IL2RA

interleukin 2 receptor subunit alpha, the group of CD molecules|Sushi domain containing|Interleukin receptors

Basic information

Region (hg38): 10:6010688-6062370

Previous symbols: [ "IL2R", "IDDM10" ]

Links

ENSG00000134460 ∙ NCBI:3559 ∙ OMIM:147730 ∙ HGNC:6008 ∙ Uniprot:P01589 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neonatal diabetes mellitus (Strong), mode of inheritance: AR
• type 1 diabetes mellitus 10 (Strong), mode of inheritance: AR
• neonatal diabetes mellitus with congenital hypothyroidism (Strong), mode of inheritance: AR
• immunodeficiency due to CD25 deficiency (Supportive), mode of inheritance: AR
• immunodeficiency due to CD25 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 41 with lymphoproliferation and autoimmunity	AR	Allergy/Immunology/Infectious	Described individuals have an increased susceptibility to bacterial, fungal, and viral infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been described	Allergy/Immunology/Infectious; Gastrointestinal	9096364; 10879793

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IL2RA gene.

• Immunodeficiency due to CD25 deficiency (264 variants)
• not provided (15 variants)
• not specified (14 variants)
• Inborn genetic diseases (7 variants)
• Type 1 diabetes mellitus 10;Immunodeficiency due to CD25 deficiency (3 variants)
• Immunodeficiency due to CD25 deficiency;Type 1 diabetes mellitus 10 (1 variants)
• Pleural effusion;Myelodysplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL2RA 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	31	4	37
missense			92	1	1	94
nonsense	3					3
start loss			1			1
frameshift						0
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	2	2			5
splice region			7	9	1	17
non coding			42	35	25	102
Total	4	2	141	67	30

Highest pathogenic variant AF is 0.00000657

Variants in IL2RA

This is a list of pathogenic ClinVar variants found in the IL2RA region.

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

Position	Type	Phenotype	Significance	ClinVar
10-6010694-A-T		Immunodeficiency due to CD25 deficiency	Uncertain significance (Jun 14, 2016)
10-6010728-A-C		Immunodeficiency due to CD25 deficiency	Uncertain significance (Jan 13, 2018)
10-6010741-T-C		Immunodeficiency due to CD25 deficiency	Uncertain significance (Jan 13, 2018)
10-6010764-A-C		Immunodeficiency due to CD25 deficiency	Benign (Jan 13, 2018)
10-6010817-A-G		Immunodeficiency due to CD25 deficiency	Uncertain significance (Jan 13, 2018)
10-6010878-C-A		Immunodeficiency due to CD25 deficiency	Benign (Jan 13, 2018)
10-6010898-G-A		Immunodeficiency due to CD25 deficiency	Uncertain significance (Jan 13, 2018)
10-6010992-G-C		Immunodeficiency due to CD25 deficiency	Benign (Jan 13, 2018)
10-6011100-T-G		Immunodeficiency due to CD25 deficiency	Likely benign (Jan 13, 2018)
10-6011106-A-G		Immunodeficiency due to CD25 deficiency	Uncertain significance (Jan 13, 2018)
10-6011170-G-A		Immunodeficiency due to CD25 deficiency	Benign (Jan 13, 2018)
10-6011200-T-A		Immunodeficiency due to CD25 deficiency	Benign (Jan 13, 2018)
10-6011222-C-T		Immunodeficiency due to CD25 deficiency	Uncertain significance (Jan 12, 2018)
10-6011229-G-T		Immunodeficiency due to CD25 deficiency	Uncertain significance (Jan 13, 2018)
10-6011253-C-T		Immunodeficiency due to CD25 deficiency	Uncertain significance (Jan 13, 2018)
10-6011297-C-T		Immunodeficiency due to CD25 deficiency	Uncertain significance (Jan 12, 2018)
10-6011298-G-A		Immunodeficiency due to CD25 deficiency	Uncertain significance (Jan 13, 2018)
10-6011323-G-A		Immunodeficiency due to CD25 deficiency	Benign (Jan 12, 2018)
10-6011333-A-G		Immunodeficiency due to CD25 deficiency	Uncertain significance (Jan 13, 2018)
10-6011372-A-G		Immunodeficiency due to CD25 deficiency	Uncertain significance (Jan 13, 2018)
10-6011411-A-G		Immunodeficiency due to CD25 deficiency	Benign (Jan 13, 2018)
10-6011418-T-C		Immunodeficiency due to CD25 deficiency	Uncertain significance (Jan 13, 2018)
10-6011429-C-G		Immunodeficiency due to CD25 deficiency	Uncertain significance (Jan 12, 2018)
10-6011446-C-T		Immunodeficiency due to CD25 deficiency	Uncertain significance (Feb 16, 2018)
10-6011605-C-T		Immunodeficiency due to CD25 deficiency	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IL2RA	protein_coding	protein_coding	ENST00000379959	8	51637

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0547	0.942	125738	0	8	125746	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.362	145	158	0.919	0.00000896	1801
Missense in Polyphen		34	43.118	0.78854		512
Synonymous	-0.844	64	56.0	1.14	0.00000377	482
Loss of Function	2.55	5	16.0	0.313	6.92e-7	187

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.000163	0.000163
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for interleukin-2. The receptor is involved in the regulation of immune tolerance by controlling regulatory T cells (TREGs) activity. TREGs suppress the activation and expansion of autoreactive T-cells. {ECO:0000269|PubMed:23416241, ECO:0000269|PubMed:24116927}.
• Disease: DISEASE: Diabetes mellitus, insulin-dependent, 10 (IDDM10) [MIM:601942]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:17676041}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Immunodeficiency 41 with lymphoproliferation and autoimmunity (IMD41) [MIM:606367]: A disorder of immune dysregulation characterized by recurrent viral, fungal, and bacterial infections, lymphadenopathy, and variable autoimmune features, such as autoimmune enteropathy and eczematous skin lesions. {ECO:0000269|PubMed:23416241, ECO:0000269|PubMed:24116927}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Endocytosis - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Measles - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);IL-7 Signaling Pathway;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;Allograft Rejection;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs);PI3K-Akt Signaling Pathway;Inflammatory Response Pathway;IL-2 Signaling Pathway;Signaling by GPCR;Signal Transduction;Gene expression (Transcription);Signaling by Interleukins;il 2 signaling pathway;il-2 receptor beta chain in t cell activation;Generic Transcription Pathway;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;IL12 signaling mediated by STAT4;RNA Polymerase II Transcription;Immune System;Interleukin receptor SHC signaling;Interleukin-2 family signaling;IL-2 signaling;SHP2 signaling;JAK STAT MolecularVariation 2;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;JAK STAT pathway and regulation;IL2;IL2-mediated signaling events;Interleukin-2 signaling;RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs);G beta:gamma signalling through PI3Kgamma;G-protein beta:gamma signalling;GPCR downstream signalling;Transcriptional regulation by RUNX1;IL2 signaling events mediated by STAT5;Downstream signaling in naïve CD8+ T cells;Calcineurin-regulated NFAT-dependent transcription in lymphocytes;IL2 signaling events mediated by PI3K;IL12-mediated signaling events;Calcium signaling in the CD4+ TCR pathway;Interleukin-3, 5 and GM-CSF signaling (Consensus)

Recessive Scores

• pRec: 0.695

Intolerance Scores

• loftool: 0.493
• rvis_EVS: -0.6
• rvis_percentile_EVS: 17.75

Haploinsufficiency Scores

• pHI: 0.0634
• hipred: N
• hipred_score: 0.443
• ghis: 0.571

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.566

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Il2ra
• Phenotype: immune system phenotype; vision/eye phenotype; digestive/alimentary 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; respiratory system phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: MAPK cascade;inflammatory response to antigenic stimulus;regulation of T cell tolerance induction;apoptotic process;activation-induced cell death of T cells;immune response;cell surface receptor signaling pathway;Notch signaling pathway;cell population proliferation;cytokine-mediated signaling pathway;interleukin-2-mediated signaling pathway;positive regulation of activated T cell proliferation;negative regulation of T cell proliferation;positive regulation of T cell differentiation;regulation of regulatory T cell differentiation;regulation of T cell homeostatic proliferation;negative regulation of defense response to virus;negative regulation of inflammatory response;negative regulation of immune response
• Cellular component: plasma membrane;external side of plasma membrane;integral component of membrane
• Molecular function: interleukin-2 receptor activity;Ras guanyl-nucleotide exchange factor activity;protein binding;interleukin-2 binding