IL2RG

interleukin 2 receptor subunit gamma, the group of CD molecules|Interleukin receptors|Fibronectin type III domain containing

Basic information

Region (hg38): X:71107404-71112108

Previous symbols: [ "SCIDX1", "IMD4", "CIDX" ]

Links

ENSG00000147168 ∙ NCBI:3561 ∙ OMIM:308380 ∙ HGNC:6010 ∙ Uniprot:P31785 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• T-B+ severe combined immunodeficiency due to gamma chain deficiency (Supportive), mode of inheritance: XL
• Omenn syndrome (Supportive), mode of inheritance: AR
• T-B+ severe combined immunodeficiency due to gamma chain deficiency (Strong), mode of inheritance: XL
• T-B+ severe combined immunodeficiency due to gamma chain deficiency (Definitive), mode of inheritance: XL
• T-B+ severe combined immunodeficiency due to gamma chain deficiency (Definitive), mode of inheritance: XL
• T-B+ severe combined immunodeficiency due to gamma chain deficiency (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined immunodeficiency, X-linked	XL	Allergy/Immunology/Infectious	Antiinfectious prophylaxis and early and aggressive treatment of infections is indicated prior to attempts at immune reconstitution; Chronic immunoglobulin therapy may be required even after treatment aimed at immune reconstitution, which is necessary for survival; BMT/HSCT has been described, as has the use of gene therapy in individuals who are not candidates for or who have failed BMT	Allergy/Immunology/Infectious	2243135; 7883965; 8462096; 9063412; 11517204; 11806989; 20301584; 21184155; 22460439

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IL2RG gene.

• X-linked severe combined immunodeficiency (67 variants)
• not provided (27 variants)
• Combined immunodeficiency, X-linked (6 variants)
• Combined immunodeficiency, X-linked;X-linked severe combined immunodeficiency (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL2RG 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	78	14	93
missense	8	29	77	19	11	144
nonsense	24	8	1			33
start loss	1					1
frameshift	32	9	2			43
inframe indel		2	2			4
splice donor/acceptor (+/-2bp)	13	5				18
splice region		3	3	27		33
non coding	1		5	41	13	60
Total	79	53	88	138	38

Variants in IL2RG

This is a list of pathogenic ClinVar variants found in the IL2RG 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-71107427-CTT-C		X-linked severe combined immunodeficiency	Uncertain significance (Mar 26, 2021)
X-71107430-T-G			Uncertain significance (Sep 10, 2018)
X-71107446-A-G		X-linked severe combined immunodeficiency	Benign (Jan 13, 2018)
X-71107603-C-T		X-linked severe combined immunodeficiency	Uncertain significance (Jan 13, 2018)
X-71107739-G-A		X-linked severe combined immunodeficiency	Likely benign (Nov 13, 2023)
X-71107741-T-C		X-linked severe combined immunodeficiency • IL2RG-related disorder	Uncertain significance (Nov 14, 2023)
X-71107747-GC-AA		X-linked severe combined immunodeficiency	Uncertain significance (Oct 14, 2021)
X-71107748-C-T		X-linked severe combined immunodeficiency	Likely benign (Sep 17, 2023)
X-71107752-A-G		X-linked severe combined immunodeficiency	Uncertain significance (Sep 01, 2021)
X-71107754-G-T		X-linked severe combined immunodeficiency	Likely benign (Mar 26, 2023)
X-71107755-G-T		X-linked severe combined immunodeficiency	Conflicting classifications of pathogenicity (Jul 20, 2023)
X-71107757-G-A		X-linked severe combined immunodeficiency	Likely benign (Oct 17, 2023)
X-71107763-TG-T		X-linked severe combined immunodeficiency	Uncertain significance (Sep 21, 2022)
X-71107765-G-T		X-linked severe combined immunodeficiency	Uncertain significance (Feb 24, 2022)
X-71107766-G-A		X-linked severe combined immunodeficiency	Likely benign (Sep 24, 2023)
X-71107766-G-T		X-linked severe combined immunodeficiency	Likely benign (Oct 14, 2023)
X-71107769-G-A		X-linked severe combined immunodeficiency	Likely benign (Jul 29, 2023)
X-71107769-G-C		X-linked severe combined immunodeficiency	Likely benign (Dec 18, 2022)
X-71107769-G-T		X-linked severe combined immunodeficiency	Likely benign (Apr 08, 2023)
X-71107770-G-A		X-linked severe combined immunodeficiency • Inborn genetic diseases	Uncertain significance (Jan 10, 2024)
X-71107780-G-A		X-linked severe combined immunodeficiency	Likely benign (Jul 16, 2023)
X-71107785-T-C		Combined immunodeficiency, X-linked • X-linked severe combined immunodeficiency	Likely benign (Jan 26, 2024)
X-71107787-C-T		X-linked severe combined immunodeficiency	Likely benign (Jun 14, 2023)
X-71107796-TG-T		X-linked severe combined immunodeficiency	Uncertain significance (May 07, 2023)
X-71107798-G-A		X-linked severe combined immunodeficiency	Likely benign (Jan 31, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IL2RG	protein_coding	protein_coding	ENST00000374202	8	4705

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.992	0.00848	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.49	86	135	0.639	0.0000102	2416
Missense in Polyphen		14	39.318	0.35607		731
Synonymous	0.0665	53	53.6	0.988	0.00000393	700
Loss of Function	3.50	0	14.3	0.00	0.00000106	221

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Common subunit for the receptors for a variety of interleukins.
• Disease: DISEASE: Severe combined immunodeficiency X-linked T-cell- negative/B-cell-positive/NK-cell-negative (XSCID) [MIM:300400]: A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. {ECO:0000269|PubMed:7557965, ECO:0000269|PubMed:7668284, ECO:0000269|PubMed:7860773, ECO:0000269|PubMed:7937790, ECO:0000269|PubMed:8027558, ECO:0000269|PubMed:8088810, ECO:0000269|PubMed:8299698, ECO:0000269|PubMed:8401490, ECO:0000269|PubMed:8900089, ECO:0000269|PubMed:9049783, ECO:0000269|PubMed:9150740}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: X-linked combined immunodeficiency (XCID) [MIM:312863]: Less severe form of X-linked immunodeficiency with a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID. {ECO:0000269|PubMed:7883965, ECO:0000269|PubMed:9399950}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Primary immunodeficiency - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Endocytosis - Homo sapiens (human);Inflammatory bowel disease (IBD) - 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);Cytokine-cytokine receptor interaction - Homo sapiens (human);JAK-STAT-Core;IL-7 Signaling Pathway;IL-9 Signaling Pathway;IL-4 Signaling Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Inflammatory Response Pathway;IL-2 Signaling Pathway;Signaling by GPCR;Interleukin-4 and 13 signaling;Interleukin-7 signaling;Signal Transduction;Signaling by Interleukins;il 2 signaling pathway;il-7 signal transduction;il-2 receptor beta chain in t cell activation;il 4 signaling pathway;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Interleukin-9 signaling;Immune System;Interleukin-15 signaling;Interleukin receptor SHC signaling;Interleukin-2 family signaling;IL-2 signaling;IL-7 signaling;IL-4 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;IL4;IL-7;G beta:gamma signalling through PI3Kgamma;G-protein beta:gamma signalling;GPCR downstream signalling;IL9;IL2 signaling events mediated by STAT5;Downstream signaling in naïve CD8+ T cells;IL2 signaling events mediated by PI3K;IL4-mediated signaling events;IL12-mediated signaling events;Interleukin-3, 5 and GM-CSF signaling (Consensus)

Recessive Scores

• pRec: 0.554

Intolerance Scores

• loftool: 0.119
• rvis_EVS: -0.23
• rvis_percentile_EVS: 36.86

Haploinsufficiency Scores

• pHI: 0.141
• hipred: N
• hipred_score: 0.370
• ghis: 0.568

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.927

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Il2rg
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; embryo phenotype; no phenotypic analysis (no description of morphological, physiological or behavioral information presented); immune system phenotype; digestive/alimentary phenotype; neoplasm; reproductive system phenotype; normal 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

Zebrafish Information Network

• Gene name: il2rga
• Affected structure: mature B cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: MAPK cascade;immune response;signal transduction;viral process;cytokine-mediated signaling pathway;interleukin-15-mediated signaling pathway;interleukin-4-mediated signaling pathway;interleukin-2-mediated signaling pathway;interleukin-7-mediated signaling pathway;interleukin-9-mediated signaling pathway;interleukin-21-mediated signaling pathway
• Cellular component: endosome;cytosol;plasma membrane;integral component of plasma membrane;external side of plasma membrane;membrane;receptor complex
• Molecular function: cytokine receptor activity;interleukin-2 receptor activity;interleukin-4 receptor activity;interleukin-7 receptor activity;Ras guanyl-nucleotide exchange factor activity;protein binding;cytokine binding;interleukin-2 binding