ELF4

Summary

ELF4 (E74 like ETS transcription factor 4, HGNC:3319) is a protein-coding gene on chromosome Xq26.1, encoding ETS-related transcription factor Elf-4 (Q99607). Transcriptional activator that binds to DNA sequences containing the consensus 5’-WGGA-3'.

The protein encoded by this gene is a transcriptional activator that binds and activates the promoters of the CSF2, IL3, IL8, and PRF1 genes. The encoded protein is involved in natural killer cell development and function, innate immunity, and induction of cell cycle arrest in naive CD8+ cells. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 2000 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autoinflammatory syndrome, familial, X-linked, Behcet-like 2 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 171 total — 7 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 28
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• Transcription factor: yes — 55 downstream targets (CollecTRI)
• MANE Select transcript: NM_001421

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3319
Approved symbol	ELF4
Name	E74 like ETS transcription factor 4
Location	Xq26.1
Locus type	gene with protein product
Status	Approved
Aliases	MEF, ELFR
Ensembl gene	ENSG00000102034
Ensembl biotype	protein_coding
OMIM	300775
Entrez	2000

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000308167, ENST00000335997, ENST00000434609, ENST00000880884, ENST00000880885, ENST00000880886, ENST00000880887, ENST00000958346

RefSeq mRNA: 2 — MANE Select: NM_001421 NM_001127197, NM_001421

CCDS: CCDS14617

Canonical transcript exons

ENST00000308167 — 9 exons

Exon	Start	End
ENSE00001095261	130110325	130110497
ENSE00001095266	130074581	130074752
ENSE00001352919	130081256	130081539
ENSE00001614860	130072226	130072417
ENSE00001703639	130071336	130071419
ENSE00001789328	130071040	130071232
ENSE00001804899	130069300	130069677
ENSE00001843723	130063955	130067525
ENSE00002193981	130074049	130074141

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 95.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.8398 / max 490.1281, expressed in 1760 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200459	14.2939	1604
200462	4.1055	1416
200463	1.8671	1087
200461	1.3945	703
200458	0.7665	214
200460	0.4122	233

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	95.22	gold quality
granulocyte	CL:0000094	94.32	gold quality
blood	UBERON:0000178	92.65	gold quality
leukocyte	CL:0000738	92.04	gold quality
mononuclear cell	CL:0000842	91.79	gold quality
monocyte	CL:0000576	91.77	gold quality
cartilage tissue	UBERON:0002418	90.34	gold quality
germinal epithelium of ovary	UBERON:0001304	89.67	gold quality
mucosa of transverse colon	UBERON:0004991	89.27	gold quality
colonic mucosa	UBERON:0000317	89.09	gold quality
ileal mucosa	UBERON:0000331	88.94	gold quality
jejunal mucosa	UBERON:0000399	88.85	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.05	gold quality
parietal pleura	UBERON:0002400	87.59	gold quality
placenta	UBERON:0001987	87.37	gold quality
bone marrow	UBERON:0002371	87.23	gold quality
decidua	UBERON:0002450	87.02	gold quality
bone marrow cell	CL:0002092	86.95	gold quality
tibia	UBERON:0000979	86.73	gold quality
squamous epithelium	UBERON:0006914	86.44	gold quality
gingival epithelium	UBERON:0001949	86.43	gold quality
visceral pleura	UBERON:0002401	86.41	gold quality
pleura	UBERON:0000977	86.12	gold quality
esophagus squamous epithelium	UBERON:0006920	86.04	gold quality
cervix squamous epithelium	UBERON:0006922	85.67	gold quality
rectum	UBERON:0001052	85.60	gold quality
stromal cell of endometrium	CL:0002255	85.58	gold quality
amniotic fluid	UBERON:0000173	85.51	gold quality
mucosa of urinary bladder	UBERON:0001259	85.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.10

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

55 targets.

Target	Regulation
ABCB1
AGTR2
ALDOA
AQP2
CARM1
CCNG1
CD79A
CD8A
CD99
CDKN2A
CDKN2B
CHD7
CKM
CSF2	Activation
CXCL8	Activation
DEFB4A
DLX5	Repression
EIF3K
ELF4
FASLG
GZMB
HBD	Activation
IFNA2	Activation
IFNA8	Activation
IFNB1	Repression
IFNL3	Activation
IL17A
LGALS3
LTBP1
LUM

JASPAR motifs

Motif	Name	Family
MA0641.1	ELF4	Ets-related

JASPAR matrix evidence (PMIDs): PMID:20517297

Upstream regulators (CollecTRI, top): E2F1, ELF4, GFI1B, KDM6A, NPM1, SP1, TP53

miRNA regulators (miRDB)

103 targeting ELF4, 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-4673	100.00	66.64	1490
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4514	99.99	67.10	1870
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192

Literature-anchored findings (GeneRIF, showing 28)

• Functional dissection of the transactivation mechanisms of the ETS transcription factor MEF (PMID:12151102)
• MEF is an important regulator of IL-8 expression (PMID:14625302)
• promyelocytic leukemia protein, but not Sp100, induced the accumulation of MEF in PML nuclear bodies and MEF and PML physically interacted, stimulating MEF transcriptional activity, resulting in the up-regulation of endogenous lysozyme expression. (PMID:14976184)
• MEF activated HBD2 promoter activity, and increased the endogenous HBD2 transcription level. The activated HBD2 promoter activity was attenuated by the antisense MEF RNA input and the loss of the ETS binding site in the HBD2 promoter (PMID:15013761)
• regulation in epithelial cells by Sp1 (PMID:15907486)
• RT-PCR analysis of RNA isolated from bone marrow samples from the patient demonstrates that the translocation occurs within intron 1 of ERG isoform 1 and intron 2 of ELF4 resulting in an in-frame fusion joining exon 2 from ELF4 with exon 2 of ERG. (PMID:16303180)
• Loss of ELF4 leads to increased quiescence in bone marrow endothelial cells by the deregulation of cyclin-dependent kinase-4 expression and to enhanced regeneration of sinusoidal blood vessels. (PMID:21350194)
• MEF is involved in PTH suppression of osteoblasts through activating the MKK4/JNK1 pathway and subsequently up-regulating Mab21l1 expression. (PMID:21465527)
• These studies implicate MEF as a previously unrecognized gatekeeper gene in gliomagenesis that promotes stem cell characteristics through Sox2 activation. (PMID:23217424)
• enhanced HDM2 expression induced by mutant NPM1 may have a role in MEF/ELF4-dependent leukemogenesis (PMID:23393136)
• The p53-MDM2-MEF axis is a feedback mechanism that exquisitely controls the balance of these transcriptional regulators. (PMID:25081543)
• The genes BCL6, NFE2, POU4F2 and ELF4 are primary 1,25(OH)2D3 targets in THP-1 cells (PMID:25482012)
• Overall, these data indicate that hypoxia or HIF-1alpha positively regulates MEF expression and function. (PMID:27040637)
• The decreased expression of miR-365 in human cervical cancer cells relieves its inhibitory effect on ELF4, which promotes the proliferation of cervical cancer cells and the formation of tumor. (PMID:31060678)
• ELF4 Is a Target of miR-124 and Promotes Neuroblastoma Proliferation and Undifferentiated State. (PMID:31624087)
• Hepatitis B Virus-Telomerase Reverse Transcriptase Promoter Integration Harnesses Host ELF4, Resulting in Telomerase Reverse Transcriptase Gene Transcription in Hepatocellular Carcinoma. (PMID:32170761)
• Elf4 regulates lysosomal biogenesis and the mTOR pathway to promote clearance of Staphylococcus aureus in macrophages. (PMID:33423322)
• High ELF4 expression in human cancers is associated with worse disease outcomes and increased resistance to anticancer drugs. (PMID:33836003)
• Human autoinflammatory disease reveals ELF4 as a transcriptional regulator of inflammation. (PMID:34326534)
• [ELF4 promotes proliferation and inhibits apoptosis of human insulinoma cells by activating Akt signaling]. (PMID:34658346)
• Loss of Function Mutation in ELF4 Causes Autoinflammatory and Immunodeficiency Disease in Human. (PMID:35266071)
• ELF4 is a critical component of a miRNA-transcription factor network and is a bridge regulator of glioblastoma receptor signaling and lipid dynamics. (PMID:35862252)
• An ELF4 hypomorphic variant results in NK cell deficiency. (PMID:36477361)
• A Multicenter Cohort Study of Immune Dysregulation Disorders Caused by ELF4 Variants in China. (PMID:36823308)
• FGF19-mediated ELF4 overexpression promotes colorectal cancer metastasis through transactivating FGFR4 and SRC. (PMID:36923538)
• ELF4 contributes to esophageal squamous cell carcinoma growth and metastasis by augmenting cancer stemness via FUT9. (PMID:37674363)
• Reciprocal regulation of lncRNA MEF and c-Myc drives colorectal cancer tumorigenesis. (PMID:38301392)
• A Novel Frameshift Variant of the ELF4 Gene in a Patient with Autoinflammatory Disease: Clinical Features, Transcriptomic Profiling and Functional Studies. (PMID:38773005)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Elf4	ENSMUSG00000031103
rattus_norvegicus	Elf4	ENSRNOG00000005352

Paralogs (28): ETV1 (ENSG00000006468), ETV7 (ENSG00000010030), SPI1 (ENSG00000066336), ETV2 (ENSG00000105672), ERF (ENSG00000105722), ELF2 (ENSG00000109381), 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)

Protein

Protein identifiers

ETS-related transcription factor Elf-4 — Q99607 (reviewed: Q99607)

Alternative names: E74-like factor 4, Myeloid Elf-1-like factor

All UniProt accessions (2): Q99607, B1AL80

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator that binds to DNA sequences containing the consensus 5’-WGGA-3’. Transactivates promoters of the hematopoietic growth factor genes CSF2, IL3, IL8, and of the bovine lysozyme gene. Acts synergistically with RUNX1 to transactivate the IL3 promoter. Transactivates the PRF1 promoter in natural killer (NK) cells and CD8+ T cells. Plays a role in the development and function of NK and NK T-cells and in innate immunity. Controls the proliferation and homing of CD8+ T-cells via the Kruppel-like factors KLF4 and KLF2. Controls cell senescence in a p53-dependent manner. Can also promote cellular transformation through inhibition of the p16 pathway. Is a transcriptional regulator of inflammation, controlling T-helper 17 (Th17) cells and macrophage inflammatory responses. Required for sustained transcription of anti-inflammatory genes, including IL1RN. Is a negative regulator of pro-inflammatory cytokines expression including IL17A, IL1B, IL6, TNFA and CXCL1. Down-regulates expression of TREM1, a cell surface receptor involved in the amplification of inflammatory responses.

Subunit / interactions. Interacts with RUNX1 (via the Runt domain); the interaction transactivates the IL3 promoter. Interacts (via its C-terminus) with PML; the interaction translocates ELF4 to PML nuclear bodies and enhances transactivation of LYZ.

Subcellular location. Nucleus. PML body.

Tissue specificity. Abundantly expressed in the placenta and in a variety of myeloid leukemia cell lines. Moderate levels of expression in heart, lung, spleen, thymus, peripheral blood lymphocytes, ovary and colon. Lower levels of expression in Jurkat T-cells and other T-cell lines and no expression in brain.

Disease relevance. A chromosomal aberration involving ELF4 has been found in a case of acute myeloid leukemia (AML). Translocation t(X;21)(q25-26;q22) with ERG. Autoinflammatory syndrome, familial, X-linked, Behcet-like 2 (AIFBL2) [MIM:301074] An X-linked recessive, autoinflammatory disorder characterized by ulceration of the oral mucosa and skin inflammation. Additional variable features may include gastrointestinal ulceration, arthritis, recurrent fevers, and iron deficiency anemia. Disease onset is in early childhood. The disease is caused by variants affecting the gene represented in this entry.

Induction. By ponisterone A in erythroleukemia cells.

Similarity. Belongs to the ETS family.

RefSeq proteins (2): NP_001120669, NP_001412* (*=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 (42 total): sequence variant 14, mutagenesis site 8, region of interest 6, compositionally biased region 5, modified residue 4, sequence conflict 2, chain 1, DNA-binding region 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99607-F1	49.77	0.13

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 (1): 25–26 (breakpoint for translocation to form elf4-erg oncogene)

Post-translational modifications (4): 151, 188, 641, 648

Mutagenesis-validated functional residues (8):

Position	Phenotype
211	loss of transcriptional activity shown in ifnb1 promoter-driven luciferase assay.
212	loss of transcriptional activity shown in ifnb1 promoter-driven luciferase assay.
219	loss of transcriptional activity shown in ifnb1 promoter-driven luciferase assay.
239	loss of transcriptional activity shown in ifnb1 promoter-driven luciferase assay.
251	loss of transcriptional activity shown in ifnb1 promoter-driven luciferase assay. loss of infb1 promoter binding. does n
252	loss of transcriptional activity shown in ifnb1 promoter-driven luciferase assay.
255	loss of transcriptional activity shown in ifnb1 promoter-driven luciferase assay.
260	loss of transcriptional activity shown in ifnb1 promoter-driven luciferase assay.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 373 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, YAATNRNNNYNATT_UNKNOWN, ACTACCT_MIR196A_MIR196B, GNF2_MSN, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GNF2_BNIP2, GOBP_INFLAMMATORY_RESPONSE, GGGNRMNNYCAT_UNKNOWN, LFA1_Q6, MODULE_45, GENTILE_RESPONSE_CLUSTER_D3, AP4_Q6, CROONQUIST_NRAS_SIGNALING_UP, TGACCTY_ERR1_Q2, TAL1ALPHAE47_01

GO Biological Process (11): natural killer cell proliferation (GO:0001787), NK T cell proliferation (GO:0001866), regulation of transcription by RNA polymerase II (GO:0006357), cell differentiation (GO:0030154), negative regulation of interleukin-1 beta production (GO:0032691), negative regulation of interleukin-6 production (GO:0032715), negative regulation of tumor necrosis factor production (GO:0032720), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of inflammatory response (GO:0050728), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (8): 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), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604), PML body (GO:0016605)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
DNA-templated transcription	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
natural killer cell activation	1
lymphocyte proliferation	1
alpha-beta T cell proliferation	1
NK T cell activation	1
cellular developmental process	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
negative regulation of interleukin-1 production	1
negative regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	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
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1

Protein interactions and networks

STRING

1032 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELF4	ELF3	P78545	979
ELF4	KLF2	Q9Y5W3	649
ELF4	PRR9	Q5T870	642
ELF4	PRR7	Q8TB68	622
ELF4	IL3	P08700	618
ELF4	KLF4	P78338	569
ELF4	CSF2	P04141	555
ELF4	RFX5	P48382	537
ELF4	SELL	P14151	537
ELF4	TBK1	Q9UHD2	537
ELF4	TP53	P04637	515
ELF4	STING1	Q86WV6	481
ELF4	EIF4E	P06730	468
ELF4	IL2RB	P14784	460
ELF4	CCR7	P32248	460

IntAct

12 interactions, top by confidence:

A	B	Type	Score
ELF4	RUNX1	psi-mi:“MI:0915”(physical association)	0.400
ELF4		psi-mi:“MI:0915”(physical association)	0.370
NFE2L2	ELF4	psi-mi:“MI:0915”(physical association)	0.370
ELF4	CASP4	psi-mi:“MI:0915”(physical association)	0.370
SET	ELF4	psi-mi:“MI:0915”(physical association)	0.370
ELF4	ORF10	psi-mi:“MI:0915”(physical association)	0.370
ELF4	S	psi-mi:“MI:0915”(physical association)	0.370
ELF4	FLOT1	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
ELF4	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
hmp	ELF4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (120): ELF4 (Biochemical Activity), ELF4 (Affinity Capture-Western), MDM2 (Affinity Capture-Western), ELF4 (Affinity Capture-MS), ELF4 (Two-hybrid), ELF4 (Affinity Capture-Western), ELF4 (Reconstituted Complex), GABPA (Proximity Label-MS), ZNF148 (Proximity Label-MS), SETD1A (Proximity Label-MS), RBBP5 (Proximity Label-MS), C11orf30 (Proximity Label-MS), PBRM1 (Proximity Label-MS), ZNF687 (Proximity Label-MS), KDM6A (Proximity Label-MS)

ESM2 similar proteins: A0A1L8GSA2, A0A1L8H0H2, A0JN51, A0JP82, A2AWL7, A2BGM5, A2RRX6, F8VPJ6, K9JHZ4, O13186, O46567, O54826, O89091, P04150, P08235, P15822, P22199, P32519, P36197, P37275, P48552, P55197, P59759, P79269, P79686, Q29131, Q2KHR2, Q3YC04, Q4JM28, Q5R9P5, Q60775, Q61321, Q62947, Q64318, Q68DE3, Q6XLJ0, Q8AYC1, Q8AYC2, Q8BMA5, Q8IZQ8

Diamond homologs: A0A1W2PQ73, A0JN51, A1A4L6, A1YF15, A1YG61, A1YG91, A2D4Z7, A2T737, A2T762, A3FEM2, A4GTP4, A8WFJ9, O00321, O01519, O70132, O70273, O95238, P01105, P10157, P11308, P11536, P13474, P14921, P15036, P15037, P15062, P18755, P18756, P19102, P19419, P20105, P26323, P27577, P28322, P28324, P29773, P29774, P29775, P29776, P32519

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
ELF4	“up-regulates quantity by expression”	CXCL8	“transcriptional regulation”
ELF4	“up-regulates quantity by expression”	LYZ	“transcriptional regulation”
ELF4	“up-regulates quantity by expression”	MDM2	“transcriptional regulation”
E2F1	“up-regulates quantity by expression”	ELF4	“transcriptional regulation”
KDM6A	“down-regulates quantity by repression”	ELF4	“transcriptional regulation”
ATM	“down-regulates activity”	ELF4	phosphorylation
TBK1	“up-regulates activity”	ELF4	phosphorylation
ELF4	“form complex”	ELF4/RUNX1	binding

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — AML, LGGNOS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	1
Uncertain significance	61
Likely benign	16
Benign	4

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1676293	NM_001421.4(ELF4):c.752G>C (p.Trp251Ser)	Pathogenic
1676294	NM_001421.4(ELF4):c.1015del (p.Ala339fs)	Pathogenic
1676295	NM_001421.4(ELF4):c.691T>C (p.Trp231Arg)	Pathogenic
4281530	NM_001421.4(ELF4):c.521_525del (p.Lys173_Ser174insTer)	Pathogenic
4282459	NM_001421.4(ELF4):c.700C>T (p.Arg234Ter)	Pathogenic
4470621	NM_001421.4(ELF4):c.985C>T (p.Arg329Ter)	Pathogenic
4848750	NC_000023.10:g.(?129197929)(129215514_129244299)del	Pathogenic
2504297	NM_001421.4(ELF4):c.553C>T (p.Arg185Ter)	Likely pathogenic

SpliceAI

1495 predictions. Top by Δscore:

Variant	Effect	Δscore
X:130067521:ATGCA:A	acceptor_gain	1.0000
X:130067522:TGCA:T	acceptor_gain	1.0000
X:130067523:GCA:G	acceptor_gain	1.0000
X:130067524:CA:C	acceptor_gain	1.0000
X:130067524:CAC:C	acceptor_gain	1.0000
X:130067526:C:CC	acceptor_gain	1.0000
X:130069294:CCTTA:C	donor_loss	1.0000
X:130069297:TA:T	donor_loss	1.0000
X:130069299:C:CT	donor_loss	1.0000
X:130069673:AGTAT:A	acceptor_gain	1.0000
X:130069674:GTAT:G	acceptor_gain	1.0000
X:130069675:TAT:T	acceptor_gain	1.0000
X:130069676:AT:A	acceptor_gain	1.0000
X:130069678:C:CC	acceptor_gain	1.0000
X:130069679:T:G	acceptor_loss	1.0000
X:130071034:TCCTA:T	donor_loss	1.0000
X:130071035:CCTA:C	donor_loss	1.0000
X:130071036:CTACC:C	donor_loss	1.0000
X:130071037:TACC:T	donor_loss	1.0000
X:130071038:A:C	donor_loss	1.0000
X:130071092:T:TA	donor_gain	1.0000
X:130071093:C:A	donor_gain	1.0000
X:130071229:CTGC:C	acceptor_gain	1.0000
X:130071233:C:CC	acceptor_gain	1.0000
X:130071234:T:C	acceptor_loss	1.0000
X:130071331:CATAC:C	donor_loss	1.0000
X:130071332:ATACC:A	donor_loss	1.0000
X:130071333:TACCT:T	donor_loss	1.0000
X:130071335:CCT:C	donor_loss	1.0000
X:130071415:CCGGA:C	acceptor_gain	1.0000

AlphaMissense

4284 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:130069617:A:C	F290L	1.000
X:130069617:A:T	F290L	1.000
X:130069618:A:C	F290C	1.000
X:130069618:A:G	F290S	1.000
X:130069619:A:C	F290V	1.000
X:130069619:A:G	F290L	1.000
X:130069619:A:T	F290I	1.000
X:130069621:T:G	Q289P	1.000
X:130069624:T:C	Y288C	1.000
X:130069625:A:C	Y288D	1.000
X:130069625:A:G	Y288H	1.000
X:130069625:A:T	Y288N	1.000
X:130069630:A:G	L286P	1.000
X:130069630:A:T	L286Q	1.000
X:130069632:C:A	R285S	1.000
X:130069632:C:G	R285S	1.000
X:130069633:C:A	R285M	1.000
X:130069633:C:G	R285T	1.000
X:130069634:T:C	R285G	1.000
X:130069639:C:A	G283V	1.000
X:130069639:C:T	G283E	1.000
X:130069640:C:A	G283W	1.000
X:130069640:C:G	G283R	1.000
X:130069640:C:T	G283R	1.000
X:130069647:T:A	K280N	1.000
X:130069647:T:G	K280N	1.000
X:130069648:T:A	K280I	1.000
X:130069649:T:C	K280E	1.000
X:130069649:T:G	K280Q	1.000
X:130069652:C:G	A279P	1.000

dbSNP variants (sampled 300 via entrez): RS1000056195 (X:130095648 T>C), RS1000218467 (X:130103556 C>A), RS1000342656 (X:130112927 C>A), RS1000379599 (X:130065355 G>GGGAA), RS1000396585 (X:130113814 T>C), RS1000433516 (X:130065623 G>A), RS1000660998 (X:130077333 T>C), RS1000668039 (X:130088629 C>T), RS1000676416 (X:130109831 C>G,T), RS1000961204 (X:130101777 C>T), RS1001031186 (X:130111562 C>T), RS1001180375 (X:130105612 C>A,T), RS1001423681 (X:130068536 G>A), RS1001477282 (X:130064128 C>T), RS1001529745 (X:130064575 T>A)

Disease associations

OMIM: gene MIM:300775 | disease phenotypes: MIM:301074

GenCC curated gene-disease

Disease	Classification	Inheritance
autoinflammatory syndrome, familial, X-linked, Behcet-like 2	Strong	X-linked
short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia	Supportive	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
autoinflammatory syndrome, familial, X-linked, Behcet-like 2	Definitive	XL

Mondo (2): autoinflammatory syndrome, familial, X-linked, Behcet-like 2 (MONDO:0024770), short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia (MONDO:0018967)

Orphanet (1): X-linked immune dysregulation with inflammatory bowel disease due to ELF4 deficiency (Orphanet:676125)

HPO phenotypes

28 total (28 of 28 shown, HPO-id order):

HPO	Term
HP:0000155	Oral ulcer
HP:0000988	Skin rash
HP:0001369	Arthritis
HP:0001419	X-linked recessive inheritance
HP:0001824	Weight loss
HP:0001891	Iron deficiency anemia
HP:0001894	Thrombocytosis
HP:0001945	Fever
HP:0001954	Recurrent fever
HP:0002014	Diarrhea
HP:0002027	Abdominal pain
HP:0002037	Inflammation of the large intestine
HP:0002205	Recurrent respiratory infections
HP:0002583	Colitis
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0005218	Anoperineal fistula
HP:0005231	Chronic gastritis
HP:0009789	Perianal abscess
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0011463	Childhood onset
HP:0012450	Chronic constipation
HP:0030374	Decreased proportion of memory B cells
HP:0030783	Increased circulating interleukin 6 concentration
HP:0040218	Reduced total natural killer cell count
HP:0100633	Esophagitis
HP:0100827	Increased total lymphocyte count

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008103_151	Bipolar disorder	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, increases methylation, affects cotreatment	7
Benzo(a)pyrene	increases expression, affects methylation	6
Tetrachlorodibenzodioxin	decreases reaction, increases expression	5
Tretinoin	decreases expression, increases expression	4
Cyclosporine	increases expression	3
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
chloroacetaldehyde	increases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	increases expression	1
benzo(e)pyrene	decreases methylation	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A1H5	SEES3-1V human ELF4, clone1	Embryonic stem cell	Male
CVCL_A1H6	SEES3-1V human ELF4, clone2	Embryonic stem cell	Male
CVCL_A1H7	SEES3-1V human ELF4, clone3	Embryonic stem cell	Male
CVCL_E1MY	HyCyte THP-1 KO-hELF4	Cancer cell line	Male

Clinical trials (associated diseases)

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