IL4R

protein-coding

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

Gene summary

This gene encodes the alpha chain of the interleukin-4 receptor, a type I transmembrane protein that can bind interleukin 4 and interleukin 13 to regulate IgE production. The encoded protein also can bind interleukin 4 to promote differentiation of Th2 cells. A soluble form of the encoded protein can be produced by proteolysis of the membrane-bound protein, and this soluble form can inhibit IL4-mediated cell proliferation and IL5 upregulation by T-cells. Allelic variations in this gene have been associated with atopy, a condition that can manifest itself as allergic rhinitis, sinusitus, asthma, or eczema. Polymorphisms in this gene are also associated with resistance to human immunodeficiency virus type-1 infection. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

MANE transcript

NM_000418.4

Inheritance

—

ClinVar variants

U:105B:34

Top phenotype

IL4R-related disorder

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr16:27,313,668-27,364,778

External References & Databases

Ensembl (ENSG00000077238)

Transcript & Mutation Effects

hg38 • Region Span ~51.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

IgE responsiveness, atopicNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0007817

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IL4R variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 109

not providedTotal: 14

IL4R-related disorderTotal: 11

IgE responsiveness, atopicTotal: 3

Susceptibility to HIV infectionTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000418.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	4 clinvar	5 clinvar	11
missense			96 clinvar	20 clinvar	5 clinvar	121
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	105	24	10	139

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 108 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000418.4	RefSeq	NP_000409.1	9	MANE Select
ENST00000395762.7	Ensembl	ENSP00000379111.2	9	MANE Select
NM_001257406.2	RefSeq	NP_001244335.1	9	Standard
NM_001257407.2	RefSeq	NP_001244336.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

production of molecular mediator involved in inflammatory response
positive regulation of immunoglobulin production
immune response
signal transduction
immunoglobulin mediated immune response

Molecular Function

interleukin-4 receptor activity
protein binding

Cellular Component

extracellular space
plasma membrane
integral component of plasma membrane
receptor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395762
Coding exons: 9
Length: 51111
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125747
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.769	428	475	0.901	0.0000260	5368
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.571

Intolerance Scores

LoFtool: 0.562
RVIS EVS: 1.21
RVIS percentile EVS: 93.05

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.986

Gene Damage Prediction

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