E2F8

Summary

E2F8 (E2F transcription factor 8, HGNC:24727) is a protein-coding gene on chromosome 11p15.1, encoding Transcription factor E2F8 (A0AVK6). Atypical E2F transcription factor that participates in various processes such as angiogenesis and polyploidization of specialized cells.

This gene encodes a member of a family of transcription factors which regulate the expression of genes required for progression through the cell cycle. The encoded protein regulates progression from G1 to S phase by ensuring the nucleus divides at the proper time. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 79733 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 9 total
• Druggable target: yes
• MANE Select transcript: NM_024680

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24727
Approved symbol	E2F8
Name	E2F transcription factor 8
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23311
Ensembl gene	ENSG00000129173
Ensembl biotype	protein_coding
OMIM	612047
Entrez	79733

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 12 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000250024, ENST00000527884, ENST00000529188, ENST00000532666, ENST00000620009, ENST00000898597, ENST00000898598, ENST00000898599, ENST00000928103, ENST00000928104, ENST00000928105, ENST00000966242, ENST00000966243

RefSeq mRNA: 3 — MANE Select: NM_024680 NM_001256371, NM_001256372, NM_024680

CCDS: CCDS7849

Canonical transcript exons

ENST00000250024 — 13 exons

Exon	Start	End
ENSE00000886635	19225732	19225864
ENSE00000886636	19229454	19229988
ENSE00000997761	19230631	19230834
ENSE00000997762	19232234	19232371
ENSE00001106987	19234360	19234521
ENSE00001128658	19230241	19230328
ENSE00001365135	19240548	19240945
ENSE00001365532	19240107	19240230
ENSE00001369020	19237314	19237470
ENSE00001374152	19237854	19238132
ENSE00001389338	19234744	19235058
ENSE00002165156	19224063	19224840
ENSE00003367906	19225221	19225615

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 89.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.6445 / max 133.7429, expressed in 927 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118988	0.9192	452
118989	0.7700	463
118985	0.6914	386
118987	0.6724	385
118986	0.5914	312

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	89.54	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.42	gold quality
secondary oocyte	CL:0000655	87.60	gold quality
oocyte	CL:0000023	87.21	gold quality
trabecular bone tissue	UBERON:0002483	86.38	gold quality
vastus lateralis	UBERON:0001379	85.09	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.71	gold quality
quadriceps femoris	UBERON:0001377	83.37	silver quality
bone marrow	UBERON:0002371	82.71	gold quality
esophagus squamous epithelium	UBERON:0006920	82.68	gold quality
skeletal muscle tissue	UBERON:0001134	82.54	gold quality
oral cavity	UBERON:0000167	81.64	gold quality
ventricular zone	UBERON:0003053	81.29	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	81.27	gold quality
triceps brachii	UBERON:0001509	79.72	silver quality
squamous epithelium	UBERON:0006914	79.51	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.00	gold quality
muscle tissue	UBERON:0002385	78.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.29	gold quality
epithelium of esophagus	UBERON:0001976	78.29	gold quality
gingival epithelium	UBERON:0001949	78.16	gold quality
pylorus	UBERON:0001166	77.43	gold quality
mucosa of transverse colon	UBERON:0004991	77.12	gold quality
colonic mucosa	UBERON:0000317	77.04	gold quality
jejunum	UBERON:0002115	77.02	gold quality
ganglionic eminence	UBERON:0004023	76.81	gold quality
bone marrow cell	CL:0002092	76.67	gold quality
rectum	UBERON:0001052	76.23	gold quality
gingiva	UBERON:0001828	76.01	gold quality
skeletal muscle organ	UBERON:0014892	75.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.23

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
CCND1	Unknown
E2F1	Repression
SPTA1
VEGFA	Activation

JASPAR motifs

Motif	Name	Family
MA0865.1	E2F8	E2F
MA0865.2	E2F8	E2F
MA0865.3	E2F8	E2F

JASPAR matrix evidence (PMIDs): PMID:18836037

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

60 targeting E2F8, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
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-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-448	99.79	72.37	2103

Literature-anchored findings (GeneRIF, showing 28)

• 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)
• E2F8 may have an important role in repressing the expression of E2F-target genes in the S-phase of the cell cycle. (PMID:16179649)
• E2F7 and E2F8 act upstream of E2F1, and influence the ability of cells to undergo a DNA-damage response. (PMID:18202719)
• Analyses indicated that E2F8 could bind to regulatory elements of cyclin D1, regulating its transcription and promoting accumulation of S-phase cells. Findings suggest that E2F8 contributes to the oncogenic potential of HCC (PMID:20068156)
• The results identify E2F8 as a repressor and E2F1 as an activator of a transcriptional network controlling polyploidization in mammalian cells. (PMID:23064264)
• transcription factor E2F8 is involved in the polyploidization during mouse and human decidualization (PMID:25892397)
• E2F8 is overexpressed in Lung Cancer and is required for the growth of LC cells. E2F8 knockdown reduced the expression of UHRF1. These findings implicate E2F8 as a novel therapeutic target for LC treatment. (PMID:26089541)
• High E2F8 expression is associated with breast cancer. (PMID:26992224)
• E2F8-mediated transcriptional repression is a critical tumor suppressor mechanism during postnatal liver development (PMID:27454291)
• Results showed that E2F8 is up-regulated in metastatic prostate cancer and associated with poor prognosis. These results indicate that E2F8 is a crucial transcription regulator controlling cell cycle and survival in prostate cancer cells. (PMID:27683099)
• Study provides evidence that E2F8 functions as a proliferation-related oncogene in papillary thyroid cancer progression. Moreover, miR-144 appears to be a tumor suppressor through direct inhibition of E2F8. (PMID:28270228)
• E2F8 can shorten cisplatin induced G2/M arrest by promoting MASTL mediated mitotic progression in ER+ breast cancer cells, conferring drug resistance. (PMID:28605876)
• miR-223-5p suppressed NSCLC progression through targeting E2F8. (PMID:29615147)
• MiR-1258 may function as a suppressive factor by negatively controlling E2F8 (PMID:30144184)
• Authors detected the expression of hsa_circ_0002468, miR-561, and E2F8 by using quantitative real-time polymerase chain reaction (qRT-PCR) analyses. (PMID:30951518)
• These results demonstrate that E2F8 modulates the growth of human colon cancer cells through promoting the NF-kappaB pathway. (PMID:31471336)
• NONO post-transcriptionally regulates the expression of cell proliferation-related genes by binding to their mRNAs, as exemplified by S-phase-associated kinase 2 and E2F transcription factor 8. (PMID:31733123)
• E2F8 regulates the proliferation and invasion through epithelial-mesenchymal transition in cervical cancer. (PMID:31929759)
• Carcinogenesis effects of E2F transcription factor 8 (E2F8) in hepatocellular carcinoma outcomes: an integrated bioinformatic report. (PMID:31990034)
• Cell cycle oscillators underlying orderly proteolysis of E2F8. (PMID:31995441)
• E2F transcription factor 8 promotes proliferation and radioresistance in glioblastoma. (PMID:32703494)
• E2F8 Induces Cell Proliferation and Invasion through the Epithelial-Mesenchymal Transition and Notch Signaling Pathways in Ovarian Cancer. (PMID:32823614)
• Opposing functions of circadian protein DBP and atypical E2F family E2F8 in anti-tumor Th9 cell differentiation. (PMID:36241625)
• E2F8 knockdown suppresses cell proliferation and induces cell cycle arrest via Wnt/beta-Catenin pathway in ovarian cancer. (PMID:37635486)
• E2F8 exerts cancer-promoting effects by transcriptionally activating RRM2 and E2F8 knockdown synergizes with WEE1 inhibition in suppressing lung adenocarcinoma. (PMID:37863324)
• Cyclosporin A inhibits prostate cancer growth through suppression of E2F8 transcription factor in a MELK-dependent manner. (PMID:37888771)
• ENO1 promotes trophoblast invasion regulated by E2F8 in recurrent miscarriage. (PMID:38661062)
• TJP1 suppresses trophoblast cell invasion by expressing E2F8 in the human placenta. (PMID:38795825)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	e2f8	ENSDARG00000057323
mus_musculus	E2f8	ENSMUSG00000046179
rattus_norvegicus	E2f8	ENSRNOG00000022537

Paralogs (7): E2F2 (ENSG00000007968), E2F1 (ENSG00000101412), E2F3 (ENSG00000112242), E2F5 (ENSG00000133740), E2F7 (ENSG00000165891), E2F6 (ENSG00000169016), E2F4 (ENSG00000205250)

Protein

Protein identifiers

Transcription factor E2F8 — A0AVK6 (reviewed: A0AVK6)

All UniProt accessions (2): A0AVK6, E9PMT9

UniProt curated annotations — full annotation on UniProt →

Function. Atypical E2F transcription factor that participates in various processes such as angiogenesis and polyploidization of specialized cells. 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: component of a feedback loop in S phase by repressing the expression of E2F1, thereby preventing p53/TP53-dependent apoptosis. 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. 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.

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.

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. Following DNA damage. Up-regulation in response to DNA damage is not confirmed by PubMed:22802528.

Similarity. Belongs to the E2F/DP family.

RefSeq proteins (3): NP_001243300, NP_001243301, NP_078956* (*=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 (37 total): helix 9, compositionally biased region 6, strand 6, modified residue 4, region of interest 4, DNA-binding region 2, mutagenesis site 2, sequence conflict 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4YO2	X-RAY DIFFRACTION	3.07

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0AVK6-F1	54.02	0.06

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 (4): 71, 102, 413, 417

Mutagenesis-validated functional residues (2):

Position	Phenotype
156	loss of dna-binding and inhibition of e2f1-dependent activation. impairs dna-binding and dimerization; when associated w
314	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: 367 (showing top): E2F_Q4, E2F_Q4_01, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GNF2_CENPF, E2F4DP1_01, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DIVISION, GOBP_CELL_CYCLE_DNA_REPLICATION, FISCHER_G1_S_CELL_CYCLE, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GNF2_RRM1

GO Biological Process (15): 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 cytokinesis (GO:0032466), positive regulation of DNA endoreduplication (GO:0032877), cell cycle comprising mitosis without cytokinesis (GO:0033301), positive regulation of transcription by RNA polymerase II (GO:0045944), fibroblast proliferation (GO:0048144), trophoblast giant cell differentiation (GO:0060707), chorionic trophoblast cell differentiation (GO:0060718), hepatocyte differentiation (GO:0070365), regulation of DNA-templated transcription (GO:0006355), positive regulation of macromolecule metabolic process (GO:0010604), obsolete positive regulation of nucleobase-containing compound metabolic process (GO:0045935)

GO Molecular Function (10): 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), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (7): chromatin (GO:0000785), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), 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
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription cis-regulatory region binding	3
cellular anatomical structure	3
negative regulation of DNA-templated transcription	2
regulation of DNA-templated transcription	2
DNA-binding transcription factor activity	2
nuclear lumen	2
animal organ development	1
angiogenesis	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
mitotic cell cycle	1
positive regulation of DNA-templated transcription	1
cell population proliferation	1
cell differentiation involved in embryonic placenta development	1
cell differentiation	1
chorion development	1
liver development	1
epithelial cell differentiation	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
positive regulation of metabolic process	1
macromolecule metabolic process	1
regulation of macromolecule metabolic 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

Protein interactions and networks

STRING

1248 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
E2F8	TFDP3	Q5H9I0	881
E2F8	CDC6	Q99741	876
E2F8	E2F6	O75461	746
E2F8	E2F4	Q16254	651
E2F8	CENPF	P49454	543
E2F8	TP53	P04637	540
E2F8	E2F1	Q01094	539
E2F8	E2F7	Q96AV8	521
E2F8	MCM3	P25205	517
E2F8	TK1	P04183	498
E2F8	MYBL2	P10244	492
E2F8	CCNE2	O96020	490
E2F8	HJURP	Q8NCD3	484
E2F8	MELK	Q14680	482
E2F8	CCNA2	P20248	474

IntAct

105 interactions, top by confidence:

A	B	Type	Score
E2F8	TFCP2	psi-mi:“MI:0915”(physical association)	0.560
FHL3	E2F8	psi-mi:“MI:0915”(physical association)	0.560
E2F8	FHL3	psi-mi:“MI:0915”(physical association)	0.560
E2F8	STUB1	psi-mi:“MI:0915”(physical association)	0.560
E2F8	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
ADRB2	E2F8	psi-mi:“MI:0915”(physical association)	0.560
E2F8	APBB2	psi-mi:“MI:0915”(physical association)	0.560
CASP6	E2F8	psi-mi:“MI:0915”(physical association)	0.560
E2F8		psi-mi:“MI:0915”(physical association)	0.560
E2F8	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	E2F8	psi-mi:“MI:0915”(physical association)	0.560
E2F8	GSN	psi-mi:“MI:0915”(physical association)	0.560
E2F8	HRAS	psi-mi:“MI:0915”(physical association)	0.560
	E2F8	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	E2F8	psi-mi:“MI:0915”(physical association)	0.560
BAG6	E2F8	psi-mi:“MI:0915”(physical association)	0.560
KLF11	E2F8	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	E2F8	psi-mi:“MI:0915”(physical association)	0.560
PEX26	E2F8	psi-mi:“MI:0915”(physical association)	0.560
E2F8	SNCA	psi-mi:“MI:0915”(physical association)	0.560
E2F8	HTT	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (38): E2F8 (Two-hybrid), E2F8 (Two-hybrid), E2F8 (Two-hybrid), TTC33 (Affinity Capture-MS), TTC33 (Affinity Capture-MS), E2F8 (Two-hybrid), E2F8 (Two-hybrid), CCNF (Affinity Capture-Western), E2F8 (Affinity Capture-Western), E2F8 (Proximity Label-MS), E2F8 (Proximity Label-MS), E2F8 (Proximity Label-MS), E2F8 (Affinity Capture-RNA), E2F8 (Affinity Capture-MS), OR1M1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IYX6, A0A1D5NVS8, A0A1L8H0H2, A0AVK6, A5GFT6, A7XYH5, A7XYJ6, B7ZS37, B8A5Y1, D4A666, E1B7L7, E1BKK0, E1BLP6, F1LMN3, F6YVB9, F8VPJ6, Q12766, Q13029, Q14B70, Q2HNT1, Q2HNT2, Q2KHR2, Q4V9H5, Q58FA4, Q5DTH5, Q5ZIE8, Q5ZIX8, Q5ZJ69, Q5ZM88, Q63679, Q63755, Q68FE9, Q69ZF8, Q6DRC5, Q6P4F7, Q6PCM1, Q6ZSZ6, Q76L83, Q80Y19, Q8BHZ4

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”	E2F8	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 41 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
Activation of BAD and translocation to mitochondria	7	183.8×	4e-13
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	162.2×	8e-13
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	139.0×	1e-10
Activation of BH3-only proteins	7	119.8×	8e-12
Intrinsic Pathway for Apoptosis	7	70.7×	2e-10
FOXO-mediated transcription	6	69.5×	7e-09
RHO GTPases activate PKNs	6	65.6×	9e-09
Apoptosis	8	46.3×	2e-10

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	45.8×	4e-05
MAPK cascade	5	19.1×	1e-03
intracellular protein localization	7	18.3×	4e-05
positive regulation of ERK1 and ERK2 cascade	5	10.6×	5e-03
positive regulation of apoptotic process	6	8.5×	4e-03
negative regulation of apoptotic process	8	7.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1921 predictions. Top by Δscore:

Variant	Effect	Δscore
11:19225560:A:C	acceptor_gain	1.0000
11:19230329:C:CC	acceptor_gain	1.0000
11:19230337:A:AC	acceptor_gain	1.0000
11:19230626:CATA:C	donor_loss	1.0000
11:19230627:ATAC:A	donor_loss	1.0000
11:19230628:TAC:T	donor_loss	1.0000
11:19230629:A:AC	donor_gain	1.0000
11:19230629:A:C	donor_loss	1.0000
11:19230630:C:CC	donor_gain	1.0000
11:19230835:C:CC	acceptor_gain	1.0000
11:19234358:A:AC	donor_gain	1.0000
11:19234359:C:CC	donor_gain	1.0000
11:19237308:A:AC	donor_gain	1.0000
11:19237308:ACTT:A	donor_loss	1.0000
11:19237309:C:CC	donor_gain	1.0000
11:19237309:CTT:C	donor_loss	1.0000
11:19237310:TTACT:T	donor_loss	1.0000
11:19237311:TA:T	donor_loss	1.0000
11:19237312:A:AC	donor_gain	1.0000
11:19237313:C:CT	donor_gain	1.0000
11:19237313:CT:C	donor_gain	1.0000
11:19237313:CTA:C	donor_gain	1.0000
11:19237313:CTAA:C	donor_gain	1.0000
11:19237313:CTAAG:C	donor_gain	1.0000
11:19225556:T:C	acceptor_gain	0.9900
11:19225556:T:TC	acceptor_gain	0.9900
11:19225559:CA:C	acceptor_gain	0.9900
11:19225560:A:AC	acceptor_gain	0.9900
11:19225613:CAC:C	acceptor_gain	0.9900
11:19225616:C:CA	acceptor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000063120 (11:19232586 A>G), RS1000130319 (11:19226342 T>C,G), RS1000199620 (11:19235781 C>A,G,T), RS1000280640 (11:19229327 T>C), RS1000388560 (11:19242368 G>GC), RS1000558126 (11:19228119 A>T), RS1000709400 (11:19229019 A>T), RS1000759664 (11:19242176 C>G,T), RS1000930863 (11:19233674 G>A,C), RS1001276032 (11:19240364 C>A,G,T), RS1001536571 (11:19227830 G>A), RS1001882571 (11:19241276 C>A), RS1001936016 (11:19235097 A>G,T), RS1002353009 (11:19227855 A>C), RS1002467548 (11:19241170 G>A)

Disease associations

OMIM: gene MIM:612047 | 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
GCST90002396_460	Mean reticulocyte volume	2.000000e-24

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010701	mean reticulocyte volume

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

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression, increases expression	5
Valproic Acid	affects cotreatment, increases expression, affects expression	5
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Benzo(a)pyrene	decreases expression, increases expression	4
Estradiol	affects cotreatment, decreases expression, increases expression	3
Tetrachlorodibenzodioxin	affects expression, decreases expression	3
Cyclosporine	decreases expression	3
Aflatoxin B1	affects expression, increases expression, increases methylation	3
lasiocarpine	decreases expression, increases metabolic processing, increases expression	2
Arsenic	decreases expression, affects cotreatment, increases abundance	2
Methotrexate	decreases expression, increases expression	2
Niclosamide	decreases expression	2
Tretinoin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	increases expression	1
tungsten carbide	increases expression, affects cotreatment	1
methylmercuric chloride	decreases expression	1
propionaldehyde	decreases expression	1
geraniol	decreases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
nobiletin	decreases expression	1
kojic acid	increases expression	1
trichostatin A	affects expression	1
2-butenal	decreases expression	1
dimethylselenide	increases expression, increases oxidation	1
riddelliine	increases metabolic processing, decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SL32	HAP1 E2F8 (-) 1	Cancer cell line	Male
CVCL_XN32	HAP1 E2F8 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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