ELF4

E74 like ETS transcription factor 4, the group of ETS transcription factor family

Basic information

Region (hg38): X:130063955-130110716

Links

ENSG00000102034 ∙ NCBI:2000 ∙ OMIM:300775 ∙ HGNC:3319 ∙ Uniprot:Q99607 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia (Supportive), mode of inheritance: XL
• autoinflammatory syndrome, familial, X-linked, Behcet-like 2 (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Autoinflammatory syndrome, familial, X-linked, Behcet-like 2	XL	Allergy/Immunology/Infectious	The condition involves autoinflammatory manifestations, and medical management (eg, with steroids, TNFA blockade) have been described as beneficial; The condition may involve frequent infections, and prophylactic measures and prompt and aggressive management of infections may be beneficial	Allergy/Immunology/Infectious	34326534; 35266071

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ELF4 gene.

• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ELF4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	2	4
missense	1		21	2	1	25
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	0	22	4	3

Highest pathogenic variant AF is 0.0000624

Variants in ELF4

This is a list of pathogenic ClinVar variants found in the ELF4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-130066735-G-C		not specified	Uncertain significance (Jun 06, 2023)
X-130066777-G-A		Autoinflammatory syndrome, familial, X-linked, Behcet-like 2	Uncertain significance (Dec 02, 2024)
X-130066785-G-C		not specified	Uncertain significance (Dec 26, 2023)
X-130066903-G-A		ELF4-related disorder	Benign (Dec 31, 2019)
X-130067050-G-A		not specified	Uncertain significance (Aug 27, 2024)
X-130067058-G-A		not specified	Uncertain significance (Jan 17, 2024)
X-130067069-C-G			Uncertain significance (Sep 01, 2024)
X-130067079-G-A		not specified	Uncertain significance (Jul 27, 2022)
X-130067096-C-T		ELF4-related disorder	Likely benign (Apr 26, 2022)
X-130067182-C-G		not specified	Uncertain significance (Sep 27, 2022)
X-130067188-G-A		not specified	Uncertain significance (Aug 05, 2024)
X-130067204-C-T		not specified	Benign (Jan 24, 2024)
X-130067217-G-A		ELF4-related disorder	Uncertain significance (May 21, 2024)
X-130067229-C-T		not specified	Uncertain significance (Nov 21, 2024)
X-130067230-G-A		not specified	Uncertain significance (Jul 12, 2022)
X-130067236-C-T		not specified	Uncertain significance (Aug 02, 2021)
X-130067286-G-A		not specified	Uncertain significance (Aug 19, 2024)
X-130067475-G-A		not specified	Uncertain significance (May 09, 2024)
X-130067487-G-A		not specified	Uncertain significance (Oct 29, 2024)
X-130067491-C-T			Likely benign (Feb 01, 2023)
X-130069343-C-T			Likely benign (-)
X-130069380-C-T			Benign (Dec 31, 2019)
X-130069381-G-A		not specified	Uncertain significance (Nov 26, 2024)
X-130069418-C-T		not specified	Uncertain significance (Sep 03, 2024)
X-130069471-GC-G		Autoinflammatory syndrome, familial, X-linked, Behcet-like 2	Pathogenic (Apr 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ELF4	protein_coding	protein_coding	ENST00000308167	8	45843

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0614	0.936	125740	1	6	125747	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.17	212	265	0.799	0.0000206	4274
Missense in Polyphen		55	92.085	0.59727		1625
Synonymous	0.629	111	120	0.927	0.0000104	1457
Loss of Function	2.60	5	16.3	0.306	0.00000126	264

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000113	0.0000980
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000618	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 (By similarity). Also transactivates the PRF1 promoter in natural killer (NK) 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 (By similarity). Controls cell senescence in a p53-dependent manner. Can also promote cellular transformation through inhibition of the p16 pathway. {ECO:0000250, ECO:0000269|PubMed:10207087, ECO:0000269|PubMed:14625302, ECO:0000269|PubMed:14976184, ECO:0000269|PubMed:19380490, ECO:0000269|PubMed:8895518, ECO:0000269|PubMed:9524226}.
• Disease: DISEASE: Note=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. {ECO:0000269|PubMed:16303180}.
• Pathway: TYROBP Causal Network (Consensus)

Recessive Scores

• pRec: 0.0870

Intolerance Scores

• loftool: 0.359
• rvis_EVS: -0.11
• rvis_percentile_EVS: 45.26

Haploinsufficiency Scores

• pHI: 0.495
• hipred: Y
• hipred_score: 0.701
• ghis: 0.531

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.632

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Elf4
• Phenotype: immune system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: natural killer cell proliferation;NK T cell proliferation;regulation of transcription by RNA polymerase II;cell differentiation;innate immune response;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus;nucleoplasm;nuclear body;PML body
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;protein binding