IL12RB1
protein-codinginterleukin 12 receptor subunit beta 1, the group of Fibronectin type III domain containing|CD molecules|Interleukin receptors
Gene summary
The protein encoded by this gene is a type I transmembrane protein that belongs to the hemopoietin receptor superfamily. This protein binds to interleukine 12 (IL12) with a low affinity, and is thought to be a part of IL12 receptor complex. This protein forms a disulfide-linked oligomer, which is required for its IL12 binding activity. The coexpression of this and IL12RB2 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. Mutations in this gene impair the development of interleukin-17-producing T lymphocytes and result in increased susceptibility to mycobacterial and Salmonella infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]
- IL12RB
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~39.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013955
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0013955
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0013955
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious
Intervention: Allergy/Immunology/Infectious
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to IL12RB1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005535.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | 154 | 4 | 164 | ||
| missense | 5 | 5 | 235 | 30 | 4 | 279 |
| nonsense | 27 | 6 | 2 | 35 | ||
| start loss | 2 | 2 | ||||
| frameshift | 16 | 3 | 2 | 21 | ||
| splice donor/acceptor (+/-2bp) | 8 | 8 | 7 | 23 | ||
| Total | 56 | 22 | 254 | 184 | 8 | 524 |
Highest pathogenic variant AF is 0.0002263707
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005526.1 | 17 | MANE Select | |
| Ensembl | ENSP00000472165.2 | 17 | MANE Select | |
| RefSeq | NP_001276952.1 | 17 | Standard | |
| RefSeq | NP_001276953.1 | 18 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
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
Molecular Function
- cytokine receptor activity
- interleukin-12 receptor binding
- interleukin-12 receptor activity
- cytokine binding
- interleukin-23 binding
Cellular Component
- plasma membrane
- external side of plasma membrane
- interleukin-12 receptor complex
- receptor complex
- interleukin-23 receptor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000600835
- Coding exons
- 17
- Length
- 39950
- Individuals with no LoFs
- 125614
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 134
- Defined
- 125748
- p
- 0.000533
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.237 | 377 | 390 | 0.966 | 0.0000240 | 4231 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00052 | 0.00049 | rare |
| Latino/Admixed American | 0.00027 | 0.00026 | rare |
| Ashkenazi Jewish | 0.00050 | 0.00050 | rare |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00076 | 0.00075 | rare |
| South Asian | 0.00047 | 0.00046 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- 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.;
Recessive Scores
- pRec
- 0.329
Intolerance Scores
- LoFtool
- 0.415
- RVIS EVS
- 0.41
- RVIS percentile EVS
- 76.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.827
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |