IL12RB1

interleukin 12 receptor subunit beta 1, the group of Fibronectin type III domain containing|CD molecules|Interleukin receptors

Basic information

Region (hg38): 19:18058995-18098944

Previous symbols: [ "IL12RB" ]

Links

ENSG00000096996

∙ NCBI:3594 ∙ OMIM:601604 ∙ HGNC:5971 ∙ Uniprot:P42701 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency (Supportive), mode of inheritance: AR
Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 30	AR	Allergy/Immunology/Infectious	Individuals have been described as susceptible to severe atypical mycobacterial infections (as well as other infections, including Salmonella, Cryptococcal, Coccidioides infections), and prophylaxis and early and aggressive treatment of infections may be beneficial; Consideration of potential adverse effects of BCG vaccination in some individuals may be beneficial	Allergy/Immunology/Infectious	9603732; 9603733; 12591909; 15736007; 21905505; 21258095; 22523911; 23864330

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IL12RB1 gene.

Mendelian_susceptibility_to_mycobacterial_diseases_due_to_complete_IL12RB1_deficiency (519 variants)
Inborn_genetic_diseases (88 variants)
not_provided (38 variants)
IL12RB1-related_disorder (24 variants)
not_specified (5 variants)
Inherited_Immunodeficiency_Diseases (2 variants)
Immunodeficiency_27A (2 variants)
Mycobacterium_tuberculosis,_susceptibility_to (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL12RB1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005535.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			8 clinvar	132 clinvar	6 clinvar	146
missense	4 clinvar	5 clinvar	222 clinvar	28 clinvar	4 clinvar	263
nonsense	24 clinvar	2 clinvar				26
start loss			1			1
frameshift	13 clinvar	2 clinvar	2 clinvar			17
splice donor/acceptor (+/-2bp)	7 clinvar	6 clinvar	2 clinvar			15
Total	48	15	235	160	10

Highest pathogenic variant AF is 0.000226371

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IL12RB1	protein_coding	protein_coding	ENST00000600835	17	39950

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.36e-15	0.861	125614	0	134	125748	0.000533

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.237	377	390	0.966	0.0000240	4231
Missense in Polyphen		80	89.989	0.889		1028
Synonymous	-0.535	182	173	1.05	0.0000117	1336
Loss of Function	2.03	29	43.5	0.667	0.00000240	425

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000791	0.000764
Ashkenazi Jewish	0.000496	0.000496
East Asian	0.000331	0.000326
Finnish	0.000190	0.000185
European (Non-Finnish)	0.000764	0.000747
Middle Eastern	0.000331	0.000326
South Asian	0.000466	0.000457
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Functions as an interleukin receptor which binds interleukin-12 with low affinity and is involved in IL12 transduction. Associated with IL12RB2 it forms a functional, high affinity receptor for IL12. Associates also with IL23R to form the interleukin-23 receptor which functions in IL23 signal transduction probably through activation of the Jak-Stat signaling cascade. {ECO:0000269|PubMed:12023369}.;
Disease: DISEASE: Immunodeficiency 30 (IMD30) [MIM:614891]: A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. IMD30 has low penetrance, and affected individuals have relatively mild disease and good prognosis. BCG disease and salmonellosis are the most frequent infections in IMD30 patients. {ECO:0000269|PubMed:11424023}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Jak-STAT signaling pathway - Homo sapiens (human);Inflammatory bowel disease (IBD) - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);JAK-STAT-Core;no2-dependent il-12 pathway in nk cells;Interleukin-12 family signaling;Signaling by Interleukins;il12 and stat4 dependent signaling pathway in th1 development;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;IL-12 signaling;Immune System;IL-23 signaling;Interleukin-23 signaling;JAK STAT MolecularVariation 2;JAK STAT pathway and regulation;Interleukin-12 signaling;IL23-mediated signaling events;IL27-mediated signaling events;IL12-mediated signaling events (Consensus)

Recessive Scores

pRec: 0.329

Intolerance Scores

loftool: 0.415
rvis_EVS: 0.41
rvis_percentile_EVS: 76.54

Haploinsufficiency Scores

pHI: 0.0953
hipred: N
hipred_score: 0.366
ghis: 0.531

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.827

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Il12rb1
Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype;

Gene ontology

Biological process: positive regulation of T cell mediated cytotoxicity;positive regulation of defense response to virus by host;positive regulation of T-helper 1 type immune response;signal transduction;cytokine-mediated signaling pathway;positive regulation of interferon-gamma production;interleukin-12-mediated signaling pathway;interleukin-23-mediated signaling pathway;positive regulation of activated T cell proliferation;positive regulation of memory T cell differentiation;cellular response to interferon-gamma;positive regulation of T-helper 17 type immune response;positive regulation of T-helper 17 cell lineage commitment
Cellular component: plasma membrane;external side of plasma membrane;interleukin-12 receptor complex;receptor complex;interleukin-23 receptor complex
Molecular function: cytokine receptor activity;interleukin-12 receptor binding;interleukin-12 receptor activity;cytokine binding;interleukin-23 binding;interleukin-23 receptor activity