CIITA

Chr 16AR

class II major histocompatibility complex transactivator

The CIITA protein functions as the master transcriptional regulator of MHC class II genes, essential for their expression, and exhibits acetyltransferase activity to activate transcription without directly binding DNA. Mutations cause MHC class II deficiency, a severe combined immunodeficiency presenting in early childhood with recurrent infections due to impaired T cell and antigen presentation function. This condition follows autosomal recessive inheritance, and the gene is highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.582 OMIM phenotypes
Clinical SummaryCIITA
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Gene-Disease Validity (ClinGen)
MHC class II deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.58LOEUF
pLI 0.000
Z-score 3.97
OE 0.40 (0.290.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.93Z-score
OE missense 1.10 (1.041.17)
733 obs / 665.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.40 (0.290.58)
00.351.4
Missense OE1.10 (1.041.17)
00.61.4
Synonymous OE1.29
01.21.6
LoF obs/exp: 21 / 51.9Missense obs/exp: 733 / 665.5Syn Z: -3.94
DN
0.6841th %ile
GOF
0.6444th %ile
LOF
0.2581th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CIITA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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