EBF4

Summary

EBF4 (EBF transcription factor 4, HGNC:29278) is a protein-coding gene on chromosome 20p13, encoding Transcription factor COE4 (Q9BQW3). Transcription factor.

EBF4 belongs to the conserved Olf/EBF family of helix-loop-helix transcription factors, members of which play important roles in neural development and B-cell maturation (Wang et al., 2002 [PubMed 12139918]).

Source: NCBI Gene 57593 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 123 total
• MANE Select transcript: NM_001395167

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29278
Approved symbol	EBF4
Name	EBF transcription factor 4
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1442, COE4, RP5-860F19.3, O/E-4
Ensembl gene	ENSG00000088881
Ensembl biotype	protein_coding
OMIM	609935
Entrez	57593

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000380648, ENST00000449079, ENST00000469215, ENST00000477287, ENST00000481662, ENST00000497450, ENST00000609451

RefSeq mRNA: 3 — MANE Select: NM_001395167 NM_001110514, NM_001395167, NM_001395168

CCDS: CCDS46573, CCDS93003

Canonical transcript exons

ENST00000609451 — 17 exons

Exon	Start	End
ENSE00000656551	2751922	2751987
ENSE00000656552	2752086	2752263
ENSE00000858667	2749620	2749753
ENSE00000858668	2749847	2749973
ENSE00000858670	2751700	2751788
ENSE00001373288	2755627	2755824
ENSE00003468809	2752357	2752545
ENSE00003472422	2706209	2706264
ENSE00003517698	2705577	2705733
ENSE00003542641	2758909	2758984
ENSE00003614658	2705974	2706037
ENSE00003705227	2709574	2709642
ENSE00003706138	2748549	2748630
ENSE00003709623	2749401	2749518
ENSE00003710977	2707947	2708020
ENSE00003978185	2759268	2760108
ENSE00003978186	2692780	2693782

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 99.85.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9603 / max 69.3452, expressed in 823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183181	2.6744	794
183180	0.2859	166

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	99.85	gold quality
right lobe of thyroid gland	UBERON:0001119	95.58	gold quality
left lobe of thyroid gland	UBERON:0001120	95.07	gold quality
body of uterus	UBERON:0009853	94.81	gold quality
left ovary	UBERON:0002119	94.69	gold quality
thyroid gland	UBERON:0002046	94.24	gold quality
right ovary	UBERON:0002118	94.10	gold quality
ganglionic eminence	UBERON:0004023	93.93	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.32	gold quality
lower esophagus	UBERON:0013473	93.29	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.28	gold quality
endocervix	UBERON:0000458	92.93	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.88	gold quality
ectocervix	UBERON:0012249	91.71	gold quality
left uterine tube	UBERON:0001303	91.66	gold quality
stromal cell of endometrium	CL:0002255	91.60	gold quality
mucosa of stomach	UBERON:0001199	91.00	gold quality
prostate gland	UBERON:0002367	90.47	gold quality
ventricular zone	UBERON:0003053	90.25	gold quality
ovary	UBERON:0000992	89.43	gold quality
uterine cervix	UBERON:0000002	89.23	gold quality
lower esophagus mucosa	UBERON:0035834	88.92	gold quality
cortical plate	UBERON:0005343	88.33	gold quality
pituitary gland	UBERON:0000007	88.32	gold quality
adenohypophysis	UBERON:0002196	88.19	gold quality
myometrium	UBERON:0001296	88.10	gold quality
amygdala	UBERON:0001876	87.98	gold quality
smooth muscle tissue	UBERON:0001135	87.60	gold quality
vena cava	UBERON:0004087	87.57	gold quality
hypothalamus	UBERON:0001898	87.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting EBF4, 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-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-374C-3P	98.47	67.93	451
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-4289	98.26	66.90	810

Literature-anchored findings (GeneRIF, showing 1)

• Early B cell factor 4 modulates FAS-mediated apoptosis and promotes cytotoxic function in human immune cells. (PMID:35939714)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000113012
mus_musculus	Ebf4	ENSMUSG00000053552
rattus_norvegicus	Ebf4	ENSRNOG00000007408
drosophila_melanogaster	kn	FBGN0001319
caenorhabditis_elegans		WBGENE00006743

Paralogs (3): EBF3 (ENSG00000108001), EBF1 (ENSG00000164330), EBF2 (ENSG00000221818)

Protein

Protein identifiers

Transcription factor COE4 — Q9BQW3 (reviewed: Q9BQW3)

Alternative names: Early B-cell factor 4, Olf-1/EBF-like 4

All UniProt accessions (6): Q9BQW3, A0A0A0MSW2, A0A6I8PL90, A0A6I8PR97, A0A6I8PRX3, E9PEI2

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor. Binds to specific sequence motif 5’-CCCNNG[GA]G-3’ in regulatory elements of putative target immunoregulatory genes such as NKG7, GZMA, and TBX21. Positively modulates transcription of NKG7. May play a role in regulating FAS/CD95-mediated apoptosis in cytotoxic NK cells and T-cells, probably downstream of interleukin IL2 signaling.

Subunit / interactions. Forms either a homodimer or a heterodimer with a related family member. Interacts with MAPK3/ERK1. Interacts with STAT5A.

Subcellular location. Nucleus.

Tissue specificity. Most highly expressed in cytotoxic NK cells, especially CD16(+) NK cells, followed by CD8(+) T-cells.

Induction. In CD8(+) T-cells mRNA levels are down-regulated following T-cell receptor (TCR) stimulation. In NK cells mRNA levels are down-regulated following KLRK1/NKG2D receptor stimulation.

Similarity. Belongs to the COE family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BQW3-2	2	yes
Q9BQW3-1	1

RefSeq proteins (3): NP_001103984, NP_001382096, NP_001382097 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002909	IPT_dom	Domain
IPR003523	Transcription_factor_COE	Family
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR018350	Transcription_factor_COE_CS	Conserved_site
IPR032200	COE_DBD	Domain
IPR032201	COE_HLH	Domain
IPR038006	COE_IPT	Domain
IPR038173	COE_DBD_sf	Homologous_superfamily

Pfam: PF01833, PF16422, PF16423

UniProt features (14 total): region of interest 5, site 2, splice variant 2, chain 1, domain 1, sequence conflict 1, zinc finger region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQW3-F1	72.60	0.47

Functional residue map

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

Catalytic / active sites (2): 173 (interaction with dna); 164 (interaction with dna)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 63 (showing top): GOBP_LEUKOCYTE_APOPTOTIC_PROCESS, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, VANTVEER_BREAST_CANCER_POOR_PROGNOSIS, GOBP_LYMPHOCYTE_APOPTOTIC_PROCESS, LIU_SMARCA4_TARGETS, GOBP_T_CELL_APOPTOTIC_PROCESS, WORSCHECH_TUMOR_REJECTION_UP, GOMF_TRANSCRIPTION_FACTOR_BINDING, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, DELACROIX_RAR_BOUND_ES, GOMF_DNA_BINDING_TRANSCRIPTION_ACTIVATOR_ACTIVITY

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of transcription by RNA polymerase II (GO:0045944), T cell apoptotic process (GO:0070231), regulation of DNA-templated transcription (GO:0006355)

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), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), zinc ion binding (GO:0008270), DNA-binding transcription factor binding (GO:0140297), 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), metal ion binding (GO:0046872)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

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 DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
transcription cis-regulatory region binding	2
positive regulation of DNA-templated transcription	1
lymphocyte apoptotic process	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
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
transcription factor binding	1
nucleic acid binding	1
transcription regulator activity	1
binding	1
cation binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

584 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EBF4	TMTC1	Q8IUR5	808
EBF4	ZNF423	Q2M1K9	577
EBF4	PAX5	Q02548	548
EBF4	TCF3	P15883	547
EBF4	PRDM16	Q9HAZ2	541
EBF4	EHMT1	Q9H9B1	469
EBF4	IGLL1	P15814	447
EBF4	VPREB1	P12018	447
EBF4	SETMAR	Q53H47	445
EBF4	PRDM8	Q9NQV8	441
EBF4	EP300	Q09472	428
EBF4	ZNF521	Q96K83	384
EBF4	IGHV4-38-2	P0DP08	307
EBF4	LGALS4	P56470	305
EBF4	REDIC1	Q86WS4	305

IntAct

2 interactions, top by confidence:

A	B	Type	Score
EBF4	CDK6	psi-mi:“MI:0217”(phosphorylation reaction)	0.440

BioGRID (4): EBF4 (Affinity Capture-RNA), EBF4 (Reconstituted Complex), APP (Reconstituted Complex), EBF4 (Biochemical Activity)

ESM2 similar proteins: A0A0R4IWI1, A5ABV9, B7ZRI2, B7ZRJ4, O08791, O08792, O13987, O73673, O73742, O74412, O74954, O93375, P06536, P06537, P49843, P49844, P56721, Q00858, Q03414, Q03571, Q07802, Q08DL5, Q10902, Q13761, Q13950, Q20937, Q23238, Q5H9I0, Q61X54, Q63398, Q64131, Q6E3C9, Q6E3D0, Q6E3D4, Q6E3D5, Q6P4K7, Q6PF39, Q700C2, Q8BYR2, Q8K4J2

Diamond homologs: A0A0R4IWI1, B7ZRI2, B7ZRJ4, O08791, O08792, O73742, O93375, P56721, Q07802, Q08DL5, Q63398, Q6P4K7, Q8K4J2, Q93705, Q9BQW3, Q9H4W6, Q9HAK2, Q9UH73, O13987

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	112
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3133 predictions. Top by Δscore:

Variant	Effect	Δscore
20:2705728:G:GT	donor_gain	1.0000
20:2705732:GA:G	donor_gain	1.0000
20:2705734:G:GG	donor_gain	1.0000
20:2705973:GGA:G	acceptor_gain	1.0000
20:2706036:TGGT:T	donor_loss	1.0000
20:2706037:GGTG:G	donor_loss	1.0000
20:2706038:G:C	donor_loss	1.0000
20:2706038:G:GG	donor_gain	1.0000
20:2706039:T:G	donor_loss	1.0000
20:2706204:CCTAG:C	acceptor_loss	1.0000
20:2706205:CTA:C	acceptor_loss	1.0000
20:2706206:TAGG:T	acceptor_loss	1.0000
20:2706208:G:GC	acceptor_loss	1.0000
20:2706208:GGACT:G	acceptor_gain	1.0000
20:2706260:AACAG:A	donor_gain	1.0000
20:2706261:ACAG:A	donor_gain	1.0000
20:2706262:CAG:C	donor_gain	1.0000
20:2706263:AG:A	donor_gain	1.0000
20:2706264:GG:G	donor_gain	1.0000
20:2706265:G:GA	donor_loss	1.0000
20:2706265:G:GG	donor_gain	1.0000
20:2709639:ACAG:A	donor_loss	1.0000
20:2709640:CAGGT:C	donor_loss	1.0000
20:2709642:GGTAC:G	donor_loss	1.0000
20:2709644:T:G	donor_loss	1.0000
20:2749395:CCGCA:C	acceptor_loss	1.0000
20:2749396:CGCAG:C	acceptor_loss	1.0000
20:2749397:GCAG:G	acceptor_loss	1.0000
20:2749398:CAGG:C	acceptor_loss	1.0000
20:2749399:AGG:A	acceptor_loss	1.0000

AlphaMissense

3916 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:2705596:G:C	A53P	1.000
20:2705597:C:A	A53E	1.000
20:2705603:T:C	F55S	1.000
20:2705614:C:T	P59S	1.000
20:2705615:C:A	P59H	1.000
20:2705615:C:G	P59R	1.000
20:2705618:C:A	P60H	1.000
20:2705625:C:A	N62K	1.000
20:2705625:C:G	N62K	1.000
20:2705627:T:A	L63H	1.000
20:2705627:T:C	L63P	1.000
20:2705629:A:G	R64G	1.000
20:2705629:A:T	R64W	1.000
20:2705630:G:C	R64T	1.000
20:2705630:G:T	R64M	1.000
20:2705631:G:C	R64S	1.000
20:2705631:G:T	R64S	1.000
20:2705632:A:C	K65Q	1.000
20:2705632:A:G	K65E	1.000
20:2705633:A:C	K65T	1.000
20:2705633:A:T	K65I	1.000
20:2705634:A:C	K65N	1.000
20:2705634:A:T	K65N	1.000
20:2705635:T:C	S66P	1.000
20:2705636:C:A	S66Y	1.000
20:2705636:C:G	S66C	1.000
20:2705636:C:T	S66F	1.000
20:2705638:A:C	N67H	1.000
20:2705638:A:G	N67D	1.000
20:2705638:A:T	N67Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000019913 (20:2723381 C>T), RS1000040650 (20:2709038 T>C), RS1000066899 (20:2708821 C>A,G), RS1000088284 (20:2740666 G>C), RS1000155560 (20:2740082 G>T), RS1000218361 (20:2759849 A>G), RS1000229546 (20:2740311 TC>T), RS1000234986 (20:2698543 G>A), RS1000269021 (20:2716799 T>C), RS1000329522 (20:2752672 C>G), RS1000352256 (20:2753357 C>A,T), RS1000453929 (20:2710585 A>G), RS1000492093 (20:2741344 T>C), RS1000546155 (20:2699427 C>A,T), RS1000580469 (20:2746440 C>T)

Disease associations

OMIM: gene MIM:609935 | 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
GCST005024_101	Pursuit maintenance gain	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008433	pursuit maintenance gain measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, increases expression	2
bisphenol A	increases expression	1
sodium arsenite	decreases expression, increases abundance, affects cotreatment	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
abrine	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Niclosamide	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	affects response to substance	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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