EAF1

Summary

EAF1 (ELL associated factor 1, HGNC:20907) is a protein-coding gene on chromosome 3p25.1, encoding ELL-associated factor 1 (Q96JC9). Acts as a transcriptional transactivator of ELL and ELL2 elongation activities. It is a selective cancer dependency (DepMap: 34.7% of cell lines).

Enables transcription elongation factor activity. Involved in regulation of transcription elongation by RNA polymerase II. Located in intercellular bridge and nuclear body. Part of transcription elongation factor complex.

Source: NCBI Gene 85403 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 48 total
• Cancer dependency (DepMap): dependent in 34.7% of screened cell lines
• MANE Select transcript: NM_033083

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20907
Approved symbol	EAF1
Name	ELL associated factor 1
Location	3p25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000144597
Ensembl biotype	protein_coding
OMIM	608315
Entrez	85403

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000396842, ENST00000449565, ENST00000617675

RefSeq mRNA: 1 — MANE Select: NM_033083 NM_033083

CCDS: CCDS2626

Canonical transcript exons

ENST00000396842 — 6 exons

Exon	Start	End
ENSE00000966108	15432087	15432223
ENSE00001815343	15439109	15442613
ENSE00003570839	15436342	15436575
ENSE00003602211	15429913	15430007
ENSE00003621193	15427598	15427882
ENSE00003668024	15434348	15434538

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 89.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.3889 / max 786.3242, expressed in 1823 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35510	42.9276	1823
35511	0.3643	120
35509	0.0970	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	89.82	gold quality
islet of Langerhans	UBERON:0000006	89.76	gold quality
esophagus squamous epithelium	UBERON:0006920	89.09	gold quality
decidua	UBERON:0002450	88.22	gold quality
monocyte	CL:0000576	88.08	gold quality
secondary oocyte	CL:0000655	88.00	gold quality
leukocyte	CL:0000738	87.95	gold quality
lower lobe of lung	UBERON:0008949	87.50	gold quality
cortical plate	UBERON:0005343	87.08	gold quality
palpebral conjunctiva	UBERON:0001812	87.02	gold quality
oocyte	CL:0000023	86.60	gold quality
epithelial cell of pancreas	CL:0000083	86.51	gold quality
prefrontal cortex	UBERON:0000451	86.45	gold quality
epithelium of nasopharynx	UBERON:0001951	86.45	gold quality
ganglionic eminence	UBERON:0004023	86.31	gold quality
bone marrow	UBERON:0002371	86.09	gold quality
oviduct epithelium	UBERON:0004804	85.71	gold quality
sperm	CL:0000019	85.62	gold quality
germinal epithelium of ovary	UBERON:0001304	85.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.37	gold quality
tendon of biceps brachii	UBERON:0008188	85.36	silver quality
bone marrow cell	CL:0002092	85.25	gold quality
anterior cingulate cortex	UBERON:0009835	84.99	gold quality
endothelial cell	CL:0000115	84.86	silver quality
nucleus accumbens	UBERON:0001882	84.55	gold quality
hypothalamus	UBERON:0001898	84.30	gold quality
granulocyte	CL:0000094	84.07	gold quality
pons	UBERON:0000988	84.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.05	gold quality
penis	UBERON:0000989	83.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.53

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ELL	Activation

Upstream regulators (CollecTRI, top): TFPT

miRNA regulators (miRDB)

178 targeting EAF1, 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-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-340-5P	100.00	72.50	4437
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-4668-3P	100.00	68.74	2635
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-1-3P	99.93	72.35	1914

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 34.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• ELL-associated factors 1 and 2 are positive regulators of RNA polymerase II elongation factor ELL. (PMID:16006523)
• ELL may be an important factor required for U19/Eaf2 function because U19/Eaf2 nuclear localization and transactivation activity are essential for its function as a transcription factor. (PMID:16114057)
• Findings provide the first convincing line of evidence that EAF and Wnt4 form an auto-regulatory negative feedback loop in vivo. (PMID:20161747)
• EAF1 (239-268) and TAF7 (205-235) peptide interactions were both mapped to the same groove formed by H3 and H4 helices of MED26 N-terminal domain. (PMID:28893534)
• Allosteric transcription stimulation by RNA polymerase II super elongation complex. (PMID:34265249)
• ATM-mediated ELL phosphorylation enhances its self-association through increased EAF1 interaction and inhibits global transcription during genotoxic stress. (PMID:36305813)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eaf1	ENSDARG00000070795
mus_musculus	Eaf1	ENSMUSG00000021890
rattus_norvegicus	Eaf1	ENSRNOG00000019559
drosophila_melanogaster	Eaf	FBGN0033166
caenorhabditis_elegans	eaf-1	WBGENE00017011

Paralogs (1): EAF2 (ENSG00000145088)

Protein

Protein identifiers

ELL-associated factor 1 — Q96JC9 (reviewed: Q96JC9)

All UniProt accessions (2): Q96JC9, F8WFA5

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional transactivator of ELL and ELL2 elongation activities.

Subunit / interactions. Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3). Interacts with ELL and ELL2.

Subcellular location. Nucleus speckle. Nucleus. Cajal body.

Tissue specificity. Strongly expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, prostate, testis, small intestine and colon. Poorly expressed in thymus.

Similarity. Belongs to the EAF family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96JC9-1	1	yes
Q96JC9-2	2

RefSeq proteins (1): NP_149074* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019194	Tscrpt_elong_fac_Eaf_N	Domain
IPR027093	EAF_fam	Family

Pfam: PF09816

UniProt features (23 total): strand 9, compositionally biased region 4, region of interest 2, sequence conflict 2, splice variant 2, chain 1, helix 1, turn 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7OKX	ELECTRON MICROSCOPY	3.3
7OKY	ELECTRON MICROSCOPY	4.14

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JC9-F1	71.79	0.33

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): 165

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-75955	RNA Polymerase II Transcription Elongation

MSigDB gene sets: 147 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, MODULE_97, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GCAAGGA_MIR502, MODULE_182, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GTGCCTT_MIR506, BRN2_01, TCF11_01, ACATTCC_MIR1_MIR206, TGANTCA_AP1_C, CHO_NR4A1_TARGETS, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, WHN_B, CUI_TCF21_TARGETS_2_DN

GO Biological Process (2): transcription elongation by RNA polymerase II (GO:0006368), regulation of transcription elongation by RNA polymerase II (GO:0034243)

GO Molecular Function (2): transcription elongation factor activity (GO:0003711), protein binding (GO:0005515)

GO Cellular Component (8): nucleoplasm (GO:0005654), transcription elongation factor complex (GO:0008023), Cajal body (GO:0015030), nuclear body (GO:0016604), nuclear speck (GO:0016607), super elongation complex (GO:0032783), intercellular bridge (GO:0045171), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RNA Polymerase II Transcription	2
RNA Polymerase II Transcription Elongation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
nucleoplasm	2
nuclear ribonucleoprotein granule	2
DNA-templated transcription elongation	1
transcription by RNA polymerase II	1
transcription elongation by RNA polymerase II	1
regulation of DNA-templated transcription elongation	1
transcription regulator activity	1
binding	1
nuclear lumen	1
nuclear protein-containing complex	1
intracellular membraneless organelle	1
transcription elongation factor complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

542 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EAF1	ELL	P55199	951
EAF1	ELL2	O00472	947
EAF1	AFF1	P51825	871
EAF1	AFF3	P51826	793
EAF1	MED26	O95402	739
EAF1	MLLT1	Q03111	656
EAF1	AFF4	Q9UHB7	648
EAF1	MLLT3	P42568	640
EAF1	METTL6	Q8TCB7	601
EAF1	RSPRY1	Q96DX4	593
EAF1	CLXN	Q9HAE3	563
EAF1	ELL3	Q9HB65	562
EAF1	GPATCH3	Q96I76	550
EAF1	ZNRF2	Q8NHG8	520
EAF1	ICE2	Q659A1	504

IntAct

209 interactions, top by confidence:

A	B	Type	Score
PSME3	EAF1	psi-mi:“MI:0915”(physical association)	0.840
EAF1	PSME3	psi-mi:“MI:0915”(physical association)	0.840
EAF1	ELL2	psi-mi:“MI:0914”(association)	0.840
EAF1	ELL3	psi-mi:“MI:0915”(physical association)	0.840
ELL2	EAF1	psi-mi:“MI:0915”(physical association)	0.840
EAF1	HOMER3	psi-mi:“MI:0915”(physical association)	0.780
HOMER3	EAF1	psi-mi:“MI:0915”(physical association)	0.780
AFF4	ELL2	psi-mi:“MI:0914”(association)	0.730
MLLT3	CDK9	psi-mi:“MI:0914”(association)	0.730
TLE5	EAF1	psi-mi:“MI:0915”(physical association)	0.680
EAF1	TLE5	psi-mi:“MI:0915”(physical association)	0.680
EAF1	GTF2H1	psi-mi:“MI:0915”(physical association)	0.670
EAF1	GTF2H4	psi-mi:“MI:0915”(physical association)	0.670
GTF2H1	EAF1	psi-mi:“MI:0915”(physical association)	0.670
GTF2H4	EAF1	psi-mi:“MI:0915”(physical association)	0.670
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640

BioGRID (248): EAF1 (Two-hybrid), EAF1 (Two-hybrid), EAF1 (Two-hybrid), EAF1 (Two-hybrid), EAF1 (Two-hybrid), EAF1 (Two-hybrid), EAF1 (Two-hybrid), MIPOL1 (Two-hybrid), BEND7 (Two-hybrid), EAF1 (Affinity Capture-MS), EAF2 (Affinity Capture-MS), ASPM (Affinity Capture-MS), TOP1 (Affinity Capture-MS), FIP1L1 (Affinity Capture-MS), LUC7L2 (Affinity Capture-MS)

ESM2 similar proteins: B2GV05, B5FXN8, G3V9R8, O08583, O75525, O77768, P07910, P23588, P52756, P55795, P70333, P97379, Q08DJ0, Q13148, Q1RMU5, Q28FB9, Q3SZF3, Q3T0I4, Q58EA2, Q5R5W2, Q5R9L3, Q5RA82, Q5RAM8, Q5RD26, Q5SRX1, Q5VWX1, Q5XIA2, Q5ZK25, Q5ZLN5, Q64012, Q6AY09, Q6GLW1, Q6NXN1, Q6ZVM7, Q86SE5, Q86V81, Q8BGD9, Q8BTF8, Q8C854, Q8VHV7

Diamond homologs: B3MI72, B3NA01, B4GCP2, B4HQT6, B4J6N6, B4KND9, B4LMA2, B4MR74, B4P1N5, B5E1I4, Q5RAM8, Q5ZHP7, Q7JRJ1, Q811X5, Q91ZD6, Q96CJ1, Q96JC9, Q9D4C5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EAF1	up-regulates	ELL	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 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
Formation of RNA Pol II elongation complex	7	27.6×	3e-07
RNA Polymerase II Transcription Elongation	7	27.6×	3e-07
Formation of HIV-1 elongation complex containing HIV-1 Tat	5	26.5×	5e-05
Tat-mediated elongation of the HIV-1 transcript	5	26.5×	5e-05
Formation of HIV elongation complex in the absence of HIV Tat	5	25.3×	5e-05
RNA polymerase II transcribes snRNA genes	8	25.2×	2e-07
RNA Polymerase II Pre-transcription Events	8	22.5×	3e-07
TP53 Regulates Transcription of DNA Repair Genes	5	18.5×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
transcription elongation by RNA polymerase II	5	35.8×	3e-05
positive regulation of transcription elongation by RNA polymerase II	6	29.1×	8e-06
transcription by RNA polymerase II	11	12.5×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

569 predictions. Top by Δscore:

Variant	Effect	Δscore
3:15427878:TCGTT:T	donor_gain	1.0000
3:15427881:TT:T	donor_gain	1.0000
3:15427883:G:GG	donor_gain	1.0000
3:15429909:TTA:T	acceptor_loss	1.0000
3:15429910:TA:T	acceptor_loss	1.0000
3:15429911:A:AC	acceptor_loss	1.0000
3:15429911:A:AG	acceptor_gain	1.0000
3:15429911:AGAT:A	acceptor_gain	1.0000
3:15429912:G:GG	acceptor_gain	1.0000
3:15429912:GAT:G	acceptor_gain	1.0000
3:15429912:GATG:G	acceptor_gain	1.0000
3:15429912:GATGA:G	acceptor_gain	1.0000
3:15430003:TCCCT:T	donor_gain	1.0000
3:15430004:CCCT:C	donor_gain	1.0000
3:15430005:CCT:C	donor_gain	1.0000
3:15430005:CCTG:C	donor_loss	1.0000
3:15430006:CT:C	donor_gain	1.0000
3:15430006:CTG:C	donor_loss	1.0000
3:15430007:TGT:T	donor_loss	1.0000
3:15430008:G:GA	donor_loss	1.0000
3:15430008:G:GG	donor_gain	1.0000
3:15430009:T:A	donor_loss	1.0000
3:15434342:TTTCA:T	acceptor_loss	1.0000
3:15434345:CAG:C	acceptor_gain	1.0000
3:15434346:A:AG	acceptor_gain	1.0000
3:15434346:AGA:A	acceptor_gain	1.0000
3:15434347:G:A	acceptor_loss	1.0000
3:15434347:G:C	acceptor_gain	1.0000
3:15434347:G:GA	acceptor_gain	1.0000
3:15434347:GA:G	acceptor_gain	1.0000

AlphaMissense

1779 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:15427834:G:A	G19R	1.000
3:15427834:G:C	G19R	1.000
3:15427834:G:T	G19W	1.000
3:15427835:G:A	G19E	1.000
3:15427835:G:T	G19V	1.000
3:15427877:T:A	I33N	1.000
3:15427879:C:A	R34S	1.000
3:15427882:T:C	Y35H	1.000
3:15429915:G:C	D36H	1.000
3:15429916:A:C	D36A	1.000
3:15429916:A:G	D36G	1.000
3:15429916:A:T	D36V	1.000
3:15429918:T:A	F37I	1.000
3:15429918:T:C	F37L	1.000
3:15429918:T:G	F37V	1.000
3:15429919:T:C	F37S	1.000
3:15429919:T:G	F37C	1.000
3:15429920:T:A	F37L	1.000
3:15429920:T:G	F37L	1.000
3:15429921:A:G	K38E	1.000
3:15429923:A:C	K38N	1.000
3:15429923:A:T	K38N	1.000
3:15429924:C:A	P39T	1.000
3:15429924:C:T	P39S	1.000
3:15429925:C:A	P39Q	1.000
3:15429925:C:G	P39R	1.000
3:15429928:C:A	A40E	1.000
3:15429931:C:A	S41Y	1.000
3:15429931:C:T	S41F	1.000
3:15429934:T:A	I42K	1.000

dbSNP variants (sampled 300 via entrez): RS1000028728 (3:15426696 T>C), RS1000062227 (3:15427819 C>T), RS1000121476 (3:15427090 G>A), RS1000349960 (3:15427608 C>A,T), RS1000493418 (3:15441258 C>G), RS1000738639 (3:15440978 T>C), RS1000834096 (3:15436089 C>G,T), RS1000932845 (3:15429117 T>G), RS1001057347 (3:15438854 A>C), RS1001285996 (3:15435856 G>A), RS1001301327 (3:15440205 G>A), RS1001464489 (3:15433217 G>A), RS1001643968 (3:15434426 A>G), RS1001793936 (3:15428200 C>T), RS1001838489 (3:15435185 A>C,G)

Disease associations

OMIM: gene MIM:608315 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
chromium hexavalent ion	increases expression, increases abundance	1
ICG 001	decreases expression	1
abrine	increases expression	1
NSC668394	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Copper	affects binding, decreases expression	1
Disulfiram	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Melphalan	increases expression	1

Clinical trials (associated diseases)

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