CIITA

Summary

CIITA (class II major histocompatibility complex transactivator, HGNC:7067) is a protein-coding gene on chromosome 16p13.13, encoding MHC class II transactivator (P33076). Essential for transcriptional activity of the HLA class II promoter; activation is via the proximal promoter.

This gene encodes a protein with an acidic transcriptional activation domain, 4 LRRs (leucine-rich repeats) and a GTP binding domain. The protein is located in the nucleus and acts as a positive regulator of class II major histocompatibility complex gene transcription, and is referred to as the “master control factor” for the expression of these genes. The protein also binds GTP and uses GTP binding to facilitate its own transport into the nucleus. Once in the nucleus it does not bind DNA but rather uses an intrinsic acetyltransferase (AT) activity to act in a coactivator-like fashion. Mutations in this gene have been associated with bare lymphocyte syndrome type II (also known as hereditary MHC class II deficiency or HLA class II-deficient combined immunodeficiency), increased susceptibility to rheumatoid arthritis, multiple sclerosis, and possibly myocardial infarction. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4261 — RefSeq curated summary.

At a glance

• Gene–disease (curated): MHC class II deficiency (Definitive, ClinGen)
• GWAS associations: 13
• Clinical variants (ClinVar): 1,914 total — 59 pathogenic, 41 likely-pathogenic
• Phenotypes (HPO): 68
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• Transcription factor: yes — 32 downstream targets (CollecTRI)
• MANE Select transcript: NM_000246

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7067
Approved symbol	CIITA
Name	class II major histocompatibility complex transactivator
Location	16p13.13
Locus type	gene with protein product
Status	Approved
Aliases	C2TA, NLRA
Ensembl gene	ENSG00000179583
Ensembl biotype	protein_coding
OMIM	600005
Entrez	4261

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 14 protein_coding, 5 protein_coding_CDS_not_defined, 5 retained_intron, 3 nonsense_mediated_decay

ENST00000324288, ENST00000381835, ENST00000537380, ENST00000570546, ENST00000571186, ENST00000571190, ENST00000571545, ENST00000572665, ENST00000573309, ENST00000573379, ENST00000575513, ENST00000576601, ENST00000618207, ENST00000618327, ENST00000636238, ENST00000637439, ENST00000644232, ENST00000646979, ENST00000695878, ENST00000695879, ENST00000886124, ENST00000886125, ENST00000886126, ENST00000886127, ENST00000886128, ENST00000886129, ENST00000969830

RefSeq mRNA: 8 — MANE Select: NM_000246 NM_000246, NM_001286402, NM_001286403, NM_001379330, NM_001379331, NM_001379332, NM_001379333, NM_001379334

CCDS: CCDS10544, CCDS66943, CCDS73826

Canonical transcript exons

ENST00000324288 — 20 exons

Exon	Start	End
ENSE00001246215	10909029	10909187
ENSE00001309507	10906499	10908149
ENSE00001936521	10923878	10936394
ENSE00003468996	10902658	10902801
ENSE00003472373	10895282	10895428
ENSE00003497467	10902038	10902184
ENSE00003499851	10898925	10899002
ENSE00003517412	10904744	10904812
ENSE00003530029	10918440	10918526
ENSE00003536860	10901514	10901558
ENSE00003544827	10903731	10903895
ENSE00003555511	10910188	10910259
ENSE00003593033	10923228	10923325
ENSE00003597515	10916367	10916459
ENSE00003617575	10922407	10922490
ENSE00003631352	10922167	10922250
ENSE00003645924	10895669	10895764
ENSE00003684812	10915570	10915650
ENSE00003689630	10898670	10898732
ENSE00003915466	10877202	10877382

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 95.80.

FANTOM5 (CAGE): breadth broad, TPM avg 20.1436 / max 1568.6170, expressed in 637 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152721	13.7913	446
152728	2.2770	439
152722	1.6009	303
152726	0.8390	207
152717	0.6446	160
152733	0.3276	119
152729	0.2184	110
207750	0.1102	51
152727	0.0802	40
152725	0.0701	26

Top tissues by expression

277 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	95.80	gold quality
granulocyte	CL:0000094	95.32	gold quality
mononuclear cell	CL:0000842	95.11	gold quality
leukocyte	CL:0000738	94.64	gold quality
vermiform appendix	UBERON:0001154	92.25	gold quality
spleen	UBERON:0002106	92.08	gold quality
lymph node	UBERON:0000029	91.61	gold quality
sural nerve	UBERON:0015488	90.25	gold quality
gall bladder	UBERON:0002110	89.34	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.69	gold quality
upper lobe of left lung	UBERON:0008952	87.64	gold quality
caecum	UBERON:0001153	87.40	gold quality
blood	UBERON:0000178	86.40	gold quality
upper lobe of lung	UBERON:0008948	86.23	gold quality
apex of heart	UBERON:0002098	86.21	gold quality
small intestine	UBERON:0002108	86.15	gold quality
tendon of biceps brachii	UBERON:0008188	86.00	gold quality
right lung	UBERON:0002167	85.81	gold quality
tonsil	UBERON:0002372	85.62	gold quality
tibial nerve	UBERON:0001323	84.80	gold quality
right coronary artery	UBERON:0001625	84.14	gold quality
metanephros cortex	UBERON:0010533	83.37	gold quality
rectum	UBERON:0001052	83.12	gold quality
right uterine tube	UBERON:0001302	82.98	gold quality
subcutaneous adipose tissue	UBERON:0002190	81.89	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.88	gold quality
endocervix	UBERON:0000458	81.02	gold quality
omental fat pad	UBERON:0010414	80.41	gold quality
peritoneum	UBERON:0002358	80.37	gold quality
bone marrow cell	CL:0002092	80.33	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	737.88
E-MTAB-8142	yes	64.92
E-ANND-3	yes	21.73
E-CURD-112	yes	14.41
E-MTAB-9067	yes	13.96
E-CURD-88	yes	12.34
E-MTAB-9801	yes	9.95
E-CURD-97	no	127.86
E-ENAD-27	no	4.02

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

32 targets.

Target	Regulation
COL1A1	Repression
COL1A2	Repression
CREBBP	Unknown
FASLG	Unknown
HLA-A	Activation
HLA-B	Activation
HLA-C	Activation
HLA-DMA	Activation
HLA-DMB	Activation
HLA-DOA	Activation
HLA-DOB	Activation
HLA-DPB1	Unknown
HLA-DQB1	Unknown
HLA-DRA	Activation
HLA-DRB1	Unknown
HLA-DRB3	Unknown
HLA-DRB4	Unknown
HLA-DRB5	Unknown
HLA-E	Activation
HLA-F	Unknown
HLA-G	Unknown
IL4	Activation
IRF1	Unknown
IRF2	Unknown
MMP9	Repression
PLXNA1	Unknown
PSMC5	Activation
RAB4B	Unknown
S100A4	Repression
SIRT1	Repression

Upstream regulators (CollecTRI, top): AP1, ATF1, CEBPB, CEBPD, CEBPG, CREB1, EZH2, FOS, HAND1, HAND2, HR, IRF1, IRF2, IRF4, IRF6, IRF8, JUN, KLF4, KMT2A, MYCN, NFATC1, NFATC2, NFYB, PHF20, PPARG, PRDM1, RELA, RFX1, RFX5, RFXANK, RFXAP, SMAD3, SPI1, SSRP1, STAT1, STAT3, TAF1, TCF23, TXK, USF1

miRNA regulators (miRDB)

55 targeting CIITA, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-1909-3P	99.03	66.56	1662

Literature-anchored findings (GeneRIF, showing 40)

• CIITA is a novel GTP-binding protein (PMID:10464099)
• Phosphorylation of CIITA by PKA inhibits activation of HLA-DR in monocytic cells (PMID:11416140)
• Cooperation between CIITA, CBP, and pCAF doesn’t require coactivator histone acetyltransferase activity (PMID:11514574)
• The AIR-1 encoded class II transactivator (CIITA): the master coordinator of MHC class II gene expression and implications in the physiopathology of the immune system. (PMID:11774613)
• In both in vivo and in vitro activated CD4+ T cells, CIITA expression is driven by CIITA promoter III only. (PMID:11777970)
• carboxy terminal leucine-rich repeat region controls Nuclear localisation of CIITA (PMID:11792431)
• Single nucleotide polymorphisms in MHC2TA (PMID:11857059)
• we investigated the molecular basis of the defect in three patients in these families, all presenting a severe immunodeficiency; CIITA transcripts were detected in all three patients (PMID:11862382)
• Interferon-gamma-induced chromatin remodeling at the CIITA locus is BRG1 dependent (PMID:11953317)
• tumor cell lines with a defective expression of CIITA transcripts lack MHC class II expression (PMID:11978778)
• Phagocytosis of bacteria can down-modulate HLA class II expression in normal human macrophages by acting at the level of expression of CIITA. (PMID:11981818)
• Kinetics of a gamma interferon response: expression and assembly of CIITA promoter IV and inhibition by methylation. (PMID:12052885)
• Leucine-rich repeats of the class II transactivator control its rate of nuclear accumulation (PMID:12072194)
• CIITA requires the ATPase subunit of an hSWI/SNF complex, brahma-related gene 1 (BRG-1), to activate transcription. (PMID:12077331)
• The promoter III isoform of MHC2TA is induced in activated T lymphocytes via the induction of binding of activation response element ARE-2. (PMID:12218128)
• CIITA inhibits HIV-1 replication by blocking Tat protein. (PMID:12355430)
• Phosphorylation of CIITA directs its oligomerization, accumulation and increased activity on MHCII promoters. (PMID:12374747)
• The 5’-untranslated region of CIITA promoter III functions as an important regulatory region in B lymphocytes. (PMID:12391222)
• DNA microarray analysis of the CIITA-expressing B cell line Raji identified a wide variety of CIITA-modulated genes with diverse functions which could impact antigen processing, signaling, proliferation, and differentiation. (PMID:12391224)
• A novel model is proposed for the dynamic regulation of CIITA cellular localization mediated by its GTP-binding domain. (PMID:12517958)
• Silencing of CIITA transcription is recessive in trophoblasts and involves an epigenetic mechanism other than promoter methylation. Trophoblasts may be missing a factor that regulates chromatin structure at the CIITA promoter. (PMID:12748124)
• TncRNA suppressed interferon-gamma-induced human leukocyte antigen-DR and CIITA expression in HeLa cells and the mechanism involves inhibition of CIITA pIV through a defined inhibitory domain on the promoter (PMID:12883198)
• identified two regions mediating degradation within the N-terminal domain of CIITA (PMID:12884309)
• CIITA strongly inhibits HTLV-2 viral replication, but not virus entry, in B- and T-cell susceptible targets (PMID:14525769)
• important role of DNA hyper-methylation in the control of CIITA expression in leukemic T cells. (PMID:14563641)
• evidenced a highly residual CIITA protein expression in a B lymphoma cell line resulting from a transcriptional defect affecting MHC2TA expression. (PMID:14973505)
• Overexpression of CIITA in a human gastric carcinoma cell line, AGS, results in decreased cathepsin E mRNA and protein. AGS cells expressing CIITA also exhibit decreased processing of ovalbumin antigen. (PMID:15100295)
• MHC2TA is the single most important transcription factor for the regulation of genes required for MHCII-restricted antigen presentation. (PMID:15162420)
• a model for CIITA function in which phosphorylation of these specific sites in CIITA in the nucleus serves to down-regulate CIITA activity. (PMID:15210796)
• characterized the various regulatory elements and interacting factors of CIITA-PIII that account for specific activation in B lymphocytes (PMID:15242870)
• There are coordinate decreases in the occupancy of RNA polymerase II on the collagen transcription start site with increasing CIITA occupancy during IFN-gamma treatment (PMID:15247294)
• CIITA inhibits MMP-9 expression by binding to and sequestering CREB-binding protein (PMID:15247301)
• Inability of uveal melanocytes and ocular melanoma cells to express class II MHC molecules after treatment with IFN-gamma maps to two distinct points in class II MHC biosynthetic pathway. (PMID:15326139)
• CIITA methylation is a key mechanism that enables some gastrointestinal cancer cells to escape immune surveillance (PMID:15467734)
• Six novel S’-Y’ regulatory modules have been identified that are controlled by the human major histocompatibility class II-specific regulatory factor CIITA. (PMID:15528357)
• No polymorphism in promoters I, III and IV of CIITA gene exists in chronic hepatitis B patients and controls suggesting that the promoter of CIITA gene might be a conserved domain. (PMID:15682480)
• CIITA induction is required for interferon gamma-mediated repression of COL1A1 and COL1A2 (PMID:15788405)
• Constitutive expression of human CIITA in transgenic mice pre-disposes CD4 T cells to produce Th2 type cytokines, indicating that CIITA expression is important for proper CD4 T-cell differentiation. (PMID:15876426)
• type IV promoter is active in B lymphocytes and potentially contributes to the expression of CIITA and MHC II in these cells; in vivo genomic footprint analysis demonstrated proteins binding at the GAS, IRF-E and E box sites of CIITA pIV (PMID:15950283)
• ANKRA, RFXANK, and CIITA are novel targets of class IIa HDACs which may deacetylases play a role in regulating MHCII expression (PMID:15964851)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ciita	ENSMUSG00000022504
rattus_norvegicus	Ciita	ENSRNOG00000002659

Paralogs (20): NLRP2 (ENSG00000022556), NLRP1 (ENSG00000091592), NOD1 (ENSG00000106100), NLRC5 (ENSG00000140853), NLRP12 (ENSG00000142405), NLRP14 (ENSG00000158077), NLRP4 (ENSG00000160505), NLRX1 (ENSG00000160703), NLRP3 (ENSG00000162711), NOD2 (ENSG00000167207), NLRP7 (ENSG00000167634), NLRC3 (ENSG00000167984), NLRP5 (ENSG00000171487), NLRP13 (ENSG00000173572), NLRP6 (ENSG00000174885), NLRP8 (ENSG00000179709), NLRP11 (ENSG00000179873), NLRP10 (ENSG00000182261), NLRP9 (ENSG00000185792), PYDC2 (ENSG00000253548)

Protein

Protein identifiers

MHC class II transactivator — P33076 (reviewed: P33076)

All UniProt accessions (10): A0A087X2I7, A0A0B4J1S1, A0A1B0GU01, A0A1B0GUQ8, A0A2R8Y7F5, A0A2R8YFU9, P33076, I3L2E5, I3L2P7, Q29704

UniProt curated annotations — full annotation on UniProt →

Function. Essential for transcriptional activity of the HLA class II promoter; activation is via the proximal promoter. Does not bind DNA. 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 PubMed:8402893, PubMed:7749984,. 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. Activates CD74 transcription. 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). Has antiviral activity against Ebola virus and coronaviruses, including SARS-CoV-2. Induces resistance by up-regulation of the p41 isoform of CD74, which blocks cathepsin-mediated cleavage of viral glycoproteins, thereby preventing viral fusion. Exhibits dominant-negative suppression of MHC class II gene expression.

Subunit / interactions. Interacts with ZXDA and ZXDC. Interacts with PML (isoform PML-2). Interacts with TAF7; interaction inhibits CIITA acetyltransferase activity, thereby repressing transcription. (Microbial infection) Interacts with human cytomegalovirus protein US28; this interaction decreases host HLA class II expression.

Subcellular location. Nucleus. PML body.

Post-translational modifications. Autophosphorylated, affecting interaction with TAF7.

Disease relevance. MHC class II deficiency 1 (MHC2D1) [MIM:209920] An autosomal recessive immunologic disorder characterized by the loss of expression of MHC class II antigens on antigen-presenting cells. Affected individuals present in early infancy with severe recurrent bacterial, viral, fungal and parasitic infections, usually affecting the gastrointestinal and respiratory tracts. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The acetyltransferase domain is necessary for activation of both class I and class II transcription. The GTP-binding motif doesn’t confer GTPase activity but promotes nuclear localization.

Isoforms (4)

UniProt ID	Names	Canonical?
P33076-1	1	yes
P33076-2	2
P33076-3	3, hCIITA’
P33076-4	4

RefSeq proteins (8): NP_000237, NP_001273331, NP_001273332, NP_001366259, NP_001366260, NP_001366261, NP_001366262, NP_001366263 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR007111	NACHT_NTPase	Domain
IPR008095	MHC_II_transact	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily

Pfam: PF05729, PF13516

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (30 total): sequence variant 13, splice variant 5, repeat 4, mutagenesis site 2, region of interest 2, chain 1, domain 1, sequence conflict 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P33076-F1	69.10	0.30

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 420–427

Mutagenesis-validated functional residues (2):

Position	Phenotype
420–421	strongly reduces gtp-binding and abolishes transactivation at mhc promoters.
561	strongly reduces gtp-binding and abolishes transactivation at mhc promoters.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-913531	Interferon Signaling

MSigDB gene sets: 415 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, IRF1_Q6, SHIN_B_CELL_LYMPHOMA_CLUSTER_5, GOBP_TYPE_II_INTERFERON_MEDIATED_SIGNALING_PATHWAY, IRF_Q6, GOBP_HOST_MEDIATED_SUPPRESSION_OF_SYMBIONT_INVASION, ZHAN_EARLY_DIFFERENTIATION_GENES_DN, GOBP_RESPONSE_TO_TYPE_II_INTERFERON, GOBP_RESPONSE_TO_ANTIBIOTIC, MODULE_46, KEGG_ANTIGEN_PROCESSING_AND_PRESENTATION

GO Biological Process (12): negative regulation of transcription by RNA polymerase II (GO:0000122), immune response (GO:0006955), negative regulation of collagen biosynthetic process (GO:0032966), response to type II interferon (GO:0034341), positive regulation of MHC class I biosynthetic process (GO:0045345), positive regulation of MHC class II biosynthetic process (GO:0045348), positive regulation of transcription by RNA polymerase II (GO:0045944), host-mediated suppression of symbiont invasion (GO:0046597), response to antibiotic (GO:0046677), type II interferon-mediated signaling pathway (GO:0060333), regulation of DNA-templated transcription (GO:0006355), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (15): transcription coactivator activity (GO:0003713), transcription corepressor activity (GO:0003714), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), GTP binding (GO:0005525), acyltransferase activity (GO:0016746), histone deacetylase binding (GO:0042826), protein-containing complex binding (GO:0044877), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein serine kinase activity (GO:0106310), DNA-binding transcription factor binding (GO:0140297), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytosol (GO:0005829), PML body (GO:0016605), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Interferon Signaling	1
Immune System	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
innate immune response	2
positive regulation of macromolecule biosynthetic process	2
positive regulation of DNA-templated transcription	2
DNA-templated transcription	2
transcription coregulator activity	2
protein kinase activity	2
purine ribonucleoside triphosphate binding	2
binding	2
cellular anatomical structure	2
immune system process	1
response to stimulus	1
negative regulation of biosynthetic process	1
negative regulation of collagen metabolic process	1
collagen biosynthetic process	1
regulation of collagen biosynthetic process	1
response to cytokine	1
MHC class I biosynthetic process	1
regulation of MHC class I biosynthetic process	1
MHC class II biosynthetic process	1
regulation of MHC class II biosynthetic process	1
host-mediated perturbation of symbiont process	1
response to chemical	1
cellular response to type II interferon	1
interferon-mediated signaling pathway	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
adenyl ribonucleotide binding	1
guanyl ribonucleotide binding	1
transferase activity	1
enzyme binding	1
DNA-binding transcription factor binding	1
transcription factor binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1

Protein interactions and networks

STRING

2301 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CIITA	RFX5	P48382	985
CIITA	RFXANK	O14593	971
CIITA	RFXAP	O00287	970
CIITA	RFX1	P22670	958
CIITA	NAIP	Q13075	928
CIITA	CREB1	P16220	789
CIITA	MEFV	O15553	778
CIITA	IFNG	P01579	759
CIITA	HLA-DRA	P01903	750
CIITA	CD74	P04233	733
CIITA	CCNT1	O60563	723
CIITA	PYCARD	Q9ULZ3	706
CIITA	CD4	P01730	703
CIITA	CDK9	P50750	676
CIITA	CLEC16A	Q2KHT3	674

IntAct

17 interactions, top by confidence:

A	B	Type	Score
CIITA	ZXDC	psi-mi:“MI:0915”(physical association)	0.670
ZXDC	CIITA	psi-mi:“MI:0914”(association)	0.670
CIITA	SIRT1	psi-mi:“MI:0915”(physical association)	0.520
SIRT1	CIITA	psi-mi:“MI:0915”(physical association)	0.520
ZXDA	CIITA	psi-mi:“MI:0915”(physical association)	0.480
CIITA	ZXDA	psi-mi:“MI:0915”(physical association)	0.480
ZXDA	CIITA	psi-mi:“MI:0914”(association)	0.480
CIITA	RFX5	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (70): PSMC5 (Affinity Capture-Western), CIITA (Co-localization), PPARG (Affinity Capture-Western), CIITA (Affinity Capture-Western), EP300 (Affinity Capture-Western), EP400 (Affinity Capture-Western), TBP (Affinity Capture-Western), RFX5 (Affinity Capture-Western), PSMC5 (Affinity Capture-Western), CIITA (Affinity Capture-Western), CIITA (Co-localization), PML (Co-localization), CCNT1 (Co-localization), CIITA (Affinity Capture-Western), CIITA (Biochemical Activity)

ESM2 similar proteins: A2ASA8, A5PJJ5, A6NE52, A6NHZ5, B6CZ46, E9QAM5, G7PWZ3, P08571, P10810, P33076, P52824, P79621, P86243, Q15048, Q15345, Q1L8H0, Q28680, Q32PG9, Q3U1Y4, Q3UJB3, Q3UWY1, Q3V1N1, Q3V3V9, Q3ZBI5, Q569B5, Q5BK65, Q5DU56, Q5M936, Q63035, Q63691, Q640Z9, Q66H52, Q68EF8, Q6F5E8, Q6GPH6, Q6P5E8, Q6QNU9, Q6R5P0, Q7RTR2, Q80VA5

Diamond homologs: A0A2H5Q1B8, A0A386CAB9, A1Z198, A6QLE5, B0FPE9, D4A523, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5R7, O15553, P10775, P13489, P29315, P33076, P59044, P59045, P59046, P59047, Q0GKD5, Q288C4, Q2LKU9, Q2LKV2, Q2LKV5, Q2LKW6, Q63035, Q647I9, Q66X01, Q66X03, Q66X19, Q6B966, Q7RTR0, Q86W24, Q86W25, Q86W26, Q86W28, Q8BU40, Q8C6J9

SIGNOR signaling

38 interactions.

A	Effect	B	Mechanism
PRKACA	“down-regulates activity”	CIITA	phosphorylation
MAPK1	up-regulates	CIITA	phosphorylation
MAPK1	down-regulates	CIITA	phosphorylation
MAPK3	up-regulates	CIITA	phosphorylation
GSK3B	up-regulates	CIITA	phosphorylation
MAPK3	down-regulates	CIITA	phosphorylation
CIITA	“up-regulates activity”	RFX5	binding
STAT1	“up-regulates quantity by expression”	CIITA	“transcriptional regulation”
CIITA	“up-regulates quantity by expression”	HLA-C	“transcriptional regulation”
CIITA	“down-regulates quantity by repression”	S100A4	“transcriptional regulation”
CIITA	“up-regulates quantity by expression”	HLA-DRB1	“transcriptional regulation”
CIITA	“up-regulates quantity by expression”	HLA-DOA	“transcriptional regulation”
CIITA	“up-regulates quantity by expression”	HLA-DPB1	“transcriptional regulation”
CIITA	“up-regulates quantity by expression”	HLA-DRA	“transcriptional regulation”
CIITA	“up-regulates quantity by expression”	HLA-DMB	“transcriptional regulation”
CIITA	“up-regulates quantity by expression”	HLA-DRB3	“transcriptional regulation”
CIITA	“up-regulates quantity by expression”	HLA-DRB4	“transcriptional regulation”
CIITA	“up-regulates quantity by expression”	HLA-DRB5	“transcriptional regulation”
CIITA	“up-regulates quantity by expression”	HLA-DOB	“transcriptional regulation”
CIITA	“up-regulates quantity by expression”	HLA-DQB1	“transcriptional regulation”
CIITA	“up-regulates quantity by expression”	HLA-F	“transcriptional regulation”
CIITA	“up-regulates quantity by expression”	HLA-E	“transcriptional regulation”
CIITA	“up-regulates quantity by expression”	HLA-A	“transcriptional regulation”
CIITA	unknown	HLA-G	“transcriptional regulation”
HDAC2	“down-regulates quantity by repression”	CIITA	deacetylation
CIITA	down-regulates	IL4	“transcriptional regulation”

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — DLBCLNOS, HNSC.

Clinical variants and AI predictions

ClinVar

1914 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	59
Likely pathogenic	41
Uncertain significance	678
Likely benign	967
Benign	54

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071007	NC_000016.9:g.(?10971168)(10971259_?)del	Pathogenic
1072600	NM_000246.4(CIITA):c.1240C>T (p.Arg414Ter)	Pathogenic
1072919	NM_000246.4(CIITA):c.1717C>T (p.Gln573Ter)	Pathogenic
1073259	NM_000246.4(CIITA):c.2014C>T (p.Gln672Ter)	Pathogenic
1076860	NM_000246.4(CIITA):c.36C>A (p.Tyr12Ter)	Pathogenic
1396255	NM_000246.4(CIITA):c.1389T>G (p.Tyr463Ter)	Pathogenic
1400898	NC_000016.9:g.(?11000336)(11017160_?)del	Pathogenic
1412942	NM_000246.4(CIITA):c.3361C>T (p.Gln1121Ter)	Pathogenic
1415818	NM_000246.4(CIITA):c.2740A>T (p.Lys914Ter)	Pathogenic
1416680	NM_000246.4(CIITA):c.1536_1537insTTGCGGTC (p.Ser513fs)	Pathogenic
1454206	NM_000246.4(CIITA):c.2479C>T (p.Gln827Ter)	Pathogenic
1454398	NM_000246.4(CIITA):c.2526del (p.Pro843fs)	Pathogenic
1455424	NM_000246.4(CIITA):c.1863dup (p.Glu622fs)	Pathogenic
1458041	NM_000246.4(CIITA):c.802_803dup (p.Pro269fs)	Pathogenic
1458155	NM_000246.4(CIITA):c.682C>T (p.Gln228Ter)	Pathogenic
1459331	NM_000246.4(CIITA):c.1502_1511del (p.Phe501fs)	Pathogenic
1459361	NM_000246.4(CIITA):c.2828_2829insTG (p.Ser944fs)	Pathogenic
1460015	NM_000246.4(CIITA):c.2490del (p.Gly831fs)	Pathogenic
1910291	NM_000246.4(CIITA):c.376G>T (p.Glu126Ter)	Pathogenic
1963807	NM_000246.4(CIITA):c.2775_2777delinsTT (p.Lys926fs)	Pathogenic
1998120	NM_000246.4(CIITA):c.1099C>T (p.Gln367Ter)	Pathogenic
2018503	NM_000246.4(CIITA):c.587_597del (p.Ala196fs)	Pathogenic
2029447	NM_000246.4(CIITA):c.1049del (p.Gly350fs)	Pathogenic
2102239	NM_000246.4(CIITA):c.2466G>A (p.Trp822Ter)	Pathogenic
2114152	NM_000246.4(CIITA):c.1922_1923del (p.Tyr641fs)	Pathogenic
2135145	NM_000246.4(CIITA):c.2103del (p.Ala702fs)	Pathogenic
2179931	NM_000246.4(CIITA):c.1423C>T (p.Gln475Ter)	Pathogenic
2422627	NC_000016.9:g.(?10637407)(10971259_?)del	Pathogenic
2698052	NM_000246.4(CIITA):c.1566del (p.Cys523fs)	Pathogenic
2703344	NM_000246.4(CIITA):c.2563del (p.Ala855fs)	Pathogenic

SpliceAI

3761 predictions. Top by Δscore:

Variant	Effect	Δscore
16:10895281:GGCA:G	acceptor_gain	1.0000
16:10898663:T:TA	acceptor_gain	1.0000
16:10898664:G:A	acceptor_gain	1.0000
16:10898668:A:AG	acceptor_gain	1.0000
16:10898668:AGC:A	acceptor_gain	1.0000
16:10898669:G:GG	acceptor_gain	1.0000
16:10898669:GCG:G	acceptor_gain	1.0000
16:10898733:G:GG	donor_gain	1.0000
16:10902037:GCT:G	acceptor_gain	1.0000
16:10902185:G:GG	donor_gain	1.0000
16:10902654:GCAGT:G	acceptor_loss	1.0000
16:10902655:CA:C	acceptor_loss	1.0000
16:10902656:A:AG	acceptor_gain	1.0000
16:10902656:A:AT	acceptor_loss	1.0000
16:10902656:AGT:A	acceptor_gain	1.0000
16:10902657:G:GA	acceptor_gain	1.0000
16:10902657:GT:G	acceptor_gain	1.0000
16:10902657:GTG:G	acceptor_gain	1.0000
16:10902657:GTGC:G	acceptor_gain	1.0000
16:10902798:CATGG:C	donor_loss	1.0000
16:10902801:GGT:G	donor_loss	1.0000
16:10902802:G:GG	donor_gain	1.0000
16:10902802:G:T	donor_loss	1.0000
16:10902803:TGAG:T	donor_loss	1.0000
16:10902804:GAGT:G	donor_loss	1.0000
16:10903891:GACAG:G	donor_gain	1.0000
16:10903896:G:GA	donor_loss	1.0000
16:10903897:T:G	donor_loss	1.0000
16:10906497:A:AG	acceptor_gain	1.0000
16:10906498:G:GG	acceptor_gain	1.0000

AlphaMissense

7273 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:10918442:T:C	L1022P	0.998
16:10922179:C:A	N1054K	0.998
16:10922179:C:G	N1054K	0.998
16:10922419:C:A	N1082K	0.998
16:10922419:C:G	N1082K	0.998
16:10918452:C:A	N1025K	0.997
16:10918452:C:G	N1025K	0.997
16:10922418:A:T	N1082I	0.997
16:10916456:T:A	L1020H	0.996
16:10916456:T:C	L1020P	0.996
16:10918442:T:A	L1022Q	0.996
16:10922417:A:T	N1082Y	0.996
16:10910256:T:C	F962S	0.994
16:10915647:T:C	L989P	0.994
16:10918442:T:G	L1022R	0.994
16:10922424:T:C	F1084S	0.994
16:10922409:T:A	V1079D	0.993
16:10922435:G:T	G1088W	0.993
16:10922448:T:C	L1092P	0.993
16:10923232:T:A	W1108R	0.993
16:10923232:T:C	W1108R	0.993
16:10916388:C:A	N997K	0.992
16:10916388:C:G	N997K	0.992
16:10918451:A:T	N1025I	0.992
16:10922177:A:T	N1054Y	0.992
16:10922198:G:C	A1061P	0.992
16:10918481:T:C	L1035P	0.991
16:10918523:T:C	L1049P	0.991
16:10922178:A:T	N1054I	0.991
16:10922199:C:A	A1061D	0.990

dbSNP variants (sampled 300 via entrez): RS1000010903 (16:10874969 T>C), RS1000054947 (16:10911949 C>T), RS1000084022 (16:10875100 C>T), RS1000126236 (16:10884863 C>A,T), RS1000129743 (16:10893112 G>C), RS1000178186 (16:10919108 A>G,T), RS1000227613 (16:10931084 G>T), RS1000244721 (16:10879116 T>G), RS1000279852 (16:10912477 G>A,T), RS1000281442 (16:10930812 C>T), RS1000282264 (16:10879874 C>T), RS1000329163 (16:10921870 C>T), RS1000331151 (16:10912783 C>A,T), RS1000372871 (16:10870971 T>C), RS1000380527 (16:10936694 G>C)

Disease associations

OMIM: gene MIM:600005 | disease phenotypes: MIM:209920, MIM:180300

GenCC curated gene-disease

Disease	Classification	Inheritance
MHC class II deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
MHC class II deficiency	Definitive	AR

Mondo (3): MHC class II deficiency (MONDO:0008855), rheumatoid arthritis (MONDO:0008383), MHC class II deficiency 1 (MONDO:0971005)

Orphanet (2): Immunodeficiency by defective expression of MHC class II (Orphanet:572), NON RARE IN EUROPE: Rheumatoid arthritis (Orphanet:284130)

HPO phenotypes

68 total (30 of 68 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000246	Sinusitis
HP:0000371	Acute otitis media
HP:0000988	Skin rash
HP:0001080	Biliary tract abnormality
HP:0001260	Dysarthria
HP:0001370	Rheumatoid arthritis
HP:0001386	Joint swelling
HP:0001387	Joint stiffness
HP:0001508	Failure to thrive
HP:0001824	Weight loss
HP:0001875	Decreased total neutrophil count
HP:0001876	Pancytopenia
HP:0001890	Autoimmune hemolytic anemia
HP:0001904	Autoimmune neutropenia
HP:0001945	Fever
HP:0001973	Autoimmune thrombocytopenia
HP:0001999	Abnormal facial shape
HP:0002014	Diarrhea
HP:0002024	Malabsorption
HP:0002066	Gait ataxia
HP:0002205	Recurrent respiratory infections
HP:0002383	Infectious encephalitis
HP:0002583	Colitis
HP:0002633	Vasculitis
HP:0002718	Recurrent bacterial infections
HP:0002726	Recurrent Staphylococcus aureus infections
HP:0002728	Chronic mucocutaneous candidiasis
HP:0002783	Recurrent lower respiratory tract infections

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000612_10	Celiac disease	3.000000e-08
GCST000624_5	Ulcerative colitis	3.000000e-06
GCST003155_19	Systemic lupus erythematosus	7.000000e-17
GCST003156_33	Systemic lupus erythematosus	2.000000e-08
GCST003578_6	Nasopharyngeal carcinoma	4.000000e-09
GCST003622_40	Systemic lupus erythematosus	4.000000e-07
GCST004866_19	Alopecia areata	2.000000e-07
GCST005523_35	Celiac disease	6.000000e-10
GCST007993_25	Asthma (adult onset)	1.000000e-08
GCST007995_46	Asthma (childhood onset)	5.000000e-14
GCST008916_12	Asthma	1.000000e-30
GCST90002393_266	Monocyte count	5.000000e-14
GCST90002394_534	Monocyte percentage of white cells	2.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:1002011	adult onset asthma
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001172	Arthritis, Rheumatoid	C05.550.114.154; C05.799.114; C17.300.775.099; C20.111.199
C537079	Bare lymphocyte syndrome 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — NOD-like receptor family

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, increases expression	3
Arsenic	increases methylation, affects methylation	2
Azacitidine	increases reaction, decreases methylation, increases expression	2
Nickel	increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
aflatoxin B2	decreases methylation	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
tamibarotene	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Dimethyl Fumarate	decreases reaction, increases expression	1
Decitabine	increases expression, increases reaction	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	decreases expression	1
Alitretinoin	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Allergens	affects cotreatment, increases expression	1
Vehicle Emissions	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cannabinoids	affects methylation, increases abundance	1
Lipopolysaccharides	decreases reaction, increases expression	1
Melphalan	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	affects expression	1

Cellosaurus cell lines

45 cell lines: 22 induced pluripotent stem cell, 13 transformed cell line, 9 cancer cell line, 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1330	KM-H2	Cancer cell line	Male
CVCL_3414	Rj2.2.5	Cancer cell line	Male
CVCL_9W21	BLS-2	Transformed cell line	Female
CVCL_B5S3	IRFMNi001-B-1	Induced pluripotent stem cell	Male
CVCL_B7K8	BCH	Transformed cell line	Male
CVCL_B7K9	VIP1	Transformed cell line	Female
CVCL_B7LT	SaA fibroblast	Transformed cell line	Female
CVCL_B7LU	SaA LCL	Transformed cell line	Female
CVCL_B7LV	SaE fibroblast	Transformed cell line	Female
CVCL_B7LW	SaE LCL	Transformed cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00056667	PHASE4	COMPLETED	Relaxation Response Training for the Treatment of Rheumatoid Arthritis
NCT00094341	PHASE4	COMPLETED	Preference of Rheumatoid Arthritis (RA) Patients of Enbrel® (Etanercept) Auto-Injector Versus Enbrel® Pre-Filled Syringes
NCT00099554	PHASE4	COMPLETED	Effectiveness and Safety of Enbrel® (Etanercept) in Rheumatoid Arthritis Subjects Who Have Failed Remicade® (Infliximab)
NCT00111410	PHASE4	COMPLETED	Evaluating the Effect of Anakinra (r-metHuIL-1ra) on Vaccine AntibodyResponse in Subjects With Rheumatoid Arthritis (RA)
NCT00115219	PHASE4	COMPLETED	Evaluating Efficacy and Safety of Etanercept 50 mg Twice Weekly (BIW) in Rheumatoid Arthritis (RA) Subjects Who Are Sub-Optimal Responders to Etanercept 50 mg Once Weekly (QW)
NCT00121043	PHASE4	COMPLETED	Evaluating Kineret® (Anakinra) in Rheumatoid Arthritis (RA) Subjects Using aSelf-Reported Questionnaire
NCT00132418	PHASE4	COMPLETED	Study of Enbrel in Rheumatoid Arthritis (RA) Subjects With Comorbid Disorders
NCT00157872	PHASE4	COMPLETED	A Study of Rofecoxib Versus Naproxen in the Treatment of Chinese Patient With Rheumatoid Arthritis (0966-231)
NCT00195494	PHASE4	COMPLETED	Study Comparing Etanercept and Methotrexate vs. Methotrexate Alone in Rheumatoid Arthritis
NCT00208364	PHASE4	TERMINATED	A Two Centre Study to Assess the Long-term Performance of the Pinnacle™ Cup With a Metal-on-Metal Bearing in Primary Total Hip Replacement
NCT00208377	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the DePuy ASR™ System in Primary Hip Resurfacing Surgery
NCT00208390	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the Summit™ Hip in Primary Total Hip Replacement
NCT00208429	PHASE4	WITHDRAWN	A Multi-centre Study to Assess the Long-term Performance of the Pinnacle™ Cup With a Polyethylene-on-metal Bearing in Primary Total Hip Replacement
NCT00208455	PHASE4	TERMINATED	A Multi-centre Study to Assess the Long-term Performance of the DePuy PROXIMA™ Hip in Primary Total Hip Replacement
NCT00209859	PHASE4	COMPLETED	Methotrexate and Cyclosporine in Treatment of Early Rheumatoid Arthritis
NCT00216177	PHASE4	UNKNOWN	Comparison of Adalimumab and Infliximab Treatment of Rheumatoid Arthritis
NCT00233558	PHASE4	TERMINATED	Open-Label Steroid Reduction Study of Adalimumab With Methotrexate in Patients With Active Rheumatoid Arthritis
NCT00234234	PHASE4	COMPLETED	Predictors of the Response to Adalimumab in Rheumatoid Arthritis
NCT00234897	PHASE4	COMPLETED	Efficacy of HUMIRA in Subjects With Active Rheumatoid Arthritis
NCT00244556	PHASE4	COMPLETED	Study Comparing Enbrel (Etanercept) Plus Methotrexate Versus Enbrel Alone in Active Rheumatoid Arthritis Despite Current Methotrexate Therapy
NCT00252668	PHASE4	COMPLETED	Study Evaluating the Combination of Etanercept and Methotrexate in Rheumatoid Arthritis Subjects
NCT00259610	PHASE4	COMPLETED	Treatment of Early Aggressive Rheumatoid Arthritis (TEAR)
NCT00291915	PHASE4	UNKNOWN	Multicenter Randomized Prospective Trial Comparing Methotrexate Alone or in Combination With Adalimumab in Early Arthritis
NCT00319917	PHASE4	COMPLETED	A Double Blind Placebo Controlled Study to Assess the Efficacy on Joint Damage in RA Patients
NCT00334620	PHASE4	COMPLETED	Effectiveness of Radon Spa Therapy in Multimodal Rehabilitative Treatment of Rheumatoid Arthritis
NCT00346294	PHASE4	COMPLETED	An Open-Label Study to Assess the Rate of Failure of an Enbrel® (Etanercept) SureClick™ Auto-injector in Subjects With Rheumatoid Arthritis
NCT00356473	PHASE4	COMPLETED	Effects of Atorvastatin on Disease Activity and HDL Cholesterol Function in Patients With Rheumatoid Arthritis
NCT00369187	PHASE4	COMPLETED	Study of a Large Protein Molecule Administered With Escalating Doses of Recombinant Human Hyaluronidase
NCT00385528	PHASE4	COMPLETED	Effects of a Multi-Faceted Psychiatric Intervention Targeted at the Complex Medically Ill: a Randomized Controlled Trial
NCT00396747	PHASE4	COMPLETED	A Comparison of Methotrexate Alone or Combined to Infliximab or to Pulse Methylprednisolone in Early Rheumatoid Arthritis: A Magnetic Resonance Imaging Study
NCT00420927	PHASE4	COMPLETED	Study of the Optimal Protocol for Methotrexate and Adalimumab Combination Therapy in Early Rheumatoid Arthritis
NCT00422227	PHASE4	COMPLETED	Study Comparing Etanercept With Usual DMARD Therapy in Subjects With Rheumatoid Arthritis in the Asia Pacific Region
NCT00424502	PHASE4	COMPLETED	A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to a TNF-Blocker.
NCT00434200	PHASE4	UNKNOWN	Rheumatoid Arthritis Patients in Training
NCT00439062	PHASE4	COMPLETED	Treatment of Rheumatoid Arthritis With Roxithromycin
NCT00447759	PHASE4	COMPLETED	The Standard Care Versus Celecoxib Outcome Trial
NCT00462072	PHASE4	COMPLETED	Centocor Microarray Study of Patients
NCT00462345	PHASE4	COMPLETED	A Study of MabThera (Rituximab) in Combination With Methotrexate in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNF Therapies.
NCT00480272	PHASE4	COMPLETED	Prospective Study on Intensive Early Rheumatoid Arthritis Treatment
NCT00502853	PHASE4	COMPLETED	A Pilot Study of MabThera (Rituximab) Evaluated by MRI in Patients With Rheumatoid Arthritis.