negative regulation of angiogenesis	1
regulation of sprouting angiogenesis	1
epithelial cell apoptotic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	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
transcription regulator activity	1
DNA binding	1
protein binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
binding	1
chromosome	1
nuclear lumen	1
RNA polymerase II transcription regulator complex	1
transcription regulator complex	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1885 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
E2F2	MYC	P01106	814
E2F2	E2F1	Q01094	810
E2F2	CCNE1	P24864	793
E2F2	TP53	P04637	786
E2F2	RBL2	Q08999	766
E2F2	RB1	P06400	756
E2F2	CCND1	P24385	747
E2F2	LIN52	Q52LA3	731
E2F2	CCND2	P30279	680
E2F2	RYBP	Q8N488	679
E2F2	CCNA2	P20248	674
E2F2	TFDP3	Q5H9I0	673
E2F2	MYCN	P04198	667
E2F2	EAPP	Q56P03	657
E2F2	CCNE2	O96020	648
E2F2	CDKN2A	P42771	648

IntAct

38 interactions, top by confidence:

A	B	Type	Score
E2F2	RB1	psi-mi:“MI:0407”(direct interaction)	0.780
RB1	E2F2	psi-mi:“MI:0407”(direct interaction)	0.780
RB1	E2F2	psi-mi:“MI:0915”(physical association)	0.780
RB1	TFDP1	psi-mi:“MI:0915”(physical association)	0.740
E2F2	TFDP1	psi-mi:“MI:0915”(physical association)	0.660
TFDP2	E2F3	psi-mi:“MI:0914”(association)	0.530
TFDP1	E2F3	psi-mi:“MI:0914”(association)	0.530
E2F2	AKT1	psi-mi:“MI:2364”(proximity)	0.470
E2F2	BRAF	psi-mi:“MI:2364”(proximity)	0.470
E2F2	AKT1	psi-mi:“MI:0915”(physical association)	0.470
E2F2	BRAF	psi-mi:“MI:0915”(physical association)	0.470
Sp1	E2F2	psi-mi:“MI:0915”(physical association)	0.400
L3MBTL3	E2F2	psi-mi:“MI:0915”(physical association)	0.400
E7	E2F2	psi-mi:“MI:0915”(physical association)	0.400
MCPH1	E2F2	psi-mi:“MI:0915”(physical association)	0.400
GIT2	E2F2	psi-mi:“MI:0915”(physical association)	0.370
GNB5	E2F2	psi-mi:“MI:0915”(physical association)	0.370
Cep152	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
	E2F2	psi-mi:“MI:0914”(association)	0.350
TFDP2	MCIDAS	psi-mi:“MI:0914”(association)	0.350
TFDP1	MCIDAS	psi-mi:“MI:0914”(association)	0.350
SMAD4	E2F2	psi-mi:“MI:2364”(proximity)	0.270
SPOP	E2F2	psi-mi:“MI:2364”(proximity)	0.270
E2F2	SPOP	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (63): E2F2 (Affinity Capture-RNA), E2F2 (Affinity Capture-RNA), E2F2 (Affinity Capture-MS), E2F2 (Two-hybrid), E2F2 (Affinity Capture-MS), E2F1 (Co-localization), UCHL5 (Reconstituted Complex), E2F2 (Affinity Capture-MS), E2F2 (Affinity Capture-MS), E2F2 (Co-localization), E2F2 (Affinity Capture-MS), E2F2 (Biochemical Activity), SPIB (Two-hybrid), CCNF (Affinity Capture-Western), RB1 (Affinity Capture-Western)

ESM2 similar proteins: A4GTP4, A6NMT0, D3ZMK9, O08686, O08696, O14901, O15353, O35261, O42367, O43151, O94993, P19419, P41969, P59598, P70178, P97691, P98177, Q00175, Q04891, Q08050, Q0GGX2, Q14209, Q4G112, Q571I4, Q5ND04, Q5W1J6, Q61575, Q63449, Q86YV5, Q8BG87, Q8BX22, Q8C0Y1, Q8IXJ9, Q8K1S5, Q8K4J6, Q90WM5, Q91X45, Q924A2, Q92766, Q969V6

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

3 interactions.

A	Effect	B	Mechanism
RB1	down-regulates	E2F2	binding
E2F2	“up-regulates quantity by expression”	CCNE1	“transcriptional regulation”
E2F2	“up-regulates activity”	TFDP1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 23 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
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	5	186.6×	6e-09
Oncogene Induced Senescence	6	118.5×	2e-09
Cyclin E associated events during G1/S transition	5	84.0×	2e-07
Cyclin A:Cdk2-associated events at S phase entry	5	78.1×	2e-07
Cyclin D associated events in G1	5	68.5×	3e-07
Pre-NOTCH Transcription and Translation	5	36.1×	8e-06
Oxidative Stress Induced Senescence	5	26.7×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	5	62.0×	4e-06
positive regulation of gene expression	5	9.7×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	57
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1703538	GRCh37/hg19 1p36.12-36.11(chr1:23814543-24163928)	Pathogenic

SpliceAI

1170 predictions. Top by Δscore:

Variant	Effect	Δscore
1:23516332:TACCT:T	donor_loss	1.0000
1:23516333:A:AC	donor_gain	1.0000
1:23516334:C:CC	donor_gain	1.0000
1:23516523:TTGTC:T	acceptor_gain	1.0000
1:23516524:TGTC:T	acceptor_gain	1.0000
1:23516525:GTC:G	acceptor_gain	1.0000
1:23516526:TC:T	acceptor_gain	1.0000
1:23516527:CC:C	acceptor_gain	1.0000
1:23516528:C:CC	acceptor_gain	1.0000
1:23519127:CAGCG:C	acceptor_gain	1.0000
1:23519128:A:T	acceptor_gain	1.0000
1:23519130:C:CT	acceptor_gain	1.0000
1:23519137:C:CT	acceptor_gain	1.0000
1:23519138:A:T	acceptor_gain	1.0000
1:23520881:C:CA	donor_gain	1.0000
1:23520911:ATCT:A	donor_gain	1.0000
1:23520928:T:TA	donor_gain	1.0000
1:23521833:TCA:T	donor_loss	1.0000
1:23521834:CA:C	donor_loss	1.0000
1:23521835:A:AC	donor_gain	1.0000
1:23521835:A:AT	donor_loss	1.0000
1:23521835:ACAC:A	donor_gain	1.0000
1:23521835:ACACC:A	donor_gain	1.0000
1:23521836:C:CA	donor_gain	1.0000
1:23521836:CA:C	donor_gain	1.0000
1:23521836:CACC:C	donor_gain	1.0000
1:23521836:CACCC:C	donor_gain	1.0000
1:23521841:A:AC	donor_gain	1.0000
1:23521842:C:CC	donor_gain	1.0000
1:23521862:T:TA	donor_gain	1.0000

AlphaMissense

2822 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:23519062:A:T	V269D	1.000
1:23521902:G:C	D171E	1.000
1:23521902:G:T	D171E	1.000
1:23521903:T:A	D171V	1.000
1:23521903:T:C	D171G	1.000
1:23521903:T:G	D171A	1.000
1:23521904:C:G	D171H	1.000
1:23521917:C:A	K166N	1.000
1:23521917:C:G	K166N	1.000
1:23516508:A:G	L291P	0.999
1:23519038:A:G	L277P	0.999
1:23521854:C:A	K187N	0.999
1:23521854:C:G	K187N	0.999
1:23521863:C:A	K184N	0.999
1:23521863:C:G	K184N	0.999
1:23521865:T:C	K184E	0.999
1:23521883:C:G	G178R	0.999
1:23521888:A:G	L176P	0.999
1:23521893:G:C	N174K	0.999
1:23521893:G:T	N174K	0.999
1:23521895:T:C	N174D	0.999
1:23521900:A:C	I172S	0.999
1:23521900:A:T	I172N	0.999
1:23521904:C:A	D171Y	0.999
1:23521904:C:T	D171N	0.999
1:23521907:A:G	Y170H	0.999
1:23521912:C:G	R168P	0.999
1:23521913:G:C	R168G	0.999
1:23521913:G:T	R168S	0.999
1:23521915:C:G	R167P	0.999

dbSNP variants (sampled 300 via entrez): RS1000019366 (1:23533028 C>T), RS1000091133 (1:23522218 G>A), RS1000249001 (1:23529040 C>G), RS1000693596 (1:23529792 C>CA), RS1000696006 (1:23510880 A>G), RS1000825324 (1:23524266 C>G,T), RS1000868358 (1:23517271 A>G,T), RS1001113828 (1:23525076 C>A), RS1001346763 (1:23514855 A>G,T), RS1001346995 (1:23518326 C>T), RS1001412584 (1:23531515 G>A), RS1001463542 (1:23507787 T>C), RS1001474602 (1:23530909 G>A), RS1001552337 (1:23521083 G>C), RS1001587028 (1:23514534 T>C)

Disease associations

OMIM: gene MIM:600426 | disease phenotypes: MIM:616803

GenCC curated gene-disease

Mondo (1): Lamb-Shaffer syndrome (MONDO:0014778)

Orphanet (3): 12p12.1 microdeletion syndrome (Orphanet:313884), Developmental and speech delay due to SOX5 deficiency (Orphanet:313892), Lamb-Shaffer syndrome (Orphanet:530983)

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST004602_5	Mean corpuscular volume	2.000000e-13
GCST004606_179	Eosinophil count	8.000000e-11
GCST004610_77	White blood cell count	1.000000e-09
GCST004621_4	Red cell distribution width	1.000000e-24
GCST004624_205	Sum eosinophil basophil counts	2.000000e-12
GCST004630_3	Mean corpuscular hemoglobin	7.000000e-13
GCST006804_8	Red cell distribution width	2.000000e-16
GCST90002381_566	Eosinophil count	1.000000e-16
GCST90002385_603	High light scatter reticulocyte count	1.000000e-15
GCST90002386_308	High light scatter reticulocyte percentage of red cells	1.000000e-11
GCST90002388_643	Lymphocyte count	7.000000e-10
GCST90002390_589	Mean corpuscular hemoglobin	1.000000e-42
GCST90002392_153	Mean corpuscular volume	4.000000e-47
GCST90002394_129	Monocyte percentage of white cells	2.000000e-09
GCST90002396_116	Mean reticulocyte volume	1.000000e-56
GCST90002397_175	Mean spheric corpuscular volume	1.000000e-45
GCST90002398_43	Neutrophil count	3.000000e-16
GCST90002403_37	Red blood cell count	2.000000e-14
GCST90002404_454	Red cell distribution width	9.000000e-41
GCST90002405_593	Reticulocyte count	9.000000e-16
GCST90002406_131	Reticulocyte fraction of red cells	6.000000e-11
GCST90002407_389	White blood cell count	2.000000e-20
GCST90020025_244	Waist-to-hip ratio adjusted for BMI	2.000000e-09
GCST90020027_1781	Waist-hip index	2.000000e-09
GCST90026414_2	Severe insulin-resistant type 2 diabetes	5.000000e-07

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count
EFO:0009188	Red cell distribution width
EFO:0005090	basophil count
EFO:0004527	mean corpuscular hemoglobin
EFO:0007986	reticulocyte count
EFO:0004587	lymphocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count
EFO:0004305	erythrocyte count
EFO:0007788	BMI-adjusted waist-hip ratio

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

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	affects binding, decreases reaction, decreases expression	6
sodium arsenite	affects expression, affects reaction, decreases expression, increases expression	5
Benzo(a)pyrene	decreases expression, increases expression, affects methylation	5
palbociclib	decreases expression, decreases reaction, decreases phosphorylation	3
Panobinostat	affects cotreatment, decreases expression	2
Arsenic	increases abundance, decreases expression	2
Cannabidiol	decreases expression	2
Estradiol	affects cotreatment, decreases expression, affects reaction, affects expression	2
Fluorouracil	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	decreases expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
UF010 compound	decreases activity	1
PF-06840003	decreases reaction, increases expression	1
sotorasib	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
lasiocarpine	increases expression	1
bisphenol A	decreases expression	1
sodium arsenate	increases abundance, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
ochratoxin A	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8EZ	Abcam HCT 116 E2F2 KO	Cancer cell line	Male
CVCL_B9H7	Abcam A-549 E2F2 KO	Cancer cell line	Male
CVCL_D2EW	Abcam MCF-7 E2F2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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