Covered on Genetics Home Reference: psoriatic arthritisFrom NCBI Gene: Immunodeficiency 29From UniProt: Psoriasis 11 (PSORS11): 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. [MIM:612599] Immunodeficiency 29 (IMD29): 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. [MIM:614890]

     From NCBI Gene: This gene encodes a subunit of interleukin 12, a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. Interleukin 12 is a disulfide-linked heterodimer composed of the 40 kD cytokine receptor like subunit encoded by this gene, and a 35 kD subunit encoded by IL12A. This cytokine is expressed by activated macrophages that serve as an essential inducer of Th1 cells development. This cytokine has been found to be important for sustaining a sufficient number of memory/effector Th1 cells to mediate long-term protection to an intracellular pathogen. Overexpression of this gene was observed in the central nervous system of patients with multiple sclerosis (MS), suggesting a role of this cytokine in the pathogenesis of the disease. The promoter polymorphism of this gene has been reported to be associated with the severity of atopic and non-atopic asthma in children. [provided by RefSeq, Jul 2008] From UniProt: Associates with IL23A to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity. IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of proinflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis. 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.

The following transcription factors affect gene expression:

• STAT1
• STAT1alpha
• STAT1beta
• TBP
• TFIID

Molecular Function:

• Cytokine Receptor Activity
• Interleukin-12 Receptor Binding
• Interleukin-12 Alpha Subunit Binding
• Identical Protein Binding
• Protein Heterodimerization Activity

Biological Processes:

• 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
• Response To Uv-B
• Positive Regulation Of Activation Of Jak2 Kinase Activity
• 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
• 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
• Positive Regulation Of Nf-Kappab Import Into Nucleus
• Regulation Of Tyrosine Phosphorylation Of Stat1 Protein
• Positive Regulation Of Tyrosine Phosphorylation Of Stat3 Protein
• Positive Regulation Of Tyrosine Phosphorylation Of Stat4 Protein
• Positive Regulation Of Tyrosine Phosphorylation Of Stat5 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 T-Helper 17 Type Immune Response
• Positive Regulation Of T-Helper 17 Cell Lineage Commitment

Drug Bank:

• Ustekinumab