RAG1

Summary

RAG1 (recombination activating 1, HGNC:9831) is a protein-coding gene on chromosome 11p12, encoding V(D)J recombination-activating protein 1 (P15918). Catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination.

The protein encoded by this gene is involved in activation of immunoglobulin V-D-J recombination. The encoded protein is involved in recognition of the DNA substrate, but stable binding and cleavage activity also requires RAG2. Defects in this gene can be the cause of several diseases.

Source: NCBI Gene 5896 — RefSeq curated summary.

At a glance

• Gene–disease (curated): recombinase activating gene 1 deficiency (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 943 total — 81 pathogenic, 50 likely-pathogenic
• Phenotypes (HPO): 122
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000448

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9831
Approved symbol	RAG1
Name	recombination activating 1
Location	11p12
Locus type	gene with protein product
Status	Approved
Aliases	RNF74, MGC43321
Ensembl gene	ENSG00000166349
Ensembl biotype	protein_coding
OMIM	179615
Entrez	5896

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000299440, ENST00000529126, ENST00000534663, ENST00000697713, ENST00000697714, ENST00000697715

RefSeq mRNA: 5 — MANE Select: NM_000448 NM_000448, NM_001377277, NM_001377278, NM_001377279, NM_001377280

CCDS: CCDS7902

Canonical transcript exons

ENST00000299440 — 2 exons

Exon	Start	End
ENSE00001102354	36568007	36568122
ENSE00001327949	36573291	36579762

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 96.02.

FANTOM5 (CAGE): breadth broad, TPM avg 4.4775 / max 3810.5748, expressed in 235 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113908	3.7491	26
113904	0.3745	205
113907	0.2504	14
113906	0.0604	10
113909	0.0266	4
113911	0.0074	3
113910	0.0040	1
113905	0.0036	2
206253	0.0015	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	96.02	gold quality
buccal mucosa cell	CL:0002336	94.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.04	gold quality
bone marrow	UBERON:0002371	71.88	gold quality
spleen	UBERON:0002106	67.64	gold quality
apex of heart	UBERON:0002098	67.09	gold quality
tendon of biceps brachii	UBERON:0008188	65.48	silver quality
stromal cell of endometrium	CL:0002255	64.16	gold quality
bone marrow cell	CL:0002092	63.80	silver quality
adrenal tissue	UBERON:0018303	63.62	gold quality
right adrenal gland cortex	UBERON:0035827	62.79	gold quality
right adrenal gland	UBERON:0001233	62.27	gold quality
metanephros cortex	UBERON:0010533	61.99	gold quality
islet of Langerhans	UBERON:0000006	61.79	gold quality
left adrenal gland	UBERON:0001234	60.87	gold quality
thyroid gland	UBERON:0002046	60.78	gold quality
left lobe of thyroid gland	UBERON:0001120	60.70	gold quality
right lobe of thyroid gland	UBERON:0001119	60.40	gold quality
heart left ventricle	UBERON:0002084	59.96	gold quality
adrenal gland	UBERON:0002369	59.65	gold quality
trabecular bone tissue	UBERON:0002483	59.60	silver quality
left adrenal gland cortex	UBERON:0035825	59.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	59.31	silver quality
cardiac ventricle	UBERON:0002082	59.31	gold quality
right lobe of liver	UBERON:0001114	59.13	gold quality
rectum	UBERON:0001052	58.91	gold quality
adrenal cortex	UBERON:0001235	58.77	gold quality
duodenum	UBERON:0002114	58.61	gold quality
adult mammalian kidney	UBERON:0000082	58.29	gold quality
gall bladder	UBERON:0002110	57.79	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	1140.49
E-CURD-6	yes	985.98
E-ANND-3	yes	4.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, FOXP1, GATA2, GATA3, GFI1, TCF3

miRNA regulators (miRDB)

171 targeting RAG1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-5696	99.98	72.36	4487
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3688-3P	99.97	72.02	2834

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• RAG expression is up-regulated in peripheral IgD+ and VpreB+ B cells of patients with active SLE. (PMID:12115231)
• Multiple PCR-SSCP analysisof RAG-1 showed shifted bands in 5 cases: Philadelphia-positive ALL, MLL, FL, and AML. An A-to-G SNP at 2571 was found. (PMID:12145704)
• B-cell differentiation arrest in bone marrow of RAG-deficient SCID patients corresponds to residual recombination activities of mutated RAG1 and RAG2 proteins. (PMID:12200379)
• RAG1 expression and non-functional TCR rearrangements continuously take place in peripheral mature T cells of all activation/differentiation stages (PMID:12355431)
• Data show that a mature nonmalignant human B cell clone producing IgMlambda-ICA can express RAG-1/RAG-2 transcripts (PMID:12757263)
• RAG1 mRNA splice forms have been identified that are expressed in immature T cells (CD2+CD7+CD3-) of the jejunal mucosa, both intraepithelially and in lamina propria. (PMID:14500629)
• Erk and Abl kinases suppress RAG-1 and -2 gene expression through T cell receptor-independent basal signaling (PMID:14624253)
• RAG1 and RAG2 interact with recombination signal sequence DNA in the coding region in pre-and post-cleavage type synaptic complexes (PMID:15249552)
• expressed in peripheral blood mononuclear cells (PBMCs) from 42% of patients with infectious mononucleosis but not from health control subjects. (PMID:15295705)
• Activated mature CD5-positive human tonsil B cells coexpress both RAG1 and RAG2 mRNA and protein, and display DNA cleavage resulting from their recombinase activity. (PMID:15843554)
• Novel RAG1 mutation in a case of severe combined immunodeficiency. A novel homozygous thymine to cytosine substitution at nucleotide position 2686 (PMID:16061569)
• novel RAG-1 mutation, E649A, that supports elevated cleavage activity in vitro by preferentially enhancing hairpin formation (PMID:16738334)
• Ths review focusses on the variation of inherited hypomorphic mutations of recombination activating genes either 1 or 2 (RAG1/2) that have been detected in most Omenn syndrome patients. (PMID:17075247)
• analysis of structure-specific nicking of small heteroduplexes by the RAG complex (PMID:17307402)
• 5 unrelated cases of combined immune deficiency due to hypomorphic RAG mutations, demonstrate the absence of invariant NKT cells (PMID:17890453)
• IL-6 initiates the expression of RAG1 in circulating B cells, and extends those in tonsil B cells. (PMID:17982069)
• the RAG-7-mer interaction is a critical step for coding DNA distortion and hairpin formation in the context of the 12/23 rule. (PMID:18089566)
• We describe three girls with a primary immunodeficiency disease associated with hypomorphic mutations in one of the two recombinase activating genes (RAG1 and RAG2). (PMID:18463379)
• Results indicate that the novel R776W missense mutation in RAG-1 is causal in the T(-)B(-)NK(+) severe combined immunodeficiency disease phenotype in Athabascan-speaking Dine Indians from the Canadian Northwest Territories (PMID:18701881)
• RAG1 Arg972Qln mutation, located in the primary sequence near catalytic amino acid Glu962, is hypersensitive to certain coding flank sequences in a patient with Omenn syndrome. (PMID:18768869)
• Karyopherin alpha 1 is a putative substrate of the RAG1 ubiquitin ligase. (PMID:19118899)
• Studies in B and T lymphocytes demonstrate that the reduction in RAG expression at the immature B and double-positive (DP) T cell stages is mediated through tonic (foreign antigen independent) receptor signaling. (PMID:19359154)
• Two independent signals are required for the induction of RAG gene expression in B cells that infiltrate the synovium of patients with RA. (PMID:19404965)
• RAG1 mutations are associated with severe combined immunodeficiencies. (PMID:19458910)
• RAG1-mediated histone monoubiquitylation activity plays a role in regulating the joining phase of chromosomal V(D)J recombination. (PMID:20122409)
• Hypomorphic Rag mutations can cause destructive midline granulomatous disease. (PMID:20489056)
• In a subset of acute lymphoblastic leukemia RAG might create one of the initiating double-strand breaks. (PMID:20703256)
• These disparate and atypical presentations of hypomorphic RAG1 mutations highlight the role of RAG1 in immune function and autoimmunity and expand the disease spectrum linked to these genes. (PMID:20956421)
• study reports 5 cases of RAG deficiency; genetic defects were heterogeneous and included 6 novel RAG mutations; all missense mutations except for Met443Ile in RAG2 were located in active core regions of RAG1 or RAG2 (PMID:21131235)
• study demonstrates that exogenous TCR alpha and beta chains transferred into the human immature RAG(+) T cell line Sup-T1 by lentiviral transduction inhibit RAG expression through tonic signaling (PMID:21481940)
• RAG mutations are associated with Idiopathic CD4+ T lymphopenia without autoimmunity or granulomatous disease. (PMID:21502542)
• In the RAG1 gene we detected two novel mutations: L454Q and 469 fs-4bpdel. In the RAG 2 gene: 3 novel mutations: D65Y, G157V, and E480X. One T-B- SCID patient had a compound heterozygote for new mutations in the adenosine deaminase gene: W264X and R235W. (PMID:21624848)
• IL7R and RAG1/2 genes mutations/polymorphisms in patients with SCID. (PMID:21625022)
• The results indicate that in cancer cells E2A, FOXO1 and FOXP1 regulate RAG1 and RAG2 expression, which initiates Ig gene rearrangement much in the way similar to B lymphocytes. (PMID:21655267)
• We report for the first time 3 children with Omenn syndrome in the Chinese population and identify 3 novel mutations in the RAG1 gene. (PMID:21771083)
• Homozygous mutation of p.R394Q/p.R394Q and p.R776Q, 3047-3049 del GCC mutations are novel and they are causing serious T-B-NK + SCID. (PMID:22424479)
• Expression of recombinase RAG-1 in diabetic patients was detected primarily in alphabetaTCR+CD40+ lymphocytes. (PMID:22803080)
• Mutations to the sequence of the nonamer and deletion of the nonamer-binding domain of RAG1 reinforced the role of the nonamer in the enhancement in RAG cleavage. (PMID:22891626)
• A dual interaction between the DNA damage response protein MDC1 and the RAG1 subunit of the V(D)J recombinase. (PMID:22942284)
• Bidirectional activity of the NWC promoter is responsible for RAG-2 transcription in non-lymphoid cells [NWC] (PMID:22984564)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rag1	ENSDARG00000052122
mus_musculus	Rag1	ENSMUSG00000061311
rattus_norvegicus	Rag1	ENSRNOG00000004630

Protein

Protein identifiers

V(D)J recombination-activating protein 1 — P15918 (reviewed: P15918)

Alternative names: RING finger protein 74

All UniProt accessions (1): P15918

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3’-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5’-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at ‘Lys-4’ (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In addition to its endonuclease activity, RAG1 also acts as an E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination. Mediates polyubiquitination of KPNA1.

Subunit / interactions. Homodimer. Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2. Interacts with DCAF1, leading to recruitment of the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex to ubiquitinate proteins and limit error-prone repair during V(D)J recombination.

Subcellular location. Nucleus.

Tissue specificity. Maturing lymphoid cells.

Post-translational modifications. Autoubiquitinated in the presence of CDC34/UBCH3.

Disease relevance. Combined cellular and humoral immune defects with granulomas (CHIDG) [MIM:233650] Immunodeficiency disease with granulomas in the skin, mucous membranes, and internal organs. Other characteristics include hypogammaglobulinemia, a diminished number of T and B-cells, and sparse thymic tissue on ultrasonography. The disease is caused by variants affecting the gene represented in this entry. Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive (T(-)B(-)NK(+) SCID) [MIM:601457] A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. The disease is caused by variants affecting the gene represented in this entry. Omenn syndrome (OS) [MIM:603554] Severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T-cells, hypereosinophilia, and high IgE levels. The disease is caused by variants affecting the gene represented in this entry. Alpha/beta T-cell lymphopenia, with gamma/delta T-cell expansion, severe cytomegalovirus infection and autoimmunity (T-CMVA) [MIM:609889] An immunological disorder characterized by oligoclonal expansion of TCR gamma/delta T-cells, TCR alpha/beta T-cell lymphopenia, severe, disseminated cytomegalovirus infection and autoimmune cytopenia. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 divalent metal cation per subunit. Mg(2+) or Mn(2+).

Domain organisation. The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity. The NBD (nonamer binding) DNA-binding domain mediates the specific binding to the nonamer RSS motif by forming a tightly interwoven homodimer that binds and synapses 2 nonamer elements, with each NBD making contact with both DNA molecules. Each RSS is composed of well-conserved heptamer (consensus 5’-CACAGTG-3’) and nonamer (consensus 5’-ACAAAAACC-3’) sequences separated by a spacer of either 12 bp or 23 bp.

Similarity. Belongs to the RAG1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P15918-1	1	yes
P15918-2	2

RefSeq proteins (5): NP_000439, NP_001364206, NP_001364207, NP_001364208, NP_001364209 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR018957	Znf_C3HC4_RING-type	Domain
IPR019485	RAG1_Znf	Domain
IPR023336	RAG_nonamer-bd_dom	Domain
IPR024627	RAG1	Family
IPR035714	RAG1_imp-bd	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR058552	RAG1_DNA-bd	Domain
IPR058553	RAG1_pre-RNase_H	Domain
IPR058554	RAG1_RNase_H	Domain
IPR058555	RAG1_ZnC2	Domain
IPR058556	RAG1_ZnH2	Domain
IPR058557	RAG1_C	Domain
IPR058558	RING-HC_RAG1	Domain

Pfam: PF00097, PF10426, PF12560, PF12940, PF26024, PF26025, PF26100, PF26101, PF26104, PF26105

UniProt features (80 total): sequence variant 51, binding site 19, zinc finger region 2, region of interest 2, chain 1, site 1, cross-link 1, splice variant 1, DNA-binding region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15918-F1	81.68	0.57

Functional residue map

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

Catalytic / active sites (1): 896 (essential for dna hairpin formation, participates in base-stacking interactions near the cleavage site)

Ligand- & substrate-binding residues (19): 296; 296; 298; 308; 310; 313; 316; 328; 331; 358; 363; 375 …

Post-translational modifications (1): 234

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1266695	Interleukin-7 signaling
R-HSA-5687128	MAPK6/MAPK4 signaling

MSigDB gene sets: 423 (showing top): GGGACCA_MIR133A_MIR133B, GOBP_REGULATION_OF_CELL_ACTIVATION, GOMF_ENDONUCLEASE_ACTIVITY, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_B_CELL_ACTIVATION, GOMF_NUCLEASE_ACTIVITY, GOBP_ASSOCIATIVE_LEARNING, GOBP_T_CELL_HOMEOSTASIS, GOBP_LYMPHOCYTE_HOMEOSTASIS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR

GO Biological Process (17): adaptive immune response (GO:0002250), pre-B cell allelic exclusion (GO:0002331), DNA recombination (GO:0006310), chromatin organization (GO:0006325), immune response (GO:0006955), visual learning (GO:0008542), B cell differentiation (GO:0030183), T cell differentiation in thymus (GO:0033077), V(D)J recombination (GO:0033151), T cell homeostasis (GO:0043029), positive regulation of T cell differentiation (GO:0045582), thymus development (GO:0048538), protein autoubiquitination (GO:0051865), negative regulation of thymocyte apoptotic process (GO:0070244), regulation of behavioral fear response (GO:2000822), regulation of T cell differentiation (GO:0045580), negative regulation of T cell apoptotic process (GO:0070233)

GO Molecular Function (16): DNA binding (GO:0003677), endonuclease activity (GO:0004519), ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), hydrolase activity (GO:0016787), histone binding (GO:0042393), protein homodimerization activity (GO:0042803), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872), ubiquitin protein ligase activity (GO:0061630), catalytic activity (GO:0003824), nuclease activity (GO:0004518), protein binding (GO:0005515), transferase activity (GO:0016740), identical protein binding (GO:0042802), double-stranded DNA endonuclease activity (GO:1990238)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), DNA recombinase complex (GO:0097519), endodeoxyribonuclease complex (GO:1905347)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Interleukins	1
MAPK family signaling cascades	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
T cell differentiation	3
catalytic activity	2
protein binding	2
immune response	1
pre-B cell differentiation	1
regulation of gene expression	1
DNA metabolic process	1
cellular component organization	1
immune system process	1
response to stimulus	1
visual behavior	1
associative learning	1
lymphocyte differentiation	1
B cell activation	1
somatic diversification of immune receptors via germline recombination within a single locus	1
lymphocyte homeostasis	1
regulation of T cell differentiation	1
positive regulation of lymphocyte differentiation	1
positive regulation of T cell activation	1
hematopoietic or lymphoid organ development	1
gland development	1
protein ubiquitination	1
negative regulation of T cell apoptotic process	1
thymocyte apoptotic process	1
regulation of thymocyte apoptotic process	1
behavioral fear response	1
regulation of defense response	1
regulation of behavior	1
regulation of fear response	1
regulation of lymphocyte differentiation	1
regulation of T cell activation	1
negative regulation of lymphocyte apoptotic process	1
T cell apoptotic process	1
regulation of T cell apoptotic process	1
nucleic acid binding	1
nuclease activity	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
identical protein binding	1
protein dimerization activity	1

Protein interactions and networks

STRING

3468 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAG1	RAG2	P55895	999
RAG1	CD4	P01730	898
RAG1	CD8A	P01732	860
RAG1	PTPRC	P08575	841
RAG1	DCLRE1C	Q96SD1	831
RAG1	IGHV4-38-2	P0DP08	817
RAG1	FOXP3	Q9BZS1	814
RAG1	IL7R	P16871	795
RAG1	IL2RG	P31785	787
RAG1	IL2	P01585	755
RAG1	IGLL1	P15814	749
RAG1	IFNG	P01579	742
RAG1	VPREB1	P12018	740
RAG1	PRKDC	P78527	738
RAG1	KPNA1	P52294	737

IntAct

19 interactions, top by confidence:

A	B	Type	Score
KPNA1	RAG1	psi-mi:“MI:0915”(physical association)	0.510
RAG1	KPNA1	psi-mi:“MI:0915”(physical association)	0.510
CRK	RAG1	psi-mi:“MI:0915”(physical association)	0.400
NCK1	RAG1	psi-mi:“MI:0915”(physical association)	0.400
RAG1	PLCG1	psi-mi:“MI:0915”(physical association)	0.400
RAG1	SERBP1	psi-mi:“MI:0915”(physical association)	0.400
HSP90AB1	RAG1	psi-mi:“MI:0915”(physical association)	0.400
FKBP5	RAG1	psi-mi:“MI:0915”(physical association)	0.400
NUDC	RAG1	psi-mi:“MI:0915”(physical association)	0.400
RAG1	NUDCD3	psi-mi:“MI:0915”(physical association)	0.400
	RAG1	psi-mi:“MI:0915”(physical association)	0.400
CACYBP	RAG1	psi-mi:“MI:0915”(physical association)	0.400
PTGES3	RAG1	psi-mi:“MI:0915”(physical association)	0.400
PPP5C	RAG1	psi-mi:“MI:0915”(physical association)	0.400
MYC		psi-mi:“MI:0914”(association)	0.350

BioGRID (62): RUNX1 (Affinity Capture-Western), RAG1 (Affinity Capture-Western), RAG1 (Reconstituted Complex), RAG1 (Synthetic Lethality), RAG1 (Reconstituted Complex), RAG1 (Affinity Capture-Western), RAG1 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2C (Reconstituted Complex), UBC (Biochemical Activity), RAG2 (Co-purification), RAG1 (Biochemical Activity), UBE2D1 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), RAG1 (PCA)

ESM2 similar proteins: A4UTQ0, A8E7C5, A8PJX4, A9CB86, B0W2W6, B3LVQ1, B3MB79, B3MJV4, B3MZY6, B3NEF0, B4GN43, B4GN46, B4IB36, B4J3A3, B4JHB4, B4K5S8, B4KVI7, B4LF72, B4LWT5, B4PIP5, B4QL99, B5DR03, B5DRY3, O00522, P15918, P24271, P34088, Q08AW5, Q08D62, Q16YA8, Q17G65, Q1LZE8, Q32KV2, Q4R786, Q5BKL1, Q5M888, Q64749, Q6S5J6, Q6TNJ1, Q7ZXY0

Diamond homologs: A7XUJ6, B5DF45, B6CJY4, B6CJY5, D3YY23, O13033, O70263, P15918, P15919, P39428, P39429, P43254, P70196, P93471, Q02084, Q13077, Q17RB8, Q1L5Z9, Q1XHT8, Q28DL4, Q3MV19, Q3UWA4, Q3ZCC3, Q54FD5, Q587N7, Q5C8U3, Q5C8U4, Q5D7I3, Q5D7J2, Q6CTZ8, Q6DJN2, Q6IWL4, Q6J2U6, Q6P9F5, Q6ZMN7, Q865W2, Q867B5, Q8TBB1, Q91187, Q9BYJ4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
RAG1	up-regulates	MTOR	relocalization
Ub:E2	“up-regulates activity”	RAG1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 13 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
ESR-mediated signaling	5	64.2×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	5	39.8×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	81
Likely pathogenic	50
Uncertain significance	394
Likely benign	312
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1034220	NM_000448.3(RAG1):c.2487_2488delinsTT (p.Arg829_Lys830delinsSerTer)	Pathogenic
1072413	NM_000448.3(RAG1):c.1211G>A (p.Arg404Gln)	Pathogenic
1072942	NM_000448.3(RAG1):c.2615T>G (p.Leu872Ter)	Pathogenic
1075542	NM_000448.3(RAG1):c.2867T>C (p.Ile956Thr)	Pathogenic
1076023	NM_000448.3(RAG1):c.1798del (p.Glu600fs)	Pathogenic
1120224	NM_000448.3(RAG1):c.1460T>G (p.Met487Arg)	Pathogenic
1175181	NM_000448.3(RAG1):c.1528G>T (p.Glu510Ter)	Pathogenic
13139	NM_000448.3(RAG1):c.2164G>A (p.Glu722Lys)	Pathogenic
13144	NM_000448.3(RAG1):c.1186C>T (p.Arg396Cys)	Pathogenic
13145	NM_000448.3(RAG1):c.2735A>G (p.Tyr912Cys)	Pathogenic
13146	NM_000448.3(RAG1):c.1187G>A (p.Arg396His)	Pathogenic
13147	NM_000448.3(RAG1):c.1286A>G (p.Asp429Gly)	Pathogenic
13148	NM_000448.3(RAG1):c.1681C>T (p.Arg561Cys)	Pathogenic
13150	NM_000448.3(RAG1):c.1612_1624del (p.Ile538fs)	Pathogenic
13154	NM_000448.3(RAG1):c.2521C>T (p.Arg841Trp)	Pathogenic
13155	NM_000448.3(RAG1):c.2942A>C (p.Gln981Pro)	Pathogenic
13158	NM_000448.3(RAG1):c.2333G>A (p.Arg778Gln)	Pathogenic
1353693	NM_000448.3(RAG1):c.2736_2737del (p.Tyr912_Ser913delinsTer)	Pathogenic
1458103	NM_000448.3(RAG1):c.2475del (p.Glu827fs)	Pathogenic
1505484	NM_000448.3(RAG1):c.2882_2891del (p.Ser961fs)	Pathogenic
191270	NM_000448.3(RAG1):c.555del (p.Lys186fs)	Pathogenic
2022529	NM_000448.3(RAG1):c.2065G>T (p.Glu689Ter)	Pathogenic
2042280	NM_000448.3(RAG1):c.1653C>G (p.Tyr551Ter)	Pathogenic
2108168	NM_000448.3(RAG1):c.354del (p.Phe118fs)	Pathogenic
2113317	NM_000448.3(RAG1):c.2627del (p.Glu876fs)	Pathogenic
2118233	NM_000448.3(RAG1):c.1297del (p.Val433fs)	Pathogenic
2137054	NM_000448.3(RAG1):c.1148_1149del (p.Lys383fs)	Pathogenic
235411	NM_000448.3(RAG1):c.775del (p.Ser259fs)	Pathogenic
2678195	NM_000448.3(RAG1):c.2615T>A (p.Leu872Ter)	Pathogenic
2678203	NM_000448.3(RAG1):c.691C>T (p.Gln231Ter)	Pathogenic

SpliceAI

176 predictions. Top by Δscore:

Variant	Effect	Δscore
11:36573286:CTCA:C	acceptor_loss	0.9900
11:36573287:TCAG:T	acceptor_loss	0.9900
11:36573288:CAG:C	acceptor_loss	0.9900
11:36573289:A:AT	acceptor_loss	0.9900
11:36573290:G:GT	acceptor_loss	0.9900
11:36573289:A:AG	acceptor_gain	0.9800
11:36573290:G:GG	acceptor_gain	0.9800
11:36568119:CAAG:C	donor_loss	0.9700
11:36568120:AAGGT:A	donor_loss	0.9700
11:36568122:GGT:G	donor_loss	0.9700
11:36568123:GT:G	donor_loss	0.9700
11:36568124:T:A	donor_loss	0.9700
11:36573280:ATT:A	acceptor_gain	0.9700
11:36568118:GCAAG:G	donor_gain	0.9500
11:36576083:TTC:T	donor_gain	0.9500
11:36572872:GC:G	donor_gain	0.9400
11:36573282:T:A	acceptor_loss	0.9400
11:36573282:T:TA	acceptor_gain	0.9400
11:36573290:GGT:G	acceptor_gain	0.9400
11:36573281:T:G	acceptor_gain	0.9300
11:36573280:A:AG	acceptor_gain	0.9200
11:36573290:GGTA:G	acceptor_gain	0.9200
11:36573287:TCAGG:T	acceptor_gain	0.9100
11:36573288:CAGG:C	acceptor_gain	0.9100
11:36573290:GGTAC:G	acceptor_gain	0.9000
11:36573289:AGGTA:A	acceptor_gain	0.8900
11:36576036:A:AG	donor_gain	0.8800
11:36576037:G:GG	donor_gain	0.8800
11:36575986:A:AG	donor_gain	0.8700
11:36575987:G:GG	donor_gain	0.8700

AlphaMissense

6958 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:36575865:G:A	G854D	1.000
11:36575874:C:A	A857D	1.000
11:36575990:T:A	W896R	1.000
11:36575990:T:C	W896R	1.000
11:36576126:A:T	K941I	1.000
11:36576179:T:A	W959R	1.000
11:36576179:T:C	W959R	1.000
11:36576191:G:A	G963R	1.000
11:36576191:G:C	G963R	1.000
11:36576219:G:C	R972T	1.000
11:36576219:G:T	R972M	1.000
11:36574665:T:C	L454P	0.999
11:36574719:C:A	A472D	0.999
11:36574725:G:C	R474P	0.999
11:36574740:T:C	L479P	0.999
11:36574754:T:C	Y484H	0.999
11:36574754:T:G	Y484D	0.999
11:36574755:A:G	Y484C	0.999
11:36574802:T:C	F500L	0.999
11:36574803:T:C	F500S	0.999
11:36574804:T:A	F500L	0.999
11:36574804:T:G	F500L	0.999
11:36574868:T:A	W522R	0.999
11:36574868:T:C	W522R	0.999
11:36575120:G:A	G606R	0.999
11:36575120:G:C	G606R	0.999
11:36575492:T:C	C730R	0.999
11:36575494:T:G	C730W	0.999
11:36575699:T:C	C799R	0.999
11:36575701:T:G	C799W	0.999

dbSNP variants (sampled 300 via entrez): RS1000010098 (11:36537405 A>G), RS1000025366 (11:36514623 G>A), RS1000060552 (11:36514394 A>G), RS1000089586 (11:36540106 A>G), RS1000099489 (11:36550002 A>T), RS1000140091 (11:36559958 A>T), RS1000160543 (11:36548655 C>T), RS1000170608 (11:36508679 A>G), RS1000187526 (11:36508872 A>C,G), RS1000257513 (11:36530581 C>A), RS1000426012 (11:36572209 G>A), RS1000432664 (11:36524697 C>G), RS1000446357 (11:36537156 C>T), RS1000586418 (11:36519034 A>T), RS1000603514 (11:36580085 T>C)

Disease associations

OMIM: gene MIM:179615 | disease phenotypes: MIM:233650, MIM:601457, MIM:603554, MIM:609889, MIM:615848, MIM:616568, MIM:608971, MIM:244400, MIM:312080, MIM:601547

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency disease	Definitive	Autosomal recessive
Omenn syndrome	Definitive	Autosomal recessive
recombinase activating gene 1 deficiency	Definitive	Autosomal recessive
severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive	Strong	Autosomal recessive
combined immunodeficiency due to partial RAG1 deficiency	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
recombinase activating gene 1 deficiency	Definitive	AR

Mondo (13): combined immunodeficiency with skin granulomas (MONDO:0009306), severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive (MONDO:0011086), Omenn syndrome (MONDO:0011338), combined immunodeficiency due to partial RAG1 deficiency (MONDO:0012359), recombinase activating gene 1 deficiency (MONDO:0000572), severe combined immunodeficiency (MONDO:0015974), tumor predisposition syndrome 3 (MONDO:0014368), immunodeficiency 104 (MONDO:0012163), primary ciliary dyskinesia (MONDO:0016575), Pelizaeus-Merzbacher spectrum disorder (MONDO:0010714), cataract 3 multiple types (MONDO:0011104), microcephaly (MONDO:0001149), immunodeficiency disease (MONDO:0021094)

Orphanet (9): Combined immunodeficiency with granulomatosis (Orphanet:157949), Severe combined immunodeficiency due to complete RAG1/2 deficiency (Orphanet:331206), Omenn syndrome (Orphanet:39041), Combined immunodeficiency due to partial RAG1 deficiency (Orphanet:231154), Severe combined immunodeficiency (Orphanet:183660), Familial melanoma (Orphanet:618), Primary ciliary dyskinesia (Orphanet:244), Pelizaeus-Merzbacher disease (Orphanet:702), Cataract-microcornea syndrome (Orphanet:1377)

HPO phenotypes

122 total (30 of 122 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000100	Nephrotic syndrome
HP:0000265	Mastoiditis
HP:0000388	Otitis media
HP:0000509	Conjunctivitis
HP:0000561	Absent eyelashes
HP:0000778	Hypoplasia of the thymus
HP:0000821	Hypothyroidism
HP:0000944	Abnormal metaphysis morphology
HP:0000958	Dry skin
HP:0000962	Hyperkeratosis
HP:0000964	Eczematoid dermatitis
HP:0000969	Edema
HP:0000980	Pallor
HP:0000988	Skin rash
HP:0000989	Pruritus
HP:0001019	Erythroderma
HP:0001036	Parakeratosis
HP:0001072	Thickened skin
HP:0001250	Seizure
HP:0001287	Meningitis
HP:0001369	Arthritis
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001581	Recurrent skin infections
HP:0001596	Alopecia
HP:0001744	Splenomegaly
HP:0001831	Short toe
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002318_161	Rheumatoid arthritis	1.000000e-07
GCST002318_35	Rheumatoid arthritis	3.000000e-07

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D002925	Ciliary Motility Disorders	C08.200; C09.150; C16.131.077.245.500; C16.320.184.500
D007619	Kartagener Syndrome	C08.127.384.500; C08.200.531; C08.695.501; C09.150.531; C14.240.400.280.500; C14.280.400.280.500; C16.131.077.245.500.531; C16.131.240.400.280.500; C16.131.740.501; C16.131.810.250.500; C16.320.184.500.531; C16.320.480
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D020371	Pelizaeus-Merzbacher Disease	C10.228.140.163.100.362.775; C10.228.140.695.625.775; C10.314.400.775; C16.320.322.906; C16.320.565.189.362.775; C18.452.132.100.362.775; C18.452.648.189.362.775
D016511	Severe Combined Immunodeficiency	C16.320.798.750; C16.614.815; C18.452.284.800; C20.673.795.750
C563691	Alpha-Beta T-Cell Lymphopenia with Gamma-Delta T-Cell Expansion, Severe Cytomegalovirus Infection, and Autoimmunity (supp.)
C563294	Cataract, Congenital, Cerulean Type, 2 (supp.)
C567115	Combined Cellular And Humoral Immune Defects With Granulomas (supp.)
C563822	Severe Combined Immunodeficiency, Autosomal Recessive, T Cell Negative, B Cell Positive, NK Cell Positive (supp.)
C563311	Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Negative, NK Cell-Positive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	6
trichostatin A	increases expression	2
perfluorooctanoic acid	decreases expression	2
perfluorooctane sulfonic acid	decreases expression	2
perfluoro-n-nonanoic acid	decreases expression	2
perfluorohexanesulfonic acid	decreases expression	2
5-amino-7-(cyclohexylamino)-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid	decreases expression	2
GSK-J4	decreases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
deoxynivalenol	increases expression	1
perfluorodecanoic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Decitabine	increases expression	1
Arsenic	affects binding, decreases reaction, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Calcitriol	increases expression	1
Dexamethasone	decreases expression	1
Folic Acid	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	decreases methylation	1
Acrylamide	increases expression	1
S-Nitrosoglutathione	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_2Z29	ID00078	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001542	PHASE4	COMPLETED	Fluconazole Prophylaxis of Thrush in AIDS
NCT00144157	PHASE4	COMPLETED	Open Label Study of NVP+CBV Treatment in Women Who Have Received sdNVP for the pMTCT of HIV
NCT00162643	PHASE4	UNKNOWN	PI Vs. NNRTI Based Therapy for HIV Advanced Disease
NCT00273988	PHASE4	COMPLETED	Pharmacokinetic Study of Interaction Between Nevirapine and Methadone in HIV-1 Infected, Opioid-dependent Adults
NCT00981318	PHASE4	TERMINATED	Pilot Assessment of Lopinavir/Ritonavir and Maraviroc
NCT01086878	PHASE4	COMPLETED	Safety of Cotrimoxazole in HIV- and HAART-exposed Infants
NCT01090102	PHASE4	COMPLETED	Mesalamine to Reduce T Cell Activation in HIV Infection
NCT01147042	PHASE4	TERMINATED	Biochemical Response to Interferon-Gamma in Subjects With Specific Gene Mutation in Chronic Granulomatous Disease
NCT01230580	PHASE4	UNKNOWN	Protease Inhibitor Monotherapy Versus Ongoing Triple-therapy in the Long Term Management of HIV Infection (PIVOT)
NCT01465958	PHASE4	COMPLETED	Pharmacokinetics, Safety, and Tolerability of Subcutaneous GAMUNEX-C in Pediatric Subjects With Primary Immunodeficiency
NCT02274662	PHASE4	COMPLETED	Expanded Access Protocol Thymus Transplantation
NCT02348177	PHASE4	COMPLETED	Pharmacokinetics of Lopinavir/Ritonavir Superboosting in Infants and Young Children Co-infected With HIV and TB
NCT02396979	PHASE4	COMPLETED	Intervention of HIV, Drug Use and the Criminal Justice System in Malaysia
NCT02490956	PHASE4	UNKNOWN	Diagnostic Immunization With Rabies Vaccine in Patients With PID
NCT02503293	PHASE4	COMPLETED	A Study to Compare Quality of Life and Satisfaction in Primary Immunodeficient Patients Treated With Subcutaneous Injections of Gammanorm® 165 mg/mL Administered With Two Different Delivery Devices: Injections Using Pump or Rapid Push
NCT02881437	PHASE4	COMPLETED	IgG Level in Primary Immunodeficiency Switching From Standard SCIG to Every Other Week HyQvia
NCT03033745	PHASE4	COMPLETED	Safety and Tolerability of Higher Infusion Parameters of IgPro20 (Hizentra) in Subjects With Primary Immunodeficiency (PID)
NCT03677557	PHASE4	UNKNOWN	Safety, Tolerability, Patient Satisfaction and Cost of 16.5% Subcutaneous Immunoglobulin (Cutaquig®) Treatment
NCT04192487	PHASE4	COMPLETED	Effects of Crofelemer on the Gut Microbiome in Healthy Volunteers and in HIV+ Patients With Non-Infectious Diarrhea
NCT04566692	PHASE4	COMPLETED	A Study to Evaluate IGSC 20% Biweekly Dosing in Treatment-Experienced Participants and Loading/Maintenance Dosing in Treatment-Naïve Participants With Primary Immunodeficiency
NCT05493969	PHASE4	NOT_YET_RECRUITING	Efficacy and Tolerability of DTG Plus 3TC in HIV Infected Adults With Virologically Suppression and TDF Toxicity
NCT06576024	PHASE4	COMPLETED	Immunogenicity and Safety of Inactivated Hepatitis A Vaccine in HIV-infected People
NCT06634641	PHASE4	RECRUITING	Clozapine-related Immunodeficiency in Parkinsons Disease
NCT07076446	PHASE4	ACTIVE_NOT_RECRUITING	An Open-label, Multicenter Study to Assess the Pharmacokinetics (PK), Safety, and Tolerability of Subcutaneous IgPro20 in Immunoglobulin (IG) Treatment-naïve Participants With Primary Immunodeficiency (PID)
NCT00000118	PHASE3	COMPLETED	Ganciclovir Implant Study for Cytomegalovirus Retinitis
NCT00000134	PHASE3	COMPLETED	Studies of the Ocular Complications of AIDS (SOCA)–Cytomegalovirus Retinitis Retreatment Trial (CRRT)
NCT00000590	PHASE3	COMPLETED	Anti-HIV Immunoglobulin (HIVIG) in Prevention of Maternal-Fetal HIV Transmission (Pediatric ACTG Protocol 185)
NCT00001267	PHASE3	COMPLETED	A Randomized Pilot Study for the Treatment of AIDS or AIDS Related Complex With an Alternating or Simultaneous Combination Regimen of AZT and 2’,3’-Dideoxyinosine
NCT00001646	PHASE3	COMPLETED	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00144183	PHASE3	COMPLETED	A Study of Single Dose Nevirapine (NVP) Combined With Combivir® for the Prevention of Mother to Child Transmission (pMTCT) - Treatment Options Preservation Study (TOPS)
NCT00243568	PHASE3	WITHDRAWN	Vicriviroc, a CCR5 Inhibitor, Added to an Optimized Antiretroviral Therapy for Previously Treated HIV (VICTOR-E2) (Study P04285
NCT00278954	PHASE3	COMPLETED	Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases.
NCT00474370	PHASE3	COMPLETED	Vicriviroc in HIV-Treatment Experienced Subjects (Study P04889AM8)(COMPLETED)
NCT00478231	PHASE3	COMPLETED	Multicenter, Safety Study Of Maraviroc
NCT00523211	PHASE3	COMPLETED	Vicriviroc in HIV-Treatment Experienced Subjects (Study P04405AM5)
NCT00698334	PHASE3	COMPLETED	Efficacy of Thrice Weekly Directly Observed Treatment, Short-course (DOTS) in HIV-associated Tuberculosis
NCT00966160	PHASE3	COMPLETED	CD4 Cell Recovery in HIV-1 Patients Comparing 2 Treatment Regimes
NCT01363011	PHASE3	COMPLETED	Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment
NCT01440569	PHASE3	COMPLETED	Safety and Efficacy of Cobicistat-boosted Darunavir in HIV Infected Adults
NCT01475838	PHASE3	COMPLETED	Study to Evaluate Switching From Regimens Consisting of a Ritonavir-boosted Protease Inhibitor Plus Emtricitabine/Tenofovir Fixed-Dose Combination to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed, HIV-1 Infected Patients