IL7R

interleukin 7 receptor, the group of CD molecules|Interleukin receptors|Fibronectin type III domain containing

Basic information

Region (hg38): 5:35852695-35879603

Links

ENSG00000168685 ∙ NCBI:3575 ∙ OMIM:146661 ∙ HGNC:6024 ∙ Uniprot:P16871 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 104 (Definitive), mode of inheritance: AR
• immunodeficiency 104 (Strong), mode of inheritance: AR
• Omenn syndrome (Supportive), mode of inheritance: AR
• T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency (Supportive), mode of inheritance: AR
• immunodeficiency 104 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Severe combined immunodeficiency, autosomal recessive, T-cell negative, B-cell positive, NK cell positive	AR	Allergy/Immunology/Infectious	Individuals are susceptible to frequent and severe bacterial, viral, fungal, and opportunistic infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; HSCT has been described	Allergy/Immunology/Infectious	9843216; 11023514; 17827065; 21184155; 21625022; 21883749

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IL7R gene.

• Immunodeficiency 104 (31 variants)
• not provided (8 variants)
• Severe combined immunodeficiency disease (4 variants)
• not specified (1 variants)
• Multiple sclerosis, susceptibility to, 3 (1 variants)
• T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL7R 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	120	4	125
missense	4	4	137	10	9	164
nonsense	6	7				13
start loss		1				1
frameshift	16	2	2			20
inframe indel			2			2
splice donor/acceptor (+/-2bp)	8		2			10
splice region			8	14	1	23
non coding			42	68	50	160
Total	34	14	186	198	63

Highest pathogenic variant AF is 0.0000527

Variants in IL7R

This is a list of pathogenic ClinVar variants found in the IL7R region.

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

Position	Type	Phenotype	Significance	ClinVar
5-35856979-T-G		Immunodeficiency 104 • Severe combined immunodeficiency disease	Likely pathogenic (Aug 10, 2024)
5-35856987-C-T		Immunodeficiency 104	Likely benign (Sep 12, 2023)
5-35856988-T-C		Immunodeficiency 104	Uncertain significance (Dec 24, 2021)
5-35856993-A-G		Immunodeficiency 104	Uncertain significance (Oct 02, 2020)
5-35856997-C-T		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)
5-35857003-G-C		Immunodeficiency 104	Uncertain significance (Jul 03, 2022)
5-35857008-GT-G		Immunodeficiency 104	Pathogenic (Feb 22, 2021)
5-35857009-T-C		Immunodeficiency 104	Uncertain significance (Jul 30, 2022)
5-35857009-T-G		Immunodeficiency 104	Uncertain significance (Mar 12, 2022)
5-35857018-T-C		Immunodeficiency 104	Uncertain significance (Apr 01, 2024)
5-35857028-C-A		Immunodeficiency 104	Likely benign (Oct 28, 2023)
5-35857028-C-T		Immunodeficiency 104	Likely benign (Dec 20, 2023)
5-35857030-T-C		Immunodeficiency 104	Uncertain significance (Nov 23, 2021)
5-35857036-G-A		Immunodeficiency 104 • Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
5-35857043-T-C		Immunodeficiency 104	Likely benign (Apr 02, 2023)
5-35857053-C-T		Immunodeficiency 104	Pathogenic (Sep 29, 2023)
5-35857053-CA-C		Immunodeficiency 104	Pathogenic (Oct 05, 2023)
5-35857058-T-A		Immunodeficiency 104	Uncertain significance (Aug 28, 2021)
5-35857061-TG-T		Immunodeficiency 104	Uncertain significance (Aug 15, 2022)
5-35857067-A-G		Immunodeficiency 104	Likely benign (Mar 26, 2023)
5-35857069-T-G		Immunodeficiency 104	Likely benign (Sep 21, 2023)
5-35857070-T-C		Immunodeficiency 104	Likely benign (Aug 29, 2023)
5-35857073-A-C		Immunodeficiency 104	Likely benign (Jan 07, 2023)
5-35857073-A-T		Immunodeficiency 104	Uncertain significance (Nov 14, 2023)
5-35857075-G-C		not specified • Immunodeficiency 104	Benign (Feb 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IL7R	protein_coding	protein_coding	ENST00000303115	8	26909

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.76e-7	0.815	125678	0	58	125736	0.000231

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.29	288	233	1.24	0.0000115	3020
Missense in Polyphen		68	62.246	1.0924		877
Synonymous	-0.552	98	91.3	1.07	0.00000477	865
Loss of Function	1.43	13	19.9	0.654	9.26e-7	263

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000481	0.000481
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000326	0.000325
Middle Eastern	0.000272	0.000272
South Asian	0.000131	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for interleukin-7. Also acts as a receptor for thymic stromal lymphopoietin (TSLP).
• Disease: DISEASE: Severe combined immunodeficiency autosomal recessive T- cell-negative/B-cell-positive/NK-cell-positive (T(-)B(+)NK(+) SCID) [MIM:608971]: 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:11023514, ECO:0000269|PubMed:9843216}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Multiple sclerosis 3 (MS3) [MIM:612595]: A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheath, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. {ECO:0000269|PubMed:17660817}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. A polymorphism at position 244 strongly influences susceptibility to multiple sclerosis. Overtransmission of the major 'C' allele coding for Thr-244 is detected in offspring affected with multiple sclerosis. In vitro analysis of transcripts from minigenes containing either 'C' allele (Thr-244) or 'T' allele (Ile-244) shows that the 'C' allele results in an approximately two-fold increase in the skipping of exon 6, leading to increased production of a soluble form of IL7R. Thus, the multiple sclerosis associated 'C' risk allele of IL7R would probably decrease membrane-bound expression of IL7R. As this risk allele is common in the general population, some additional triggers are probably required for the development and progression of MS.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Primary immunodeficiency - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);FoxO signaling pathway - 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-7 Signaling Pathway;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;Apoptosis-related network due to altered Notch3 in ovarian cancer;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Interleukin-7 signaling;Signaling by Interleukins;Vesicle-mediated transport;Membrane Trafficking;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Immune System;KitReceptor;IL-7 signaling;Clathrin-mediated endocytosis;JAK STAT MolecularVariation 2;JAK STAT pathway and regulation;Cargo recognition for clathrin-mediated endocytosis;IL-7 (Consensus)

Recessive Scores

• pRec: 0.580

Intolerance Scores

• loftool: 0.563
• rvis_EVS: 0.93
• rvis_percentile_EVS: 89.83

Haploinsufficiency Scores

• pHI: 0.554
• hipred: N
• hipred_score: 0.264
• ghis: 0.401

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.646

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Il7r
• Phenotype: neoplasm; normal phenotype; hematopoietic system phenotype; cellular phenotype; immune system phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: il7r
• Affected structure: pro-T cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: regulation of DNA recombination;cell morphogenesis;negative regulation of T cell mediated cytotoxicity;immunoglobulin production;immune response;signal transduction;cell surface receptor signaling pathway;positive regulation of cell population proliferation;regulation of cell size;positive regulation of gene expression;T cell differentiation;positive regulation of T cell differentiation in thymus;interleukin-7-mediated signaling pathway;B cell proliferation;lymph node development;homeostasis of number of cells;membrane organization;negative regulation of T cell apoptotic process;positive regulation of STAT cascade
• Cellular component: extracellular region;plasma membrane;external side of plasma membrane;integral component of membrane;clathrin-coated vesicle membrane
• Molecular function: antigen binding;cytokine receptor activity;interleukin-7 receptor activity;protein binding