ELF2

Summary

ELF2 (E74 like ETS transcription factor 2, HGNC:3317) is a protein-coding gene on chromosome 4q31.1, encoding ETS-related transcription factor Elf-2 (Q15723). Isoform 1 transcriptionally activates the LYN and BLK promoters and acts synergistically with RUNX1 to transactivate the BLK promoter.

Enables DNA-binding transcription factor activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of DNA-templated transcription; positive regulation of DNA-templated transcription; and regulation of transcription by RNA polymerase II. Located in nuclear body.

Source: NCBI Gene 1998 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Clinical variants (ClinVar): 88 total — 1 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈13% of expected missense variation)
• GTEx eGene: eQTL in 17 tissues, sQTL in 18 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.27 (highly constrained)
• Transcription factor: yes — 12 downstream targets (CollecTRI)
• MANE Select transcript: NM_001331036
• Notable: 88 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3317
Approved symbol	ELF2
Name	E74 like ETS transcription factor 2
Location	4q31.1
Locus type	gene with protein product
Status	Approved
Aliases	EU32, NERF, NERF-2, NERF-1A, NERF-1B
Ensembl gene	ENSG00000109381
Ensembl biotype	protein_coding
OMIM	619798
Entrez	1998

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 21 protein_coding, 10 nonsense_mediated_decay, 4 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000686138

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 4, TSL 3: 1, TSL 5: 4

ENST00000686138, ENST00000358635, ENST00000379549, ENST00000379550, ENST00000394235, ENST00000504314, ENST00000510408, ENST00000511006, ENST00000511184, ENST00000512627, ENST00000514577, ENST00000514606, ENST00000515489, ENST00000864104, ENST00000864105, ENST00000935561, ENST00000977244, ENST00000977246, ENST00000977247, ENST00001029834, ENST00001029835, ENST00001071508, ENST00001071509, ENST00001071510, ENST00001071511, ENST00001109330, ENST00001109331, ENST00001109332, ENST00001109333, ENST00001111702, ENST00001111703, ENST00001111704, ENST00001121627, ENST00001130094, ENST00001130095, ENST00001134098

RefSeq mRNA: 11 — MANE Select: NM_001331036 NM_001276457, NM_001276458, NM_001276459, NM_001331036, NM_001371324, NM_001371336, NM_001371337, NM_001371338, NM_001371339, NM_006874, NM_201999

CCDS: CCDS3744, CCDS3745, CCDS64062, CCDS64063, CCDS82954

Canonical transcript exons

ENST00000686138 — 10 exons

Exon	Start	End
ENSE00000739091	139060324	139060674
ENSE00000970367	139125164	139125329
ENSE00001192730	139137630	139137867
ENSE00001403285	139071866	139072039
ENSE00001517815	139139413	139139497
ENSE00001517816	139176967	139177218
ENSE00001744714	139061865	139062057
ENSE00003582840	139073454	139073567
ENSE00003653488	139067684	139067770
ENSE00003932468	139057265	139059607

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 97.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.0719 / max 579.2423, expressed in 1807 samples.

Highest expression (Bgee): calcaneal tendon, colonic epithelium, cortical plate, adrenal tissue, ganglionic eminence.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ELF2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 17 tissues and its splicing (sQTL) in 18 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 35 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	2.9e-15	-0.84	4:139167913:C:G
Thyroid	sqtl	6.0e-12	-0.57	4:139167913:C:G
Artery Tibial	sqtl	8.5e-12	+0.60	4:139167913:C:G
Esophagus Muscularis	sqtl	3.6e-11	-0.59	4:139167913:C:G
Skin Not Sun Exposed Suprapubic	sqtl	4.2e-10	+0.57	4:139167913:C:G
Pituitary	sqtl	4.5e-10	-0.84	4:139167913:C:G
Brain Spinal cord cervical c-1	eqtl	1.2e-08	+0.38	4:139192927:C:T
Colon Sigmoid	sqtl	2.1e-08	-0.62	4:139167913:C:G
Artery Aorta	sqtl	2.8e-08	-0.65	4:139167913:C:G
Skin Sun Exposed Lower leg	eqtl	3.9e-08	+0.17	4:139177591:C:T
Skin Sun Exposed Lower leg	sqtl	4.1e-07	+0.46	4:139059873:G:C
Skin Not Sun Exposed Suprapubic	eqtl	4.1e-07	-0.14	4:139074535:G:C
Adipose Subcutaneous	sqtl	1.5e-06	+0.47	4:139060764:T:G
Whole Blood	sqtl	6.8e-06	+0.38	4:139167913:C:G
Adipose Visceral Omentum	sqtl	7.2e-06	+0.48	4:139188887:A:G
Lung	sqtl	2.8e-05	+0.48	4:139059873:G:C
Testis	eqtl	4.8e-05	+0.16	4:139220982:C:T
Stomach	eqtl	1.1e-04	+0.25	4:139177591:C:T
Esophagus Muscularis	eqtl	1.3e-04	+0.19	4:139173850:G:C
Esophagus Gastroesophageal Junction	sqtl	2.7e-04	+0.58	4:139124640:G:A

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
54050	11.5191	1725
54046	5.9945	1635
54045	4.5582	1537

Top tissues by expression

showing 100 of 289 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.19	gold quality
colonic epithelium	UBERON:0000397	94.64	gold quality
cortical plate	UBERON:0005343	94.60	gold quality
adrenal tissue	UBERON:0018303	93.88	gold quality
ganglionic eminence	UBERON:0004023	93.48	gold quality
ventricular zone	UBERON:0003053	92.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.97	gold quality
descending thoracic aorta	UBERON:0002345	91.72	gold quality
tendon	UBERON:0000043	91.70	gold quality
right lung	UBERON:0002167	91.46	gold quality
upper leg skin	UBERON:0004262	91.17	gold quality
thoracic aorta	UBERON:0001515	91.08	gold quality
skin of hip	UBERON:0001554	91.07	gold quality
ascending aorta	UBERON:0001496	91.05	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.01	gold quality
blood	UBERON:0000178	90.94	gold quality
corpus callosum	UBERON:0002336	90.83	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.82	gold quality
lower esophagus	UBERON:0013473	90.81	gold quality
aorta	UBERON:0000947	90.77	gold quality
minor salivary gland	UBERON:0001830	90.68	gold quality
muscle of leg	UBERON:0001383	90.66	gold quality
mucosa of stomach	UBERON:0001199	90.58	gold quality
tibial artery	UBERON:0007610	90.58	gold quality
popliteal artery	UBERON:0002250	90.57	gold quality
sural nerve	UBERON:0015488	90.47	gold quality
tonsil	UBERON:0002372	90.45	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.38	gold quality
gastrocnemius	UBERON:0001388	90.34	gold quality
omental fat pad	UBERON:0010414	90.23	gold quality
peritoneum	UBERON:0002358	90.22	gold quality
right coronary artery	UBERON:0001625	90.09	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.07	gold quality
body of uterus	UBERON:0009853	90.04	gold quality
monocyte	CL:0000576	89.89	gold quality
leukocyte	CL:0000738	89.82	gold quality
mononuclear cell	CL:0000842	89.82	gold quality
subcutaneous adipose tissue	UBERON:0002190	89.78	gold quality
rectum	UBERON:0001052	89.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.66	gold quality
left uterine tube	UBERON:0001303	89.59	gold quality
skin of abdomen	UBERON:0001416	89.58	gold quality
pituitary gland	UBERON:0000007	89.49	gold quality
stromal cell of endometrium	CL:0002255	89.48	gold quality
bone marrow	UBERON:0002371	89.48	gold quality
left coronary artery	UBERON:0001626	89.47	gold quality
mouth mucosa	UBERON:0003729	89.45	gold quality
left ovary	UBERON:0002119	89.38	gold quality
body of pancreas	UBERON:0001150	89.37	gold quality
endocervix	UBERON:0000458	89.33	gold quality
coronary artery	UBERON:0001621	89.29	gold quality
esophagus	UBERON:0001043	89.27	gold quality
right testis	UBERON:0004534	89.17	gold quality
adenohypophysis	UBERON:0002196	89.11	gold quality
gall bladder	UBERON:0002110	89.10	gold quality
right lobe of thyroid gland	UBERON:0001119	89.08	gold quality
sigmoid colon	UBERON:0001159	89.06	gold quality
muscle organ	UBERON:0001630	89.01	gold quality
left testis	UBERON:0004533	89.01	gold quality
thyroid gland	UBERON:0002046	88.96	gold quality
stomach	UBERON:0000945	88.95	gold quality
left lobe of thyroid gland	UBERON:0001120	88.94	gold quality
skin of leg	UBERON:0001511	88.90	gold quality
right ovary	UBERON:0002118	88.90	gold quality
tibial nerve	UBERON:0001323	88.84	gold quality
connective tissue	UBERON:0002384	88.84	gold quality
adipose tissue	UBERON:0001013	88.83	gold quality
saliva-secreting gland	UBERON:0001044	88.82	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.81	gold quality
testis	UBERON:0000473	88.71	gold quality
ovary	UBERON:0000992	88.55	gold quality
vagina	UBERON:0000996	88.53	gold quality
spinal cord	UBERON:0002240	88.53	gold quality
embryo	UBERON:0000922	88.50	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.48	silver quality
granulocyte	CL:0000094	88.47	gold quality
myometrium	UBERON:0001296	88.46	gold quality
spleen	UBERON:0002106	88.45	gold quality
body of stomach	UBERON:0001161	88.44	gold quality
ectocervix	UBERON:0012249	88.42	gold quality
upper lobe of left lung	UBERON:0008952	88.40	gold quality
pericardium	UBERON:0002407	88.39	gold quality
periodontal ligament	UBERON:0008266	88.32	gold quality
cardia of stomach	UBERON:0001162	88.31	gold quality
zone of skin	UBERON:0000014	88.28	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.28	gold quality
pancreas	UBERON:0001264	88.26	gold quality
apex of heart	UBERON:0002098	88.18	gold quality
cerebellar hemisphere	UBERON:0002245	88.16	gold quality
cerebellar cortex	UBERON:0002129	88.12	gold quality
right atrium auricular region	UBERON:0006631	88.07	gold quality
right lobe of liver	UBERON:0001114	88.06	gold quality
epithelium of nasopharynx	UBERON:0001951	88.05	gold quality
lymph node	UBERON:0000029	88.02	gold quality
bone marrow cell	CL:0002092	87.94	gold quality
colon	UBERON:0001155	87.93	gold quality
buccal mucosa cell	CL:0002336	87.92	gold quality
cardiac atrium	UBERON:0002081	87.87	gold quality
upper lobe of lung	UBERON:0008948	87.87	gold quality
intestine	UBERON:0000160	87.86	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.32
E-GEOD-125970	no	3.13

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 74 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	44.7	high
Testis	tissue	35.0	high
Skeletal muscle	tissue	33.7	high
Medulla oblongata	tissue	33.0
Tongue	tissue	31.4
Thymus	tissue	30.6
Retina	tissue	28.4
Spinal cord	tissue	27.7
Nucleus accumbens	tissue	27.5
Substantia nigra	tissue	27.5
Putamen	tissue	27.0
Ovary	tissue	26.6	medium
Placenta	tissue	25.2	high
Retrosplenial cortex	tissue	23.8
Endometrium 1	tissue	23.1	medium
Breast	tissue	23.0	high
Locus coeruleus	tissue	22.9
Cerebellum	tissue	22.4	medium
Hippocampus	tissue	22.0	medium
Olfactory bulb	tissue	22.0
Skin 1	tissue	21.9	high
Postcentral gyrus	tissue	21.7
Thyroid gland	tissue	21.6	high
Smooth muscle	tissue	21.5	high
Pituitary gland	tissue	21.3
Cervix	tissue	20.5	high
Seminal vesicle	tissue	20.4	medium
Prostate	tissue	20.1	medium
Tonsil	tissue	20.1	high
Salivary gland	tissue	19.9	high
Choroid plexus	tissue	19.6
Fallopian tube	tissue	19.5	high
Liver	tissue	19.0	medium
Heart muscle	tissue	18.9	medium
Parathyroid gland	tissue	18.8	medium
Lymph node	tissue	18.6	medium
Spleen	tissue	18.5	high
Rectum	tissue	18.1	high
Lung	tissue	17.8	high
Corpus callosum	tissue	17.8
Urinary bladder	tissue	17.5	high
Epididymis	tissue	17.5	medium
Adipose tissue	tissue	17.4	medium
Vagina	tissue	17.3	medium
Gallbladder	tissue	16.7	high
Stomach 1	tissue	16.5	high
Esophagus	tissue	16.2	medium
Pancreas	tissue	15.8	high
Midbrain	tissue	15.6
Hippocampal formation	tissue	15.1
Colon	tissue	14.9	high
Hypothalamus	tissue	14.9
Pons	tissue	14.7
Basal ganglia	tissue	14.6	high
Caudate putamen	tissue	14.6
Thalamus	tissue	14.5
Kidney	tissue	14.4	high
Appendix	tissue	14.4	high
Duodenum	tissue	14.1	high
Small intestine	tissue	13.7	high

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Parieto-temporal junction (white matter) (40.2), Cerebellar cortex (39.4), Temporal white matter (39.3), Cerebellar white matter (38.0), Corpus callosum, genu (white matter) (37.9).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

12 targets:

Target	Regulation
ANGPT1
ANGPT2
BLK	Unknown
CD3D	Activation
CD79A
CEL
LYN
MMP1
NOS2
TEK	Activation
TIE1
VCP	Activation

JASPAR motifs

Motif	Name	Family
MA1483.1	ELF2	Ets-related
MA1483.2	ELF2	Ets-related
MA1483.3	ELF2	Ets-related
UN0955.1	ELF2::FOXD2	Ets-related,FOX
UN0956.1	ELF2::HOXA2	Ets-related,HOX
UN0957.1	ELF2::HOXB2	Ets-related,HOX
UN0958.1	ELF2::ONECUT1	Ets-related,HD-CUT
UN0959.1	ELF2::TBX21	Ets-related,T-Box factors
UN0960.1	ELF2::TEAD4	Ets-related,TEF-1-related factors
UN1021.1	FOXO1::ELF2	FOX,Ets-related
UN1023.1	FOXO3::ELF2	FOX,Ets-related
UN1024.1	FOXO6::ELF2	FOX,Ets-related
UN1093.1	MLX::ELF2	bHLH-ZIP,Ets-related

JASPAR matrix evidence (PMIDs): PMID:20517297

miRNA regulators (miRDB)

Targeting ELF2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 126 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4713-3P	100.00	65.92	505
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-3924	100.00	72.09	2394
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-627-3P	99.90	71.42	3316

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.271, missense Z 2.85 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000686138 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈13% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
4:139,058,986–139,060,612	291 / 366.1	0.79	no
4:139,060,613–139,062,043	19 / 91.0	0.21	yes (p 4.4e-14)
4:139,062,044–139,137,701	203 / 245.9	0.83	no

Literature-anchored findings (GeneRIF, showing 10)

• angiopoietin-1 regulates expression of NERF2 and its own receptor in hypoxic cells. (PMID:11967990)
• NERF/ELF-2 physically interacts with AML1 and mediates opposing effects on AML1-mediated transcription of the B cell-specific blk gene (PMID:14970218)
• These findings indicate that ELF2/NERF promotes VCP transcription and that ELF2/NERF-VCP pathway might be important for cell survival and proliferation under cytokine stress. (PMID:17368566)
• ELF2 transactivates VCP promoter through binding to two motifs, with a predominant contribution of the upstream one. (PMID:18544453)
• Affinity of the CAL PDZ domain for the cystic fibrosis transmembrane conductance regulator (CFTR) C-terminus is much weaker than that of the NHERF1/NHERF2 domains, enabling wild-type CFTR to avoid premature entrapment in the lysosomal pathway. (PMID:18754678)
• Our findings collectively support a potential role of triiodothyronine and its receptor in tumor growth inhibition through regulation of ELF2 (PMID:26968954)
• PCAT7 contributed to the progression of nasopharyngeal carcinoma through regulating miR-134-5p/ELF2 signaling pathway. (PMID:28728844)
• Mutations in eIF2B genes cause vanishing white matter disease due to translation defects. (PMID:29632131)
• Circ_0028007 Aggravates the Malignancy of Nasopharyngeal Carcinoma by Regulating miR-656-3p/ELF2 Axis. (PMID:35239093)
• c-Myc-induced long noncoding RNA MIRE cooperates with hnRNPK to stabilize ELF2 mRNA and promotes clear cell renal cell carcinogenesis. (PMID:37248433)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	elf2a	ENSDARG00000019459
danio_rerio	elf2b	ENSDARG00000079626
mus_musculus	Elf2	ENSMUSG00000037174
rattus_norvegicus	Elf2	ENSRNOG00000010815

Paralogs (28): ETV1 (ENSG00000006468), ETV7 (ENSG00000010030), SPI1 (ENSG00000066336), ELF4 (ENSG00000102034), ETV2 (ENSG00000105672), ERF (ENSG00000105722), ELK3 (ENSG00000111145), ETV3 (ENSG00000117036), ELF1 (ENSG00000120690), SPDEF (ENSG00000124664), ELK1 (ENSG00000126767), ETS1 (ENSG00000134954), EHF (ENSG00000135373), ELF5 (ENSG00000135374), ETV6 (ENSG00000139083), FLI1 (ENSG00000151702), GABPA (ENSG00000154727), ERG (ENSG00000157554), ETS2 (ENSG00000157557), ELK4 (ENSG00000158711), ELF3 (ENSG00000163435), FEV (ENSG00000163497), SPIC (ENSG00000166211), ETV4 (ENSG00000175832), ETV5 (ENSG00000244405), ETV3L (ENSG00000253831), ERFL (ENSG00000268041), SPIB (ENSG00000269404)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Drosophila melanogaster	P11536	99.8%	Diamond
Pan paniscus	A1YG61	99.7%	Diamond
Pan troglodytes	A2T737	99.7%	Diamond
Gorilla gorilla gorilla	A1YF15	99.6%	Diamond
Gallus gallus	P13474	99.5%	Diamond
Xenopus laevis	P18755	98.5%	Diamond
Bos taurus	Q2KIC2	98.1%	Diamond
Ateles geoffroyi	A2D4Z7	97.5%	Diamond
Lytechinus variegatus	P29773	93.8%	Diamond
Caenorhabditis elegans	Q18579	87.2%	Diamond
Drosophila virilis	Q7M3M6	79.6%	Diamond
Avian leukemia virus e26	P01105	99.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ELF2-DT	ncRNA	105379412
MGARP	protein-coding	84709
NOCT	protein-coding	25819

Protein

Protein identifiers

ETS-related transcription factor Elf-2 — Q15723 (reviewed: Q15723)

Alternative names: E74-like factor 2, New ETS-related factor

All UniProt accessions (4): B7Z720, D6RGD9, D6RHI1, Q15723

UniProt curated annotations — full annotation on UniProt →

Function. Isoform 1 transcriptionally activates the LYN and BLK promoters and acts synergistically with RUNX1 to transactivate the BLK promoter. Isoform 2 may function in repression of RUNX1-mediated transactivation.

Subunit / interactions. Interacts with the LIM domains of LMO2. Interacts via its N-terminal region with RUNX1.

Subcellular location. Nucleus.

Tissue specificity. Expressed in all fetal and adult tissues examined. Among fetal tissues, highest levels of expression detected in heart, lung, liver and kidney, and lower levels in brain. Among adult tissues, highest levels of expression detected in heart, placenta, lung, skeletal muscle, spleen, thymus, testis and ovary. Moderate expression in prostate, small intestine, kidney, liver and pancreas, and weak expression in colon, brain and peripheral blood lymphocytes.

Similarity. Belongs to the ETS family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q15723-5	5, NERF-2b	yes
Q15723-1	1, NERF-2, NERF-2a
Q15723-2	2, NERF-1a
Q15723-3	3, NERF-1b
Q15723-4	4

RefSeq proteins (11): NP_001263386, NP_001263387, NP_001263388, NP_001317965, NP_001358253, NP_001358265, NP_001358266, NP_001358267, NP_001358268, NP_006865, NP_973728 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000418	Ets_dom	Domain
IPR022084	TF_Elf_N	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR046328	ETS_fam	Family

Pfam: PF00178, PF12310

UniProt features (19 total): modified residue 10, splice variant 3, compositionally biased region 2, chain 1, DNA-binding region 1, cross-link 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
9IGJ	structure of two human ELF2 transcription factors in complex with a nucleosome	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15723-F1	50.58	0.14

Human Protein Atlas

Protein class: Predicted intracellular proteins, Transcription factors, Helix-turn-helix domains

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; nuclear bodies

Antibody reliability (HPA): IH enhanced · IF supported

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 (11)

Type	Positions
Phosphoserine	372, 430, 107, 185, 191, 363
Phosphothreonine	376, 521, 182
Omega-n-methylarginine	494
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	536

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-8939245	RUNX1 regulates transcription of genes involved in BCR signaling	curated
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-8878171	Transcriptional regulation by RUNX1	—

MSigDB gene sets: 166 (showing top): WENDT_COHESIN_TARGETS_UP, GGGACCA_MIR133A_MIR133B, TGGTGCT_MIR29A_MIR29B_MIR29C, BROWNE_HCMV_INFECTION_6HR_DN, RIZKI_TUMOR_INVASIVENESS_3D_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, AAAGGGA_MIR204_MIR211, KAYO_AGING_MUSCLE_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, ATGTTTC_MIR494, YAGI_AML_WITH_T_9_11_TRANSLOCATION, GOCC_NUCLEAR_BODY, CAGTGTT_MIR141_MIR200A, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, CAGTATT_MIR200B_MIR200C_MIR429

GO Biological Process (6): DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), cell differentiation (GO:0030154), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (6): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription factor activity (GO:0003700), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Transcriptional regulation by RUNX1	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1

GO top-level categories

27 GO namespaces:

Category	Terms
regulation of DNA-templated transcription	4
DNA-templated transcription	3
cellular anatomical structure	2
gene expression	1
RNA biosynthetic process	1
transcription by RNA polymerase II	1
cellular developmental process	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nucleoplasm	1
intracellular membraneless organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 16 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of DNA-templated transcription	BP	direct assay
positive regulation of DNA-templated transcription	BP	direct assay
regulation of transcription by RNA polymerase II	BP	direct assay
nuclear body	CC	direct assay
nucleoplasm	CC	direct assay
DNA-binding transcription factor activity	MF	direct assay
DNA-binding transcription factor activity, RNA polymerase II-specific	MF	direct assay
sequence-specific DNA binding	MF	direct assay
sequence-specific double-stranded DNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 922 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELF2	DYTN	A2CJ06	413
ELF2	WFS1	O76024	370
ELF2	NR1D2	Q14995	364
ELF2	PAN3	Q58A45	364
ELF2	KLHL15	Q96M94	362
ELF2	WNT8B	Q93098	357
ELF2	NOCT	Q9UK39	338
ELF2	EEF2	P13639	338
ELF2	THAP5	Q7Z6K1	329
ELF2	CIROP	A0A1B0GTW7	326
ELF2	LMLN	Q96KR4	326
ELF2	KCNH8	Q96L42	323
ELF2	CSPP1	Q1MSJ5	321
ELF2	ABHD2	P08910	316
ELF2	SLC7A5	Q01650	315

IntAct

Human interaction partners of ELF2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
RUNX1	direct interaction	0.540	2
CCL2	physical association	0.370	2
CCL1	physical association	0.370	1
DBP	physical association	0.370	1
IL18	physical association	0.370	1
IL23A	physical association	0.370	1
IL36A	physical association	0.370	1
ZBTB32	physical association	0.370	1
FLOT1	association	0.350	1
SETD1A	proximity	0.270	1

BioGRID (179 interactions; top human partners by supporting records): HSPBP1 (Affinity Capture-MS; 3 records), PRPS1 (Affinity Capture-MS; 3 records), PSMC3 (Affinity Capture-MS; 3 records), PSME3 (Affinity Capture-MS; 3 records), SPINT2 (Affinity Capture-MS; 3 records), ASH2L (Proximity Label-MS; 2 records), BAP1 (Proximity Label-MS; 2 records), HIST1H2BG (Proximity Label-MS; 2 records), HIST1H3A (Proximity Label-MS; 2 records), IKZF5 (Affinity Capture-MS; 2 records), MYC (Proximity Label-MS; 2 records), NFATC2IP (Affinity Capture-MS; 2 records), NFIA (Proximity Label-MS; 2 records), NFIC (Reconstituted Complex; 2 records), NFIX (Proximity Label-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
ELF2	“up-regulates quantity by expression”	VCP	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 10 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.

GO biological processes:

GO term	Partners	Fold	FDR
inflammatory response	5	18.9×	2e-04

Disease & clinical

Genetic variants

Variant evidence for ELF2: 88 ClinVar records (1 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	73
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
431175	NM_001331036.3(ELF2):c.10G>A (p.Ala4Thr)	Likely pathogenic	criteria provided, single submitter	2

Per-variant reference — Sugi Variant

Explore ELF2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 1,551):

Position(s)	Effect	Δscore	Sites
4:139060322–139060323	donor_loss	1.0000	4
4:139060675–139060676	acceptor_loss	1.0000	2
4:139071864–139071865	donor_loss	1.0000	5
4:139073452–139073453	donor_loss	1.0000	5
4:139073568	acceptor_loss	1.0000
4:139125162–139125163	donor_loss	1.0000	6
4:139125330	acceptor_loss	1.0000	2
4:139139503	acceptor_gain	1.0000
4:139139506	acceptor_gain	1.0000
4:139176965–139176966	donor_loss	1.0000	2

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	6.79e-06
Kidney Renal Clear Cell Carcinoma (validation)	favorable	1.04e-05

Disease associations

OMIM: gene MIM:619798 | disease phenotypes: MIM:608088, MIM:614575

GenCC curated gene-disease

Mondo (1): cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (MONDO:0044720)

Orphanet (2): Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (Orphanet:504476), Hereditary sensory and autonomic neuropathy type 1B (Orphanet:139564)

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C564296	Neuropathy, Hereditary Sensory And Autonomic, Type I, With Cough And Gastroesophageal Reflux *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases expression, increases oxidation, affects expression	2
Ozone	increases abundance, affects expression, affects cotreatment, increases expression, increases oxidation	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
arsenite	increases methylation	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	increases abundance, affects cotreatment, increases expression, increases oxidation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acrolein	increases expression, increases oxidation, increases abundance, affects cotreatment	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Calcitriol	increases expression	1
Carbamazepine	affects expression	1
Curcumin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	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_A1G9	SEES3-1V human ELF2, clone1	Embryonic stem cell	Male
CVCL_A1H0	SEES3-1V human ELF2, clone2	Embryonic stem cell	Male
CVCL_A1H1	SEES3-1V human ELF2, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

2 trials:

NCT	Phase	Status	Title
NCT04153110	Not specified	COMPLETED	Cerebello-Spinal tDCS as Rehabilitative Intervention in Neurodegenerative Ataxia
NCT05621200	Not specified	COMPLETED	Transcranial Alternating Current Stimulation (tACS) in Patients With Ataxia