SOCS1

Summary

SOCS1 (suppressor of cytokine signaling 1, HGNC:19383) is a protein-coding gene on chromosome 16p13.13, encoding Suppressor of cytokine signaling 1 (O15524). Essential negative regulator of type I and type II interferon (IFN) signaling, as well as that of other cytokines, including IL2, IL4, IL6 and leukemia inhibitory factor (LIF).

This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by a subset of cytokines, including IL2, IL3 erythropoietin (EPO), CSF2/GM-CSF, and interferon (IFN)-gamma. The protein encoded by this gene functions downstream of cytokine receptors, and takes part in a negative feedback loop to attenuate cytokine signaling. Knockout studies in mice suggested the role of this gene as a modulator of IFN-gamma action, which is required for normal postnatal growth and survival.

Source: NCBI Gene 8651 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autoinflammatory syndrome with immunodeficiency (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 25
• Clinical variants (ClinVar): 63 total — 5 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 22
• Cancer driver (intOGen): activating (oncogene-like) across 4 cancer types
• MANE Select transcript: NM_003745

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19383
Approved symbol	SOCS1
Name	suppressor of cytokine signaling 1
Location	16p13.13
Locus type	gene with protein product
Status	Approved
Aliases	SOCS-1, SSI-1, JAB, TIP3, Cish1
Ensembl gene	ENSG00000185338
Ensembl biotype	protein_coding
OMIM	603597
Entrez	8651

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000332029, ENST00000644787, ENST00000858080

RefSeq mRNA: 1 — MANE Select: NM_003745 NM_003745

CCDS: CCDS10546

Canonical transcript exons

ENST00000332029 — 2 exons

Exon	Start	End
ENSE00001291036	11254417	11255528
ENSE00001380148	11256079	11256204

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 93.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.3667 / max 7897.1614, expressed in 1748 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156240	48.1095	1747
156239	0.2573	131

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	93.34	gold quality
sperm	CL:0000019	83.56	gold quality
endocervix	UBERON:0000458	82.09	gold quality
male germ cell	CL:0000015	81.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.65	gold quality
spleen	UBERON:0002106	80.59	gold quality
vermiform appendix	UBERON:0001154	80.21	gold quality
superficial temporal artery	UBERON:0001614	79.51	gold quality
granulocyte	CL:0000094	78.56	gold quality
lymph node	UBERON:0000029	78.51	gold quality
metanephros cortex	UBERON:0010533	77.80	gold quality
ectocervix	UBERON:0012249	77.67	gold quality
blood	UBERON:0000178	77.46	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.16	gold quality
lower lobe of lung	UBERON:0008949	77.12	gold quality
pituitary gland	UBERON:0000007	77.08	gold quality
decidua	UBERON:0002450	77.06	gold quality
adenohypophysis	UBERON:0002196	76.99	gold quality
mucosa of transverse colon	UBERON:0004991	76.94	gold quality
mucosa of stomach	UBERON:0001199	76.50	gold quality
right ovary	UBERON:0002118	76.27	gold quality
thymus	UBERON:0002370	76.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.06	gold quality
body of stomach	UBERON:0001161	75.96	gold quality
stromal cell of endometrium	CL:0002255	75.80	gold quality
upper lobe of left lung	UBERON:0008952	75.71	gold quality
upper lobe of lung	UBERON:0008948	75.58	gold quality
right lobe of liver	UBERON:0001114	75.48	gold quality
omental fat pad	UBERON:0010414	75.45	gold quality
caecum	UBERON:0001153	75.44	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-8	yes	457.22
E-CURD-88	yes	37.33
E-MTAB-8410	yes	14.64
E-ANND-3	yes	14.08
E-CURD-122	yes	10.00
E-HCAD-1	yes	7.57
E-HCAD-30	no	73.27

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
STAT1	Repression

Upstream regulators (CollecTRI, top): CEBPB, CSF1R, DNMT1, EGR1, EGR2, ETS1, FOXC1, GFI1, GLI1, GLI2, HIF1A, HOXD1, IFNG, IRF1, IRF6, NFKB, NTS, SP1, SP2, STAT1, STAT3, STAT5A, STAT6, TBX21

miRNA regulators (miRDB)

73 targeting SOCS1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4645-5P	99.98	65.81	1284
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-548AT-5P	99.96	70.83	2666
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-548J-3P	99.94	72.61	4881

Literature-anchored findings (GeneRIF, showing 40)

• In keratinocytes overexpressing SOCS-1, the IFN-gamma-induced transactivation of an IFN-gamma-responsive reporter gene is markedly inhibited, as are phosphorylation of IFN-gamma R alpha and activation of STAT1 and STAT3. (PMID:12077274)
• Loss of function of SAOS-1 in collaboration with hematopoietic oncogenes facilitates tumor progression (PMID:12080466)
• interacts with TRIM8/GERP RING finger protein (PMID:12163497)
• SOCS1 is frequently silenced by methylation in multiple myeloma, which may impair negative regulation of the Jak/STAT pathway and result in greater responsiveness to cytokines (PMID:12456503)
• inhibits interferon-gamma-induced activation of human keratinocytes (PMID:12485838)
• Inactivation of this protein is associated with hypermethylation in human hepatoblastomas. (PMID:12601549)
• Methylation of the SOCS1 gene, resulting in transcriptional silencing, has been found in 65% of hepatocellular carcinoma cases, correlates with cytogenetic abnormalities, and may play an important role in the development of the cancer. (PMID:12759928)
• SOCS-1 gene associated with transcriptional silencing in pancreatic ductal neoplasms and may have growth-promoting effects; its methylation may be useful marker (PMID:12865927)
• Is the SOCS-1 gene silenced by CpG methylation? (PMID:12900355)
• SOCS1 has a role in mediating Janus kinase 2 ubiquitination/degradation downstream of the prolactin receptor and is regulated by SHP-2 (PMID:14522994)
• Methylation-mediated silencing of SOCS-1 gene is associated with hepatocellular carcinoma (PMID:14614012)
• SOCS-1 is faintly expressed in the hippocampus under basal conditions following status epilepticus, corroborating the hypothesis that seizure-induced gp130 cytokines play a direct neuromodulatory role in the hippocampus. (PMID:14614901)
• Up-regulation of suppressor of cytokine signaling 1 is associated with adult T-cell leukemia (PMID:14630083)
• Three functional STAT6- interferon-gamma-activated sequence-binding motifs situated close to each other 600 bp upstream of the SOCS-1 transcriptional initiation site mediate IL-4-IL-13-induced SOCS-1 transcription. (PMID:14634100)
• Methylation of SOCS1 was absent in both AML and ALL patients. Frequent methylation of SHP1, but not SOCS1, may be important in the pathogenesis, but not prognosis, of acute leukaemias. (PMID:14762685)
• hypermethylated in multiple myeloma. (PMID:14976049)
• SOCS1 overexpression increased Rb protein levels and suppressed proliferation of cervical cancer cell lines infected with HPV (PMID:15021916)
• These findings suggested that SOCS-1 may act as a tumor suppressor in at least some colorectal cancers and that SOCS-1 methylation may be a particular phenomenon related to a nearly onset of colorectal cancer. (PMID:15074307)
• this gene is silenced in a substantial portion of pancreatic cancers through mechanisms that cause methylation in the promoter region (PMID:15121754)
• HSOCP-1 is involved in cell cycle control and apoptosis (PMID:15166476)
• Severity of liver fibrosis is strongly correlated with SOCS1 gene methylation. (PMID:15197228)
• Although the methylation frequency of SOCS-1 is low, the data of Fujitake et al. indicate role of JAK/STAT/SOCS pathway in gastrointestinal tumorigenesis. (PMID:15198092)
• Aberrant methylation of SOCS-1 may be associated with hepatocarcinogenesis. (PMID:15235874)
• Our results demonstrate that SOCS-1 and SOCS-3 proteins inhibit IFN-alpha-induced activation of the Jak-STAT pathway and expression of the antiviral proteins 2’,5’-OAS and MxA. (PMID:15240148)
• SOCS1 and SOCS2 but not SOCS3 suppressed the growth of ovarian and breast cancer cells. (PMID:15361843)
• SOCS-1 is a progression marker of human melanoma and may downregulate biological responses by endogenous and/or therapeutically administered cytokines. (PMID:15373779)
• Methylation of the SOCS-1 gene was associated with lymph node metastasis, advanced tumor stage and reduced expression of SOCS-1 in GC tissues. (PMID:15386345)
• Data link SOCS-1 directly with the proteasome pathway and suggest another function for the SH2 domain of SOCS-1 in the regulation of Jak/STAT signaling. (PMID:15456882)
• Egr-1 has roles in regulating both the basal and LPS-induced activity of the SOCS-1 promoter (PMID:15545275)
• The insertion of amino acid exchanges into the kinase inhibitory regions of SOCS-1 demonstrated a requirement of these domains for a proper inhibitory function. (PMID:15589317)
• Similar to SOCS-1, Tkip peptide binds to the autophosphorylation site of JAK2. (PMID:15688010)
• IL-28A and IL-29 induced mRNA expression of the antiviral proteins 2’,5’-OAS and MxA was abolished by overexpression of SOCS-1 (PMID:15850793)
• Suppressor of cytokine signaling-1 expression by infectivity-enhanced adenoviral vector inhibits IL-6-dependent proliferation of multiple myeloma cells. (PMID:16082380)
• loss of SOCS-1 function either by mutation or by the complete deletion of the gene plays an important role in the dysregulation of JAK/STAT signaling in Karpas1106P and primary mediastinal b-cell lymphoma (PMID:16287070)
• Data suggest that SOCS1 functions as a negative regulator in TNF-induced inflammation and activation of c-jun N-terminal kinase in endothelial cells, in part by inducing ASK1 degradation. (PMID:16407264)
• Results suggest a novel interaction between the SOCS1 and SOCS3 proteins and the FGFR3 signaling pathway. (PMID:16410555)
• The data is compatible with epigenetic silencing of the SOCS-1 gene and constitutive activation of the JAK-STAT pathway in pituitary adenomas. (PMID:16421738)
• Hypermethylation of SOCS-1 was found in about one-third of human head and neck squamous cell carcinomas tissues,SOCS-1 methylation status can differentially affect STAT3 activation (PMID:16432158)
• Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation (PMID:16532038)
• The STAT1-SOCS1 pathway regulates the innate immune response via TLR3 signaling in epidermal keratinocytes. (PMID:16628196)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	socs1a	ENSDARG00000038095
mus_musculus	Socs1	ENSMUSG00000038037
rattus_norvegicus	Socs1	ENSRNOG00000002568
drosophila_melanogaster	Socs44A	FBGN0033266
drosophila_melanogaster	Socs36E	FBGN0041184

Paralogs (7): CISH (ENSG00000114737), SOCS2 (ENSG00000120833), SOCS6 (ENSG00000170677), SOCS5 (ENSG00000171150), SOCS4 (ENSG00000180008), SOCS3 (ENSG00000184557), SOCS7 (ENSG00000274211)

Protein

Protein identifiers

Suppressor of cytokine signaling 1 — O15524 (reviewed: O15524)

Alternative names: JAK-binding protein, STAT-induced STAT inhibitor 1, Tec-interacting protein 3

All UniProt accessions (2): O15524, Q4JHT5

UniProt curated annotations — full annotation on UniProt →

Function. Essential negative regulator of type I and type II interferon (IFN) signaling, as well as that of other cytokines, including IL2, IL4, IL6 and leukemia inhibitory factor (LIF). Downregulates cytokine signaling by inhibiting the JAK/STAT signaling pathway. Acts by binding to JAK proteins and to IFNGR1 and inhibiting their kinase activity. In vitro, suppresses Tec protein-tyrosine activity. Regulates IFN-gamma (IFNG)-mediated sensory neuron survival. Probable substrate recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

Subunit / interactions. Interacts with multiple activated signaling proteins of the tyrosine kinase signaling pathway including JAK family kinases, TEC, KIT, GRB2 and VAV. Binding to JAKs is mediated through the KIR and SH2 domains to a phosphorylated tyrosine residue within the JAK JH1 domain. Binds the SH3 domain of GRB2 via diproline determinants in the N-terminus, and the N-terminal regulatory domain of VAV. Interacts with the Elongin BC complex (ELOB and ELOC). Component of an ECS CBC(SOCS1) E3 ubiquitin-protein ligase complex which contains Elongin BC, CUL5, RBX1 and SOCS1. Interacts (via SH2 domain and SOCS box) with TRIM8. Interacts with AXL, CUL2 and FGFR3. Interacts with INSR. Interacts with TRIM8. Interacts with DCUN1D1. Interacts with IFNGR1.

Subcellular location. Nucleus. Cytoplasmic vesicle.

Tissue specificity. Expressed in all tissues with high expression in spleen, small intestine and peripheral blood leukocytes.

Disease relevance. Autoinflammatory syndrome, familial, with or without immunodeficiency (AISIMD) [MIM:619375] An autosomal dominant, autoinflammatory disorder with incomplete penetrance characterized by autoimmune cytopenia, hemolytic anemia, thrombocytopenia, and lymphadenopathy. Additional variable features may include autoimmune thyroiditis, psoriasis or eczema, nephritis, hepatitis, and symptoms of systemic lupus erythematosus. Immunodeficiency is present in some patients. Disease onset is usually in the first decades of life, although later onset has been reported. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The ESS and SH2 domains are required for JAK phosphotyrosine binding. Further interaction with the KIR domain is necessary for signal and kinase inhibition. The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV] and is part of the SOCS box.

Induction. By a subset of cytokines including those belonging to the interferon, interleukin and colony-stimulating factor families.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the SOCS1 family.

RefSeq proteins (1): NP_003736* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000980	SH2	Domain
IPR001496	SOCS_box	Domain
IPR035861	SOCS1_SH2	Domain
IPR036036	SOCS_box-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily

Pfam: PF00017, PF07525

UniProt features (18 total): sequence variant 5, sequence conflict 4, region of interest 4, domain 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15524-F1	84.20	0.68

Function

Pathways and Gene Ontology

Reactome pathways

27 pathways

ID	Pathway
R-HSA-1266695	Interleukin-7 signaling
R-HSA-1433559	Regulation of KIT signaling
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-877300	Interferon gamma signaling
R-HSA-877312	Regulation of IFNG signaling
R-HSA-909733	Interferon alpha/beta signaling
R-HSA-912694	Regulation of IFNA/IFNB signaling
R-HSA-9674555	Signaling by CSF3 (G-CSF)
R-HSA-9705462	Inactivation of CSF3 (G-CSF) signaling
R-HSA-982772	Growth hormone receptor signaling
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1280218	Adaptive Immune System
R-HSA-1433557	Signaling by SCF-KIT
R-HSA-162582	Signal Transduction
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-181438	Toll Like Receptor 2 (TLR2) Cascade
R-HSA-449147	Signaling by Interleukins
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-913531	Interferon Signaling
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 579 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_MYELOID_CELL_DIFFERENTIATION, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, ZHAN_MULTIPLE_MYELOMA_PR_DN, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, LU_IL4_SIGNALING, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_ACID_CHEMICAL

GO Biological Process (16): regulation of cytokine production (GO:0001817), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), protein ubiquitination (GO:0016567), cytokine-mediated signaling pathway (GO:0019221), macrophage differentiation (GO:0030225), intracellular signal transduction (GO:0035556), positive regulation of CD4-positive, alpha-beta T cell differentiation (GO:0043372), negative regulation of CD8-positive, alpha-beta T cell differentiation (GO:0043377), fat cell differentiation (GO:0045444), positive regulation of regulatory T cell differentiation (GO:0045591), negative regulation of receptor signaling pathway via JAK-STAT (GO:0046426), negative regulation of insulin receptor signaling pathway (GO:0046627), cellular response to amino acid stimulus (GO:0071230), negative regulation of signal transduction (GO:0009968), developmental process (GO:0032502), regulation of receptor signaling pathway via JAK-STAT (GO:0046425)

GO Molecular Function (6): protein kinase inhibitor activity (GO:0004860), cytokine receptor binding (GO:0005126), insulin-like growth factor receptor binding (GO:0005159), kinase inhibitor activity (GO:0019210), protein kinase binding (GO:0019901), protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic vesicle (GO:0031410), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Immune System	3
Signaling by Interleukins	2
Interferon Signaling	2
Cytokine Signaling in Immune system	2
Toll Like Receptor 2 (TLR2) Cascade	2
Signaling by SCF-KIT	1
Toll Like Receptor 4 (TLR4) Cascade	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
Interferon gamma signaling	1
Interferon alpha/beta signaling	1
Signaling by CSF3 (G-CSF)	1
Class I MHC mediated antigen processing & presentation	1
Signaling by Receptor Tyrosine Kinases	1
Toll-like Receptor Cascades	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular anatomical structure	2
signal transduction	2
cell surface receptor signaling pathway via JAK-STAT	2
signaling receptor binding	2
cytoplasm	2
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
cell surface receptor signaling pathway via STAT	1
protein modification by small protein conjugation	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
myeloid leukocyte differentiation	1
mononuclear cell differentiation	1
CD4-positive, alpha-beta T cell differentiation	1
regulation of CD4-positive, alpha-beta T cell differentiation	1
positive regulation of alpha-beta T cell differentiation	1
positive regulation of CD4-positive, alpha-beta T cell activation	1
CD8-positive, alpha-beta T cell differentiation	1
regulation of CD8-positive, alpha-beta T cell differentiation	1
negative regulation of alpha-beta T cell differentiation	1
negative regulation of CD8-positive, alpha-beta T cell activation	1
cell differentiation	1
regulatory T cell differentiation	1
positive regulation of T cell differentiation	1
regulation of regulatory T cell differentiation	1
regulation of receptor signaling pathway via JAK-STAT	1
negative regulation of receptor signaling pathway via STAT	1
insulin receptor signaling pathway	1
negative regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
negative regulation of cellular response to insulin stimulus	1
response to amino acid	1
cellular response to acid chemical	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
biological_process	1

Protein interactions and networks

STRING

3066 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SOCS1	JAK2	O60674	994
SOCS1	TYK2	P29597	991
SOCS1	JAK1	P23458	983
SOCS1	CUL2	Q13617	980
SOCS1	ELOB	Q15370	973
SOCS1	IFNAR1	P17181	970
SOCS1	CUL5	Q93034	956
SOCS1	TRIM8	Q9BZR9	936
SOCS1	IFNGR1	P15260	934
SOCS1	COMMD1	Q8N668	932
SOCS1	STAT1	P42224	887
SOCS1	TIRAP	P58753	858
SOCS1	IRAK1	P51617	857
SOCS1	ELOC	Q15369	825
SOCS1	JAK3	P52333	820

IntAct

51 interactions, top by confidence:

A	B	Type	Score
ELOC	SOCS1	psi-mi:“MI:0915”(physical association)	0.680
SOCS1	ELOC	psi-mi:“MI:0915”(physical association)	0.680
SOCS1	SH3GL1	psi-mi:“MI:0915”(physical association)	0.560
SOCS1	SMAD4	psi-mi:“MI:0915”(physical association)	0.550
SOCS1	SMAD4	psi-mi:“MI:2364”(proximity)	0.550
SMAD4	SOCS1	psi-mi:“MI:2364”(proximity)	0.550
SMAD4	SOCS1	psi-mi:“MI:0915”(physical association)	0.550
gag	SOCS1	psi-mi:“MI:0915”(physical association)	0.520
SOCS1	gag	psi-mi:“MI:0915”(physical association)	0.520
COMMD1	SOCS1	psi-mi:“MI:0915”(physical association)	0.520
SOCS1	COMMD1	psi-mi:“MI:0915”(physical association)	0.520
SOCS1	PIK3R1	psi-mi:“MI:0915”(physical association)	0.490
CRKL	SOCS1	psi-mi:“MI:0915”(physical association)	0.490
CRK	SOCS1	psi-mi:“MI:0915”(physical association)	0.490
SOCS1	CRKL	psi-mi:“MI:0915”(physical association)	0.490
SOCS1	CRK	psi-mi:“MI:0915”(physical association)	0.490
SOCS1	ERBB2	psi-mi:“MI:0407”(direct interaction)	0.440
SOCS1	MET	psi-mi:“MI:0407”(direct interaction)	0.440
gag	SOCS1	psi-mi:“MI:0403”(colocalization)	0.430
SOCS1	RELA	psi-mi:“MI:0915”(physical association)	0.400
SOCS1	JAK2	psi-mi:“MI:0915”(physical association)	0.370
SOCS1	NDUFA4	psi-mi:“MI:0914”(association)	0.350

BioGRID (318): SOCS1 (Two-hybrid), SOCS1 (Affinity Capture-Western), SOCS1 (Synthetic Growth Defect), SOCS1 (Two-hybrid), SOCS1 (Two-hybrid), PIK3R1 (Two-hybrid), SOCS1 (Affinity Capture-Western), MET (Affinity Capture-Western), MET (Reconstituted Complex), SOCS1 (Affinity Capture-Western), SOCS1 (Affinity Capture-Western), IRS2 (Affinity Capture-Western), Pvrl4 (Affinity Capture-Western), Pvrl3 (Affinity Capture-Western), PVRL1 (Affinity Capture-Western)

ESM2 similar proteins: A0FI79, A1A5B6, A5PJU7, A5PKD8, A8MQ27, D3ZL52, D7PF45, F1SAM7, I3L5V6, O15524, O35716, O60346, O76050, P60827, Q03160, Q08DG4, Q0MW30, Q14451, Q1RMW5, Q2MJR0, Q3UPE3, Q60806, Q6P6N5, Q6SZW1, Q6UKI2, Q6WVG3, Q6ZT52, Q8BNW9, Q8CHE4, Q8N119, Q8N2R8, Q8N4B1, Q8TF61, Q96BM1, Q96CD0, Q96E14, Q96S99, Q9BR09, Q9BYB0, Q9D0S4

Diamond homologs: O00459, O08908, O14508, O14512, O14543, O14544, O15524, O35716, O35717, O35718, O46404, O54928, O55033, O70512, O75159, O88582, O88583, P23726, P23727, P26450, P27986, Q0VC91, Q29RN6, Q2HJ53, Q54RB7, Q5R685, Q5RCM6, Q5RDX2, Q62225, Q63787, Q63788, Q63789, Q64143, Q68AM8, Q7YRV6, Q861R0, Q8UUU2, Q8VHQ2, Q8WXH5, Q90X67

SIGNOR signaling

22 interactions.

A	Effect	B	Mechanism
SOCS1	“down-regulates quantity by destabilization”	JAK2	ubiquitination
PTPN6	up-regulates	SOCS1	binding
SOCS1	down-regulates	IFNGR1	binding
SOCS1	down-regulates	JAK1	binding
IRF1	“up-regulates quantity by expression”	SOCS1	“transcriptional regulation”
STAT1	“up-regulates quantity by expression”	SOCS1	“transcriptional regulation”
IFNG	“up-regulates quantity by expression”	SOCS1	“transcriptional regulation”
SOCS1	“down-regulates activity”	JAK3	binding
STAT6	“up-regulates quantity by expression”	SOCS1	“transcriptional regulation”
SOCS1	down-regulates	IFNG
SOCS1	“down-regulates quantity by repression”	STAT1	“transcriptional regulation”
CSF1R	“up-regulates quantity by expression”	SOCS1	“transcriptional regulation”
SOCS1	down-regulates	Proliferation
YES1	“up-regulates quantity by stabilization”	SOCS1	phosphorylation
SOCS1	down-regulates	IRAK1	binding
SOCS1	“down-regulates quantity by destabilization”	VAV1	binding
SOCS1	“up-regulates activity”	VCB-Cul2	binding
SRC	“down-regulates activity”	SOCS1	phosphorylation
YES1	“down-regulates activity”	SOCS1	phosphorylation
LYN	“down-regulates activity”	SOCS1	phosphorylation
BLK	“down-regulates activity”	SOCS1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 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
Downstream signal transduction	5	82.8×	8e-07
Constitutive Signaling by Aberrant PI3K in Cancer	6	33.1×	3e-06
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	7	29.4×	8e-07
PIP3 activates AKT signaling	7	20.3×	4e-06
RAF/MAP kinase cascade	7	18.6×	6e-06
Diseases of signal transduction by growth factor receptors and second messengers	5	12.3×	8e-04
Signaling by Receptor Tyrosine Kinases	5	11.2×	1e-03
Infectious disease	7	7.6×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
phosphatidylinositol 3-kinase/protein kinase B signal transduction	6	55.0×	7e-07
epidermal growth factor receptor signaling pathway	5	53.9×	7e-06
cytokine-mediated signaling pathway	5	28.4×	1e-04
negative regulation of apoptotic process	7	10.6×	2e-04
intracellular signal transduction	6	9.9×	8e-04
protein ubiquitination	5	9.0×	3e-03
positive regulation of gene expression	5	8.4×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 4 cancer types — DLBCLNOS, MLYM, NHL, READ.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	5
Uncertain significance	38
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1172797	NM_003745.2(SOCS1):c.480_481insGCGGC (p.Met161fs)	Pathogenic
2671890	NM_003745.2(SOCS1):c.462C>A (p.Tyr154Ter)	Pathogenic
4072794	NM_003745.2(SOCS1):c.202_203del (p.Thr68fs)	Pathogenic
977212	NM_003745.2(SOCS1):c.368C>G (p.Pro123Arg)	Pathogenic
977214	NM_003745.2(SOCS1):c.476_480dup (p.Met161fs)	Pathogenic
1013116	GRCh37/hg19 16p13.13(chr16:11348700-11349387)x1	Likely pathogenic
1120219	NM_003745.2(SOCS1):c.192C>G (p.Tyr64Ter)	Likely pathogenic
1175882	NM_003745.2(SOCS1):c.95C>A (p.Ser32Ter)	Likely pathogenic
3068305	NM_003745.2(SOCS1):c.454G>T (p.Glu152Ter)	Likely pathogenic
3340478	NM_003745.2(SOCS1):c.147_153dup (p.Asp52fs)	Likely pathogenic

SpliceAI

182 predictions. Top by Δscore:

Variant	Effect	Δscore
16:11255527:CG:C	acceptor_gain	0.9800
16:11255529:C:CC	acceptor_gain	0.9800
16:11255525:TGCG:T	acceptor_gain	0.9700
16:11256073:GCTCA:G	donor_loss	0.9700
16:11256074:CTCA:C	donor_loss	0.9700
16:11256075:TCA:T	donor_loss	0.9700
16:11256076:CA:C	donor_loss	0.9700
16:11255526:GCG:G	acceptor_gain	0.9600
16:11255527:CGC:C	acceptor_gain	0.9600
16:11255524:GTGCG:G	acceptor_gain	0.9500
16:11256078:CCTGG:C	donor_gain	0.9400
16:11255528:GC:G	acceptor_loss	0.9200
16:11255530:T:G	acceptor_loss	0.9200
16:11256077:A:AC	donor_gain	0.9200
16:11256078:C:CC	donor_gain	0.9200
16:11255531:G:C	acceptor_loss	0.9000
16:11255710:C:CA	donor_gain	0.8400
16:11255532:C:CT	acceptor_gain	0.8300
16:11255130:CG:C	acceptor_gain	0.8200
16:11255533:G:T	acceptor_gain	0.8200
16:11255613:C:CA	donor_gain	0.8200
16:11255643:CGGA:C	donor_gain	0.8000
16:11255644:GGAG:G	donor_gain	0.8000
16:11255688:G:C	donor_gain	0.7900
16:11255723:C:A	donor_gain	0.7900
16:11255722:T:TA	donor_gain	0.7400
16:11255774:G:T	acceptor_gain	0.7400
16:11255646:A:AC	donor_gain	0.7300
16:11255707:A:AC	donor_gain	0.7100
16:11255708:C:CC	donor_gain	0.7100

AlphaMissense

1349 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:11255047:G:C	F144L	1.000
16:11255047:G:T	F144L	1.000
16:11255049:A:G	F144L	1.000
16:11255104:G:C	S125R	1.000
16:11255104:G:T	S125R	1.000
16:11255106:T:G	S125R	1.000
16:11255176:G:C	F101L	1.000
16:11255176:G:T	F101L	1.000
16:11255177:A:G	F101S	1.000
16:11255178:A:G	F101L	1.000
16:11254852:G:C	F209L	0.999
16:11254852:G:T	F209L	0.999
16:11254854:A:G	F209L	0.999
16:11255074:A:C	F135L	0.999
16:11255074:A:T	F135L	0.999
16:11255075:A:G	F135S	0.999
16:11255076:A:G	F135L	0.999
16:11255131:G:C	S116R	0.999
16:11255131:G:T	S116R	0.999
16:11255133:T:G	S116R	0.999
16:11255135:A:T	L115H	0.999
16:11255141:A:G	F113S	0.999
16:11255165:T:A	D105V	0.999
16:11255169:G:T	R104S	0.999
16:11255174:A:G	L102P	0.999
16:11255183:C:A	G99V	0.999
16:11255242:G:C	F79L	0.999
16:11255242:G:T	F79L	0.999
16:11255244:A:G	F79L	0.999
16:11254858:G:C	F207L	0.998

dbSNP variants (sampled 300 via entrez): RS1000257037 (16:11256206 G>A), RS1000309354 (16:11256083 C>A,T), RS1000592734 (16:11256967 G>A), RS1000644962 (16:11256837 G>A), RS1001440147 (16:11256734 C>G,T), RS1002272086 (16:11257893 C>G,T), RS1002729209 (16:11257716 G>A), RS1003204094 (16:11258081 A>T), RS1003388713 (16:11254183 CA>C), RS1003388799 (16:11256051 C>G), RS1003439604 (16:11255782 G>A), RS1003910638 (16:11254341 C>A), RS1004405777 (16:11258114 C>A,T), RS1004665149 (16:11257457 A>C), RS1004847464 (16:11254768 A>G,T)

Disease associations

OMIM: gene MIM:603597 | disease phenotypes: MIM:619375, MIM:188030, MIM:205700, MIM:152700, MIM:601744

GenCC curated gene-disease

Disease	Classification	Inheritance
autoinflammatory syndrome with immunodeficiency	Strong	Autosomal dominant
autoimmune disease	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
autoinflammatory syndrome with immunodeficiency	Definitive	AD

Mondo (7): autoinflammatory syndrome with immunodeficiency (MONDO:0800130), diffuse large B-cell lymphoma (MONDO:0018905), autoimmune thrombocytopenic purpura (MONDO:0008558), autoimmune thrombocytopenia (MONDO:0019098), autoimmune hemolytic anemia (MONDO:0020108), systemic lupus erythematosus (MONDO:0007915), autoimmune disease (MONDO:0007179)

Orphanet (5): Diffuse large B-cell lymphoma (Orphanet:544), Immune thrombocytopenia (Orphanet:3002), Autoimmune thrombocytopenia (Orphanet:71203), Autoimmune hemolytic anemia (Orphanet:98375), Systemic lupus erythematosus (Orphanet:536)

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000099	Glomerulonephritis
HP:0001744	Splenomegaly
HP:0001973	Autoimmune thrombocytopenia
HP:0002205	Recurrent respiratory infections
HP:0002240	Hepatomegaly
HP:0002608	Celiac disease
HP:0002716	Lymphadenopathy
HP:0002725	Systemic lupus erythematosus
HP:0003493	Antinuclear antibody positivity
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0004844	Coombs-positive hemolytic anemia
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0012189	Hodgkin lymphoma
HP:0020151	Anti-dsDNA antibody positivity
HP:0030384	Decreased proportion of marginal zone B cells
HP:0030388	Decreased class-switched memory B cell proportion
HP:0033028	Anti-U1 ribonucleoprotein antibody positivity
HP:0033631	Spondylitis
HP:0100646	Thyroiditis

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000612_10	Celiac disease	3.000000e-08
GCST001473_2	Crohn’s disease and psoriasis	1.000000e-13
GCST001725_27	Inflammatory bowel disease	2.000000e-16
GCST001958_14	Bulimia nervosa	2.000000e-06
GCST003129_23	Primary biliary cholangitis	2.000000e-14
GCST003155_19	Systemic lupus erythematosus	7.000000e-17
GCST003156_33	Systemic lupus erythematosus	2.000000e-08
GCST003268_27	Psoriasis vulgaris	3.000000e-07
GCST003622_40	Systemic lupus erythematosus	4.000000e-07
GCST003990_3	Allergy	2.000000e-16
GCST004131_115	Inflammatory bowel disease	1.000000e-06
GCST004132_39	Crohn’s disease	1.000000e-07
GCST005212_32	Asthma	3.000000e-10
GCST005527_32	Psoriasis	5.000000e-08
GCST005581_11	Primary biliary cirrhosis	7.000000e-15
GCST005581_12	Primary biliary cirrhosis	2.000000e-13
GCST005581_13	Primary biliary cirrhosis	3.000000e-08
GCST005581_35	Primary biliary cirrhosis	6.000000e-20
GCST005581_36	Primary biliary cirrhosis	2.000000e-23
GCST006862_9	Asthma	2.000000e-10
GCST009597_87	Multiple sclerosis	5.000000e-16
GCST009798_15	Asthma	2.000000e-33
GCST90002385_74	High light scatter reticulocyte count	6.000000e-16
GCST90002386_281	High light scatter reticulocyte percentage of red cells	1.000000e-14
GCST90011899_21	Aspartate aminotransferase levels	8.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:1001494	psoriasis vulgaris
EFO:0007986	reticulocyte count
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D000744	Anemia, Hemolytic, Autoimmune	C15.378.050.141.125; C20.111.175
D001327	Autoimmune Diseases	C20.111
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590
D016403	Lymphoma, Large B-Cell, Diffuse	C04.557.386.480.150.585; C15.604.515.569.480.150.585; C20.683.515.761.480.150.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases cleavage, increases expression, decreases expression, increases reaction, decreases reaction	4
Estradiol	affects binding, increases expression, decreases reaction, affects cotreatment	4
Arsenic Trioxide	decreases expression, decreases methylation, increases expression	3
Cisplatin	increases expression, decreases expression, affects expression, decreases response to substance, affects cotreatment	3
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Dexamethasone	increases expression	2
Progesterone	affects cotreatment, increases expression, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	increases expression, increases methylation	2
Cyclosporine	decreases expression, decreases methylation	2
Cadmium Chloride	increases expression, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
TL8-506	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
4-oxoretinoic acid	decreases expression	1
urushiol	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
afimoxifene	affects cotreatment, increases expression, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
pentanal	increases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1821	Karpas-1106P	Cancer cell line	Female
CVCL_B2Q7	Abcam A-549 SOCS1 KO	Cancer cell line	Male
CVCL_D8EM	Ubigene BEAS-2B SOCS1 KO	Transformed cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001658	PHASE4	COMPLETED	Amoxicillin for the Treatment of Pediatric Autoimmune Disorders Associated With Streptococcal Infections
NCT00820469	PHASE4	COMPLETED	Study of the Influence of Plasma Exchange on the Pharmacokinetics of Rituximab
NCT00862693	PHASE4	UNKNOWN	Calcitriol in the Treatment of Immunoglobulin A Nephropathy
NCT01065285	PHASE4	COMPLETED	Vaccination Against Influenza in Autoimmune Diseases
NCT04015596	PHASE4	TERMINATED	Trial of Naproxen Sodium for the Treatment of OCD in Children With PANDAS
NCT04127747	PHASE4	UNKNOWN	Efficacy of Individualized Rituximab in Maintaining Remission of Moderate and Severe Systemic Lupus Erythematosus
NCT04297592	PHASE4	ENROLLING_BY_INVITATION	Antibiotic Prophylaxis in High-Risk Arthroplasty Patients
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT06723548	PHASE4	NOT_YET_RECRUITING	Telitacicept and Low-dose Steroids in Refractory Myasthenia Gravis
NCT06964269	PHASE4	RECRUITING	Use of Acthar Gel Single-Dose Pre-Filled SelfJectTM Injector in Patients With Moderate-Severe Keratitis and Autoimmune Disease
NCT00466258	PHASE4	COMPLETED	LINFOTARGAM: Treatment With Chemotherapy Plus Rituximab and Highly Active Antiretroviral Therapy in Patients With Diffuse Large B Cell Lymphoma and Infection With the Human Immunodeficiency Virus (HIV)
NCT01949818	PHASE4	UNKNOWN	Treatment of Diffuse Large B Cell Lymphoma
NCT02752815	PHASE4	UNKNOWN	Reduced Chemotherapy in Low Risk DLBCL
NCT03376958	PHASE4	COMPLETED	Apatinib for Relapsed and Refractory Diffuse Large B Cell Lymphoma
NCT03513601	PHASE4	UNKNOWN	Treatment of Elderly Patients With Diffuse Large B-cell Lymphoma
NCT03579082	PHASE4	UNKNOWN	A Clinical Trial of Decitabine in Relapse and Refractory Diffuse Large B Cell Lymphoma
NCT05108805	PHASE4	COMPLETED	Chimeric Antigen Receptor (CAR) T Cell Therapy With YESCARTA in the Outpatient Setting
NCT05518383	PHASE4	RECRUITING	B-cell Mature Non-Hodgkin’s Lymphoma Treatment Protocol in Children and Adolescents 2021
NCT00001768	PHASE3	COMPLETED	Treatment of Childhood Onset Psychiatric Disorders With Intravenous Immunoglobulin (IVIg)
NCT00035308	PHASE3	COMPLETED	Safety and Efficacy Study of LJP 394 (Abetimus Sodium) to Treat Lupus Kidney Disease
NCT00351377	PHASE3	COMPLETED	Gastrointestinal and Health-related Quality of Life Outcomes in Patients With Autoimmune Diseases Treated With Mycophenolate
NCT00419419	PHASE3	COMPLETED	Phase III Study of a Topical Gel Formulation for Treatment and Prevention of Raynaud’s Phenomenon
NCT01004432	PHASE3	COMPLETED	Golimumab in Rheumatoid Arthritis Participants With an Inadequate Response to Etanercept (ENBREL) or Adalimumab (HUMIRA)
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01210716	PHASE3	COMPLETED	Evaluation of Therapeutic Plasma Exchange (TPE) Procedure Using the AMICUS Device
NCT01281969	PHASE3	COMPLETED	Intravenous Immunoglobulin for PANDAS
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT01601028	PHASE3	COMPLETED	Hydroxychloroquine Treatment of Dry Eyes in Patients With Primary Sjögren’s Syndrome
NCT02263703	PHASE3	COMPLETED	Immunogenicity of HPV Vaccine in Immunosuppressed Children
NCT03790293	PHASE3	COMPLETED	Clinical and Immunological Long-term Follow-up of Patients With Pemphigus Included in the RITUXIMAB 3 Trial
NCT05069714	PHASE3	COMPLETED	One or Two Week Methotrexate Discontinuation on Efficacy of Influenza Vaccination in Rheumatoid Arthritis.
NCT00075478	PHASE3	COMPLETED	Total-Body Irradiation With or Without Fludarabine Phosphate Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer
NCT00355199	PHASE3	COMPLETED	Comparison of HD Chemotherapy Followed by Auto-transplant and R-CHOP in High Risk Patients With DLBCL.
NCT00400478	PHASE3	COMPLETED	A Multicentre, Randomized Phase III Study of Rituximab as Maintenance Treatment Versus Observation in Patients With Aggressive B-cell Lymphoma: NHL-13
NCT00499018	PHASE3	UNKNOWN	Dose Dense Chemotherapy + Rituximab +/-Intensified High Dose Chemoimmunotherapy With Support of Peripheral Autologous Stem Cell in Diffuse Large B-Cell Lymphoma
NCT00790036	PHASE3	COMPLETED	Phase III Study of RAD001 Adjuvant Therapy in Poor Risk Patients With Diffuse Large B-Cell Lymphoma (DLBCL) of RAD001 Versus Matching Placebo After Patients Have Achieved Complete Response With First-line Rituximab-chemotherapy
NCT00846157	PHASE3	UNKNOWN	Biocell Natural Killer Mixture in Diffuse Large B Cell Lymphoma (DLBCL) Patients
NCT01122472	PHASE3	COMPLETED	Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP
NCT01148446	PHASE3	COMPLETED	R-CHOP Versus R-mini-CEOP in Elderly Patients(>65)With DLBCL