CIITA

class II major histocompatibility complex transactivator, the group of NLR family

Basic information

Region (hg38): 16:10866221-10943021

Previous symbols: [ "MHC2TA" ]

Links

ENSG00000179583 ∙ NCBI:4261 ∙ OMIM:600005 ∙ HGNC:7067 ∙ Uniprot:P33076 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• MHC class II deficiency (Supportive), mode of inheritance: AR
• MHC class II deficiency (Strong), mode of inheritance: AR
• MHC class II deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bare lymphocyte syndrome, type II	AR	Allergy/Immunology/Infectious	Prophylaxis and early and aggressive treatment of infections can be beneficial; BMT has been reported in Bare lymphocyte syndrome, type II	Allergy/Immunology/Infectious; Gastrointestinal	8402893; 9099848; 11862382

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CIITA gene.

• MHC class II deficiency (1336 variants)
• Inborn genetic diseases (62 variants)
• not provided (46 variants)
• MHC class II deficiency;Rheumatoid arthritis (18 variants)
• not specified (14 variants)
• Rheumatoid arthritis;MHC class II deficiency (7 variants)
• Rheumatoid arthritis (3 variants)
• CIITA-related condition (2 variants)
• Bare lymphocyte syndrome type 2, complementation group A (2 variants)
• Colitis;Thrombocytopenia;Inflammation of the large intestine;Hematochezia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CIITA 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			7	544	14	565
missense			431	10	12	453
nonsense	21	1				22
start loss			1			1
frameshift	22	3				25
inframe indel			3			3
splice donor/acceptor (+/-2bp)		14				14
splice region		1	10	55	4	70
non coding			50	103	29	182
Total	43	18	492	657	55

Highest pathogenic variant AF is 0.0000197

Variants in CIITA

This is a list of pathogenic ClinVar variants found in the CIITA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-10876635-C-T			not provided (-)
16-10876810-A-G			not provided (-)
16-10876852-C-T			not provided (-)
16-10876916-C-T			not provided (-)
16-10877045-G-A		MHC class II deficiency	Benign (Jan 22, 2024)
16-10877045-G-G		Rheumatoid arthritis	risk factor (Oct 01, 2006)
16-10877163-G-A			not provided (-)
16-10877216-T-G		MHC class II deficiency	Likely benign (Jan 13, 2018)
16-10877247-C-T		MHC class II deficiency	Conflicting classifications of pathogenicity (Jan 01, 2023)
16-10877248-C-T		MHC class II deficiency	Uncertain significance (Jan 12, 2018)
16-10877249-G-A		MHC class II deficiency	Uncertain significance (Jan 13, 2018)
16-10877285-G-A		MHC class II deficiency	Benign (Jan 13, 2018)
16-10877327-C-T		MHC class II deficiency	Uncertain significance (Apr 24, 2020)
16-10877332-T-G		MHC class II deficiency	Uncertain significance (Aug 29, 2022)
16-10877334-C-A		MHC class II deficiency	Uncertain significance (Nov 15, 2019)
16-10877335-G-A		MHC class II deficiency • Inborn genetic diseases	Uncertain significance (Sep 13, 2022)
16-10877342-G-C		MHC class II deficiency	Likely benign (Jun 03, 2023)
16-10877344-C-G		MHC class II deficiency	Uncertain significance (Sep 01, 2021)
16-10877349-C-A		MHC class II deficiency	Uncertain significance (Jan 15, 2024)
16-10877349-C-T		MHC class II deficiency	Uncertain significance (Jul 06, 2022)
16-10877350-G-A		MHC class II deficiency • Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 10, 2022)
16-10877351-C-A		MHC class II deficiency	Likely benign (Apr 13, 2023)
16-10877351-C-G		MHC class II deficiency	Likely benign (Jun 28, 2023)
16-10877353-C-G		MHC class II deficiency	Uncertain significance (Jun 26, 2022)
16-10877360-G-A		MHC class II deficiency	Likely benign (May 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CIITA	protein_coding	protein_coding	ENST00000324288	19	55025

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.36e-7	1.00	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.930	733	665	1.10	0.0000453	7197
Missense in Polyphen		134	169.33	0.79137		2055
Synonymous	-3.94	388	301	1.29	0.0000214	2422
Loss of Function	3.97	21	51.9	0.405	0.00000285	559

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000393	0.000391
Ashkenazi Jewish	0.000310	0.000298
East Asian	0.000328	0.000326
Finnish	0.0000942	0.0000924
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000328	0.000326
South Asian	0.000163	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential for transcriptional activity of the HLA class II promoter; activation is via the proximal promoter. No DNA binding of in vitro translated CIITA was detected. May act in a coactivator-like fashion through protein-protein interactions by contacting factors binding to the proximal MHC class II promoter, to elements of the transcription machinery, or both. Alternatively it may activate HLA class II transcription by modifying proteins that bind to the MHC class II promoter. Also mediates enhanced MHC class I transcription; the promoter element requirements for CIITA-mediated transcription are distinct from those of constitutive MHC class I transcription, and CIITA can functionally replace TAF1 at these genes. Exhibits intrinsic GTP-stimulated acetyltransferase activity. Exhibits serine/threonine protein kinase activity: can phosphorylate the TFIID component TAF7, the RAP74 subunit of the general transcription factor TFIIF, histone H2B at 'Ser-37' and other histones (in vitro). {ECO:0000269|PubMed:11172716, ECO:0000269|PubMed:16600381, ECO:0000269|PubMed:17493635, ECO:0000269|PubMed:24036077}.
• Disease: DISEASE: Bare lymphocyte syndrome 2 (BLS2) [MIM:209920]: A severe combined immunodeficiency disease with early onset. It is characterized by a profound defect in constitutive and interferon- gamma induced MHC II expression, absence of cellular and humoral T-cell response to antigen challenge, hypogammaglobulinemia and impaired antibody production. The consequence include extreme susceptibility to viral, bacterial and fungal infections. {ECO:0000269|PubMed:10501838, ECO:0000269|PubMed:11466404, ECO:0000269|PubMed:11862382, ECO:0000269|PubMed:7749984, ECO:0000269|PubMed:8402893}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Antigen processing and presentation - Homo sapiens (human);Primary immunodeficiency - Homo sapiens (human);Influenza A - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Type II interferon signaling (IFNG);Cytokine Signaling in Immune system;Immune System;Interferon gamma signaling;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.515

Intolerance Scores

• loftool: 0.480
• rvis_EVS: -0.89
• rvis_percentile_EVS: 10.19

Haploinsufficiency Scores

• pHI: 0.189
• hipred: N
• hipred_score: 0.429
• ghis: 0.592

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.945

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ciita
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; skeleton phenotype; immune system phenotype; hematopoietic system phenotype; normal phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;inflammatory response;immune response;phosphorylation;negative regulation of collagen biosynthetic process;response to interferon-gamma;positive regulation of MHC class I biosynthetic process;positive regulation of MHC class II biosynthetic process;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;response to antibiotic;interferon-gamma-mediated signaling pathway
• Cellular component: nucleoplasm;PML body
• Molecular function: DNA binding;transcription coactivator activity;protein binding;ATP binding;GTP binding;protein C-terminus binding;kinase activity;transferase activity, transferring acyl groups;activating transcription factor binding;transcription regulatory region DNA binding;protein-containing complex binding