STAT1 Gene

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This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/stat1

Signal transducer and activator of transcription 1: The STAT1 gene provides instructions for making a protein that is involved in multiple immune system functions, including the body's defense against a fungus called Candida.

genes

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Subjects: Genetics & Heredity

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Rui Liu

View Times: 242

Entry Collection: MedlinePlus

Update Date: 22 Dec 2020

Table of Contents

1. Normal Function

The STAT1 gene provides instructions for making a protein that is involved in multiple immune system functions, including the body's defense against a fungus called Candida. When the immune system recognizes Candida, it generates cells called Th17 cells. These cells produce signaling molecules (cytokines) called the interleukin-17 (IL-17) family as part of an immune process called the IL-17 pathway. The IL-17 pathway creates inflammation, sending other cytokines and white blood cells that fight foreign invaders and promote tissue repair. In addition, the IL-17 pathway promotes the production of certain antimicrobial protein segments (peptides) that control growth of Candida on the surface of mucous membranes.

The STAT1 protein helps keep the immune system in balance by controlling the IL-17 pathway. When the STAT1 protein is turned on (activated), it blocks (inhibits) this pathway.

In contrast to its inhibitory role in the IL-17 pathway, the STAT1 protein helps promote other immune processes called the interferon-alpha/beta (IFNA/B) and interferon-gamma (IFNG) signaling pathways. The IFNA/B pathway is important in defense against viruses, and the IFNG pathway helps fight a type of bacteria called mycobacteria, which includes the bacterium that causes tuberculosis.

2. Health Conditions Related to Genetic Changes

2.1. Familial candidiasis

At least 35 STAT1 gene mutations have been identified in people with familial candidiasis, an inherited tendency to develop infections caused by the Candida fungus (commonly called yeast infections). Most people with familial candidiasis have chronic infections of the skin, nails, and mucous membranes such as the lining of the mouth, collectively called chronic mucocutaneous candidiasis, beginning in early childhood. Some people with STAT1 gene mutations have additional features such as increased susceptibility to other infections and an increased risk of autoimmune disorders, in which the immune system attacks the body's own tissues or organs. This combination of signs and symptoms caused by STAT1 gene mutations is sometimes called immunodeficiency 31C.

The STAT1 gene mutations that have been identified in people with familial candidiasis are described as "gain of function" because they increase the amount of activated STAT1 protein in cells. By increasing STAT1's inhibitory effect on the IL-17 pathway, the mutations impair the body's ability to fight Candida and result in the chronic infection that occurs in familial candidiasis. The effects of the increase in activated STAT1 protein on other signaling pathways are thought to underlie the variety of features that can occur in immunodeficiency 31C, but the specific mechanisms are not well understood.

2.2. Other disorders

STAT1 gene mutations can also cause other immune system problems called immunodeficiency 31A and immunodeficiency 31B. In contrast with the gain-of-function mutations associated with familial candidiasis (described above), these STAT1 gene mutations are described as "loss-of-function" mutations because they impair or eliminate the protein's normal action. The STAT1 gene mutations that cause immunodeficiency 31A impair the STAT1 protein's function in the IFNG pathway, resulting in an increased susceptibility to mycobacteria. In the more severe disorder immunodeficiency 31B, the STAT1 gene mutations impair both the IFNG pathway and the IFNA/B pathway, resulting in susceptibility to both viral infections such as herpes simplex and viral encephalitis, and mycobacterial infections such as tuberculosis.

3. Other Names for This Gene

IMD31A
IMD31B
IMD31C
ISGF-3
signal transducer and activator of transcription 1, 91kDa
signal transducer and activator of transcription-1
STAT91
transcription factor ISGF-3 components p91/p84

References

Boisson-Dupuis S, Kong XF, Okada S, Cypowyj S, Puel A, Abel L, Casanova JL.Inborn errors of human STAT1: allelic heterogeneity governs the diversity ofimmunological and infectious phenotypes. Curr Opin Immunol. 2012Aug;24(4):364-78. doi: 10.1016/j.coi.2012.04.011.
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Soltész B, Tóth B, Shabashova N, Bondarenko A, Okada S, Cypowyj S, AbhyankarA, Csorba G, Taskó S, Sarkadi AK, Méhes L, Rozsíval P, Neumann D, Chernyshova L, Tulassay Z, Puel A, Casanova JL, Sediva A, Litzman J, Maródi L. New and recurrentgain-of-function STAT1 mutations in patients with chronic mucocutaneouscandidiasis from Eastern and Central Europe. J Med Genet. 2013 Sep;50(9):567-78. doi: 10.1136/jmedgenet-2013-101570.
Toubiana J, Okada S, Hiller J, Oleastro M, Lagos Gomez M, Aldave Becerra JC,Ouachée-Chardin M, Fouyssac F, Girisha KM, Etzioni A, Van Montfrans J, Camcioglu Y, Kerns LA, Belohradsky B, Blanche S, Bousfiha A, Rodriguez-Gallego C, Meyts I, Kisand K, Reichenbach J, Renner ED, Rosenzweig S, Grimbacher B, van de VeerdonkFL, Traidl-Hoffmann C, Picard C, Marodi L, Morio T, Kobayashi M, Lilic D, Milner JD, Holland S, Casanova JL, Puel A; International STAT1 Gain-of-Function StudyGroup. Heterozygous STAT1 gain-of-function mutations underlie an unexpectedlybroad clinical phenotype. Blood. 2016 Jun 23;127(25):3154-64. doi:10.1182/blood-2015-11-679902.
Yamazaki Y, Yamada M, Kawai T, Morio T, Onodera M, Ueki M, Watanabe N, Takada H, Takezaki S, Chida N, Kobayashi I, Ariga T. Two novel gain-of-functionmutations of STAT1 responsible for chronic mucocutaneous candidiasis disease:impaired production of IL-17A and IL-22, and the presence of anti-IL-17Fautoantibody. J Immunol. 2014 Nov 15;193(10):4880-7. doi:10.4049/jimmunol.1401467.

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