IL6R

interleukin 6 receptor, the group of CD molecules|Interleukin receptors|Immunoglobulin like domain containing

Basic information

Region (hg38): 1:154405193-154469450

Links

ENSG00000160712 ∙ NCBI:3570 ∙ OMIM:147880 ∙ HGNC:6019 ∙ Uniprot:P08887 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyper-IgE recurrent infection syndrome 5, autosomal recessive (Strong), mode of inheritance: AR
• hyper-IgE recurrent infection syndrome 5, autosomal recessive (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyper-IgE recurrent infection syndrome 5, autosomal recessive	AR	Allergy/Immunology/Infectious	The condition can involve early-onset recurrent and sever inffections, and awareness may allow prophylaxis and early and aggressive treatment of infections	Allergy/Immunology/Infectious	31235509

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IL6R gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL6R 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	70	6	78
missense			98	6	2	106
nonsense			1			1
start loss						0
frameshift			3			3
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			7	11	2	20
non coding			1	27	11	39
Total	0	0	106	103	19

Variants in IL6R

This is a list of pathogenic ClinVar variants found in the IL6R region.

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

Position	Type	Phenotype	Significance	ClinVar
1-154405634-TGGCCGTC-T			Uncertain significance (Aug 11, 2021)
1-154405636-G-T		IL6R-related disorder	Uncertain significance (Jun 09, 2022)
1-154405639-G-T			Uncertain significance (Aug 19, 2022)
1-154405676-C-T			Uncertain significance (Jul 12, 2022)
1-154405679-G-C			Uncertain significance (Jan 08, 2024)
1-154405680-A-G		IL6R-related disorder	Benign/Likely benign (Jan 29, 2024)
1-154405684-G-A			Uncertain significance (Jun 17, 2022)
1-154405706-C-T			Uncertain significance (Aug 13, 2021)
1-154405725-C-A			Likely benign (Aug 09, 2023)
1-154405726-G-T			Likely benign (Sep 26, 2022)
1-154405728-G-A			Likely benign (Jan 22, 2023)
1-154405733-C-T			Likely benign (Jun 06, 2023)
1-154429203-G-A		IL6R-related disorder	Benign (Jan 31, 2024)
1-154429209-C-T		IL6R-related disorder	Likely benign (Jul 22, 2023)
1-154429210-G-A			Uncertain significance (Sep 26, 2022)
1-154429212-G-A			Likely benign (Nov 06, 2023)
1-154429215-G-C			Likely benign (Dec 09, 2023)
1-154429216-A-G			Uncertain significance (Aug 10, 2023)
1-154429233-C-G			Uncertain significance (Jun 03, 2022)
1-154429236-C-T		IL6R-related disorder	Benign (Jan 26, 2024)
1-154429237-G-A		Hyper-IgE recurrent infection syndrome 5, autosomal recessive	Uncertain significance (Nov 15, 2022)
1-154429253-C-A			Uncertain significance (May 30, 2022)
1-154429253-C-T			Uncertain significance (Dec 07, 2023)
1-154429254-G-A			Likely benign (Jan 12, 2023)
1-154429254-G-C			Likely benign (Jul 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IL6R	protein_coding	protein_coding	ENST00000368485	10	64258

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000317	0.988	125708	0	39	125747	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.689	254	287	0.885	0.0000173	3017
Missense in Polyphen		51	72.546	0.703		813
Synonymous	-0.196	128	125	1.02	0.00000849	971
Loss of Function	2.23	11	22.4	0.491	0.00000102	245

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000412	0.000412
Ashkenazi Jewish	0.000397	0.000397
East Asian	0.000163	0.000163
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.000133	0.000132
Middle Eastern	0.000163	0.000163
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal. Signal activation necessitate an association with IL6ST. Activation may lead to the regulation of the immune response, acute-phase reactions and hematopoiesis.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Th17 cell differentiation - 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;Differentiation Pathway;IL-6 signaling pathway;Hepatitis C and Hepatocellular Carcinoma;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Interleukin-4 and 13 signaling;PI3K-Akt Signaling Pathway;Senescence and Autophagy in Cancer;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Signal Transduction;Signaling by Interleukins;il 6 signaling pathway;role of erbb2 in signal transduction and oncology;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Immune System;MAPK1 (ERK2) activation;IL-6 signaling;RAF-independent MAPK1/3 activation;SHP2 signaling;JAK STAT MolecularVariation 2;MAPK1/MAPK3 signaling;MAPK family signaling cascades;JAK STAT pathway and regulation;IL6;MAPK3 (ERK1) activation;Interleukin-6 signaling;Interleukin-6 family signaling;IL6-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.707

Intolerance Scores

• loftool: 0.530
• rvis_EVS: -0.16
• rvis_percentile_EVS: 42.16

Haploinsufficiency Scores

• pHI: 0.120
• hipred: Y
• hipred_score: 0.542
• ghis: 0.464

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.985

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Il6ra
• Phenotype: endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm; 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); normal phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: hepatic immune response;monocyte chemotaxis;positive regulation of leukocyte chemotaxis;positive regulation of T-helper 1 type immune response;acute-phase response;positive regulation of cell population proliferation;regulation of signaling receptor activity;positive regulation of activation of Janus kinase activity;cytokine-mediated signaling pathway;endocrine pancreas development;positive regulation of chemokine production;positive regulation of interferon-gamma production;positive regulation of interleukin-6 production;positive regulation of natural killer cell activation;response to cytokine;positive regulation of activated T cell proliferation;positive regulation of tyrosine phosphorylation of STAT protein;positive regulation of osteoblast differentiation;positive regulation of smooth muscle cell proliferation;positive regulation of lymphocyte proliferation;positive regulation of peptidyl-tyrosine phosphorylation;defense response to Gram-negative bacterium;positive regulation of NK T cell activation;interleukin-6-mediated signaling pathway;ciliary neurotrophic factor-mediated signaling pathway;extrinsic apoptotic signaling pathway
• Cellular component: extracellular region;plasma membrane;interleukin-6 receptor complex;external side of plasma membrane;basolateral plasma membrane;apical plasma membrane;receptor complex;interleukin-12 complex;ciliary neurotrophic factor receptor complex;interleukin-23 complex
• Molecular function: cytokine receptor activity;ciliary neurotrophic factor receptor activity;interleukin-6 receptor activity;interleukin-6 receptor binding;interleukin-12 receptor binding;protein binding;growth factor activity;enzyme binding;cytokine binding;interleukin-6 binding;interleukin-12 alpha subunit binding;protein homodimerization activity;interleukin-23 receptor binding;ciliary neurotrophic factor binding