E2F7

Summary

E2F7 (E2F transcription factor 7, HGNC:23820) is a protein-coding gene on chromosome 12q21.2, encoding Transcription factor E2F7 (Q96AV8). Atypical E2F transcription factor that participates in various processes such as angiogenesis, polyploidization of specialized cells and DNA damage response.

Enables DNA-binding transcription repressor activity; cis-regulatory region sequence-specific DNA binding activity; and identical protein binding activity. Involved in DNA damage response, signal transduction by p53 class mediator; regulation of transcription by RNA polymerase II; and sprouting angiogenesis. Located in nuclear speck.

Source: NCBI Gene 144455 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 132 total
• Druggable target: yes
• MANE Select transcript: NM_203394

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23820
Approved symbol	E2F7
Name	E2F transcription factor 7
Location	12q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000165891
Ensembl biotype	protein_coding
OMIM	612046
Entrez	144455

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000322886, ENST00000416496, ENST00000547316, ENST00000550669, ENST00000551058, ENST00000551558, ENST00000552907, ENST00000919446, ENST00000919447

RefSeq mRNA: 1 — MANE Select: NM_203394 NM_203394

CCDS: CCDS9016

Canonical transcript exons

ENST00000322886 — 13 exons

Exon	Start	End
ENSE00001097726	77027883	77028138
ENSE00001380569	77065345	77065569
ENSE00001382944	77021251	77024185
ENSE00001387789	77025558	77025982
ENSE00001593263	77033857	77034042
ENSE00001660203	77033050	77033122
ENSE00001664523	77029831	77030332
ENSE00001672430	77044637	77044795
ENSE00001757317	77046038	77046328
ENSE00003462953	77055855	77056130
ENSE00003506743	77043065	77043199
ENSE00003510063	77050576	77050744
ENSE00003645786	77064543	77064635

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 84.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.3933 / max 500.8036, expressed in 1499 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132236	17.3933	1499

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	84.85	gold quality
thymus	UBERON:0002370	83.11	gold quality
upper arm skin	UBERON:0004263	79.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.31	gold quality
ganglionic eminence	UBERON:0004023	78.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.90	gold quality
secondary oocyte	CL:0000655	76.21	gold quality
stromal cell of endometrium	CL:0002255	75.21	gold quality
esophagus squamous epithelium	UBERON:0006920	74.01	gold quality
ileal mucosa	UBERON:0000331	72.90	gold quality
bone marrow cell	CL:0002092	72.40	gold quality
bone marrow	UBERON:0002371	71.52	gold quality
pancreatic ductal cell	CL:0002079	68.95	silver quality
buccal mucosa cell	CL:0002336	68.71	silver quality
tibialis anterior	UBERON:0001385	68.53	silver quality
gingival epithelium	UBERON:0001949	66.17	gold quality
oviduct epithelium	UBERON:0004804	65.53	gold quality
upper leg skin	UBERON:0004262	65.11	gold quality
rectum	UBERON:0001052	64.74	gold quality
epithelium of nasopharynx	UBERON:0001951	64.69	gold quality
esophagus mucosa	UBERON:0002469	64.19	gold quality
trabecular bone tissue	UBERON:0002483	64.18	gold quality
deltoid	UBERON:0001476	64.15	silver quality
tibia	UBERON:0000979	63.22	gold quality
sperm	CL:0000019	62.78	silver quality
mucosa of transverse colon	UBERON:0004991	62.47	gold quality
vermiform appendix	UBERON:0001154	62.26	gold quality
gingiva	UBERON:0001828	62.21	gold quality
bronchial epithelial cell	CL:0002328	62.20	gold quality
islet of Langerhans	UBERON:0000006	61.84	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6142	no	112.25
E-ANND-3	no	4.92

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
CCBE1	Activation
CDKN1A	Repression
E2F1	Repression
E2F2	Repression
FLT4	Unknown
SP1	Repression
VEGFA	Unknown

JASPAR motifs

Motif	Name	Family
MA0758.1	E2F7	E2F

JASPAR matrix evidence (PMIDs): PMID:18836037

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

210 targeting E2F7, 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-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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4533	100.00	69.48	2758
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622

Literature-anchored findings (GeneRIF, showing 40)

• Plays an essential role in the regulation of cell cycle progression. (PMID:14633988)
• The similarities between E2F-7 and E2F-8 define a new subgroup of the E2F family, and further imply that E2F-7 and E2F-8 may act through overlapping mechanisms in mediating cell cycle control. (PMID:15897886)
• down-regulation of E2F7 may contribute to mechanisms underlying platinum resistance in ovarian neoplasms (PMID:17200349)
• E2F7 and E2F8 act upstream of E2F1, and influence the ability of cells to undergo a DNA-damage response. (PMID:18202719)
• selected disruption of E2F1 and E2F7 in keratinocytes is likely to contribute to cutaneous squamous cell carcinomas (CSCC) formation and may prove to be a viable therapeutic target. (PMID:19223542)
• These data indicate that loss of E2F7 during the initiation of differentiation leads to the derepression of Sp1 and subsequent transcription of differentiation-specific genes such as epidermal type I transglutaminase. (PMID:21248772)
• E2F7-dependent mechanism contributes to p53-dependent cell cycle arrest in response to DNA damage. (PMID:22802528)
• identify a causal role for E2F7 in cellular senescence and uncover a novel link between the RB and p53 pathways. (PMID:22802529)
• Low E2F7 expression is associated with B-chronic lymphocytic leukemia. (PMID:23054209)
• MicroRNA-26a target E2F7 sustains cell proliferation and inhibits monocytic differentiation of acute myeloid leukemia cells. (PMID:23096114)
• E2F7 recruits the co-repressor C-terminal-binding protein (CtBP) and that CtBP2 is essential for E2F7 to repress E2F1 transcription. (PMID:23853115)
• E2F-7 can co-localize with gammaH2AX and 53BP1 in DNA damaged cells, bind directly to the recombining DNA, and, importantly, interact and recruit accessory factors, including CtBP and HDAC1 and 2, to the DSB. (PMID:23974101)
• E2F7 directly increases the transcription and activity of the Sphk1/S1P axis resulting in activation of AKT and subsequent drug resistance. (PMID:25411162)
• Findings indicate that miR-424 targets the E2F7 transcript and suppresses endometrial cancer cell growth. Knockdown of E2F7 inhibited Ishikawa and HEC-1B cell growth. (PMID:25708247)
• RacGAP1 Is a Novel Downstream Effector of E2F7-Dependent Resistance to Doxorubicin and Is Prognostic for Overall Survival in Squamous Cell Carcinoma (PMID:26018753)
• E2F7 overexpression leads to tamoxifen resistance in breast cancer by competing with E2F1 at miR-15a/16 promoter. (PMID:26397135)
• E2F7 might act as an independent prognostic factor of gliomas and might constitute a potential therapeutic target for this disease (PMID:27460513)
• E2F transcription factor 7 (E2F7) was a direct target of miR-30a-5p and antagonized the effects induced by miR-30a-5p downregulation in gallbladder cancer cells. (PMID:29540696)
• Results reveal an E2F7-dependent transcriptional program that contributes to the regulation of DNA repair and genomic integrity. (PMID:29590434)
• results expand the target gene repertoire influenced by E2F7 to include Pol I-regulated genes, and more generally suggest a mechanism mediated by effects on Pol I transcription where E2F7 links cell cycle arrest with protein synthesis. (PMID:29760477)
• MiR-3666/E2F7 may play a key role in regulating the inhibitory effects of ATRA on HCT116 cells. (PMID:29772445)
• E2F7 modulates the chemosensitivity of BRCA2-deficient cells, which are less sensitive to PARP inhibitor and cisplatin treatment after E2F7 depletion, via increased expression of RAD51, a target for E2F7-mediated transcriptional repression, which enhances both HR DNA repair, and replication fork stability in BRCA2-deficient cells. (PMID:30032296)
• These findings revealed that a feedback loop between miR-26a and E2F7 may promote Tamoxifen resistance in estrogen receptor -positive breast cancer. (PMID:30066905)
• miR-935 is down-regulated in non-small cell lung cancer tissue, is linked to poor outcome, and acts on signal transduction mediator E2F7 and the AKT pathway. (PMID:30203720)
• KPNA2 mediated nuclear localization of E2F1 and E2F7, where they in turn controlled KPNA2 expression. Taken together, our data provided mechanistic insights into divergently transcriptional regulation of KPNA2, thus pointing to KPNA2 as a potential target for cancer therapy. (PMID:30254209)
• E2F7, EREG, miR-451a and miR-106b-5p were likely to be related to the cervical cancer development. (PMID:30607582)
• results show that dysregulation of circPRKCI-miR-545/589-E2F7 axis mediated H2O2-induced neuronal cell injury; targeting this novel cascade could be a fine strategy to protect neurons from oxidative stress (PMID:31053300)
• Result of survival analysis showed that circ-PRKCI target gene E2F7 can reduce liver cancer patients’ survival rate. And clinical data suggested that the distribution of circ-PRKCI rose with the depth of invasion, lymph node metastasis, distant metastasis, and TNM stage, indicating that circ-PRKCI may affect the survival and prognosis of patients with hepatocellular carcinoma by regulating E2F7. (PMID:31086464)
• Long non-coding RNA DLEU2 promotes the progression of esophageal cancer through miR-30e-5p/E2F7 axis. (PMID:31884338)
• miR-129-5p inhibits proliferation, migration, and invasion in rectal adenocarcinoma cells through targeting E2F7. (PMID:32052431)
• E2F7, regulated by miR30c, inhibits apoptosis and promotes cell cycle of prostate cancer cells. (PMID:32582990)
• MiR-10b inhibits migration and invasion of pancreatic ductal adenocarcinoma via regulating E2F7. (PMID:32592206)
• E2F7-EZH2 axis regulates PTEN/AKT/mTOR signalling and glioblastoma progression. (PMID:32814835)
• LncRNA CASC19 contributed to the progression of pancreatic cancer through modulating miR-148b/E2F7 axis. (PMID:33155202)
• MiR-424-5p regulates cell cycle and inhibits proliferation of hepatocellular carcinoma cells by targeting E2F7. (PMID:33201900)
• Identification of E2F transcription factor 7 as a novel potential biomarker for oral squamous cell carcinoma. (PMID:33637098)
• LINC00174 Facilitates Proliferation and Migration of Colorectal Cancer Cells via MiR-3127-5p/ E2F7 Axis. (PMID:34226413)
• SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7. (PMID:35197448)
• E2F7 promotes mammalian target of rapamycin inhibitor resistance in hepatocellular carcinoma after liver transplantation. (PMID:35729702)
• E2F7 enhances hepatocellular carcinoma growth by preserving the SP1/SOX4/Anillin axis via repressing miRNA-383-5p transcription. (PMID:35924788)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	e2f7	ENSDARG00000008986
mus_musculus	E2f7	ENSMUSG00000020185
rattus_norvegicus	E2f7	ENSRNOG00000026252
caenorhabditis_elegans		WBGENE00009899

Paralogs (7): E2F2 (ENSG00000007968), E2F1 (ENSG00000101412), E2F3 (ENSG00000112242), E2F8 (ENSG00000129173), E2F5 (ENSG00000133740), E2F6 (ENSG00000169016), E2F4 (ENSG00000205250)

Protein

Protein identifiers

Transcription factor E2F7 — Q96AV8 (reviewed: Q96AV8)

All UniProt accessions (5): Q96AV8, F8VSE7, F8VXV5, H0YHW2, H0YIF4

UniProt curated annotations — full annotation on UniProt →

Function. Atypical E2F transcription factor that participates in various processes such as angiogenesis, polyploidization of specialized cells and DNA damage response. Mainly acts as a transcription repressor that binds DNA independently of DP proteins and specifically recognizes the E2 recognition site 5’-TTTC[CG]CGC-3’. Directly represses transcription of classical E2F transcription factors such as E2F1. Acts as a regulator of S-phase by recognizing and binding the E2-related site 5’-TTCCCGCC-3’ and mediating repression of G1/S-regulated genes. Plays a key role in polyploidization of cells in placenta and liver by regulating the endocycle, probably by repressing genes promoting cytokinesis and antagonizing action of classical E2F proteins (E2F1, E2F2 and/or E2F3). Required for placental development by promoting polyploidization of trophoblast giant cells. Also involved in DNA damage response: up-regulated by p53/TP53 following genotoxic stress and acts as a downstream effector of p53/TP53-dependent repression by mediating repression of indirect p53/TP53 target genes involved in DNA replication. Acts as a promoter of sprouting angiogenesis, possibly by acting as a transcription activator: associates with HIF1A, recognizes and binds the VEGFA promoter, which is different from canonical E2 recognition site, and activates expression of the VEGFA gene. Acts as a negative regulator of keratinocyte differentiation.

Subunit / interactions. Homodimer and heterodimer: mainly forms homodimers and, to a lesser extent, heterodimers with E2F8. Dimerization is important for DNA-binding. Interacts with HIF1A. Interacts with MN1.

Subcellular location. Nucleus.

Domain organisation. In contrast to classical members of the E2F transcription factor, atypical members contain 2 DNA-binding domains and regulate transcription in a DP-independent manner. Both DNA-binding domains are required for DNA-binding and are proposed to form an intramolecular structure that is similar to the winged helix structure of the E2F-DP heterodimer.

Induction. By p53/TP53 following DNA damage: expression is directly activated by p53/TP53 (at protein level).

Similarity. Belongs to the E2F/DP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96AV8-1	1, E2F7b	yes
Q96AV8-2	2, E2F7a
Q96AV8-3	3

RefSeq proteins (1): NP_976328* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003316	E2F_WHTH_DNA-bd_dom	Domain
IPR015633	E2F	Family
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily

Pfam: PF02319

UniProt features (23 total): region of interest 5, compositionally biased region 3, modified residue 3, splice variant 3, sequence variant 3, mutagenesis site 3, DNA-binding region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96AV8-F1	51.31	0.12

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): 95, 410, 840

Mutagenesis-validated functional residues (3):

Position	Phenotype
147–148	loss of dna-binding and e2f-dependent repression.
185	loss of dna-binding and inhibition of e2f1-dependent activation. impairs dna-binding and dimerization; when associated w
334	loss of dna-binding and inhibition of e2f1-dependent activation. impairs dna-binding and dimerization; when associated w

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6804116	TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest

MSigDB gene sets: 334 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, E2F_Q4, E2F_Q4_01, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, E2F4DP1_01, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DIVISION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_CELL_CYCLE_DNA_REPLICATION, FISCHER_G1_S_CELL_CYCLE, TGCACTT_MIR519C_MIR519B_MIR519A

GO Biological Process (18): negative regulation of transcription by RNA polymerase II (GO:0000122), placenta development (GO:0001890), sprouting angiogenesis (GO:0002040), regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of cell population proliferation (GO:0008285), DNA damage response, signal transduction by p53 class mediator (GO:0030330), negative regulation of cytokinesis (GO:0032466), positive regulation of DNA endoreduplication (GO:0032877), positive regulation of transcription by RNA polymerase II (GO:0045944), trophoblast giant cell differentiation (GO:0060707), chorionic trophoblast cell differentiation (GO:0060718), hepatocyte differentiation (GO:0070365), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134), regulation of DNA-templated transcription (GO:0006355), DNA damage response (GO:0006974), positive regulation of macromolecule metabolic process (GO:0010604), negative regulation of DNA-templated transcription (GO:0045892), obsolete positive regulation of nucleobase-containing compound metabolic process (GO:0045935)

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 repressor activity (GO:0001217), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), identical protein binding (GO:0042802), 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), nucleoplasm (GO:0005654), nuclear speck (GO:0016607), RNA polymerase II transcription regulator complex (GO:0090575), nucleus (GO:0005634), transcription regulator complex (GO:0005667)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
TP53 Regulates Transcription of Cell Cycle Genes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription cis-regulatory region binding	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
negative regulation of DNA-templated transcription	2
DNA-templated transcription	2
DNA-binding transcription factor activity	2
cellular anatomical structure	2
animal organ development	1
angiogenesis	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
signal transduction in response to DNA damage	1
signal transduction by p53 class mediator	1
cytokinesis	1
negative regulation of cell cycle process	1
regulation of cytokinesis	1
negative regulation of cell division	1
regulation of DNA endoreduplication	1
DNA endoreduplication	1
positive regulation of cell cycle process	1
positive regulation of DNA-templated DNA replication	1
positive regulation of DNA-templated transcription	1
cell differentiation involved in embryonic placenta development	1
cell differentiation	1
chorion development	1
liver development	1
epithelial cell differentiation	1
G1/S transition of mitotic cell cycle	1
negative regulation of mitotic cell cycle phase transition	1
negative regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular response to stress	1
positive regulation of metabolic process	1
macromolecule metabolic process	1
regulation of macromolecule metabolic process	1

Protein interactions and networks

STRING

1576 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
E2F7	CDC6	Q99741	883
E2F7	TFDP3	Q5H9I0	872
E2F7	HIF1A	Q16665	730
E2F7	E2F1	Q01094	621
E2F7	TP53	P04637	586
E2F7	E2F8	A0AVK6	521
E2F7	DCBLD2	Q96PD2	514
E2F7	E2F5	Q15329	483
E2F7	TFDP1	Q14186	482
E2F7	ASPM	Q8IZT6	479
E2F7	E2F4	Q16254	463
E2F7	FOXM1	Q08050	461
E2F7	CCNA2	P20248	460
E2F7	RBL2	Q08999	455
E2F7	CCNE1	P24864	447

IntAct

46 interactions, top by confidence:

A	B	Type	Score
DCP1B	DDX6	psi-mi:“MI:0914”(association)	0.890
DCAF7	PFDN6	psi-mi:“MI:0914”(association)	0.570
E2F7	E2F7	psi-mi:“MI:0915”(physical association)	0.540
E2F7	E2F7	psi-mi:“MI:0407”(direct interaction)	0.540
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
HSFY1	NDUFS1	psi-mi:“MI:0914”(association)	0.530
E2F8	E2F7	psi-mi:“MI:0915”(physical association)	0.520
E2F7	E2F8	psi-mi:“MI:0915”(physical association)	0.520
E2F7	BRAF	psi-mi:“MI:2364”(proximity)	0.470
E2F7	BRAF	psi-mi:“MI:0915”(physical association)	0.470
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
C6orf141	KRBA1	psi-mi:“MI:0914”(association)	0.350
LCK	CDK1	psi-mi:“MI:0914”(association)	0.350
CTBP1	GSN	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
KRAS		psi-mi:“MI:0914”(association)	0.350
E2F7		psi-mi:“MI:0914”(association)	0.350
CTBP1	SEC16A	psi-mi:“MI:2364”(proximity)	0.270
AKT1	E2F7	psi-mi:“MI:2364”(proximity)	0.270
FBXW7	E2F7	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (55): E2F7 (Affinity Capture-MS), E2F7 (Affinity Capture-MS), E2F7 (Affinity Capture-Western), E2F7 (Reconstituted Complex), E2F7 (Affinity Capture-MS), E2F7 (Affinity Capture-MS), E2F7 (Affinity Capture-MS), E2F7 (Affinity Capture-MS), E2F7 (Affinity Capture-MS), HIF1A (Reconstituted Complex), E2F7 (Affinity Capture-MS), E2F7 (Affinity Capture-MS), E2F7 (Affinity Capture-Western), E2F7 (Affinity Capture-MS), E2F7 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5NVS8, A0AVK6, A2A891, A5GFT6, A5PLL1, A5X7A0, A7XYH5, A7XYJ6, B7ZS37, D3ZGB1, D4A4D7, D4A666, E1B7L7, E1BE02, E1BKK0, E1BLP6, E7F888, F1LMN3, F1QZ88, F6YVB9, F7EA39, O35914, O54916, P0C6C1, Q01804, Q14B70, Q3U1C4, Q3UUF8, Q566I1, Q58FA4, Q5RIX9, Q5ZJ69, Q68FE9, Q69ZF8, Q6A098, Q6S7F2, Q6ZSZ6, Q6ZU65, Q76L83, Q80WC1

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

1 interactions.

A	Effect	B	Mechanism
CHEK1	“down-regulates activity”	E2F7	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 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.

GO biological processes:

GO term	Partners	Fold	FDR
protein stabilization	6	14.3×	7e-04
positive regulation of gene expression	8	11.1×	3e-04
negative regulation of apoptotic process	6	7.5×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	109
Likely benign	5
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

2305 predictions. Top by Δscore:

Variant	Effect	Δscore
12:77024186:C:CC	acceptor_gain	1.0000
12:77033042:CTACT:C	donor_loss	1.0000
12:77033043:TACTT:T	donor_loss	1.0000
12:77033044:ACT:A	donor_loss	1.0000
12:77033045:CT:C	donor_loss	1.0000
12:77033046:TT:T	donor_loss	1.0000
12:77033047:TACTG:T	donor_loss	1.0000
12:77033048:A:AC	donor_gain	1.0000
12:77033049:C:CA	donor_gain	1.0000
12:77033049:CT:C	donor_gain	1.0000
12:77033049:CTG:C	donor_gain	1.0000
12:77033118:TGATC:T	acceptor_gain	1.0000
12:77033119:GATC:G	acceptor_gain	1.0000
12:77033121:TC:T	acceptor_gain	1.0000
12:77033122:CC:C	acceptor_gain	1.0000
12:77033122:CCTGA:C	acceptor_loss	1.0000
12:77033123:C:CC	acceptor_gain	1.0000
12:77033123:CTGA:C	acceptor_loss	1.0000
12:77033852:GATA:G	donor_loss	1.0000
12:77033853:ATAC:A	donor_loss	1.0000
12:77033854:TACCT:T	donor_loss	1.0000
12:77033856:C:A	donor_loss	1.0000
12:77033899:T:A	donor_gain	1.0000
12:77034040:CAT:C	acceptor_gain	1.0000
12:77034042:TC:T	acceptor_loss	1.0000
12:77034043:C:CC	acceptor_gain	1.0000
12:77034043:CTAC:C	acceptor_loss	1.0000
12:77034047:A:C	acceptor_gain	1.0000
12:77043064:CCA:C	donor_gain	1.0000
12:77044632:CTTA:C	donor_loss	1.0000

AlphaMissense

5894 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:77043093:C:A	W365C	1.000
12:77043093:C:G	W365C	1.000
12:77043094:C:G	W365S	1.000
12:77043095:A:G	W365R	1.000
12:77043095:A:T	W365R	1.000
12:77043099:G:C	F363L	1.000
12:77043099:G:T	F363L	1.000
12:77043100:A:C	F363C	1.000
12:77043100:A:G	F363S	1.000
12:77043101:A:G	F363L	1.000
12:77043103:G:T	A362D	1.000
12:77043145:A:T	I348K	1.000
12:77043148:A:G	L347P	1.000
12:77043163:A:G	L342P	1.000
12:77043166:A:T	V341D	1.000
12:77043168:A:C	N340K	1.000
12:77043168:A:T	N340K	1.000
12:77043172:G:T	A339D	1.000
12:77043173:C:G	A339P	1.000
12:77043175:A:T	I338K	1.000
12:77043177:G:C	D337E	1.000
12:77043177:G:T	D337E	1.000
12:77043178:T:A	D337V	1.000
12:77043178:T:C	D337G	1.000
12:77043178:T:G	D337A	1.000
12:77043179:C:A	D337Y	1.000
12:77043179:C:G	D337H	1.000
12:77043179:C:T	D337N	1.000
12:77043182:A:G	Y336H	1.000
12:77043184:A:G	L335P	1.000

dbSNP variants (sampled 300 via entrez): RS1000030066 (12:77034732 A>G), RS1000057283 (12:77064899 G>A), RS1000194821 (12:77058396 C>T), RS1000206175 (12:77058200 A>AG), RS1000303672 (12:77066796 A>G), RS1000336503 (12:77052043 T>C), RS1000344018 (12:77022139 A>G), RS1000369335 (12:77026018 T>A,C), RS1000388218 (12:77022407 T>C), RS1000723334 (12:77024153 T>C), RS1000768322 (12:77061815 G>T), RS1000930594 (12:77041137 C>T), RS1000992937 (12:77039215 ACAC>A), RS1001100614 (12:77047578 G>A), RS1001113946 (12:77033300 A>G)

Disease associations

OMIM: gene MIM:612046 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST002198_25	Tuberculosis	4.000000e-06
GCST003806_4	Response to bupropion and depression	1.000000e-06
GCST004136_16	Methadone dose in opioid dependence	2.000000e-06
GCST004136_22	Methadone dose in opioid dependence	4.000000e-06
GCST005156_2	Alloimmunization response to pregnancy (HLA class I)	2.000000e-07
GCST006138_32	Resting-state electroencephalogram vigilance	9.000000e-06
GCST007576_197	Chronotype	6.000000e-09
GCST008152_89	Weight	3.000000e-06
GCST008839_551	Height	9.000000e-09
GCST009391_1707	Metabolite levels	7.000000e-06
GCST009936_3	Venous thromboembolism	6.000000e-06
GCST010422_1	Mean arterial pressure x educational attainment (some college) interaction (2df)	1.000000e-11
GCST010422_2	Mean arterial pressure x educational attainment (some college) interaction (2df)	2.000000e-11
GCST011541_8	Tinnitus	5.000000e-07
GCST012227_538	Hip circumference adjusted for BMI	2.000000e-08
GCST012292_6	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	3.000000e-06
GCST012295_3	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	7.000000e-07
GCST012298_7	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	9.000000e-07
GCST012299_22	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction (3df)	2.000000e-06
GCST012300_1	Schizophrenia, bipolar disorder or major depressive disorder	5.000000e-06
GCST012301_14	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	2.000000e-07
GCST90000025_979	Appendicular lean mass	2.000000e-10
GCST90000025_980	Appendicular lean mass	9.000000e-14
GCST90000027_40	Appendicular lean mass	2.000000e-06

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0007907	methadone dose measurement
EFO:0008462	pregnancy induced alloimmunization
EFO:0004357	electroencephalogram measurement
EFO:0008328	chronotype measurement
EFO:0004338	body weight
EFO:0010340	cholesteryl ester 14:0 measurement
EFO:0004784	self reported educational attainment
EFO:0006340	mean arterial pressure
EFO:0008039	BMI-adjusted hip circumference
EFO:0004952	disease recurrence
EFO:0008343	sex interaction measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630726 (PROTEIN FAMILY)

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs310786	Efficacy	3	tamoxifen
rs310786	Toxicity	3	tamoxifen	Breast Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs310786	E2F7	3	2.00	2	tamoxifen

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression, decreases expression	7
Aflatoxin B1	affects expression, decreases methylation, increases expression	6
Tetrachlorodibenzodioxin	increases expression, affects expression, decreases expression, affects cotreatment	4
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
Acetaminophen	affects expression, increases expression	3
Air Pollutants	increases oxidation, decreases expression, increases expression, affects cotreatment, increases abundance	3
Cisplatin	increases expression	3
Estradiol	affects cotreatment, increases expression, increases activity	3
Cyclosporine	affects expression, decreases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
lasiocarpine	increases expression, increases metabolic processing	2
Arsenic	decreases expression, affects cotreatment, increases abundance	2
Doxorubicin	increases expression, decreases expression	2
Endosulfan	affects cotreatment, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
sotorasib	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
tungsten carbide	affects cotreatment, increases expression	1
methylmercuric chloride	increases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects expression	1
arsenite	decreases reaction, affects binding	1
o,p’-DDT	increases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	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_A1D3	SEES3-1V human E2F7, clone1	Embryonic stem cell	Male
CVCL_A1D4	SEES3-1V human E2F7, clone2	Embryonic stem cell	Male
CVCL_A1D5	SEES3-1V human E2F7, clone3	Embryonic stem cell	Male
CVCL_E5FF	U2OS E2F7 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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