E2F6

Summary

E2F6 (E2F transcription factor 6, HGNC:3120) is a protein-coding gene on chromosome 2p25.1, encoding Transcription factor E2F6 (O75461). Inhibitor of E2F-dependent transcription.

This gene encodes a member of a family of transcription factors that play a crucial role in the control of the cell cycle. The protein encoded by this gene lacks the transactivation and tumor suppressor protein association domains found in other family members, and contains a modular suppression domain that functions in the inhibition of transcription. It interacts in a complex with chromatin modifying factors. There are pseudogenes for this gene on chromosomes 22 and X. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1876 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 49 total — 1 likely-pathogenic
• Druggable target: yes
• Transcription factor: yes — 44 downstream targets (CollecTRI)
• MANE Select transcript: NM_198256

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3120
Approved symbol	E2F6
Name	E2F transcription factor 6
Location	2p25.1
Locus type	gene with protein product
Status	Approved
Aliases	E2F-6
Ensembl gene	ENSG00000169016
Ensembl biotype	protein_coding
OMIM	602944
Entrez	1876

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 8 protein_coding, 5 nonsense_mediated_decay, 3 retained_intron

ENST00000307236, ENST00000381525, ENST00000421117, ENST00000428221, ENST00000437573, ENST00000444832, ENST00000455198, ENST00000468775, ENST00000471343, ENST00000498701, ENST00000542100, ENST00000546212, ENST00000908571, ENST00000908572, ENST00000938567, ENST00000938568

RefSeq mRNA: 6 — MANE Select: NM_198256 NM_001278275, NM_001278276, NM_001278277, NM_001278278, NM_198256, NM_212540

CCDS: CCDS1680, CCDS62858, CCDS62859

Canonical transcript exons

ENST00000381525 — 7 exons

Exon	Start	End
ENSE00001901457	11465772	11466161
ENSE00003471320	11457179	11457233
ENSE00003499036	11451651	11451806
ENSE00003511529	11453582	11453798
ENSE00003592466	11447627	11447774
ENSE00003634899	11444375	11446523
ENSE00003642203	11450012	11450126

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 92.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1.6245 / max 16.2662, expressed in 1108 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26917	1.2481	898
26916	0.3764	181

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.05	gold quality
gastrocnemius	UBERON:0001388	89.91	gold quality
muscle of leg	UBERON:0001383	89.46	gold quality
adrenal tissue	UBERON:0018303	88.59	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.44	gold quality
skeletal muscle tissue	UBERON:0001134	87.37	gold quality
muscle tissue	UBERON:0002385	86.89	gold quality
islet of Langerhans	UBERON:0000006	86.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.28	gold quality
ventricular zone	UBERON:0003053	85.18	gold quality
endometrium	UBERON:0001295	85.06	gold quality
smooth muscle tissue	UBERON:0001135	84.77	gold quality
left uterine tube	UBERON:0001303	84.52	gold quality
heart left ventricle	UBERON:0002084	84.10	gold quality
right adrenal gland cortex	UBERON:0035827	83.92	gold quality
body of uterus	UBERON:0009853	83.79	gold quality
placenta	UBERON:0001987	83.59	gold quality
uterus	UBERON:0000995	83.57	gold quality
omental fat pad	UBERON:0010414	83.44	gold quality
heart	UBERON:0000948	83.37	gold quality
myometrium	UBERON:0001296	83.01	gold quality
right atrium auricular region	UBERON:0006631	82.98	gold quality
right adrenal gland	UBERON:0001233	82.93	gold quality
lower esophagus	UBERON:0013473	82.88	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.87	gold quality
fallopian tube	UBERON:0003889	82.76	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	82.60	gold quality
right ovary	UBERON:0002118	82.54	gold quality
pituitary gland	UBERON:0000007	82.48	gold quality
adenohypophysis	UBERON:0002196	82.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.06

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

44 targets.

Target	Regulation
ADAM2
APAF1	Repression
BRCA1	Unknown
BRD7	Unknown
CAMTA2
CBX5	Repression
CCNB2	Repression
CHEK2
CYC1	Unknown
DCTN4
DDX11
DEPDC5	Repression
DHPS
DTL	Activation
E2F1	Repression
EFNA5
FNTB
GRIK1
H19	Repression
IL13	Unknown
KDM3A
KIFBP	Repression
MCM3
METTL2B
NEK11
PRKAR1A
PTGS1	Repression
RAD51AP1
RBBP4	Repression
RBBP8	Repression

JASPAR motifs

Motif	Name	Family
MA0471.1	E2F6	E2F
MA0471.2	E2F6	E2F
MA0471.3	E2F6	E2F

JASPAR matrix evidence (PMIDs): PMID:17908821

Upstream regulators (CollecTRI, top): BRCA1, DNMT3B, E2F1, NRF1

Literature-anchored findings (GeneRIF, showing 32)

• data suggest that E2F- and Myc-responsive genes are coregulated by E2F6 complex in quiescent cells (PMID:12004135)
• results suggest that E2F6 represses transcription of the brca1, ctip, art27, hp1alpha, and the rbap48 genes and depletion of E2F6 resulted in the recruitment of E2F1 to the target promoters (PMID:12909625)
• contains nine exons distributed along 20.4kbp of genomic DNA on chromosome 2 leading to the transcription of six alternatively spliced E2F6 mRNAs that encode four different E2F6 proteins (PMID:15081404)
• E2F6 does not contain the domains required for modulation of squamous differentiation (PMID:15474455)
• showed that E2F6, DP1, EPC1, EZH2, and Sin3B co-elute, suggesting the identification of a novel E2F6 complex that exists in vivo in both normal and transformed human cell lines (PMID:15536069)
• functions as a repressor of E2F-dependent transcription during S phase (PMID:15574595)
• the expression of the E2F6 repressor is influenced at the transcriptional level by E2F family members and suggest that interplay among these transcriptional regulators, especially E2F1, may be critical for cell cycle regulation (PMID:16107498)
• PHC3 and E2F6 showed nuclear colocalization in a punctate pattern which was not seen in proliferating cells suggesting that PHC3 may be part of an E2F6-polycomb complex that has been shown to occupy and silence target promoters in G(0) (PMID:17001316)
• E2F-6 inhibited Apaf-1 upregulation by competing with E2F-1 for promoter binding. It enhanced the clonogenic growth of granulocyte, erythroid, macrophage, & megakaryocyte cells.It may prevent hematopoietic progenitor cell loss during proliferation. (PMID:17600109)
• E2F6 binding sites are located within 2 kb of a transcription start site, in both normal and tumor cells (PMID:17908821)
• E2F6 has a role in control of hypoxia-induced apoptosis through regulation of E2F1 (PMID:18562691)
• findings indicate an inhibitory role of E2F6 in the regulation of IL-13 and allergy (PMID:22981205)
• E2F6 may recruit BRG1 in transcriptional regulation of genes important for G1/S phase transition of the cell cycle. (PMID:23082233)
• After replication stress, the checkpoint kinase Chk1 phosphorylates E2F6, leading to its dissociation from promoters. This promotes E2F-dependent transcription, which mediates cell survival by preventing DNA damage and cell death (PMID:23954429)
• Analysis data from a panel of cell cycle transcription factors (E2F1, E2F4, E2F6, and GABPA) finds that a set of core cell cycle genes regulated in both U2OS and HeLa cells are bound by multiple cell cycle transcription factors. (PMID:24109597)
• miR-185 suppresses tumor proliferation by directly targeting E2F6 and DNMT1 and indirectly upregulating BRCA1 in triple-negative breast cancer. (PMID:25319390)
• E2F1 forms a protein complex with EBNA3C and E2F6, and EBNA3C competes with E2F1 for E2F6 binding. E2F6 is also recruited by EBNA3C to the E2F1 promoter, which is critical for EBNA3C-mediated cell proliferation. (PMID:27548379)
• This analysis showed a relative increase in the expression of E2F6 in gastric adenocarcinoma with no lymph node metastasis (chi (2), P = 0.04 and OR, P = 0.08), while overexpression of RhoA and SMUG1 was found more often in the diffuse subtype of gastric adenocarcinoma as compared to the intestinal subtype. (PMID:27909884)
• Target gene prediction software indicated that E2F6 was the potential downstream target gene of miR-425. E2F6 expression was found to be negatively regulated by miR-425 in clear cell renal carcinoma. (PMID:30338798)
• An estrogen-mediated E2F6 ceRNA network epigenetically and competitively inhibits microRNA-193a activity, promoting ovarian cancer stemness and tumorigenesis. (PMID:30582655)
• LINC01436 exerted biological functions by acting as a microRNA (miR)-30a-3p sponge to regulate the expression of its target gene EPAS1. (PMID:30614188)
• data demonstrated that E2F6 could regulate the proliferation, invasion and apoptosis of gastric carcinoma (GC) cells via inhibiting the expression of CASC2, suggesting that E2F6/CASC2 axis is another regulator of GC progression (PMID:31301415)
• E2F6-Mediated Downregulation of MIR22HG Facilitates the Progression of Laryngocarcinoma by Targeting the miR-5000-3p/FBXW7 Axis. (PMID:32094308)
• Circular RNA ZNF609 functions as a competing endogenous RNA in regulating E2F transcription factor 6 through competitively binding to microRNA-197-3p to promote the progression of cervical cancer progression. (PMID:33734009)
• Long noncoding RNA SLC9A3AS1 increases E2F6 expression by sponging microRNA4865p and thus facilitates the oncogenesis of nasopharyngeal carcinoma. (PMID:34165171)
• Deubiquitination of the repressor E2F6 by USP22 facilitates AKT activation and tumor growth in hepatocellular carcinoma. (PMID:34339800)
• Long Noncoding RNA LAMTOR5-AS1 Interference Affects MicroRNA-506-3p/E2F6-Mediated Behavior of Non-Small Cell Lung Cancer Cells. (PMID:34588094)
• A positive feedback loop of CENPU/E2F6/E2F1 facilitates proliferation and metastasis via ubiquitination of E2F6 in hepatocellular carcinoma. (PMID:35844791)
• The E2F6 Transcription Factor is Associated with the Mammalian SUZ12-Containing Polycomb Complex. (PMID:36464274)
• lncRNA ENST00000585827 Contributes to the Progression of Endometrial Carcinoma via Regulating miR-424/E2F6/E2F7 Axis. (PMID:36525235)
• The osteoporosis susceptibility SNP rs188303909 at 2q14.2 regulates EN1 expression by modulating DNA methylation and E2F6 binding. (PMID:38153509)
• A hsa_circ_001726 axis regulated by E2F6 contributes to metastasis of hepatocellular carcinoma. (PMID:38166853)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	e2f6	ENSDARG00000008119
mus_musculus	E2f6	ENSMUSG00000057469
rattus_norvegicus	E2f6	ENSRNOG00000004449
caenorhabditis_elegans		WBGENE00009899

Paralogs (7): E2F2 (ENSG00000007968), E2F1 (ENSG00000101412), E2F3 (ENSG00000112242), E2F8 (ENSG00000129173), E2F5 (ENSG00000133740), E2F7 (ENSG00000165891), E2F4 (ENSG00000205250)

Protein

Protein identifiers

Transcription factor E2F6 — O75461 (reviewed: O75461)

All UniProt accessions (7): O75461, A0A0S2Z3K8, F8WC40, F8WEZ5, Q2Z196, Q2Z197, Q53YM3

UniProt curated annotations — full annotation on UniProt →

Function. Inhibitor of E2F-dependent transcription. Binds DNA cooperatively with DP proteins through the E2 recognition site, 5’-TTTC[CG]CGC-3’. Has a preference for the 5’-TTTCCCGC-3’ E2F recognition site. E2F6 lacks the transcriptional activation and pocket protein binding domains. Appears to regulate a subset of E2F-dependent genes whose products are required for entry into the cell cycle but not for normal cell cycle progression. Represses expression of some meiosis-specific genes, including SLC25A31/ANT4. May silence expression via the recruitment of a chromatin remodeling complex containing histone H3-K9 methyltransferase activity. Overexpression delays the exit of cells from the S-phase.

Subunit / interactions. Forms heterodimers with DP family members TFDP1 or TFDP2. Component of the DRTF1/E2F transcription factor complex. Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2, MBLR, L3MBTL2 and YAF2. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BACC1, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10.

Subcellular location. Nucleus.

Tissue specificity. Expressed in all tissues examined. Highest levels in placenta, skeletal muscle, heart, ovary, kidney, small intestine and spleen.

Similarity. Belongs to the E2F/DP family.

Isoforms (3)

UniProt ID	Names	Canonical?
O75461-1	1	yes
O75461-2	2
O75461-3	3

RefSeq proteins (6): NP_001265204, NP_001265205, NP_001265206, NP_001265207, NP_937987, NP_997705 (=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 (15 total): sequence conflict 4, region of interest 4, splice variant 2, chain 1, DNA-binding region 1, mutagenesis site 1, short sequence motif 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75461-F1	71.37	0.35

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 (1): 9

Mutagenesis-validated functional residues (1):

Position	Phenotype
68	reduction in repressor activity, little effect on s-phase entry.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-69205	G1/S-Specific Transcription
R-HSA-8953750	Transcriptional Regulation by E2F6

MSigDB gene sets: 230 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, chr2p25, REACTOME_G1_S_SPECIFIC_TRANSCRIPTION, TGCGCANK_UNKNOWN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, BROWNE_HCMV_INFECTION_16HR_UP, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, YY1_02, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOCC_NUCLEAR_UBIQUITIN_LIGASE_COMPLEX, HNF1_01, GOBP_CHROMATIN_REMODELING

GO Biological Process (4): G1/S transition of mitotic cell cycle (GO:0000082), negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (9): 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 repressor activity, RNA polymerase II-specific (GO:0001227), protein dimerization activity (GO:0046983), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), MLL1 complex (GO:0071339), RNA polymerase II transcription regulator complex (GO:0090575), transcription regulator complex (GO:0005667)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
G1/S Transition	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
transcription cis-regulatory region binding	2
cellular anatomical structure	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	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
protein binding	1
nucleic acid binding	1
transcription regulator activity	1
binding	1
DNA binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
MLL1/2 complex	1
transcription regulator complex	1
nuclear protein-containing complex	1
protein-containing complex	1

Protein interactions and networks

STRING

1596 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
E2F6	TFDP1	Q14186	980
E2F6	CBX3	Q13185	956
E2F6	RING1	Q06587	929
E2F6	PCGF6	Q9BYE7	923
E2F6	RYBP	Q8N488	845
E2F6	BMI1	P35226	811
E2F6	R4GMX3	R4GMX3	811
E2F6	TFDP3	Q5H9I0	780
E2F6	YAF2	Q8IY57	778
E2F6	L3MBTL2	Q969R5	776
E2F6	EHMT2	Q96KQ7	766
E2F6	EHMT1	Q9H9B1	751
E2F6	RNF2	Q99496	747
E2F6	E2F8	A0AVK6	746
E2F6	DNMT3B	Q9UBC3	734

IntAct

169 interactions, top by confidence:

A	B	Type	Score
TFDP1	E2F6	psi-mi:“MI:0915”(physical association)	0.950
E2F6	TFDP1	psi-mi:“MI:0915”(physical association)	0.950
TFDP2	E2F6	psi-mi:“MI:0915”(physical association)	0.910
E2F6	TFDP2	psi-mi:“MI:0915”(physical association)	0.910
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
E2F6	TFDP2	psi-mi:“MI:0915”(physical association)	0.740
TFDP2	E2F6	psi-mi:“MI:0915”(physical association)	0.740
E2F6	RYBP	psi-mi:“MI:0915”(physical association)	0.740
RYBP	E2F6	psi-mi:“MI:0914”(association)	0.740
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
E2F6	WDR5	psi-mi:“MI:0914”(association)	0.730
L3MBTL2	E2F6	psi-mi:“MI:0914”(association)	0.730

BioGRID (343): TFDP1 (Two-hybrid), TFDP2 (Two-hybrid), KRTAP10-7 (Two-hybrid), MGA (Affinity Capture-MS), TFDP1 (Affinity Capture-MS), RYBP (Affinity Capture-MS), COMMD6 (Affinity Capture-MS), COMMD4 (Affinity Capture-MS), TFDP2 (Affinity Capture-MS), WDR5 (Affinity Capture-MS), RNF2 (Affinity Capture-MS), L3MBTL2 (Affinity Capture-MS), PCGF6 (Affinity Capture-MS), E2F6 (Affinity Capture-MS), E2F6 (Affinity Capture-MS)

ESM2 similar proteins: A0A097I2D0, A0A1W2PP81, A0A1W2PPE2, A0A1W2PPH5, A0A1W2PPL8, A0A1W2PPW3, A0A1W2PQ09, A0A1W2PR64, A0A1W2PRV1, A6NLC8, F4HR03, O54825, O75461, P0C1H6, P0CV38, P0DMV1, P0DMV2, P0DW11, P0DW12, P0DW13, P0DW14, P40914, P49585, P49906, P81195, Q0MTC0, Q13895, Q15544, Q2N2K6, Q3SZB8, Q5DJT8, Q5RA91, Q5U1X0, Q6CER9, Q6RG77, Q6XL73, Q75DE4, Q7XHR2, Q7Z2G1, Q80WL2

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

2 interactions.

A	Effect	B	Mechanism
CHEK1	“down-regulates activity”	E2F6	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 125 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
SUMOylation of DNA methylation proteins	6	42.9×	3e-07
Transcriptional Regulation by E2F6	13	40.5×	2e-15
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	10	32.0×	8e-11
Transcription of E2F targets under negative control by DREAM complex	5	28.9×	3e-05
G0 and Early G1	5	23.4×	1e-04
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	13	20.2×	2e-11
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	5	19.6×	2e-04
Deactivation of the beta-catenin transactivating complex	7	17.4×	9e-06

GO biological processes:

GO term	Partners	Fold	FDR
heterochromatin formation	7	15.5×	4e-05
positive regulation of miRNA transcription	5	12.6×	3e-03
rhythmic process	5	10.9×	5e-03
chromatin remodeling	17	10.8×	1e-10
transcription by RNA polymerase II	11	6.7×	8e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	36
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3779577	NM_198256.4(E2F6):c.380_380+16del	Likely pathogenic

SpliceAI

2330 predictions. Top by Δscore:

Variant	Effect	Δscore
2:11447770:GAGTC:G	acceptor_gain	1.0000
2:11447773:TC:T	acceptor_gain	1.0000
2:11447774:CC:C	acceptor_gain	1.0000
2:11447775:C:CA	acceptor_loss	1.0000
2:11447776:T:C	acceptor_loss	1.0000
2:11451642:A:AC	donor_gain	1.0000
2:11451643:A:C	donor_gain	1.0000
2:11451654:T:A	donor_gain	1.0000
2:11451713:AT:A	donor_gain	1.0000
2:11451714:T:C	donor_gain	1.0000
2:11451803:TCCT:T	acceptor_gain	1.0000
2:11451804:CCTC:C	acceptor_gain	1.0000
2:11451805:CT:C	acceptor_gain	1.0000
2:11451807:C:CC	acceptor_gain	1.0000
2:11451808:T:C	acceptor_gain	1.0000
2:11451809:T:C	acceptor_gain	1.0000
2:11453577:CTCA:C	donor_loss	1.0000
2:11453578:TCA:T	donor_loss	1.0000
2:11453579:CACA:C	donor_loss	1.0000
2:11453580:A:AC	donor_gain	1.0000
2:11453580:AC:A	donor_loss	1.0000
2:11453580:ACAT:A	donor_gain	1.0000
2:11453580:ACATC:A	donor_gain	1.0000
2:11453581:C:CA	donor_gain	1.0000
2:11453581:CAT:C	donor_gain	1.0000
2:11453581:CATC:C	donor_gain	1.0000
2:11453581:CATCC:C	donor_gain	1.0000
2:11453583:T:TA	donor_gain	1.0000
2:11453796:CTT:C	acceptor_gain	1.0000
2:11453797:TT:T	acceptor_gain	1.0000

AlphaMissense

1837 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:11450058:A:T	V202D	1.000
2:11453586:A:G	W126R	1.000
2:11453586:A:T	W126R	1.000
2:11453618:A:G	L115P	1.000
2:11453627:C:T	G112E	1.000
2:11453633:A:G	L110S	1.000
2:11453645:A:T	I106N	1.000
2:11453647:G:C	D105E	1.000
2:11453647:G:T	D105E	1.000
2:11453648:T:A	D105V	1.000
2:11453648:T:C	D105G	1.000
2:11453648:T:G	D105A	1.000
2:11453649:C:A	D105Y	1.000
2:11453649:C:G	D105H	1.000
2:11453652:A:G	Y104H	1.000
2:11453656:T:A	R102S	1.000
2:11453656:T:G	R102S	1.000
2:11453662:C:A	K100N	1.000
2:11453662:C:G	K100N	1.000
2:11453664:T:C	K100E	1.000
2:11453696:A:G	L89S	1.000
2:11453737:A:C	F75L	1.000
2:11453737:A:T	F75L	1.000
2:11453738:A:G	F75S	1.000
2:11453739:A:G	F75L	1.000
2:11453759:A:T	L68Q	1.000
2:11453584:C:A	W126C	0.999
2:11453584:C:G	W126C	0.999
2:11453585:C:G	W126S	0.999
2:11453591:A:T	I124N	0.999

dbSNP variants (sampled 300 via entrez): RS1000088206 (2:11461417 T>A,C), RS1000323699 (2:11447107 G>A), RS1000380248 (2:11452531 G>A), RS1000442786 (2:11460042 G>A), RS1000552470 (2:11466409 T>G), RS1000583537 (2:11466628 A>G), RS1000702276 (2:11455887 T>C,G), RS1000776472 (2:11463987 A>G), RS1000877150 (2:11460364 T>C), RS1000936965 (2:11448369 G>C), RS1001019698 (2:11444864 G>A), RS1001168533 (2:11452173 G>A), RS1001484262 (2:11450633 T>C), RS1001616846 (2:11458987 T>G), RS1001661357 (2:11463558 C>G,T)

Disease associations

OMIM: gene MIM:602944 | disease phenotypes: MIM:618300

GenCC curated gene-disease

Mondo (1): ciliary dyskinesia, primary, 40 (MONDO:0032664)

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001099_20	Sudden cardiac arrest	6.000000e-07
GCST002875_39	Diisocyanate-induced asthma	1.000000e-06
GCST010796_5257	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-11
GCST010796_5258	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_5259	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004278	sudden cardiac arrest
EFO:0006995	response to diisocyanate
EFO:0004327	electrocardiography

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

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	increases expression, increases methylation	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects expression	1
sodium arsenite	increases expression	1
cupric oxide	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects methylation	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Arsenic	affects methylation	1
Benzene	increases expression	1
Benzo(a)pyrene	affects methylation	1
Estradiol	increases expression	1
Eugenol	increases expression	1
Formaldehyde	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Plant Extracts	increases expression, affects cotreatment	1
Selenium	affects cotreatment, increases expression, decreases expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Vitamin E	affects cotreatment, increases expression, decreases expression	1
Zinc	affects cotreatment, increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A1D0	SEES3-1V human E2F6, clone1	Embryonic stem cell	Male
CVCL_A1D1	SEES3-1V human E2F6, clone2	Embryonic stem cell	Male
CVCL_A1D2	SEES3-1V human E2F6, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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