On this page
CIITA
class II major histocompatibility complex transactivator
The CIITA gene provides instructions for a protein crucial in regulating the immune system's response to foreign invaders by controlling major histocompatibility complex (MHC) class II genes. The CIITA gene, or class II major histocompatibility complex transactivator, is essential for immune function.
CIITA is located on the short (p) arm of chromosome 16, at band 16p13.13. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 16 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The CIITA gene is formally known as the class II major histocompatibility complex transactivator. It plays a central role in the human immune system by governing the expression of MHC class II genes.
The protein encoded by CIITA acts as a master regulator, ensuring that specific immune cells can effectively identify and respond to pathogens such as bacteria, viruses, and fungi.
What the gene does
The CIITA protein primarily functions as a transcriptional coactivator, meaning it helps to activate the transcription of other genes without directly binding to DNA itself. Its key role is in controlling the activity of major histocompatibility complex (MHC) class II genes. These genes are responsible for producing MHC class II proteins, which are displayed on the surface of certain immune cells.
MHC class II proteins bind to fragments of foreign proteins (peptides) derived from pathogens. This presentation allows other specialised immune cells, particularly T lymphocytes, to recognise these peptides as harmful and initiate an immune response to eliminate the invaders. While primarily regulating MHC class II genes, the CIITA protein also appears to enhance the transcription of MHC class I genes, which serve a similar function in presenting antigens, although it is not their primary regulator.
Video: Genetics 101
Chromosome location
The CIITA gene is situated on chromosome 16 at position 16p13.13. This specific location on the short arm of chromosome 16 helps define its genomic context within the human genome.
Protein structure
The CIITA protein consists of 1130 amino acids. Key functional regions include a segment required for acetyltransferase activity spanning amino acids 94-132. A disordered region is found between amino acids 270-303. A significant NACHT domain is present from amino acids 414-724. Additionally, the protein contains multiple Leucine-rich repeat (LRR) regions: LRR 1 from 985-1008, LRR 2 from 1016-1037, LRR 3 from 1045-1066, and LRR 4 from 1073-1093.
Key variants
Genetic variations within the CIITA gene can alter the protein's structure or function, potentially impacting its ability to regulate immune responses. These variations may include single nucleotide changes, insertions, or deletions, which could lead to a range of effects on gene expression and protein activity.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1383dup | p.Ala462fs | Pathogenic/Likely pathogenic | ★★☆☆ | MHC class II deficiency |
c.1518del | p.Gln507fs | Pathogenic/Likely pathogenic | ★★☆☆ | MHC class II deficiency |
c.1615C>T | p.Arg539Ter | Pathogenic/Likely pathogenic | ★★☆☆ | MHC class II deficiency |
c.1962del | p.Ala656fs | Pathogenic/Likely pathogenic | ★★☆☆ | MHC class II deficiency |
c.1962dup | p.Gly655fs | Pathogenic/Likely pathogenic | ★★☆☆ | MHC class II deficiency |
c.2888+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | MHC class II deficiency |
c.2889-1G>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | MHC class II deficiency |
c.2959C>T | p.Gln987Ter | Pathogenic/Likely pathogenic | ★★☆☆ | MHC class II deficiency |
c.632del | p.Pro211fs | Pathogenic/Likely pathogenic | ★★☆☆ | MHC class II deficiency 1 |
c.682C>T | p.Gln228Ter | Pathogenic | ★★☆☆ | MHC class II deficiency |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Alterations in the CIITA gene are associated with inherited conditions primarily affecting the immune system. For instance, more than a dozen different changes in CIITA have been linked to bare lymphocyte syndrome type II (BLS II), a severe immunodeficiency where individuals have very limited protection against foreign pathogens.
No disease links recorded for this gene in our reference set.
UK clinical status
The CIITA gene is included in several NHS England Genomic Medicine Service approved panels. It is listed on the 'COVID-19 research' panel and the 'Primary immunodeficiency or monogenic inflammatory bowel disease' panel (R15), both of which are classified as 'green', indicating they are genes for which there is strong evidence of association with the condition.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the CIITA gene?
The CIITA gene provides instructions for a protein that primarily controls the activity of MHC class II genes. This regulation is crucial for immune cells to recognise and respond to foreign invaders like bacteria and viruses.
What is bare lymphocyte syndrome type II?
Bare lymphocyte syndrome type II (BLS II) is a rare inherited immune disorder caused by mutations in the CIITA gene. Individuals with BLS II have a severely compromised immune system, making them highly susceptible to recurrent and severe infections.
Why is the CIITA gene important for the immune system?
The CIITA gene is vital because it ensures the production of MHC class II proteins. These proteins are essential for presenting fragments of pathogens to T lymphocytes, enabling the immune system to mount an effective defence against infections.
References
- Ahmed A, Reith W, Puck JM. Novel Mutation in the Class II Transactivator Associated with Immunodeficiency and Autoimmunity. Journal of clinical immunology. 2015. PMID: 26271388
- Devaiah BN, Singer DS. CIITA and Its Dual Roles in MHC Gene Transcription. Frontiers in immunology. 2013. PMID: 24391648
- Gobin SJ, Peijnenburg A, van Eggermond M. The RFX complex is crucial for the constitutive and CIITA-mediated transactivation of MHC class I and beta2-microglobulin genes. Immunity. 1998. PMID: 9806639
- Bontron S, Steimle V, Ucla C. Two novel mutations in the MHC class II transactivator CIITA in a second patient from MHC class II deficiency complementation group A. Human genetics. 1997. PMID: 9099848
- Martin BK, Chin KC, Olsen JC. Induction of MHC class I expression by the MHC class II transactivator CIITA. Immunity. 1997. PMID: 9175837