IL12B
interleukin 12B, the group of Interleukins|Immunoglobulin like domain containing
Basic information
Region (hg38): 5:159314779-159330863
Previous symbols: [ "NKSF2" ]
Links
Phenotypes
GenCC
Source:
- Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency (Definitive), mode of inheritance: AR
- Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency (Strong), mode of inheritance: AR
- Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency (Supportive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Immunodeficiency 28; Immunodeficiency 29 | AR | Allergy/Immunology/Infectious | Individuals may be susceptible to severe and recurrent infections, including adverse sequelae from BCG vaccination, and prophylaxis and early and aggressive treatment of infections may be beneficial | Allergy/Immunology/Infectious | 9603732; 9789052; 11753820 |
ClinVar
This is a list of variants' phenotypes submitted to
- Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency (177 variants)
- Inborn genetic diseases (11 variants)
- Familial Atypical Mycobacteriosis, Autosomal Recessive (6 variants)
- not specified (3 variants)
- not provided (2 variants)
- Inherited susceptibility to mycobacterial diseases (1 variants)
- IL12B-related condition (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the IL12B 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 | 35 | 41 | ||||
| missense | 73 | 79 | ||||
| nonsense | 4 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 1 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| splice region ? | 1 | 5 | 3 | 2 | 11 | |
| non coding ? | 24 | 14 | 46 | |||
| Total | 4 | 1 | 103 | 52 | 12 |
Highest pathogenic variant AF is 0.00000660
Variants in IL12B
This is a list of pathogenic ClinVar variants found in the IL12B region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-159314789-A-T | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Jan 12, 2018) | ||
| 5-159314825-AAAAT-A | Familial Atypical Mycobacteriosis, Autosomal Recessive | Uncertain significance (Jun 14, 2016) | ||
| 5-159314869-T-C | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Jan 13, 2018) | ||
| 5-159315006-G-T | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Benign (Jan 13, 2018) | ||
| 5-159315018-AG-A | Familial Atypical Mycobacteriosis, Autosomal Recessive | Uncertain significance (Jun 14, 2016) | ||
| 5-159315032-C-A | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Jan 12, 2018) | ||
| 5-159315065-G-A | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Jan 13, 2018) | ||
| 5-159315085-A-T | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Jan 13, 2018) | ||
| 5-159315109-TA-T | Familial Atypical Mycobacteriosis, Autosomal Recessive | Uncertain significance (Jun 14, 2016) | ||
| 5-159315117-T-A | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Jan 13, 2018) | ||
| 5-159315144-G-A | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Jan 12, 2018) | ||
| 5-159315199-AT-A | Familial Atypical Mycobacteriosis, Autosomal Recessive | Benign (Jun 14, 2016) | ||
| 5-159315199-A-AT | Familial Atypical Mycobacteriosis, Autosomal Recessive | Uncertain significance (Jun 14, 2016) | ||
| 5-159315218-G-T | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Benign (Jan 13, 2018) | ||
| 5-159315261-C-T | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Jan 12, 2018) | ||
| 5-159315321-C-T | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Jan 12, 2018) | ||
| 5-159315355-G-A | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Jan 13, 2018) | ||
| 5-159315405-G-C | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Apr 28, 2017) | ||
| 5-159315581-G-A | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Likely benign (Jan 12, 2018) | ||
| 5-159315604-G-A | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Jan 12, 2018) | ||
| 5-159315615-T-C | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Jan 12, 2018) | ||
| 5-159315664-T-C | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Jan 13, 2018) | ||
| 5-159315693-G-A | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Jan 13, 2018) | ||
| 5-159315706-T-A | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Jan 15, 2018) | ||
| 5-159315777-A-G | Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency | Uncertain significance (Jan 13, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| IL12B | protein_coding | protein_coding | ENST00000231228 | 6 | 16105 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000114 | 0.956 | 125728 | 0 | 19 | 125747 | 0.0000756 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.567 | 154 | 175 | 0.879 | 0.00000991 | 2154 |
| Missense in Polyphen | 21 | 41.537 | 0.50558 | 567 | ||
| Synonymous | 0.583 | 66 | 72.3 | 0.913 | 0.00000450 | 612 |
| Loss of Function | 1.81 | 9 | 17.1 | 0.527 | 7.41e-7 | 210 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000124 | 0.000123 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000115 | 0.000114 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000326 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Cytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine- activated killer cells, and stimulate the production of IFN-gamma by resting PBMC. {ECO:0000269|PubMed:11114383}.;
- Disease
- DISEASE: Immunodeficiency 29 (IMD29) [MIM:614890]: 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. IMD29 is characterized by undetectable IL12B secretion from leukocytes. Affected individuals generally present with BCG disease after vaccination in childhood, and at least half also have Salmonella infection. Disease phenotype is relatively mild, and patients have a good prognosis. {ECO:0000269|PubMed:11753820, ECO:0000269|PubMed:9854038}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Psoriasis 11 (PSORS11) [MIM:612599]: A common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
- Pathway
- Type I diabetes mellitus - Homo sapiens (human);Pertussis - Homo sapiens (human);Legionellosis - Homo sapiens (human);Allograft rejection - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Influenza A - Homo sapiens (human);Inflammatory bowel disease (IBD) - Homo sapiens (human);African trypanosomiasis - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Measles - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;Allograft Rejection;Aryl Hydrocarbon Receptor Pathway;Nuclear Receptors Meta-Pathway;Lung fibrosis;Development and heterogeneity of the ILC family;Interleukin-10 signaling;Interleukin-4 and 13 signaling;Fibrin Complement Receptor 3 Signaling Pathway;no2-dependent il-12 pathway in nk cells;Cytokines and Inflammatory Response;Toll-like Receptor Signaling Pathway;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;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Immune System;IL-23 signaling;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;Interleukin-23 signaling;JAK STAT pathway and regulation;GPCR signaling-G alpha i;Interleukin-12 signaling;IL23-mediated signaling events;IL27-mediated signaling events;IL12-mediated signaling events
(Consensus)
Recessive Scores
- pRec
- 0.769
Intolerance Scores
- loftool
- 0.690
- rvis_EVS
- 0.44
- rvis_percentile_EVS
- 77.8
Haploinsufficiency Scores
- pHI
- 0.126
- hipred
- N
- hipred_score
- 0.182
- ghis
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.719
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Il12b
- Phenotype
- skeleton phenotype; immune system phenotype; digestive/alimentary phenotype; neoplasm; hematopoietic system 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); respiratory system phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; growth/size/body region phenotype;
Gene ontology
- Biological process
- positive regulation of T cell mediated cytotoxicity;positive regulation of defense response to virus by host;natural killer cell activation involved in immune response;positive regulation of T-helper 1 type immune response;positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target;negative regulation of inflammatory response to antigenic stimulus;cell cycle arrest;cell population proliferation;response to UV-B;regulation of signaling receptor activity;positive regulation of activation of Janus kinase activity;cell migration;cytokine-mediated signaling pathway;sensory perception of pain;sexual reproduction;natural killer cell activation;negative regulation of interleukin-10 production;negative regulation of interleukin-17 production;positive regulation of granulocyte macrophage colony-stimulating factor production;positive regulation of interferon-gamma production;positive regulation of interleukin-10 production;positive regulation of interleukin-12 production;positive regulation of interleukin-17 production;positive regulation of tumor necrosis factor production;positive regulation of natural killer cell activation;positive regulation of natural killer cell proliferation;positive regulation of mononuclear cell proliferation;positive regulation of tissue remodeling;positive regulation of smooth muscle cell apoptotic process;interleukin-12-mediated signaling pathway;T-helper 1 cell cytokine production;interleukin-23-mediated signaling pathway;regulation of cytokine biosynthetic process;T-helper 1 type immune response;T-helper cell differentiation;interferon-gamma biosynthetic process;positive regulation of T cell proliferation;positive regulation of activated T cell proliferation;regulation of tyrosine phosphorylation of STAT protein;positive regulation of tyrosine phosphorylation of STAT protein;defense response to protozoan;positive regulation of memory T cell differentiation;negative regulation of growth of symbiont in host;positive regulation of interferon-gamma biosynthetic process;positive regulation of osteoclast differentiation;positive regulation of cell adhesion;negative regulation of smooth muscle cell proliferation;positive regulation of lymphocyte proliferation;positive regulation of inflammatory response;defense response to Gram-negative bacterium;positive regulation of NK T cell activation;positive regulation of NK T cell proliferation;defense response to virus;cellular response to lipopolysaccharide;cellular response to interferon-gamma;positive regulation of NIK/NF-kappaB signaling;positive regulation of T-helper 17 type immune response;positive regulation of T-helper 17 cell lineage commitment
- Cellular component
- extracellular region;extracellular space;endoplasmic reticulum lumen;cytosol;external side of plasma membrane;late endosome lumen;receptor complex;interleukin-12 complex;interleukin-23 complex
- Molecular function
- cytokine receptor activity;cytokine activity;interleukin-12 receptor binding;protein binding;growth factor activity;cytokine binding;interleukin-12 alpha subunit binding;identical protein binding;protein homodimerization activity;interleukin-23 receptor binding;protein heterodimerization activity