E2F5

Summary

E2F5 (E2F transcription factor 5, HGNC:3119) is a protein-coding gene on chromosome 8q21.2, encoding Transcription factor E2F5 (Q15329). Transcriptional activator that binds to E2F sites, these sites are present in the promoter of many genes whose products are involved in cell proliferation.

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 evolutionarily conserved domains that are present 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 is differentially phosphorylated and is expressed in a wide variety of human tissues. It has higher identity to E2F4 than to other family members. Both this protein and E2F4 interact with tumor suppressor proteins p130 and p107, but not with pRB. Alternative splicing results in multiple variants encoding different isoforms.

Source: NCBI Gene 1875 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 63 total
• Druggable target: yes
• Transcription factor: yes — 13 downstream targets (CollecTRI)
• MANE Select transcript: NM_001951

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3119
Approved symbol	E2F5
Name	E2F transcription factor 5
Location	8q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000133740
Ensembl biotype	protein_coding
OMIM	600967
Entrez	1875

Gene structure

Transcript identifiers

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

ENST00000256117, ENST00000416274, ENST00000418930, ENST00000517476, ENST00000518234, ENST00000520225, ENST00000521234, ENST00000521429, ENST00000955915

RefSeq mRNA: 3 — MANE Select: NM_001951 NM_001083588, NM_001083589, NM_001951

CCDS: CCDS47885, CCDS47886, CCDS55254

Canonical transcript exons

ENST00000416274 — 8 exons

Exon	Start	End
ENSE00000698384	85212157	85212204
ENSE00002103062	85213753	85214518
ENSE00002107139	85177154	85177654
ENSE00003488784	85206177	85206220
ENSE00003544753	85202147	85202256
ENSE00003567814	85207425	85207489
ENSE00003577919	85209142	85209409
ENSE00003591647	85203094	85203255

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 97.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.1520 / max 230.6003, expressed in 1480 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89594	3.2489	1172
89595	2.8144	887
89599	1.1346	383
89593	0.7613	456
89601	0.6007	59
89597	0.4835	269
89598	0.3832	111
89602	0.3691	116
89596	0.3073	184
89600	0.0491	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	97.10	gold quality
ganglionic eminence	UBERON:0004023	92.45	gold quality
embryo	UBERON:0000922	89.55	gold quality
cortical plate	UBERON:0005343	85.54	gold quality
lymph node	UBERON:0000029	83.02	gold quality
islet of Langerhans	UBERON:0000006	81.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.34	gold quality
adrenal tissue	UBERON:0018303	81.03	gold quality
rectum	UBERON:0001052	80.11	gold quality
vermiform appendix	UBERON:0001154	79.43	gold quality
granulocyte	CL:0000094	78.74	gold quality
tibial nerve	UBERON:0001323	78.40	gold quality
right uterine tube	UBERON:0001302	78.22	gold quality
adenohypophysis	UBERON:0002196	78.08	gold quality
right adrenal gland	UBERON:0001233	77.99	gold quality
left adrenal gland	UBERON:0001234	77.59	gold quality
pancreas	UBERON:0001264	77.55	gold quality
right adrenal gland cortex	UBERON:0035827	77.39	gold quality
spleen	UBERON:0002106	77.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.13	gold quality
body of pancreas	UBERON:0001150	77.08	gold quality
left adrenal gland cortex	UBERON:0035825	77.07	gold quality
left lobe of thyroid gland	UBERON:0001120	76.72	gold quality
lower esophagus mucosa	UBERON:0035834	76.49	gold quality
adrenal gland	UBERON:0002369	76.42	gold quality
endometrium	UBERON:0001295	76.38	gold quality
right lobe of thyroid gland	UBERON:0001119	76.33	gold quality
left ovary	UBERON:0002119	76.23	gold quality
gall bladder	UBERON:0002110	76.17	gold quality
thyroid gland	UBERON:0002046	76.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-112	yes	2112.50
E-ANND-3	yes	9.20

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

13 targets.

Target	Regulation
ASF1B	Activation
BRCA1
CBX5	Repression
CD74
DIRAS3
DTL	Activation
E2F1	Unknown
FGFR2	Activation
FSHR	Unknown
LOXL2	Unknown
MT1G
MYC	Unknown
TERT

Upstream regulators (CollecTRI, top): TFDP3, TP53

miRNA regulators (miRDB)

125 targeting E2F5, 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-4262	100.00	73.26	3931
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-190A-3P	100.00	80.35	5520
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
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-3065-5P	99.97	71.56	3281
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650

Literature-anchored findings (GeneRIF, showing 35)

• the subcellular distribution of E2F-5 is tightly regulated in intact cells, through multiple functional domains that direct nucleocytoplasmic shuttling of this protein. (PMID:12089160)
• We investigated occupancy of ER-alpha promoter by pRb2/p130-E2F4/5-HDAC1-SUV39 H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 complexes, and provided a link between pRb2/p130 and chromatin-modifying enzymes in the regulation of ER-alpha transcription (PMID:12789259)
• EBV LPM1 blocks p16INK4 pathway by promoting nuclear export of E2F-5. (PMID:12860972)
• E2F5 protein is down-regulated late in embryogenesis (PMID:16172982)
• Overexpression of E2F5/p130 in post-mitotic lens fiber cells does not affect normal differentiation, but can inhibit inappropriate cell cycle reentry induced by activator E2Fs. P130 is key player in inhibitory process. (PMID:18385796)
• Overexpression of E2F-5 correlates with a pathological basal phenotype and a worse clinical outcome. (PMID:19259095)
• cell-cycle regulatory protein E2F5 might play a significant role in epithelial ovarian cancer pathogenesis (PMID:20181230)
• Diverting the function of E2F5 from a cell-cycle repressor into an activator might contribute to the higher oncogenic potential of HPV18 when compared with other high-risk HPV types. (PMID:20639900)
• Data indicate that E2F5 is commonly overexpressed in primary hepatocellular carcinomas and show that E2F5 knockdown significantly repressed the growth of HCC cells. (PMID:21274376)
• E2F5 may be a novel potential candidate marker for malignant prostate cancer (PMID:23377984)
• expression of E2F5 in esphageal squamous cell cancer (ESCC) may be correlated with a worse prognosis of patients with ESCC (PMID:24324077)
• In hepatocellular carcinoma cells hepatitis B virus down-regulates E2F5 expression by up-regulating expression of miR-181a. (PMID:24529171)
• miR-98 regulates muscle differentiation by altering the expression of the transcription factor E2F5 and, in turn, of multiple E2F5 targets. (PMID:25422988)
• MiR-34a was down-regulated in colorectal cancer cells and inversely correlated with FMNL2 and E2F5 expressions. Our study suggests that miR-34a is an important tumor suppressor of CRC progression by targeting FMNL2 and E2F5. (PMID:26103003)
• E2F5/p38 axis played a cardinal role in uncontrolled cellular proliferation in prostate cancer through pSMAD3L activation. (PMID:26919443)
• FOXN3 functions as a tumor suppressor in hepatocellular carcinoma by downregulating the expression of E2F5. (PMID:27259277)
• Taken together, these findings indicated that SNHG16 induces breast cancer cell migration by competitively binding miR-98 with E2F5. (PMID:28232182)
• Our data collectively indicate that miR-613 functions as a tumor suppressor in retinoblastoma through downregulating E2F5, supporting the targeting of the novel miR-613/E2F5 axis as a potentially effective therapeutic approach for retinoblastoma. (PMID:28351331)
• High E2F5 expression is associated with Glioma. (PMID:29362021)
• Knockdown of the target gene of MIRN129, E2F5, inhibited the proliferation of glioblastoma cells. (PMID:29509253)
• miR-1179 overexpression could also inhibit tumor growth in vivo by suppressing the expression of E2F5. (PMID:29859832)
• knockdown of E2F5 and PFTK1 mimicked the tumor-suppressive effects of miR-1-3p overexpression on PCa progression. Conversely, concomitant knockdown of miR-1-3p and E2F5 and PFTK1 substantially reversed the inhibitory effects of either E2F5 or PFTK1 silencing alone. (PMID:30185212)
• MYCN induces E2F5 expression in neuroblastoma cells. E2F5 is a direct target of MYCN in neuroblastoma cells. (PMID:30765227)
• High E2F5 expression is associated with esophageal squamous cell carcinoma progression. (PMID:31983127)
• E2F5 promotes prostate cancer cell migration and invasion through regulation of TFPI2, MMP-2 and MMP-9. (PMID:32386317)
• Circular RNA ABCB10 promotes non-small cell lung cancer progression by increasing E2F5 expression through sponging miR-584-5p. (PMID:32420810)
• Knockdown of E2F5 induces cell death via the TP53dependent pathway in breast cancer cells carrying wildtype TP53. (PMID:33000282)
• CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 contributes to prostate carcinogenesis. (PMID:33390186)
• E2F5 Promotes the Malignancy of Ovarian Cancer Via the Regulation of Hippo and Wnt Pathways. (PMID:33734894)
• Targeting CALM2 Inhibits Hepatocellular Carcinoma Growth and Metastasis by Suppressing E2F5-mediated Cell Cycle Progression. (PMID:33788723)
• E2F5 promotes proliferation and invasion of gastric cancer through directly upregulating UBE2T transcription. (PMID:34583905)
• METTL3 promotes the growth and metastasis of pancreatic cancer by regulating the m6A modification and stability of E2F5. (PMID:35985439)
• Transcriptional induction of NF-kappaB-inducing kinase by E2F4/5 facilitates collective invasion of GBM cells. (PMID:37567906)
• Expression of CD44 is regulated by ELF3 in 5-FU treated colorectal cancer cells. (PMID:37832805)
• Knockdown of RNA-binding protein IMP3 suppresses oral squamous cell carcinoma proliferation by destabilizing E2F5 transcript. (PMID:38271139)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	e2f5	ENSDARG00000038812
mus_musculus	E2f5	ENSMUSG00000027552
rattus_norvegicus	E2f5	ENSRNOG00000010760
caenorhabditis_elegans		WBGENE00009899

Paralogs (7): E2F2 (ENSG00000007968), E2F1 (ENSG00000101412), E2F3 (ENSG00000112242), E2F8 (ENSG00000129173), E2F7 (ENSG00000165891), E2F6 (ENSG00000169016), E2F4 (ENSG00000205250)

Protein

Protein identifiers

Transcription factor E2F5 — Q15329 (reviewed: Q15329)

All UniProt accessions (5): C9JYE9, Q15329, E5RHD4, H0YBK0, H0YBW8

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator that binds to E2F sites, these sites are present in the promoter of many genes whose products are involved in cell proliferation. May mediate growth factor-initiated signal transduction. It is likely involved in the early responses of resting cells to growth factor stimulation. Specifically required for multiciliate cell differentiation: together with MCIDAS and E2F5, binds and activate genes required for centriole biogenesis.

Subunit / interactions. Component of the DRTF1/E2F transcription factor complex. Binds cooperatively with DP-1 to E2F sites. Interaction with retinoblastoma protein RB1 or proteins RBL1 and RBL2 inhibits the E2F transactivation domain. Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2.

Subcellular location. Nucleus.

Similarity. Belongs to the E2F/DP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q15329-1	1	yes
Q15329-2	2
Q15329-3	3

RefSeq proteins (3): NP_001077057, NP_001077058, NP_001942* (*=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 (24 total): region of interest 6, strand 5, compositionally biased region 3, helix 3, splice variant 2, chain 1, DNA-binding region 1, sequence variant 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5TUV	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15329-F1	72.06	0.27

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1362277	Transcription of E2F targets under negative control by DREAM complex
R-HSA-1362300	Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1
R-HSA-1538133	G0 and Early G1
R-HSA-2173796	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-69202	Cyclin E associated events during G1/S transition
R-HSA-69205	G1/S-Specific Transcription
R-HSA-69231	Cyclin D associated events in G1
R-HSA-69656	Cyclin A:Cdk2-associated events at S phase entry

MSigDB gene sets: 282 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, REACTOME_G1_S_SPECIFIC_TRANSCRIPTION, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, HOFMANN_CELL_LYMPHOMA_UP, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, BROWNE_HCMV_INFECTION_16HR_UP, FOXD3_01, PUJANA_CHEK2_PCC_NETWORK, GTGCCTT_MIR506, BROWNE_HCMV_INFECTION_24HR_UP, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, FISCHER_G2_M_CELL_CYCLE, FOXJ2_01

GO Biological Process (5): regulation of transcription by RNA polymerase II (GO:0006357), animal organ morphogenesis (GO:0009887), cell projection organization (GO:0030030), regulation of DNA-templated transcription (GO:0006355), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity (GO:0001216), DNA-binding transcription factor activity (GO:0003700), protein dimerization activity (GO:0046983), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (9): chromatin (GO:0000785), fibrillar center (GO:0001650), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), RNA polymerase II transcription regulator complex (GO:0090575), nucleus (GO:0005634), transcription regulator complex (GO:0005667), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
G0 and Early G1	2
G1/S Transition	2
Mitotic G1 phase and G1/S transition	1
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1
G1 Phase	1
S Phase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
regulation of DNA-templated transcription	3
DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
DNA-binding transcription factor activity	2
transcription cis-regulatory region binding	2
nuclear lumen	2
transcription by RNA polymerase II	1
anatomical structure morphogenesis	1
animal organ development	1
cellular component organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
transcription regulator activity	1
protein binding	1
nucleic acid binding	1
binding	1
chromosome	1
nucleolus	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
transcription regulator complex	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1200 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
E2F5	RBL2	Q08999	992
E2F5	SMAD3	P84022	967
E2F5	E2F4	Q16254	900
E2F5	GMNC	A6NCL1	899
E2F5	SMAD4	Q13485	870
E2F5	TFDP1	Q14186	849
E2F5	TFDP3	Q5H9I0	841
E2F5	TFDP2	Q14188	841
E2F5	MCIDAS	D6RGH6	813
E2F5	LIN52	Q52LA3	738
E2F5	LIN9	Q5TKA1	701
E2F5	LIN37	Q96GY3	691
E2F5	MYBL2	P10244	663
E2F5	CDK2	P24941	654
E2F5	MYC	P01106	650

IntAct

40 interactions, top by confidence:

A	B	Type	Score
CDK2	CCNE2	psi-mi:“MI:0914”(association)	0.940
CDKN1A	CCNE2	psi-mi:“MI:0914”(association)	0.890
GMNN	MCIDAS	psi-mi:“MI:0914”(association)	0.770
RB1	TFDP1	psi-mi:“MI:0915”(physical association)	0.740
LIN37	MYBL1	psi-mi:“MI:0914”(association)	0.640
RB1	E2F5	psi-mi:“MI:0407”(direct interaction)	0.610
TFDP1	E2F3	psi-mi:“MI:0914”(association)	0.530
TFDP2	E2F3	psi-mi:“MI:0914”(association)	0.530
PRPF38A	H2BC17	psi-mi:“MI:0914”(association)	0.510
SPOP	E2F5	psi-mi:“MI:2364”(proximity)	0.470
E2F5	SPOP	psi-mi:“MI:2364”(proximity)	0.470
SPOP	E2F5	psi-mi:“MI:0915”(physical association)	0.470
RBL2	CCNE2	psi-mi:“MI:0914”(association)	0.460
E7	AP2A1	psi-mi:“MI:0914”(association)	0.350
	E2F3	psi-mi:“MI:0914”(association)	0.350
LIN54	HDAC3	psi-mi:“MI:0914”(association)	0.350
RBL2	GSTM3	psi-mi:“MI:0914”(association)	0.350
MAGEA9	CIBAR1	psi-mi:“MI:0914”(association)	0.350
GGA1	RABGAP1L	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
BRAF	E2F5	psi-mi:“MI:2364”(proximity)	0.270
FBXW7	E2F5	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (38): E2F5 (Affinity Capture-MS), E2F5 (Reconstituted Complex), E2F5 (Affinity Capture-MS), E2F5 (Affinity Capture-MS), E2F5 (Affinity Capture-MS), PRPF38A (Affinity Capture-MS), E2F5 (Affinity Capture-MS), TFDP1 (Co-purification), RBL2 (Co-purification), E2F5 (Two-hybrid), E2F5 (Proximity Label-MS), E2F5 (Affinity Capture-MS), E2F5 (Affinity Capture-MS), E2F5 (Affinity Capture-MS), E2F1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0K3AV08, A5HWA8, A5JYW9, K8ERR8, O13987, O17862, O44757, O60291, O74986, O77051, O94532, O96838, P32351, P34379, P87152, Q02645, Q08639, Q09446, Q09663, Q14186, Q14693, Q15329, Q17QZ4, Q20619, Q22811, Q22992, Q24318, Q5H9I0, Q60JJ0, Q61502, Q621Z7, Q62814, Q64163, Q6DE14, Q8C9X6, Q95Q98, Q9FNY0, Q9FNY2, Q9FNY3, Q9FV70

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
E2F5	“down-regulates quantity by repression”	CBX5	“transcriptional regulation”
CyclinE/CDK2	“up-regulates activity”	E2F5	phosphorylation
E2F5	“up-regulates activity”	CBP/p300	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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)	7	177.6×	4e-13
G0 and Early G1	7	123.0×	5e-12
Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1	5	120.2×	2e-08
Cyclin E associated events during G1/S transition	10	114.2×	1e-16
Transcription of E2F targets under negative control by DREAM complex	5	108.8×	2e-08
TP53 Regulates Transcription of Cell Cycle Genes	5	108.8×	2e-08
Cyclin A:Cdk2-associated events at S phase entry	10	106.2×	1e-16
Aberrant regulation of mitotic cell cycle due to RB1 defects	5	81.6×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
regulation of mitotic cell cycle	5	41.5×	6e-05
G1/S transition of mitotic cell cycle	5	34.6×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1574 predictions. Top by Δscore:

Variant	Effect	Δscore
8:85177652:GCG:G	donor_gain	1.0000
8:85177653:CGG:C	donor_loss	1.0000
8:85177655:G:GG	donor_gain	1.0000
8:85177655:GT:G	donor_loss	1.0000
8:85177656:T:G	donor_loss	1.0000
8:85202254:G:GT	donor_gain	1.0000
8:85202254:GAA:G	donor_gain	1.0000
8:85202257:G:GG	donor_gain	1.0000
8:85209261:ACCT:A	acceptor_gain	1.0000
8:85209264:T:TA	acceptor_gain	1.0000
8:85212156:GCA:G	acceptor_gain	1.0000
8:85212205:G:GA	donor_loss	1.0000
8:85212206:T:G	donor_loss	1.0000
8:85213751:A:AG	acceptor_gain	1.0000
8:85213752:G:GG	acceptor_gain	1.0000
8:85213752:GT:G	acceptor_gain	1.0000
8:85214915:GCTTA:G	donor_loss	1.0000
8:85214916:CTTAC:C	donor_loss	1.0000
8:85214917:TTAC:T	donor_loss	1.0000
8:85214918:TACC:T	donor_loss	1.0000
8:85215038:C:CC	acceptor_gain	1.0000
8:85215039:T:C	acceptor_gain	1.0000
8:85177631:G:GT	donor_gain	0.9900
8:85177650:AAGCG:A	donor_gain	0.9900
8:85177651:AGCG:A	donor_gain	0.9900
8:85177652:GCGG:G	donor_gain	0.9900
8:85202253:GGAA:G	donor_gain	0.9900
8:85202256:AG:A	donor_loss	0.9900
8:85202258:TA:T	donor_loss	0.9900
8:85202259:AA:A	donor_loss	0.9900

AlphaMissense

2268 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:85177568:A:T	R50W	1.000
8:85177569:G:T	R50M	1.000
8:85177580:A:C	S54R	1.000
8:85177581:G:T	S54I	1.000
8:85177582:C:A	S54R	1.000
8:85177582:C:G	S54R	1.000
8:85177584:T:A	L55Q	1.000
8:85177584:T:C	L55P	1.000
8:85177586:G:A	G56R	1.000
8:85177586:G:C	G56R	1.000
8:85177587:G:A	G56E	1.000
8:85177590:T:C	L57P	1.000
8:85177593:T:A	L58H	1.000
8:85177593:T:C	L58P	1.000
8:85177596:C:A	T59N	1.000
8:85177596:C:T	T59I	1.000
8:85177604:T:A	F62I	1.000
8:85177604:T:C	F62L	1.000
8:85177605:T:C	F62S	1.000
8:85177605:T:G	F62C	1.000
8:85177606:C:A	F62L	1.000
8:85177606:C:G	F62L	1.000
8:85177614:T:C	L65P	1.000
8:85177617:T:C	L66P	1.000
8:85177625:G:C	A69P	1.000
8:85177635:G:A	G72D	1.000
8:85177635:G:T	G72V	1.000
8:85177641:T:C	L74P	1.000
8:85177644:A:T	D75V	1.000
8:85177646:C:T	L76F	1.000

dbSNP variants (sampled 300 via entrez): RS1000042933 (8:85196430 C>G), RS1000210403 (8:85177482 A>C), RS1000272070 (8:85211031 G>A), RS1000312074 (8:85188865 A>T), RS1000330864 (8:85183063 A>G), RS1000406162 (8:85183220 C>T), RS1000410396 (8:85203457 G>A,C), RS1000583707 (8:85177340 G>T), RS1000602150 (8:85209623 T>C,G), RS1000669630 (8:85184394 T>C), RS1000863273 (8:85183781 A>G), RS1000911499 (8:85194553 G>C,T), RS1000937280 (8:85176702 T>A,C), RS1001041181 (8:85183445 A>G), RS1001074150 (8:85189129 T>C)

Disease associations

OMIM: gene MIM:600967 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002360_5	Plasma amyloid beta peptide concentrations (ABx-40)	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005659	plasma beta-amyloid 1-40 measurement

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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, affects cotreatment, increases abundance, increases expression	3
Arsenic Trioxide	decreases expression	2
Arsenic	affects cotreatment, increases abundance, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Formaldehyde	decreases expression	2
Quercetin	decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
lasiocarpine	decreases expression, increases metabolic processing	1
triphenyl phosphate	affects expression	1
methylselenic acid	decreases expression	1
riddelliine	decreases expression, increases metabolic processing	1
methylparaben	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
JP8 aviation fuel	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	increases expression	1

Cellosaurus cell lines

5 cell lines: 3 embryonic stem cell, 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A1C7	SEES3-1V human E2F5, clone1	Embryonic stem cell	Male
CVCL_A1C8	SEES3-1V human E2F5, clone2	Embryonic stem cell	Male
CVCL_A1C9	SEES3-1V human E2F5, clone3	Embryonic stem cell	Male
CVCL_D9DW	Ubigene HEK293 E2F5 KO	Transformed cell line	Female
CVCL_GZ80	K562 eGFP-E2F5	Cancer cell line	Female

Clinical trials (associated diseases)

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