IL5RA

Summary

IL5RA (interleukin 5 receptor subunit alpha, HGNC:6017) is a protein-coding gene on chromosome 3p26.2, encoding Interleukin-5 receptor subunit alpha (Q01344). Cell surface receptor that plays an important role in the survival, differentiation, and chemotaxis of eosinophils.

The protein encoded by this gene is an interleukin 5 specific subunit of a heterodimeric cytokine receptor. The receptor is comprised of a ligand specific alpha subunit and a signal transducing beta subunit shared by the receptors for interleukin 3 (IL3), colony stimulating factor 2 (CSF2/GM-CSF), and interleukin 5 (IL5). The binding of this protein to IL5 depends on the beta subunit. The beta subunit is activated by the ligand binding, and is required for the biological activities of IL5. This protein has been found to interact with syndecan binding protein (syntenin), which is required for IL5 mediated activation of the transcription factor SOX4. Several alternatively spliced transcript variants encoding four distinct isoforms have been reported.

Source: NCBI Gene 3568 — RefSeq curated summary.

At a glance

• GWAS associations: 32
• Clinical variants (ClinVar): 81 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_175726

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6017
Approved symbol	IL5RA
Name	interleukin 5 receptor subunit alpha
Location	3p26.2
Locus type	gene with protein product
Status	Approved
Aliases	CDw125, CD125
Ensembl gene	ENSG00000091181
Ensembl biotype	protein_coding
OMIM	147851
Entrez	3568

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000256452, ENST00000311981, ENST00000383846, ENST00000418488, ENST00000427088, ENST00000430514, ENST00000438560, ENST00000445701, ENST00000446632, ENST00000456302, ENST00000466722

RefSeq mRNA: 7 — MANE Select: NM_175726 NM_000564, NM_001243099, NM_175724, NM_175725, NM_175726, NM_175727, NM_175728

CCDS: CCDS2559, CCDS2560, CCDS46739, CCDS58813

Canonical transcript exons

ENST00000446632 — 12 exons

Exon	Start	End
ENSE00000912357	3074782	3074866
ENSE00000912359	3076531	3076627
ENSE00000997127	3108550	3108691
ENSE00001606141	3066324	3070311
ENSE00001613317	3109945	3110374
ENSE00001619473	3095299	3095444
ENSE00001624596	3102675	3102820
ENSE00001634426	3098137	3098290
ENSE00001657506	3092224	3092362
ENSE00001730405	3101692	3101830
ENSE00001733184	3097870	3098057
ENSE00002726718	3104903	3104987

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 84.04.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9667 / max 184.7353, expressed in 118 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40814	0.5241	58
40818	0.1428	22
40821	0.0982	54
40820	0.0971	37
40819	0.0591	18
40817	0.0278	11
40816	0.0143	8
40815	0.0034	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	84.04	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.03	gold quality
bronchial epithelial cell	CL:0002328	76.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.43	gold quality
epithelium of bronchus	UBERON:0002031	72.14	gold quality
bronchus	UBERON:0002185	71.19	gold quality
sperm	CL:0000019	70.45	gold quality
male germ cell	CL:0000015	68.86	gold quality
nasal cavity mucosa	UBERON:0001826	68.22	gold quality
bone marrow	UBERON:0002371	67.98	gold quality
blood	UBERON:0000178	67.44	gold quality
bone marrow cell	CL:0002092	66.65	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	66.06	gold quality
Brodmann (1909) area 10	UBERON:0013541	65.87	gold quality
bone element	UBERON:0001474	65.69	gold quality
cervix squamous epithelium	UBERON:0006922	65.07	gold quality
gingival epithelium	UBERON:0001949	64.36	gold quality
inferior olivary complex	UBERON:0002127	63.50	gold quality
pancreatic ductal cell	CL:0002079	63.43	silver quality
rectum	UBERON:0001052	62.47	gold quality
gall bladder	UBERON:0002110	62.32	gold quality
gingiva	UBERON:0001828	62.11	gold quality
fallopian tube	UBERON:0003889	61.71	gold quality
mucosa of paranasal sinus	UBERON:0005030	61.70	silver quality
monocyte	CL:0000576	61.63	gold quality
leukocyte	CL:0000738	61.58	gold quality
mononuclear cell	CL:0000842	61.55	gold quality
right lung	UBERON:0002167	60.75	gold quality
spleen	UBERON:0002106	60.63	gold quality
endometrium epithelium	UBERON:0004811	60.27	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	701.75
E-MTAB-9067	yes	375.63
E-ANND-3	yes	9.37
E-HCAD-10	yes	6.67
E-MTAB-9801	yes	5.58

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, CREM, JUN, POU2F2, RFX1, RFX2, RFX3, SPI1, TCF3

miRNA regulators (miRDB)

113 targeting IL5RA, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-219A-5P	99.91	73.36	735

Literature-anchored findings (GeneRIF, showing 39)

• findings indicate that retinoids can differentially regulate expression of IL-5Ralpha and that these effects have functional consequences in vitro on eosinophil and basophil differentiation (PMID:11842302)
• findings are consistent with an airway tissue-selective expression of the IL-5 receptor that mediates IL-5-induced airway hyperresponsiveness independent of eosinophils (PMID:11897983)
• expression of membrane IL-5Ralpha on bronchoalveolar lavage eosinophils following airway Ag challenge (PMID:12444154)
• expression of membrane IL-5 receptor alpha on human eosinophils (PMID:12444155)
• IL-5 receptor expression in cultured human eosinophils is downregulated by its ligand (PMID:12943658)
• Our findings suggest that polymorphisms in IL5RA might be among the genetic risk factors for asthma development, especially in atopic populations. (PMID:16217591)
• These data argue that the charged residues of AF17121 are utilized asymmetrically in the pathway of inhibitor-receptor complex formation to deactivate the receptor function (PMID:16430207)
• Multifactor dimensionality reduction (MDR) test was applied to detect epistasis, and identified single-IL4R(Q576R)- and three-IL4R(Q576R), IL5RA(-80), CD14(-260)- locus association models that predict multiple sclerosis risk with 75-76% accuracy. (PMID:16625214)
• These data establish a critical role for JAK kinases and the Ub/proteasome degradation pathway in IL-5R down-regulation. (PMID:17227823)
• In chronic eosinophilic leukemia, there was a non-significant association between a SNP at rs4054760 and eosinophil count & IL5RA expression. There was no association with FIP1L1-PDGFRA positivity. (PMID:17914408)
• The genetic association between CCR3 polymorphisms and the number of circulating eosinophils was revealed;it was more pronounced when the CCR3 polymorphisms were paired with polymorphisms in IL5RA. (PMID:17983872)
• variants of IL5RA and TNFRSF6B may predispose to sporadic IgA nephropathy (PMID:18256354)
• IL-5-induced effects on betac assembly in the presence of nontagged IL-5Ralpha provide direct evidence that IL-5 can cause higher order rearrangements of betac homo-oligomers (PMID:18326494)
• IL-5Rs segregate and traffic into two distinct plasma membrane compartments, and establish that IL-5R endocytosis regulates signaling both positively and negatively. (PMID:18511572)
• The expression of SOL-IL-5Ralpha and TM-IL-5Ralpha differs according to the eosinophil activation state and localization in the body (blood vs tissue) and may therefore be involved in the fine-tuning of the eosinophil homeostasis. (PMID:19170670)
• Syntenin forms complexes with multiple IL-5Ralpha chains (PMID:19654410)
• Increased serum level precedes the development of eczema in children (PMID:20735756)
• Polymorphisms in IL5RA, LPL, ITGA2 and NOS3 genes were independently associated with ischemic stroke in Chinese diabetic population. (PMID:21193198)
• IL-5Ralpha expression on eosinophils inversely correlated with eosinophilia and was significantly elevated in patients with systemic mastocytosis without eosinophilia (PMID:21762978)
• Study of engineered deglycosylated IL-5 receptor alpha variant proves that unique carbohydrate groups in multiglycosylated receptors can be utilized asymmetrically for function. (PMID:21770429)
• REVIEW: Interleukin-5 and IL-5 receptor in health and disease (PMID:21986312)
• we determined the structure of IL-5 bound to the extracellular domain of IL-5Ralpha. (PMID:22153509)
• The study reports the crystal structure of dimeric IL-5 in complex with the IL5RA extracellular domains. (PMID:22528658)
• The MDR analysis showed a potential interaction of C1GALT1-330G/T (rs1008898) and IL5RA31+197A/G (rs340833) on the susceptibility of IgAN (P<0.001). Gene-gene interaction may have some influence on the susceptibility to IgA nephropathy. (PMID:23190752)
• These findings suggest that a functional polymorphism in IL5RA may contribute to eosinophil and mast cell activation along with specific IgE responses to staphylococcal enterotoxin A in aspirin-exacerbated respiratory disease patients. (PMID:23470716)
• This is the first study to show significant associations between IL5RA SNP rs6771148, the ACTAGA haplotype, and the GTAGCA haplotype and the risk of rhinoconjunctivitis. (PMID:24332579)
• This is the first study to show significant associations between IL5RA SNP rs17881144, the ATTAGA haplotype, the GTAGCA haplotype, and the GCTGCA haplotype and eczema. (PMID:25523412)
• Interleukin-5Ralpha-targeted treatments offer promises to patients with eosinophilic respiratory disorders; review (PMID:26859368)
• Increased activation of B-cells is present following successful Tuberculosis treatment, and the expression of FASLG and IL5RA could potentially be utilized as a signature to monitor treatment response. (PMID:27682872)
• Expression of IL-5 receptor alpha by murine and human lung neutrophils. (PMID:31415658)
• IL-5Ralpha marks nasal polyp IgG4- and IgE-expressing cells in aspirin-exacerbated respiratory disease. (PMID:32199912)
• MiRNA-495-3p Attenuates TNF-alpha Induced Apoptosis and Inflammation in Human Nucleus Pulposus Cells by Targeting IL5RA. (PMID:32445070)
• Ceruloplasmin and oxidative stress in severe eosinophilic asthma patients treated with Mepolizumab and Benralizumab. (PMID:33176218)
• Treatment Challenges in Severe Eosinophilic Asthma: Differential Response to Anti-IL-5 and Anti-IL-5R Therapy. (PMID:33921360)
• Transcriptional Regulation of the Human IL5RA Gene through Alternative Promoter Usage during Eosinophil Development. (PMID:34638583)
• IL5RA as an immunogenic cell death-related predictor in progression and therapeutic response of multiple myeloma. (PMID:37236993)
• The Study of the Influence of IL5RA Variants on Chronic Obstructive Pulmonary Disease. (PMID:37905709)
• Epithelial IL5RA promotes epithelial-mesenchymal transition in pulmonary fibrosis via Jak2/STAT3 cascade. (PMID:38191068)
• Structure of the interleukin-5 receptor complex exemplifies the organizing principle of common beta cytokine signaling. (PMID:38614096)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Il5ra	ENSMUSG00000005364
rattus_norvegicus	Il5ra	ENSRNOG00000005954

Paralogs (23): CRLF1 (ENSG00000006016), IL12RB2 (ENSG00000081985), IL12RB1 (ENSG00000096996), IL27RA (ENSG00000104998), EBI3 (ENSG00000105246), GHR (ENSG00000112964), PRLR (ENSG00000113494), LIFR (ENSG00000113594), LEPR (ENSG00000116678), CSF3R (ENSG00000119535), CNTFR (ENSG00000122756), IL13RA2 (ENSG00000123496), IL13RA1 (ENSG00000131724), IL6ST (ENSG00000134352), IL11RA (ENSG00000137070), OSMR (ENSG00000145623), IL2RG (ENSG00000147168), IL6R (ENSG00000160712), IL23R (ENSG00000162594), IL31RA (ENSG00000164509), IL3RA (ENSG00000185291), CSF2RA (ENSG00000198223), CRLF2 (ENSG00000205755)

Protein

Protein identifiers

Interleukin-5 receptor subunit alpha — Q01344 (reviewed: Q01344)

Alternative names: CDw125

All UniProt accessions (4): Q01344, C9J3K8, C9J6C4, E7ERY4

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface receptor that plays an important role in the survival, differentiation, and chemotaxis of eosinophils. Acts by forming a heterodimeric receptor with CSF2RB subunit and subsequently binding to interleukin-5. In unstimulated conditions, interacts constitutively with JAK2. Heterodimeric receptor activation leads to JAK2 stimulation and subsequent activation of the JAK-STAT pathway.

Subunit / interactions. Interacts with IL5. Interacts with CSF2RB. Interacts with JAK2. Interacts with SDCBP.

Subcellular location. Membrane.

Tissue specificity. Expressed on eosinophils and basophils.

Domain organisation. The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. The box 1 motif is required for JAK interaction and/or activation.

Similarity. Belongs to the type I cytokine receptor family. Type 5 subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
Q01344-1	1, Membrane-bound	yes
Q01344-2	2, Soluble-S1
Q01344-3	3, Soluble-S2
Q01344-4	4
Q01344-5	5

RefSeq proteins (7): NP_000555, NP_001230028, NP_783851, NP_783852, NP_783853, NP_783854, NP_783855 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003532	Short_hematopoietin_rcpt_2_CS	Conserved_site
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015321	TypeI_recpt_CBD	Domain
IPR036116	FN3_sf	Homologous_superfamily

Pfam: PF09240

UniProt features (58 total): strand 28, splice variant 6, glycosylation site 4, disulfide bond 3, helix 3, topological domain 2, sequence variant 2, domain 2, turn 2, short sequence motif 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
1OBX	X-RAY DIFFRACTION	1.35
1OBZ	X-RAY DIFFRACTION	1.7
3QT2	X-RAY DIFFRACTION	2.55
3VA2	X-RAY DIFFRACTION	2.7
6H41	X-RAY DIFFRACTION	2.75
8TLD	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01344-F1	83.93	0.67

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (3): 134–155, 182–196, 269–316

Glycosylation sites (4): 131, 216, 244, 35

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-912526	Interleukin receptor SHC signaling

MSigDB gene sets: 178 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOCC_CELL_SURFACE, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, MODULE_59, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_LEUKOCYTE_PROLIFERATION, GOBP_CYTOKINE_PRODUCTION, PID_IL5_PATHWAY, GOBP_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS

GO Biological Process (9): inflammatory response to antigenic stimulus (GO:0002437), signal transduction (GO:0007165), positive regulation of cell population proliferation (GO:0008284), cytokine-mediated signaling pathway (GO:0019221), regulation of interleukin-5 production (GO:0032674), interleukin-5-mediated signaling pathway (GO:0038043), positive regulation of leukocyte proliferation (GO:0070665), cell surface receptor signaling pathway (GO:0007166), eosinophil differentiation (GO:0030222)

GO Molecular Function (4): cytokine receptor activity (GO:0004896), interleukin-5 receptor activity (GO:0004914), cytokine binding (GO:0019955), protein binding (GO:0005515)

GO Cellular Component (5): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020), signaling receptor complex (GO:0043235)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Signaling by Interleukins	1
MAPK1/MAPK3 signaling	1
Interleukin-2 family signaling	1
Interleukin-3, Interleukin-5 and GM-CSF signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytokine-mediated signaling pathway	2
inflammatory response	1
immune response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
regulation of cytokine production	1
interleukin-5 production	1
positive regulation of cell population proliferation	1
leukocyte proliferation	1
regulation of leukocyte proliferation	1
signal transduction	1
granulocyte differentiation	1
cell development	1
transmembrane signaling receptor activity	1
cytokine binding	1
immune receptor activity	1
cytokine receptor activity	1
interleukin-5 binding	1
interleukin-5-mediated signaling pathway	1
protein binding	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
cellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

1145 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL5RA	IL5	P05113	998
IL5RA	IL3	P08700	966
IL5RA	CSF2	P04141	937
IL5RA	CSF2RB	P32927	932
IL5RA	SDCBP	O00560	816
IL5RA	IL4	P05112	802
IL5RA	IL4R	P24394	763
IL5RA	UNC119	Q13432	731
IL5RA	IL33	O95760	723
IL5RA	IL6R	P08887	715
IL5RA	SOX4	Q06945	707
IL5RA	IL2RB	P14784	703
IL5RA	SIGLEC8	Q9NYZ4	662
IL5RA	CCR3	P51677	645
IL5RA	SDC1	P18827	628

IntAct

14 interactions, top by confidence:

A	B	Type	Score
IL5RA	CSF2RB	psi-mi:“MI:0915”(physical association)	0.590
IL5RA	IL5	psi-mi:“MI:0915”(physical association)	0.520
CSF2RB	IL5	psi-mi:“MI:0915”(physical association)	0.520
IL5	IL5RA	psi-mi:“MI:0915”(physical association)	0.520
IL5RA	JAK2	psi-mi:“MI:0915”(physical association)	0.500
IL5RA	JAK2	psi-mi:“MI:0914”(association)	0.500
SDCBP	IL5RA	psi-mi:“MI:0407”(direct interaction)	0.440
GRB2	IL5RA	psi-mi:“MI:0915”(physical association)	0.400
IL5RA	C4A	psi-mi:“MI:0914”(association)	0.350
IL5RA	POTEF	psi-mi:“MI:0914”(association)	0.350
IL5RA	LETM1	psi-mi:“MI:0914”(association)	0.350

BioGRID (132): IL5RA (Reconstituted Complex), IL5 (Reconstituted Complex), EGFR (Reconstituted Complex), UNC119 (Affinity Capture-Western), UNC119 (Two-hybrid), IL5RA (Reconstituted Complex), JAK2 (Affinity Capture-Western), JAK1 (Affinity Capture-Western), CSF2RB (Affinity Capture-Western), JAK2 (Reconstituted Complex), SDCBP (Two-hybrid), SDCBP (Reconstituted Complex), SDCBP (Affinity Capture-Western), IL5RA (Co-fractionation), IL5RA (Reconstituted Complex)

ESM2 similar proteins: K7NA32, K7NAJ3, O09030, O70458, O70535, O88786, O95256, P17181, P20352, P21183, P26951, P29460, P31785, P33896, P34902, P40321, P42533, P42702, P42703, P43432, P46658, P48095, P78552, P97378, Q01344, Q04790, Q14627, Q28589, Q28938, Q5XNR9, Q61729, Q65Z14, Q6UXL0, Q764M8, Q865Y3, Q8K4B4, Q8K5B1, Q8MJS1, Q8NI17, Q8VHK6

Diamond homologs: P21183, Q01344, P15509

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
IL5RA	up-regulates	ERK1/2
IL5RA	“up-regulates activity”	JAK2	phosphorylation
LYN	“up-regulates activity”	IL5RA	phosphorylation
IL5RA	“up-regulates activity”	SOX4	binding
IL5	up-regulates	IL5RA	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	65
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
57172	GRCh38/hg38 3p26.3-26.1(chr3:1984526-6852981)x1	Pathogenic

SpliceAI

1642 predictions. Top by Δscore:

Variant	Effect	Δscore
3:3074818:A:AC	donor_gain	1.0000
3:3074819:C:CC	donor_gain	1.0000
3:3074864:CAT:C	acceptor_gain	1.0000
3:3076529:A:AC	donor_gain	1.0000
3:3076530:C:CC	donor_gain	1.0000
3:3101826:TCATA:T	acceptor_gain	1.0000
3:3101827:CATA:C	acceptor_gain	1.0000
3:3101827:CATAC:C	acceptor_gain	1.0000
3:3101828:ATA:A	acceptor_gain	1.0000
3:3101829:TA:T	acceptor_gain	1.0000
3:3101831:C:CC	acceptor_gain	1.0000
3:3101832:T:G	acceptor_loss	1.0000
3:3102668:CACT:C	donor_loss	1.0000
3:3102669:ACTT:A	donor_loss	1.0000
3:3102670:CT:C	donor_loss	1.0000
3:3102671:TT:T	donor_loss	1.0000
3:3102672:TACG:T	donor_loss	1.0000
3:3102673:A:AC	donor_gain	1.0000
3:3102673:A:T	donor_loss	1.0000
3:3102674:C:CC	donor_gain	1.0000
3:3102674:C:T	donor_loss	1.0000
3:3102674:CGT:C	donor_gain	1.0000
3:3102816:TGAAA:T	acceptor_gain	1.0000
3:3102817:GAAA:G	acceptor_gain	1.0000
3:3102821:C:CC	acceptor_gain	1.0000
3:3102830:C:CT	acceptor_gain	1.0000
3:3102831:A:T	acceptor_gain	1.0000
3:3104901:A:AC	donor_gain	1.0000
3:3104901:ACT:A	donor_gain	1.0000
3:3104902:C:CC	donor_gain	1.0000

AlphaMissense

2772 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:3095382:A:G	W258R	0.993
3:3095382:A:T	W258R	0.993
3:3095380:C:A	W258C	0.992
3:3095380:C:G	W258C	0.992
3:3102753:C:A	W50C	0.991
3:3102753:C:G	W50C	0.991
3:3102755:A:G	W50R	0.990
3:3102755:A:T	W50R	0.990
3:3098187:C:A	W157C	0.989
3:3098187:C:G	W157C	0.989
3:3092243:C:A	W325C	0.988
3:3092243:C:G	W325C	0.988
3:3098189:A:G	W157R	0.986
3:3098189:A:T	W157R	0.986
3:3092245:A:G	W325R	0.982
3:3092245:A:T	W325R	0.982
3:3098194:C:G	C155S	0.980
3:3098195:A:T	C155S	0.980
3:3092249:A:C	S323R	0.978
3:3092249:A:T	S323R	0.978
3:3092251:T:G	S323R	0.978
3:3097991:G:C	C196W	0.978
3:3098034:C:G	C182S	0.977
3:3098035:A:T	C182S	0.977
3:3098193:G:C	C155W	0.977
3:3098035:A:G	C182R	0.975
3:3102754:C:G	W50S	0.975
3:3092240:G:C	S326R	0.974
3:3092240:G:T	S326R	0.974
3:3092242:T:G	S326R	0.974

dbSNP variants (sampled 300 via entrez): RS1000206168 (3:3111271 C>G), RS1000207507 (3:3086733 G>A), RS1000275057 (3:3074283 A>C), RS1000304252 (3:3111460 G>A,C,T), RS1000338642 (3:3084489 T>C), RS1000369463 (3:3096498 A>G,T), RS1000432087 (3:3084726 T>A), RS1000439753 (3:3106247 G>A,C), RS1000470249 (3:3087375 C>A,G), RS1000525424 (3:3088857 G>A,C), RS1000528331 (3:3069268 G>A), RS1000529876 (3:3101082 G>A), RS1000610149 (3:3079596 G>A,C,T), RS1000699231 (3:3092596 C>G), RS1000808199 (3:3088444 T>G)

Disease associations

OMIM: gene MIM:147851 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST001491_2	Immune response to smallpox vaccine (IL-6)	1.000000e-06
GCST001502_2	Asthma (childhood onset)	2.000000e-08
GCST001834_6	Oleic acid (18:1n-9) levels	1.000000e-06
GCST004600_182	Eosinophil percentage of white cells	2.000000e-13
GCST004600_183	Eosinophil percentage of white cells	3.000000e-14
GCST004606_112	Eosinophil count	2.000000e-16
GCST004617_77	Eosinophil percentage of granulocytes	5.000000e-12
GCST004618_5	White blood cell count (basophil)	4.000000e-20
GCST004618_58	White blood cell count (basophil)	6.000000e-13
GCST004623_171	Neutrophil percentage of granulocytes	2.000000e-10
GCST004624_46	Sum eosinophil basophil counts	3.000000e-13
GCST004631_20	Basophil percentage of white cells	1.000000e-23
GCST004631_62	Basophil percentage of white cells	2.000000e-09
GCST004631_63	Basophil percentage of white cells	3.000000e-10
GCST004634_21	Basophil percentage of granulocytes	5.000000e-20
GCST006585_2388	Blood protein levels	2.000000e-36
GCST006585_2536	Blood protein levels	2.000000e-33
GCST009391_2073	Metabolite levels	1.000000e-07
GCST009391_251	Metabolite levels	9.000000e-07
GCST009391_299	Metabolite levels	9.000000e-06
GCST009391_383	Metabolite levels	2.000000e-06
GCST009391_540	Metabolite levels	6.000000e-06
GCST90002379_34	Basophil count	1.000000e-15
GCST90002380_135	Basophil percentage of white cells	3.000000e-17
GCST90002381_130	Eosinophil count	1.000000e-09
GCST90002381_131	Eosinophil count	4.000000e-15
GCST90002381_132	Eosinophil count	3.000000e-15
GCST90002381_133	Eosinophil count	5.000000e-59
GCST90002382_94	Eosinophil percentage of white cells	5.000000e-15
GCST90002382_95	Eosinophil percentage of white cells	2.000000e-30

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0007994	neutrophil percentage of granulocytes
EFO:0007992	basophil percentage of leukocytes
EFO:0007995	basophil percentage of granulocytes
EFO:0010347	cholesteryl ester 20:3 measurement
EFO:0010426	triacylglycerol 54:8 measurement
EFO:0010425	triacylglycerol 54:7 measurement
EFO:0010437	triacylglycerol 58:10 measurement
EFO:0010528	quinolinic acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3580483 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — IL-3 receptor family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
benralizumab	Binding	8.67	pKd

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases reaction, increases expression, decreases expression	4
sodium arsenite	increases expression	2
Acetylcholine	affects response to substance, increases response to substance	2
Air Pollutants	affects expression, increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
2,3-dimethoxy-6,6-dimethyl-5,6-dihydrobenzo(7,8)indolizino (2,3-b)quinoxaline	affects binding, decreases reaction	1
theaflavin-3,3’-digallate	affects expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Adrenal Cortex Hormones	increases expression, decreases reaction	1
Arsenates	affects cotreatment, increases expression	1
Atrazine	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Dexamethasone	decreases expression, decreases reaction	1
Dithiothreitol	affects binding, decreases reaction	1
Isoproterenol	affects response to substance	1
Ozone	affects expression, increases abundance	1
Smoke	increases abundance, increases expression	1
Tetradecanoylphorbol Acetate	decreases expression	1
Thiazoles	decreases reaction, affects binding	1
Tobacco Smoke Pollution	decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E6QV	Genomeditech CHO-K1 H_IL5RA	Spontaneously immortalized cell line	Female
CVCL_E6UA	Genomeditech HEK-293 H_IL5RA	Transformed cell line	Female

Clinical trials (associated diseases)

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