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 nucleoplasm.

Source: NCBI Gene 144455 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 134 total
• GTEx eGene: eQTL in 11 tissues, sQTL in 1 (q < 0.05)
• Drug target: yes — 1 via a complex or family
• Constraint (gnomAD): pLI 0.02 (LoF-tolerant), LOEUF 0.58 (moderately constrained)
• MANE Select transcript: NM_203394
• Notable: 134 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 12 — 8 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000322886

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

ENST00000322886, ENST00000416496, ENST00000547316, ENST00000550669, ENST00000551058, ENST00000551558, ENST00000552907, ENST00000919446, ENST00000919447, ENST00001078532, ENST00001078533, ENST00001141955

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.

Highest expression (Bgee): ventricular zone, thymus, upper arm skin, primordial germ cell in gonad, ganglionic eminence.

Genetic regulation across tissues (GTEx eQTL / sQTL)

E2F7 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

12 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	1.5e-13	-0.77	12:77042011:A:G
Cells Cultured fibroblasts	eqtl	1.9e-13	-0.15	12:77132029:CAT:C
Brain Cortex	eqtl	3.6e-09	-0.65	12:77043602:T:C
Brain Frontal Cortex BA9	eqtl	2.9e-06	-0.57	12:77045571:C:T
Brain Amygdala	eqtl	7.5e-06	-0.59	12:77045571:C:T
Brain Caudate basal ganglia	eqtl	7.8e-04	-0.28	12:77052578:C:T
Pituitary	eqtl	1.2e-03	+0.38	12:77052769:T:C
Esophagus Mucosa	eqtl	1.3e-03	+0.14	12:77107585:G:A
Artery Aorta	eqtl	6.3e-03	+0.40	12:77061774:T:A
Skin Not Sun Exposed Suprapubic	eqtl	1.7e-02	+0.15	12:77086734:T:C
Adipose Subcutaneous	eqtl	2.6e-02	-0.17	12:78018442:C:T
Whole Blood	eqtl	4.3e-02	-0.39	12:77063690:G:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
132236	17.3933	1499

Top tissues by expression

showing 100 of 234 tissues 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
adrenal tissue	UBERON:0018303	61.56	gold quality
endometrium	UBERON:0001295	61.48	gold quality
bronchus	UBERON:0002185	61.21	gold quality
cartilage tissue	UBERON:0002418	61.09	silver quality
lymph node	UBERON:0000029	60.51	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	60.41	gold quality
oocyte	CL:0000023	60.28	gold quality
duodenum	UBERON:0002114	58.72	gold quality
tonsil	UBERON:0002372	58.39	gold quality
caecum	UBERON:0001153	58.34	gold quality
gall bladder	UBERON:0002110	58.30	gold quality
lower esophagus mucosa	UBERON:0035834	58.26	gold quality
jejunal mucosa	UBERON:0000399	57.99	gold quality
placenta	UBERON:0001987	57.25	gold quality
smooth muscle tissue	UBERON:0001135	56.21	gold quality
testis	UBERON:0000473	55.45	gold quality
skin of hip	UBERON:0001554	55.30	gold quality
cortical plate	UBERON:0005343	54.91	gold quality
quadriceps femoris	UBERON:0001377	54.68	gold quality
visceral pleura	UBERON:0002401	54.59	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
fallopian tube	UBERON:0003889	54.22	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
palpebral conjunctiva	UBERON:0001812	53.69	silver quality
nasal cavity mucosa	UBERON:0001826	53.61	gold quality
parotid gland	UBERON:0001831	53.45	gold quality
left testis	UBERON:0004533	53.35	gold quality
oral cavity	UBERON:0000167	53.17	silver quality
adult organism	UBERON:0007023	53.05	gold quality
colonic epithelium	UBERON:0000397	52.75	gold quality
vastus lateralis	UBERON:0001379	52.50	gold quality
right testis	UBERON:0004534	51.98	gold quality
esophagus	UBERON:0001043	51.50	gold quality
right uterine tube	UBERON:0001302	51.36	gold quality
decidua	UBERON:0002450	51.30	gold quality
vagina	UBERON:0000996	51.24	gold quality
metanephros	UBERON:0000081	50.30	silver quality
pancreas	UBERON:0001264	50.26	gold quality
myocardium	UBERON:0002349	50.25	gold quality
jejunum	UBERON:0002115	49.91	gold quality
pigmented layer of retina	UBERON:0001782	49.81	silver quality
uterus	UBERON:0000995	49.78	gold quality
blood	UBERON:0000178	49.49	gold quality
female reproductive system	UBERON:0000474	48.82	gold quality
skin of abdomen	UBERON:0001416	48.67	gold quality
small intestine	UBERON:0002108	48.56	gold quality
cerebellar vermis	UBERON:0004720	48.32	gold quality
muscle tissue	UBERON:0002385	48.21	gold quality
urinary bladder	UBERON:0001255	48.10	gold quality
zone of skin	UBERON:0000014	47.76	gold quality
transverse colon	UBERON:0001157	47.67	gold quality
skin of leg	UBERON:0001511	47.67	gold quality
lung	UBERON:0002048	47.65	gold quality
nasal cavity epithelium	UBERON:0005384	47.61	gold quality
stomach	UBERON:0000945	46.65	gold quality
small intestine Peyer’s patch	UBERON:0003454	46.65	gold quality
leukocyte	CL:0000738	46.08	gold quality
lateral globus pallidus	UBERON:0002476	45.97	gold quality
intestine	UBERON:0000160	45.94	gold quality
spleen	UBERON:0002106	45.93	gold quality
layer of synovial tissue	UBERON:0007616	45.84	gold quality
lower lobe of lung	UBERON:0008949	45.73	silver quality
monocyte	CL:0000576	45.52	gold quality
liver	UBERON:0002107	45.32	silver quality
body of stomach	UBERON:0001161	44.96	gold quality
cardiac atrium	UBERON:0002081	44.80	gold quality
biceps brachii	UBERON:0001507	44.75	gold quality
mucosa of sigmoid colon	UBERON:0004993	44.62	silver quality
large intestine	UBERON:0000059	44.44	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 71 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Thalamus	tissue	16.9
Pons	tissue	9.6
Midbrain	tissue	8.9
Superior colliculi	tissue	8.1
Thymus	tissue	7.7
Bone marrow	tissue	4.7
Testis	tissue	2.7
Tonsil	tissue	1.5
Lymph node	tissue	1.4
Rectum	tissue	1.4
Cerebellum	tissue	1.4
Esophagus	tissue	1.2
Caudate putamen	tissue	1.1
Skin 1	tissue	1.0
Appendix	tissue	1.0
Colon	tissue	0.9
Frontal cortex	tissue	0.9
Placenta	tissue	0.9
Choroid plexus	tissue	0.8
Small intestine	tissue	0.8
Duodenum	tissue	0.7
Stomach 1	tissue	0.6
Cerebral cortex	tissue	0.6
Gallbladder	tissue	0.6
Fallopian tube	tissue	0.6
Occipital cortex	tissue	0.6
Vagina	tissue	0.5
Urinary bladder	tissue	0.5
Hippocampal formation	tissue	0.5
Entorhinal cortex	tissue	0.5
Somatosensory cortex	tissue	0.5
Pituitary gland	tissue	0.4
Prefrontal cortex	tissue	0.4
Motor cortex	tissue	0.4
Basal ganglia	tissue	0.4
Retrosplenial and cingulate cortex	tissue	0.4
Retrosplenial cortex	tissue	0.4
Temporal cortex	tissue	0.4
Insular cortex	tissue	0.4
Smooth muscle	tissue	0.3
Putamen	tissue	0.3
Amygdala	tissue	0.3
Nucleus accumbens	tissue	0.3
Medulla oblongata	tissue	0.3
Spinal cord	tissue	0.3
Hippocampus	tissue	0.3
Postcentral gyrus	tissue	0.3
Ventral forebrain	tissue	0.3
Breast	tissue	0.2
Retina	tissue	0.2
Ovary	tissue	0.2
Adipose tissue	tissue	0.2
Endometrium 1	tissue	0.2
Hypothalamus	tissue	0.2
Substantia nigra	tissue	0.2
Lung	tissue	0.2
Spleen	tissue	0.2
Periaqueductal gray	tissue	0.2
Olfactory bulb	tissue	0.2
Septum	tissue	0.2

Brain sub-regions (HPA Brain Atlas): detected in 178; highest nTPM — Periaquaductal grey, lateral (1.9), Nucleus tractus solitarii (1.6), Cervical spinal cord, central gray (1.4), Dorsal raphe nucleus (1.3), Superior vestibular nucleus (1.1).

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)

Targeting E2F7 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 210 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.0189, LOEUF 0.58, missense Z 1.88 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000322886 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
12:77,024,018–77,033,978	587 / 620.3	0.95	no
12:77,033,979–77,056,043	301 / 405.0	0.74	no
12:77,056,044–77,064,635	73 / 68.4	1.07	no

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)

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Bos taurus	Q08DY6	93.0%	Diamond
Xenopus laevis	Q6DE14	66.5%	Diamond
Gallus gallus	Q90977	62.6%	Diamond
Arabidopsis thaliana	Q8RWL0	57.0%	Diamond
Xenopus tropicalis	F6YVB9	49.6%	Diamond

Genomic neighbors (locus context)

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

Symbol	Type	Entrez
LINC02464	ncRNA	105369854
CSRP2	protein-coding	1466
ZDHHC17	protein-coding	23390

Protein

Protein identifiers

Transcription factor E2F7 — Q96AV8 (reviewed: Q96AV8)

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

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Transcription factors, Helix-turn-helix domains

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol; primary cilium; primary cilium tip

Antibody reliability (HPA): IF supported

Functional residue map

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

Post-translational modifications (3)

Type	Positions
Phosphoserine	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 with a-334.
334	loss of dna-binding and inhibition of e2f1-dependent activation. impairs dna-binding and dimerization; when associated with a-185.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-6804116	TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	curated
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-9938024	Somatic hypermutation of immunoglobulin genes	electronic
R-HSA-6791312	TP53 Regulates Transcription of Cell Cycle Genes	—
R-HSA-3700989	Transcriptional Regulation by TP53	—

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 (17): negative regulation of transcription by RNA polymerase II (GO:0000122), placenta development (GO:0001890), sprouting angiogenesis (GO:0002040), DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), 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)

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

Reactome top-level categories

6 top-level categories:

Category	Pathways
TP53 Regulates Transcription of Cell Cycle Genes	1
Affinity selection of immunoglobulins	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Gene expression (Transcription)	1

GO top-level categories

57 GO namespaces:

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
gene expression	1
RNA biosynthetic 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
negative regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transcription regulator activity	1
protein binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1
nuclear lumen	1
transcription regulator complex	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 33 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
DNA damage response, signal transduction by p53 class mediator	BP	direct assay
negative regulation of transcription by RNA polymerase II	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	mutant phenotype
sprouting angiogenesis	BP	mutant phenotype
nucleoplasm	CC	direct assay
DNA-binding transcription factor activity	MF	mutant phenotype
DNA-binding transcription repressor activity	MF	direct assay
cis-regulatory region sequence-specific DNA binding	MF	direct assay
identical protein binding	MF	physical interaction
sequence-specific double-stranded DNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,314 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
E2F7	CDC6	Q99741	859
E2F7	TFDP3	Q5H9I0	836
E2F7	TP53	P04637	590
E2F7	E2F5	Q15329	496
E2F7	ETS1	P14921	488
E2F7	FOXM1	Q08050	473
E2F7	ESR1	P03372	470
E2F7	E2F4	Q16254	464
E2F7	HINFP	Q9BQA5	438
E2F7	E2F2	Q14209	438
E2F7	CCNA2	P20248	433
E2F7	E2F1	Q01094	430
E2F7	TFDP1	Q14186	430
E2F7	ETS2	P15036	429
E2F7	CCNE2	O96020	421

IntAct

Human interaction partners of E2F7 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

12 partners by confidence:

Partner	Interaction type	MIscore	Records
E2F8	physical association	0.520	4
BRAF	proximity	0.470	2
FBXW7	proximity	0.270	4
SMARCA4	proximity	0.270	4
SPOP	proximity	0.270	4
SMAD4	proximity	0.270	2
AKT1	proximity	0.270	1
EGFR	proximity	0.270	1
PTEN	proximity	0.270	1
PTPN11	proximity	0.270	1
TP53	proximity	0.270	1
RUVBL1	physical association	0.000	1

BioGRID (58 interactions; top human partners by supporting records): C6orf141 (Affinity Capture-MS; 2 records), CCNF (Affinity Capture-Western; 2 records), CTBP1 (Affinity Capture-MS; 2 records), DCP1B (Affinity Capture-Luminescence; 2 records), HSFY1 (Affinity Capture-Luminescence; 2 records), KIAA1429 (Affinity Capture-RNA; 2 records), APEX1 (Affinity Capture-RNA), CCND1 (Affinity Capture-MS), CDC123 (Affinity Capture-MS), CIC (Affinity Capture-MS), CRYAA (Reconstituted Complex), CYLD (Affinity Capture-MS), DCAF7 (Affinity Capture-MS), FASN (Negative Genetic), FHL2 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

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

Disease & clinical

Genetic variants

Variant evidence for E2F7: 134 ClinVar records (0 pathogenic / likely pathogenic); 2 PharmGKB clinical annotations; 24 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	111
Likely benign	5
Benign	6

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 1,302):

Position(s)	Effect	Δscore	Sites
12:77024186–77024187	acceptor_loss	1.0000	6
12:77033048–77033049	donor_loss	1.0000	5
12:77033123–77033124	acceptor_loss	1.0000	6
12:77033855–77033856	donor_loss	1.0000	4
12:77033899	donor_gain	1.0000
12:77034043–77034044	acceptor_loss	1.0000	3
12:77034047	acceptor_gain	1.0000
12:77044635–77044636	donor_loss	1.0000	2
12:77044796–77044797	acceptor_loss	1.0000	5
12:77046071	donor_gain	1.0000

AlphaMissense

1,125 missense substitutions predicted likely pathogenic (of 5,894 scored), across 243 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M290	9	0.941	0.998
M296	9	0.932	0.993
D188	8	1.000	1.000
D337	8	1.000	1.000
N191	8	0.995	1.000
N205	8	0.995	0.999
F294	8	0.994	1.000
F154	8	0.993	1.000
N340	8	0.993	1.000
F363	8	0.993	1.000
F298	8	0.991	0.999
S146	8	0.990	0.999
D173	8	0.982	0.996
S344	8	0.959	0.999
S291	8	0.927	1.000
D284	8	0.915	0.983
H352	8	0.870	0.986
D309	8	0.864	0.973
D10	8	0.789	0.919
N33	8	0.751	0.925

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

4 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000107
Lung Adenocarcinoma (TCGA)	unfavorable	0.000113
Lung Adenocarcinoma (validation)	unfavorable	0.000446
Kidney Renal Clear Cell Carcinoma (validation)	unfavorable	0.000502

Disease associations

OMIM: gene MIM:612046 | disease phenotypes:

GWAS associations

24 associations:

Study	Trait	p-value
GCST90000025_296	Appendicular lean mass	9e-14
GCST010422_1	Mean arterial pressure x educational attainment (some college) interaction (2df)	1e-11
GCST010422_2	Mean arterial pressure x educational attainment (some college) interaction (2df)	2e-11
GCST90000025_295	Appendicular lean mass	2e-10
GCST007576_85	Chronotype	6e-9
GCST008839_476	Height	9e-9
GCST012227_1109	Hip circumference adjusted for BMI	2e-8
GCST005156_2	Alloimmunization response to pregnancy (HLA class I)	2e-7
GCST012301_14	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	2e-7
GCST011541_8	Tinnitus	5e-7
GCST012295_3	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	7e-7
GCST012298_4	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	9e-7
GCST003806_5	Response to bupropion and depression	1e-6
GCST004136_4	Methadone dose in opioid dependence	2e-6
GCST012299_22	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction (3df)	2e-6
GCST90000027_45	Appendicular lean mass	2e-6
GCST008152_39	Weight	3e-6
GCST012292_6	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	3e-6
GCST002198_25	Tuberculosis	4e-6
GCST004136_10	Methadone dose in opioid dependence	4e-6
GCST012300_1	Schizophrenia, bipolar disorder or major depressive disorder	5e-6
GCST009936_5	Venous thromboembolism	6e-6
GCST009391_1832	Metabolite levels	7e-6
GCST006138_32	Resting-state electroencephalogram vigilance	9e-6

EFO canonical traits (from GWAS)

12 canonical traits:

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)

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes E2F7 — the drug acts on the assembly or class, not necessarily on this subunit alone.

1 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
EDIFOLIGIDE SODIUM	E2F	8	3

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

2 annotations by evidence level (1 strongest → 4):

Variant	Association	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

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

2 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs310786	tamoxifen	Toxicity	Genotype CC is associated with increased lumbar bone loss when treated with tamoxifen in women with Breast Neoplasms as compared to genotypes CT + TT.	PMID:23508821
rs310786	tamoxifen	Other	Genotype CC is associated with increased sensitivity to tamoxifen in lymphoblastoid cell lines as compared to genotypes CT + TT.	PMID:23508821

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	increases expression, affects expression, decreases methylation	6
Tetrachlorodibenzodioxin	decreases expression, affects cotreatment, increases expression, affects expression	4
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
Acetaminophen	affects expression, increases expression	3
Air Pollutants	increases expression, affects cotreatment, increases abundance, increases oxidation, decreases expression	3
Cisplatin	increases expression	3
Estradiol	affects cotreatment, increases expression, increases activity	3
Cyclosporine	affects expression, decreases expression	3
Particulate Matter	increases expression, decreases expression, increases abundance	3
lasiocarpine	increases metabolic processing, increases expression	2
Arsenic	decreases expression, affects cotreatment, increases abundance	2
Doxorubicin	decreases expression, increases expression	2
Endosulfan	increases expression, decreases expression, affects cotreatment	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 oxidation, increases abundance, affects cotreatment	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	affects binding, decreases reaction	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)

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