IL4R

interleukin 4 receptor, the group of CD molecules|Interleukin receptors

Basic information

Region (hg38): 16:27313667-27364778

Links

ENSG00000077238 ∙ NCBI:3566 ∙ OMIM:147781 ∙ HGNC:6015 ∙ Uniprot:P24394 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• IgE responsiveness, atopic (No Known Disease Relationship), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IL4R gene.

• Inborn genetic diseases (29 variants)
• not provided (14 variants)
• IgE responsiveness, atopic;Susceptibility to HIV infection (2 variants)
• IL4R-related condition (1 variants)
• IgE responsiveness, atopic (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL4R 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				1	4	5
missense			28	4	4	36
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding				1	1	2
Total	0	0	28	6	9

Variants in IL4R

This is a list of pathogenic ClinVar variants found in the IL4R region.

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

Position	Type	Phenotype	Significance	ClinVar
16-27342158-C-T		IL4R-related disorder	Benign (Dec 19, 2019)
16-27342183-G-A		not specified	Uncertain significance (Dec 19, 2023)
16-27342184-A-G		IgE responsiveness, atopic	Uncertain significance (Feb 07, 2022)
16-27342219-G-A		not specified	Uncertain significance (Jan 24, 2023)
16-27342225-C-T		not specified	Uncertain significance (Jul 09, 2021)
16-27342268-G-C			Benign (Jun 18, 2018)
16-27344882-A-G		Atopy, resistance to	Benign (Oct 01, 2005)
16-27344896-C-T			Benign (Aug 14, 2018)
16-27344903-G-A		IL4R-related disorder	Benign (Aug 21, 2019)
16-27344904-C-T		not specified	Likely benign (Jan 30, 2024)
16-27344950-T-C			Benign (Aug 14, 2018)
16-27345014-G-A		not specified	Uncertain significance (Oct 06, 2021)
16-27346475-A-G		not specified	Uncertain significance (May 05, 2023)
16-27346542-C-T		not specified	Uncertain significance (Jan 08, 2024)
16-27346601-G-C		not specified	Uncertain significance (Sep 16, 2021)
16-27352546-A-G		not specified	Likely benign (Nov 09, 2023)
16-27352621-G-A		not specified	Uncertain significance (Oct 05, 2021)
16-27352627-G-A		not specified	Uncertain significance (Sep 14, 2022)
16-27352674-C-A		not specified	Uncertain significance (Dec 07, 2021)
16-27355824-C-G		not specified	Likely benign (Feb 23, 2023)
16-27355825-G-A		not specified	Uncertain significance (Feb 26, 2024)
16-27355905-C-G			Benign (Dec 31, 2019)
16-27358957-G-A		IL4R-related disorder	Benign (Mar 20, 2020)
16-27358962-C-T		not specified	Uncertain significance (Feb 06, 2023)
16-27358963-G-A		not specified	Likely benign (Feb 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IL4R	protein_coding	protein_coding	ENST00000395762	9	51111

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000230	0.982	125729	0	18	125747	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.769	428	475	0.901	0.0000260	5368
Missense in Polyphen		75	100.98	0.74272		1234
Synonymous	0.242	200	204	0.978	0.0000126	1671
Loss of Function	2.11	9	18.9	0.477	9.06e-7	194

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000880	0.0000879
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for both interleukin 4 and interleukin 13. Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and, chemokine and mucus production at sites of allergic inflammation. In certain cell types, can signal through activation of insulin receptor substrates, IRS1/IRS2. {ECO:0000269|PubMed:8124718}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Inflammatory bowel disease (IBD) - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);JAK-STAT-Core;IL-4 Signaling Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Interleukin-4 and 13 signaling;PI3K-Akt Signaling Pathway;Inflammatory Response Pathway;Interleukin-4 and 13 signaling;Signaling by Interleukins;il 4 signaling pathway;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Immune System;p73 transcription factor network;IL-4 signaling;JAK STAT MolecularVariation 2;JAK STAT pathway and regulation;IL4;IL4-mediated signaling events;IL-13 signaling (Consensus)

Recessive Scores

• pRec: 0.571

Intolerance Scores

• loftool: 0.562
• rvis_EVS: 1.21
• rvis_percentile_EVS: 93.05

Haploinsufficiency Scores

• pHI: 0.181
• hipred: Y
• hipred_score: 0.542
• ghis: 0.432

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.986

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Il4ra
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; immune system phenotype; liver/biliary system phenotype; respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: production of molecular mediator involved in inflammatory response;positive regulation of immunoglobulin production;immune response;signal transduction;immunoglobulin mediated immune response;cytokine-mediated signaling pathway;ovulation;interleukin-4-mediated signaling pathway;regulation of cell population proliferation;defense response to protozoan;positive regulation of macrophage activation;positive regulation of mast cell degranulation;response to estrogen;negative regulation of T-helper 1 cell differentiation;positive regulation of T-helper 2 cell differentiation;positive regulation of chemokine secretion;positive regulation of cold-induced thermogenesis;positive regulation of myoblast fusion;response to odorant
• Cellular component: extracellular space;plasma membrane;integral component of plasma membrane;receptor complex
• Molecular function: interleukin-4 receptor activity;protein binding