MEFV

Summary

MEFV (MEFV innate immunity regulator, pyrin, HGNC:6998) is a protein-coding gene on chromosome 16p13.3, encoding Pyrin (O15553). Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma.

This gene encodes a protein, also known as pyrin or marenostrin, that is an important modulator of innate immunity. Mutations in this gene are associated with Mediterranean fever, a hereditary periodic fever syndrome.

Source: NCBI Gene 4210 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial Mediterranean fever (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 1,113 total — 5 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 164
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000243

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6998
Approved symbol	MEFV
Name	MEFV innate immunity regulator, pyrin
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FMF, TRIM20
Ensembl gene	ENSG00000103313
Ensembl biotype	protein_coding
OMIM	608107
Entrez	4210

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 nonsense_mediated_decay, 5 protein_coding, 2 retained_intron

ENST00000219596, ENST00000339854, ENST00000536379, ENST00000536980, ENST00000537682, ENST00000538326, ENST00000539145, ENST00000539154, ENST00000541159, ENST00000542898, ENST00000570511, ENST00000572244, ENST00000574583, ENST00000576315, ENST00000697124, ENST00000956137

RefSeq mRNA: 2 — MANE Select: NM_000243 NM_000243, NM_001198536

CCDS: CCDS10498, CCDS55981

Canonical transcript exons

ENST00000219596 — 10 exons

Exon	Start	End
ENSE00000666508	3248909	3249004
ENSE00001160048	3249431	3249780
ENSE00001160054	3254158	3254790
ENSE00003459661	3244254	3244286
ENSE00003570135	3244473	3244588
ENSE00003588551	3247016	3247246
ENSE00003594628	3246525	3246547
ENSE00003634440	3243860	3243892
ENSE00003900481	3242027	3243694
ENSE00003902985	3256311	3256633

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 98.75.

FANTOM5 (CAGE): breadth broad, TPM avg 10.3980 / max 679.2045, expressed in 302 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156019	10.3980	302

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	98.75	gold quality
monocyte	CL:0000576	96.17	gold quality
mononuclear cell	CL:0000842	95.04	gold quality
leukocyte	CL:0000738	95.00	gold quality
granulocyte	CL:0000094	92.63	gold quality
blood	UBERON:0000178	88.93	gold quality
diaphragm	UBERON:0001103	87.87	gold quality
olfactory bulb	UBERON:0002264	86.94	gold quality
bone marrow cell	CL:0002092	83.59	gold quality
mucosa of urinary bladder	UBERON:0001259	82.33	silver quality
type B pancreatic cell	CL:0000169	81.96	gold quality
spleen	UBERON:0002106	79.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.08	gold quality
vermiform appendix	UBERON:0001154	74.41	gold quality
right lung	UBERON:0002167	74.30	gold quality
upper lobe of left lung	UBERON:0008952	73.99	gold quality
tendon of biceps brachii	UBERON:0008188	73.17	silver quality
upper lobe of lung	UBERON:0008948	71.48	gold quality
caecum	UBERON:0001153	71.24	gold quality
medial globus pallidus	UBERON:0002477	69.58	gold quality
oocyte	CL:0000023	68.97	gold quality
oviduct epithelium	UBERON:0004804	67.61	silver quality
hair follicle	UBERON:0002073	66.54	gold quality
periodontal ligament	UBERON:0008266	66.00	silver quality
globus pallidus	UBERON:0001875	65.85	gold quality
smooth muscle tissue	UBERON:0001135	65.08	gold quality
left ventricle myocardium	UBERON:0006566	64.63	gold quality
vastus lateralis	UBERON:0001379	64.48	gold quality
epithelial cell of pancreas	CL:0000083	64.45	gold quality
secondary oocyte	CL:0000655	64.12	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, E2F1, ELF4, SP1, TP53

miRNA regulators (miRDB)

61 targeting MEFV, 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-3613-3P	100.00	76.36	7965
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-7106-5P	99.53	67.47	3574

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• mutational spectrum in the genes in patients suffering from AA amyloidosis and recurrent inflammatory attacks (PMID:12105243)
• The effects of I591T mutation imply possibly a mild mutation, benign polymorphism, or a variant influenced by another modifier. (PMID:12124996)
• MEFV message levels are related to both the genotype and the phenotype, and suggest that the pathophysiology of FMF relies on a quantitative defect of MEFV mRNA expression. (PMID:12384939)
• In phenotype II amyloidosis patients, the distribution of the four common MEFV mutations was not significantly different from that found in all FMF patients with typical symptoms who do or do not develop amyloidosis. (PMID:12401847)
• penetrance of paired recognised pathogenic MEFV mutations may frequently be incomplete (PMID:12461684)
• there is a cryopyrin signaling pathway activated through the induced proximity of ASC, which is negatively regulated by pyrin (PMID:12615073)
• Disease severity and the development of amyloidosis in failial Mediterranean Fever are differentially affected by genetic variations within and outside the MEFV gene. (PMID:12687559)
• In 412 FMF patients genotyped for MEFV mutations, M694V/M694V was the most common genotype (27%), followed by M694V/V726A (16%). The full genotype could be assessed in 57% of the patients, and one disease-causing mutation in an additional 26%. (PMID:12929299)
• Pyrin binds the PSTPIP1/CD2BP1 protein (PMID:14595024)
• S1791 was in compound heterozygosity with MEFV mutation M694V (PMID:14636645)
• cellular location of mutant isoforms, in the presence or absence of ASC protein (PMID:14985395)
• MEFV mutations are not associated with Crohn Disease susceptibility, yet the presence of these mutations appears to be associated with a stricturing disease pattern and extraintestinal disease manifestations of Crohn Disease. (PMID:15667491)
• E148Q mutation is significantly frequent in familial Mediterranean fever (PMID:15717684)
• In Egyptian familial Mediterranean fever patients, the M694V mutation was detected in 20 patients (100%) and V726A mutation in 17 patients (85%). (PMID:15724392)
• FMF is caused by mutations in the MEFV gene that encodes pyrin/marenostrin. (PMID:15805719)
• The occurrence of frequent MEFV mutations in BD patients suggests that the MEFV gene is involved in the pathogenesis of Behcet’s disease. (PMID:15903027)
• data suggest that both pyrin and cryopyrin are capable of assembling independent inflammasome complexes with ASC and procaspase-1, and activating caspase-1 via ASC oligomerization (PMID:16037825)
• Our results indicate a relationship between some HLA-DR/DQ alleles and MEFV mutations in Mediterranean fever patients. (PMID:16245224)
• MEFV protein mutations are associated with Familial Mediterranean fever (PMID:16378925)
• Carrying the proinflammatory M694V pyrin allele increases the risk for myocardial infarction. Conversely, the wild-type pyrin genotype leads to longevity in a modern environment with reduced pathogen load and improved infection control. (PMID:16387839)
• The gene coding the disease (MEFV) is identified on the 16th chromosome. The most common MEFV mutations are M694V, M680I, V726A and M694I located on exon 10 and E148Q located on exon 2. (PMID:16523434)
• MEFV protein mutations are associated with Familial Mediterranean fever (PMID:16523438)
• MEFV gene mutation show correlation between ulcertive colitis and familial mediterranean fever gene alteration. (PMID:16614989)
• The severity of the disease and development of amyloidosis seem to have an association with M694V, the most common mutation in Syrian FMF patients. (PMID:16627024)
• MEFV mutations may act as a genetic susceptibility factor for vasculitides in familial mediterranean fever patients. (PMID:16721494)
• A putative novel MEFV missense mutation, S702C, was localized on the constructed 3-D model. (PMID:16730661)
• The C-terminal B30.2 domain of pyrin is necessary and sufficient for the interaction with caspase-1 to modulate IL-1beta production. (PMID:16785446)
• one MEFV mutation may indeed be conferring a heightened inflammation as suggested by the increased frequency in inflammatory symptoms; the carrier status for MEFV mutations seem to be unique, in that they cause an alteration in the state of “health”. (PMID:17067442)
• in Ethiopian Jews in Israel, comon polymorphism in MEFV locus was found and a relatively high rate of mutation E148Q was detected (PMID:17067447)
• Though the effects of the MEFV genotypes seem clear, there are definitely other modifying factors or genes such as MICA on the development of amyloidosis and on the course of the disease (PMID:17102945)
• Reduced expression of the MEFV gene is associated with inflammation and that it may be one of the pathogenic mechanisms of the attacks of inflammation in familial Mediterranean fever patients. (PMID:17195238)
• The profile of the MEFV gene mutations in the Tunisian population is concordant with other Arab populations but with some differences. (PMID:17276496)
• MEFV appears to be a susceptibility and modifier gene in Behcet’s disease. (PMID:17454935)
• Country of recruitment, rather than MEFV genotype, is the key risk factor for renal amyloidosis in familial Mediterranean fever. (PMID:17469185)
• spectrum of MEFV alterations in familial Mediterranean fever patients and healthy individuals in Greece (PMID:17489852)
• The onset of UC in infants should prompt a search for MEFV mutations as this association may influence the management of the disease. (PMID:17520284)
• spectrum of the MEFV mutations among our sampled Lebanese Familial Mediterranean Fever patients shows the high heterogeneity at the allelic level when compared to Arab and non-Arab populations (PMID:17566872)
• A novel mutation of the MEFV gene in a Greek family related to a non-classical, variably expressed FMF phenotype is reported. (PMID:17594097)
• This study shows a high prevalence of mutations of the MEFV gene in patients with anti-citrullinated protein antibody-negative palindromic rheumatism. (PMID:17665427)
• critically ill patients with systemic inflammatory response syndrome and sepsis have increased pyrin mutations, and patients with SIRS and sepsis carrying the pyrin mutation seem to be susceptible for a severe disease course (PMID:17696266)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mefv	ENSMUSG00000022534
rattus_norvegicus	Mefv	ENSRNOG00000008134

Paralogs (80): MID2 (ENSG00000080561), TRIM9 (ENSG00000100505), MID1 (ENSG00000101871), TRIM35 (ENSG00000104228), TRIM14 (ENSG00000106785), TRIM37 (ENSG00000108395), TRIM2 (ENSG00000109654), TRIM3 (ENSG00000110171), TRIM38 (ENSG00000112343), TRIM62 (ENSG00000116525), TRIM67 (ENSG00000119283), TRIM32 (ENSG00000119401), BSPRY (ENSG00000119411), TRIM25 (ENSG00000121060), TRIM6 (ENSG00000121236), TRIM24 (ENSG00000122779), TRIM51 (ENSG00000124900), TRIM28 (ENSG00000130726), TRIM21 (ENSG00000132109), TRIM5 (ENSG00000132256), TRIM22 (ENSG00000132274), TRIM47 (ENSG00000132481), TRIM45 (ENSG00000134253), TRIM29 (ENSG00000137699), TRIM54 (ENSG00000138100), PML (ENSG00000140464), TRIM65 (ENSG00000141569), TRIM43B (ENSG00000144010), TRIM43 (ENSG00000144015), TRIM7 (ENSG00000146054), TRIM41 (ENSG00000146063), TRIM50 (ENSG00000146755), TRIM4 (ENSG00000146833), TRIM55 (ENSG00000147573), TRIM48 (ENSG00000150244), TRIM36 (ENSG00000152503), TRIM11 (ENSG00000154370), TRIM74 (ENSG00000155428), TRIM42 (ENSG00000155890), TRIM63 (ENSG00000158022)

Protein

Protein identifiers

Pyrin — O15553 (reviewed: O15553)

Alternative names: Marenostrin

All UniProt accessions (9): O15553, D2DTW1, E3P8H6, F5GZV9, F5H2E5, F5H595, F5H6N9, F8W6Z2, I3L0S7

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma. Organizes autophagic machinery by serving as a platform for the assembly of ULK1, Beclin 1/BECN1, ATG16L1, and ATG8 family members and recognizes specific autophagy targets, thus coordinating target recognition with assembly of the autophagic apparatus and initiation of autophagy. Acts as an autophagy receptor for the degradation of several inflammasome components, including CASP1, NLRP1 and NLRP3, hence preventing excessive IL1B- and IL18-mediated inflammation. However, it can also have a positive effect in the inflammatory pathway, acting as an innate immune sensor that triggers PYCARD/ASC specks formation, caspase-1 activation, and IL1B and IL18 production. Together with AIM2, also acts as a mediator of pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of host defense against pathogens, in response to bacterial infection. It is required for PSTPIP1-induced PYCARD/ASC oligomerization and inflammasome formation. Recruits PSTPIP1 to inflammasomes, and is required for PSTPIP1 oligomerization.

Subunit / interactions. Homotrimer. Interacts (via the B box-type zinc finger) with PSTPIP1. Interacts (via the B30.2/SPRY domain) with several components of the inflammasome complex, including CASP1 p20 and p10 subunits, CASP5, PYCARD, NLRP1, NLRP2 and NLRP3, as well as with unprocessed IL1B; this interaction may lead to autophagic degradation of these proteins. Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis). Interacts with NFKBIA and RELA. Interacts weakly with VASP and ACTR3. Interacts with active ULK1 (phosphorylated on ‘Ser-317’) and BECN1 simultaneously. Also interacts with ATG16L1 (via WD repeats), and with ATG8 family members, including GABARAP, GABARAPL1 and, to a lesser extent, GABARAPL2, MAP1LC3A/LC3A and MAP1LC3C/LC3C. Interacts with TRIM21. Interacts with YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ and YWHAZ; the interaction is required for the down-regulation of pyrin pro-inflammatory activity.

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Ruffle. Lamellipodium. Nucleus. Cytoplasmic vesicle. Autophagosome Nucleus.

Tissue specificity. Expressed in peripheral blood leukocytes, particularly in mature granulocytes and to a lesser extent in monocytes but not in lymphocytes. Detected in spleen, lung and muscle, probably as a result of leukocyte infiltration in these tissues. Not expressed in thymus, prostate, testis, ovary, small intestine, colon, heart, brain, placenta, liver, kidney, pancreas. Expression detected in several myeloid leukemic, colon cancer, and prostate cancer cell lines.

Post-translational modifications. Cleaved by CASP1. The N-terminal cleavage product localizes to the nucleus as a filamentous network and to the cytoplasm, interacts more strongly with RELA and NFKBIA than the full-length protein, enhances the nuclear localization of RELA and induces NFKBIA proteolysis. The C-terminal cleavage product localizes to the cytoplasm. Phosphorylation at Ser-242 is required for the interaction with 14-3-3 proteins and down-regulation of pyrin pro-inflammatory activity. Degraded along with the delivery of its substrates to autolysosomal compartments (at protein level).

Disease relevance. Familial Mediterranean fever, autosomal recessive (ARFMF) [MIM:249100] A hereditary periodic fever syndrome characterized by recurrent episodic fever, serosal inflammation and pain in the abdomen, chest or joints. It is frequently complicated by reactive amyloidosis, which leads to renal failure and can be prophylactically treated with colchicine. The disease is caused by variants affecting the gene represented in this entry. The disease-associated mutations in the B30.2/SPRY domain perturb ULK1 recruitment and autophagic degradation of inflammasome components, including NLRP3, and hence may contribute to the inflammatory phenotype associated with ARFMF. Familial Mediterranean fever, autosomal dominant (ADFMF) [MIM:134610] A hereditary periodic fever syndrome characterized by periodic fever, serosal inflammation and pain in the abdomen, chest or joints as seen also in the autosomal recessive form of the disease. It is associated with reactive renal amyloidosis and characterized by colchicine unresponsiveness. The disease is caused by variants affecting the gene represented in this entry. Pyrin-associated autoinflammatory disease (PAAND) [MIM:608068] An autosomal dominant autoinflammatory disorder characterized by childhood onset of recurrent episodes of fever, neutrophilic dermatosis, myalgia and arthralgia. The neutrophilic dermatosis comprises a spectrum of clinical manifestations, including severe acne, sterile skin abscesses, pyoderma gangrenosum, and neutrophilic small-vessel vasculitis. Pathological examination of affected skin shows a dense, predominantly neutrophilic, vascular, perivascular, and interstitial infiltrate. PAAND has incomplete penetrance and variable expressivity. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The B box-type zinc finger interacts, possibly intramolecularly, with the pyrin domain; this may be an autoinhibitory mechanism released by PSTPIP1 binding.

Induction. In monocytes, up-regulated by treatment with colchicine and IFN-alpha, by the pro-inflammatory cytokines IFNG/IFN-gamma and TNF, by bacterial lipopolysaccharides (LPS) and by retroviral infection. Repressed in monocytes by the anti-inflammatory cytokines IL10/interleukin-10, TGFB1 and IL4/interleukin-4. In neutrophils and macrophages, up-regulated by IFNG/IFN-gamma with a peak after 8 hours of treatment.

Isoforms (3)

UniProt ID	Names	Canonical?
O15553-2	1, FL	yes
O15553-1	2, D2
O15553-3	3

RefSeq proteins (2): NP_000234, NP_001185465 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001870	B30.2/SPRY	Domain
IPR003877	SPRY_dom	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR004020	DAPIN	Domain
IPR006574	PRY	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050143	TRIM/RBCC	Family

Pfam: PF00622, PF00643, PF02758, PF13765

UniProt features (124 total): sequence variant 63, strand 15, helix 14, mutagenesis site 10, region of interest 5, turn 4, compositionally biased region 3, domain 2, splice variant 2, chain 1, short sequence motif 1, site 1, modified residue 1, zinc finger region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
9R6Y	X-RAY DIFFRACTION	1.26
2WL1	X-RAY DIFFRACTION	1.35
8C30	X-RAY DIFFRACTION	1.4
9R73	X-RAY DIFFRACTION	1.44
8C2Y	X-RAY DIFFRACTION	1.46
9R70	X-RAY DIFFRACTION	1.5
8C28	X-RAY DIFFRACTION	1.6
9R74	X-RAY DIFFRACTION	2
4CG4	X-RAY DIFFRACTION	2.4
8SDJ	X-RAY DIFFRACTION	2.4
2MPC	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15553-F1	73.64	0.50

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): 330–331 (cleavage; by casp1)

Post-translational modifications (1): 242

Mutagenesis-validated functional residues (10):

Position	Phenotype
16	does not form mefv- and pstpip1-containing perinuclear specks.
24	does not form mefv- and pstpip1-containing perinuclear specks.
208	loss of interaction with 14-3-3 proteins.
244	no effect on pycard/asc specks formation. no effect on interaction with 14-3-3 proteins.
244	no effect on pycard/asc specks formation. increased interaction with 14-3-3 proteins.
244	increased pycard/asc specks formation. decreased interaction with 14-3-3 proteins.
330	loss of cleavage by casp1.
397–404	no effect on gabarap-binding. loss of gabarap-binding; when associated with 470-y–g-488 and 523-s–d-530.
470–488	no effect on gabarap-binding. loss of gabarap-binding; when associated with 397-i–h-404 and 523-s–d-530.
523–530	no effect on gabarap-binding. loss of gabarap-binding; when associated with 397-i–h-404 and 470-y–g-488.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-844456	The NLRP3 inflammasome
R-HSA-9660826	Purinergic signaling in leishmaniasis infection
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168643	Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
R-HSA-5663205	Infectious disease
R-HSA-622312	Inflammasomes
R-HSA-9658195	Leishmania infection
R-HSA-9664424	Cell recruitment (pro-inflammatory response)
R-HSA-9824443	Parasitic Infection Pathways

MSigDB gene sets: 491 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOBP_INFLAMMATORY_RESPONSE, REACTOME_THE_NLRP3_INFLAMMASOME, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_INFLAMMASOMES, REACTOME_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_NLR_SIGNALING_PATHWAYS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOCC_RUFFLE, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_INTERLEUKIN_1_PRODUCTION, HATADA_METHYLATED_IN_LUNG_CANCER_DN

GO Biological Process (20): pattern recognition receptor signaling pathway (GO:0002221), inflammatory response (GO:0006954), regulation of gene expression (GO:0010468), positive regulation of autophagy (GO:0010508), regulation of interleukin-1 beta production (GO:0032651), negative regulation of interleukin-1 beta production (GO:0032691), negative regulation of interleukin-12 production (GO:0032695), positive regulation of interleukin-1 beta production (GO:0032731), response to type II interferon (GO:0034341), innate immune response (GO:0045087), negative regulation of inflammatory response (GO:0050728), positive regulation of inflammatory response (GO:0050729), pyroptotic inflammatory response (GO:0070269), negative regulation of macrophage inflammatory protein 1 alpha production (GO:0071641), negative regulation of cytokine production involved in inflammatory response (GO:1900016), negative regulation of NLRP3 inflammasome complex assembly (GO:1900226), pyroptosome complex assembly (GO:1904270), immune system process (GO:0002376), regulation of inflammatory response (GO:0050727), response to other organism (GO:0051707)

GO Molecular Function (6): actin binding (GO:0003779), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (13): ruffle (GO:0001726), nucleus (GO:0005634), cytoplasm (GO:0005737), autophagosome (GO:0005776), cytosol (GO:0005829), microtubule (GO:0005874), microtubule associated complex (GO:0005875), plasma membrane (GO:0005886), lamellipodium (GO:0030027), cytoplasmic vesicle (GO:0031410), canonical inflammasome complex (GO:0061702), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Inflammasomes	1
Cell recruitment (pro-inflammatory response)	1
Immune System	1
Innate Immune System	1
Disease	1
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1
Parasitic Infection Pathways	1
Leishmania infection	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
inflammatory response	4
interleukin-1 beta production	3
cellular anatomical structure	3
regulation of interleukin-1 beta production	2
negative regulation of cytokine production	2
regulation of inflammatory response	2
cell leading edge	2
plasma membrane bounded cell projection	2
cytoplasm	2
microtubule cytoskeleton	2
protein-containing complex	2
innate immune response-activating signaling pathway	1
defense response	1
gene expression	1
regulation of macromolecule biosynthetic process	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
regulation of interleukin-1 production	1
negative regulation of interleukin-1 production	1
interleukin-12 production	1
regulation of interleukin-12 production	1
positive regulation of interleukin-1 production	1
response to cytokine	1
innate immune response	1
immune response	1
defense response to symbiont	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
negative regulation of chemokine production	1
macrophage inflammatory protein-1 alpha production	1
regulation of macrophage inflammatory protein 1 alpha production	1
cytokine production involved in inflammatory response	1
regulation of cytokine production involved in inflammatory response	1
negative regulation of protein-containing complex assembly	1
NLRP3 inflammasome complex assembly	1
negative regulation of inflammasome-mediated signaling pathway	1
regulation of NLRP3 inflammasome complex assembly	1

Protein interactions and networks

STRING

2164 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEFV	AIM2	O14862	999
MEFV	CASP1	P29466	999
MEFV	NLRP1	Q9C000	999
MEFV	NLRC4	Q9NPP4	999
MEFV	PSTPIP1	O43586	997
MEFV	NLRP3	Q96P20	990
MEFV	PYCARD	Q9ULZ3	978
MEFV	NLRP6	P59044	966
MEFV	NAIP	Q13075	954
MEFV	IFI16	Q16666	929
MEFV	IL18	Q14116	928
MEFV	IL1B	P01584	925
MEFV	NLRP2	Q9NX02	922
MEFV	NLRP12	P59046	909
MEFV	NLRP7	Q8WX94	904

IntAct

29 interactions, top by confidence:

A	B	Type	Score
PYCARD	MEFV	psi-mi:“MI:0407”(direct interaction)	0.800
PYCARD	MEFV	psi-mi:“MI:0915”(physical association)	0.800
MEFV	PYCARD	psi-mi:“MI:0915”(physical association)	0.800
PYCARD	MEFV	psi-mi:“MI:0403”(colocalization)	0.800
MEFV	MEFV	psi-mi:“MI:0407”(direct interaction)	0.770
MEFV	MEFV	psi-mi:“MI:0915”(physical association)	0.770
PSTPIP1	MEFV	psi-mi:“MI:0915”(physical association)	0.580
MEFV	PSTPIP1	psi-mi:“MI:0915”(physical association)	0.580
MEFV	PSTPIP1	psi-mi:“MI:0914”(association)	0.580
MEFV	CASP1	psi-mi:“MI:0915”(physical association)	0.400
CASP1	MEFV	psi-mi:“MI:0915”(physical association)	0.400
MEFV	H1-2	psi-mi:“MI:0915”(physical association)	0.400
SPICE1	MEFV	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
MEFV	YWHAQ	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): SIVA1 (Two-hybrid), SIVA1 (Affinity Capture-Western), ULK1 (Affinity Capture-Western), BECN1 (Affinity Capture-Western), ULK1 (Reconstituted Complex), ATG16L1 (Affinity Capture-Western), GABARAP (Reconstituted Complex), GABARAPL1 (Reconstituted Complex), MAP1LC3A (Reconstituted Complex), MAP1LC3C (Reconstituted Complex), GABARAPL2 (Reconstituted Complex), GABARAP (Protein-peptide), MEFV (Reconstituted Complex), NLRP3 (Affinity Capture-Western), MEFV (Two-hybrid)

ESM2 similar proteins: A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A6NDS4, A6NER0, A6QPT6, B9A6J9, M3WHG5, O14771, O15482, O15553, O19110, O76081, P0C7X1, P0C7X3, P0C7X4, P35125, P48778, P48967, P79209, Q13670, Q15697, Q2TBC4, Q3T191, Q3UZD7, Q4R2Z8, Q5DRQ5, Q5SSQ6, Q5XFX8, Q69ZB3, Q6DHY5, Q6IPX1, Q6ZMN8, Q8BLR5, Q8BWA8, Q8IYF1, Q8IZP1, Q8JZW5, Q8N7G0

Diamond homologs: A0JN74, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NK02, A6NLI5, B1H278, C9J1S8, K7N6K2, O00635, O15553, O19085, O77666, P0CI25, P0CI26, P14373, P15533, P18892, P19474, Q02084, Q0PF16, Q12899, Q13410, Q1ACD5, Q1ACD6, Q1ACD7, Q1ACD8, Q1XHU0, Q2T9Z0, Q2YEM8, Q2YEM9, Q2YEN0, Q2YEN2, Q3UWZ0, Q3ZEE5, Q495X7, Q587N6, Q587N7, Q58DK8

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
PKN1	“down-regulates activity”	MEFV	phosphorylation
PKN2	“down-regulates activity”	MEFV	phosphorylation
MEFV	“form complex”	“Pyrin inflammasome”	binding
DAMPS	“up-regulates activity”	MEFV
PAMPs	“up-regulates activity”	MEFV

Disease & clinical

Clinical variants and AI predictions

ClinVar

1113 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	6
Uncertain significance	444
Likely benign	384
Benign	31

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1179060	NM_000243.3(MEFV):c.1510C>T (p.Gln504Ter)	Pathogenic
430715	NM_000243.3(MEFV):c.332G>A (p.Gly111Glu)	Pathogenic
917511	NM_000243.3(MEFV):c.730G>A (p.Glu244Lys)	Pathogenic
966299	NM_000243.3(MEFV):c.265del (p.Ala89fs)	Pathogenic
971850	NM_000243.3(MEFV):c.214C>T (p.Gln72Ter)	Pathogenic
1179055	NM_000243.3(MEFV):c.1597_1598dup (p.Asp533fs)	Likely pathogenic
1677080	NM_000243.3(MEFV):c.1506_1507dup (p.Ser503fs)	Likely pathogenic
1694332	NM_000243.3(MEFV):c.1321C>T (p.Arg441Ter)	Likely pathogenic
3239681	NM_000243.3(MEFV):c.590del (p.Gly197fs)	Likely pathogenic
4817969	NM_000243.3(MEFV):c.724A>G (p.Ser242Gly)	Likely pathogenic
987917	NM_000243.2:c.(?911)(1356_?)del	Likely pathogenic

SpliceAI

1781 predictions. Top by Δscore:

Variant	Effect	Δscore
16:3243695:C:CC	acceptor_gain	1.0000
16:3243893:C:CC	acceptor_gain	1.0000
16:3247014:A:AT	donor_loss	1.0000
16:3247015:C:CA	donor_loss	1.0000
16:3247242:TGTTT:T	acceptor_gain	1.0000
16:3247247:C:CC	acceptor_gain	1.0000
16:3256306:CTTA:C	donor_loss	1.0000
16:3256307:TTAC:T	donor_loss	1.0000
16:3256308:TA:T	donor_loss	1.0000
16:3256309:A:AC	donor_gain	1.0000
16:3256309:AC:A	donor_gain	1.0000
16:3256309:ACC:A	donor_gain	1.0000
16:3256309:ACCCT:A	donor_loss	1.0000
16:3256310:C:CA	donor_loss	1.0000
16:3256310:C:CC	donor_gain	1.0000
16:3256310:CC:C	donor_gain	1.0000
16:3256310:CCC:C	donor_gain	1.0000
16:3256310:CCCTG:C	donor_gain	1.0000
16:3243690:ATTAA:A	acceptor_gain	0.9900
16:3243691:TTAA:T	acceptor_gain	0.9900
16:3243892:ACTAC:A	acceptor_loss	0.9900
16:3243907:C:CT	acceptor_gain	0.9900
16:3243908:A:T	acceptor_gain	0.9900
16:3244287:C:CC	acceptor_gain	0.9900
16:3244292:A:AC	acceptor_gain	0.9900
16:3244292:A:C	acceptor_gain	0.9900
16:3244294:G:C	acceptor_gain	0.9900
16:3244482:A:AC	donor_gain	0.9900
16:3244483:C:CC	donor_gain	0.9900
16:3247012:CCACC:C	donor_gain	0.9900

AlphaMissense

5072 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:3256517:A:G	F24S	0.992
16:3243494:A:G	W665R	0.990
16:3243494:A:T	W665R	0.990
16:3256505:A:G	L28P	0.988
16:3243579:A:C	F636L	0.987
16:3243579:A:T	F636L	0.987
16:3243581:A:G	F636L	0.987
16:3249533:G:C	F386L	0.983
16:3249533:G:T	F386L	0.983
16:3249535:A:G	F386L	0.983
16:3256367:A:G	L74P	0.983
16:3243216:G:C	S757R	0.982
16:3243216:G:T	S757R	0.982
16:3243218:T:G	S757R	0.982
16:3243524:A:G	W655R	0.982
16:3243524:A:T	W655R	0.982
16:3256516:G:C	F24L	0.980
16:3256516:G:T	F24L	0.980
16:3256518:A:G	F24L	0.980
16:3256382:A:G	L69P	0.979
16:3256469:A:G	I40T	0.979
16:3256510:G:C	F26L	0.979
16:3256510:G:T	F26L	0.979
16:3256512:A:G	F26L	0.979
16:3256513:C:A	K25N	0.978
16:3256513:C:G	K25N	0.978
16:3243294:A:C	F731L	0.976
16:3243294:A:T	F731L	0.976
16:3243296:A:G	F731L	0.976
16:3256391:G:T	A66D	0.976

dbSNP variants (sampled 300 via entrez): RS1000206830 (16:3254894 T>C), RS1000657059 (16:3254711 C>A,G,T), RS1000771273 (16:3252879 G>A,T), RS1000923269 (16:3249253 A>G), RS1001220599 (16:3253792 G>A,C), RS1001256948 (16:3244733 G>A,C), RS1001641114 (16:3248585 G>A,T), RS1001713133 (16:3248350 G>A,C), RS1001938136 (16:3253322 C>A,T), RS1001986425 (16:3249785 G>A,T), RS1002291138 (16:3254618 C>G,T), RS1002530785 (16:3245720 T>C), RS1003619678 (16:3255063 T>A,C), RS1003659192 (16:3250853 G>A,C), RS1003679881 (16:3257772 T>C)

Disease associations

OMIM: gene MIM:608107 | disease phenotypes: MIM:134610, MIM:608068, MIM:152700, MIM:601744, MIM:115200, MIM:109650, MIM:242300, MIM:117000, MIM:193300, MIM:256730

GenCC curated gene-disease

Disease	Classification	Inheritance
familial Mediterranean fever	Definitive	Autosomal recessive
autosomal recessive familial Mediterranean fever	Definitive	Autosomal recessive
familial Mediterranean fever, autosomal dominant	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
familial Mediterranean fever	Definitive	SD

Mondo (12): familial Mediterranean fever (MONDO:0018088), familial Mediterranean fever, autosomal dominant (MONDO:0007601), sweet syndrome (MONDO:0011959), autoinflammatory syndrome (MONDO:0019751), systemic lupus erythematosus (MONDO:0007915), dilated cardiomyopathy 1A (MONDO:0007269), Behcet disease (MONDO:0007191), autosomal recessive congenital ichthyosis (MONDO:0017265), central core myopathy (MONDO:0007294), von Hippel-Lindau disease (MONDO:0008667), neuronal ceroid lipofuscinosis (MONDO:0016295), autosomal recessive familial Mediterranean fever (MONDO:0009572)

Orphanet (11): Familial Mediterranean fever (Orphanet:342), Sweet syndrome (Orphanet:3243), Autoinflammatory syndrome (Orphanet:93665), Systemic lupus erythematosus (Orphanet:536), Familial dilated cardiomyopathy with conduction defect due to LMNA mutation (Orphanet:300751), Behçet disease (Orphanet:117), Autosomal recessive congenital ichthyosis (Orphanet:281097), Central core disease (Orphanet:597), Von Hippel-Lindau disease (Orphanet:892), Neuronal ceroid lipofuscinosis (Orphanet:216), OBSOLETE: Infantile neuronal ceroid lipofuscinosis (Orphanet:79263)

HPO phenotypes

164 total (30 of 164 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000031	Epididymitis
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000099	Glomerulonephritis
HP:0000100	Nephrotic syndrome
HP:0000112	Nephropathy
HP:0000121	Nephrocalcinosis
HP:0000155	Oral ulcer
HP:0000271	Abnormality of the face
HP:0000464	Abnormality of the neck
HP:0000488	Retinopathy
HP:0000518	Cataract
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000737	Irritability
HP:0000739	Anxiety
HP:0000934	Chondrocalcinosis
HP:0000988	Skin rash
HP:0001055	Erysipelas
HP:0001061	Acne
HP:0001097	Keratoconjunctivitis sicca
HP:0001155	Abnormality of the hand
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001269	Hemiparesis
HP:0001287	Meningitis

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007844_18	Ankylosing spondylitis	2.000000e-12

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D001528	Behcet Syndrome	C07.465.075; C11.941.879.780.880.200; C14.907.940.100; C16.320.382.250; C17.800.827.368.250; C17.800.862.150
D010505	Familial Mediterranean Fever	C16.320.382.625
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590
D020512	Myopathy, Central Core	C05.651.575.300; C10.668.491.550.300
D016463	Sweet Syndrome	C17.800.229.800
D006623	von Hippel-Lindau Disease	C10.562.925; C14.907.077.925; C16.131.077.245.750; C16.320.184.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6196061 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Aflatoxin B1	increases methylation	2
Asian ginseng	decreases reaction, increases expression	1
TL8-506	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants, Occupational	decreases expression	1
Antimycin A	increases expression	1
Beclomethasone	increases response to substance	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Diethylhexyl Phthalate	decreases reaction, increases expression	1
Estradiol	affects cotreatment, increases expression	1
Gold	increases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression, affects response to substance, increases expression	1
Nickel	decreases expression	1
Ozone	increases abundance, affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Thiram	decreases expression	1
Valproic Acid	increases methylation	1
Particulate Matter	increases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL6076381	Binding	Inhibition of pyrin inflammasome activation in human U-937 cells assessed as IL-1beta secretion preincubated for 1 hr followed by BAA473 addition and measured after 4 hrs	Discovery of NP3-253, a Potent Brain Penetrant Inhibitor of the NLRP3 Inflammasome. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 induced pluripotent stem cell, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_9T92	GM14978	Finite cell line	Male
CVCL_9U21	KU_FMF_iPSC_1	Induced pluripotent stem cell	Male
CVCL_E4EL	RAUi002-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02602028	PHASE4	COMPLETED	The Comparison of the Efficacy of Once and Twice Daily Colchicine Dosage in Pediatric Patients With FMF
NCT06666335	PHASE4	NOT_YET_RECRUITING	A Study to Evaluate Efficacy and Safety of Anakinra in Chinese Patients With Colchicine-resistent FMF
NCT00120887	PHASE4	COMPLETED	Lupus Atherosclerosis Prevention Study
NCT00125307	PHASE4	COMPLETED	Tacrolimus for the Treatment of Systemic Lupus Erythematosus With Membranous Nephritis
NCT00188188	PHASE4	UNKNOWN	Study of Endothelial Dysfunction in Systemic Lupus and Its Role in Heart Disease
NCT00371501	PHASE4	COMPLETED	Aspirin and Statins for Prevention of Atherosclerosis and Arterial Thromboembolism in Systemic Lupus Erythematosus
NCT00392093	PHASE4	COMPLETED	Effect of Hormone Replacement Therapy on Lupus Activity
NCT00413361	PHASE4	COMPLETED	The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
NCT00508898	PHASE4	WITHDRAWN	The Efficacy and Safety of Calcitriol for the Treatment of Lupus Nephritis and Persistent Proteinuria
NCT00668330	PHASE4	COMPLETED	Steroid Induced Osteoporosis in Patients With Systemic Lupus Erythematosus
NCT00739050	PHASE4	TERMINATED	Effect of Simvastatin on Endothelial Function in Premenopausal Women With Systemic Lupus Erythematosus (0733-271)(TERMINATED)
NCT00815282	PHASE4	COMPLETED	Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
NCT00828178	PHASE4	COMPLETED	Efficacy of Fish Oil in Lupus Patients
NCT00866229	PHASE4	UNKNOWN	Efficacy and Adverse Effect of Simvastatin Compare to Rosuvastatin in Systemic Lupus Erythematosus (SLE) Patients With Corticosteroid Therapy and High Low-Density Lipoprotein (LDL) Cholesterol Level
NCT00911521	PHASE4	COMPLETED	Immunogenicity and Safety of a Quadrivalent Human Papillomavirus (HPV) Vaccine in Patients With SLE: a Controlled Study
NCT01101802	PHASE4	COMPLETED	Mycophenolate Mofetil in Systemic Lupus Erythematosus (MISSILE)
NCT01112215	PHASE4	COMPLETED	Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT01276782	PHASE4	WITHDRAWN	Levothyroxine in Pregnant SLE Patients
NCT01322308	PHASE4	COMPLETED	Effect of Pioglitazone on Endothelial Function in Premenopausal Women With Uncomplicated Systemic Lupus Erythematosus
NCT01359826	PHASE4	WITHDRAWN	The Effect of Milnacipran on Fatigue and Quality of Life in Lupus Patients
NCT01597492	PHASE4	COMPLETED	A Study to Evaluate the Effect of Belimumab on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE)
NCT01632241	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)
NCT01705977	PHASE4	COMPLETED	Belimumab Assessment of Safety in SLE
NCT01753401	PHASE4	COMPLETED	Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease
NCT02270970	PHASE4	UNKNOWN	Evaluation of Belimumab Impact on a BLyS Activity Signature Test in the Absence of Confounding Polypharmacy
NCT02477150	PHASE4	COMPLETED	Safety and Immunogenicity of a Zoster Vaccine in SLE
NCT02741960	PHASE4	COMPLETED	The Effect of Metformin on Reducing Lupus Flares
NCT02779153	PHASE4	WITHDRAWN	Acthar SLE (Systemic Lupus Erythematosus)
NCT02953821	PHASE4	COMPLETED	Acthar Gel for Active Systemic Lupus Erythematosus (SLE)
NCT03042260	PHASE4	UNKNOWN	Prophylactic Trimethoprim/Sulfamethoxazole to Prevent Severe Infections in Patients With Lupus Erythematous
NCT03098823	PHASE4	COMPLETED	A Crossover Study to Compare RAYOS to IR Prednisone to Improve Fatigue and Morning Symptoms for SLE
NCT03122431	PHASE4	COMPLETED	Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases
NCT03543839	PHASE4	RECRUITING	Trial of Belimumab in Early Lupus
NCT04447053	PHASE4	UNKNOWN	Sequential Belimumab and T-cell Based Therapy in SLE
NCT04515719	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in SLE Patients
NCT04893161	PHASE4	UNKNOWN	A Model About the Response of Belimumab in SLE
NCT04908865	PHASE4	COMPLETED	Open-label Study of Belimumab Plus Standard Therapy in Chinese Pediatric Participants With Active Systemic Lupus Erythematosus (SLE)
NCT04956484	PHASE4	COMPLETED	Belimumab In Early Systemic Lupus Erythematosus
NCT05559671	PHASE4	RECRUITING	Safety of the Herpes Zoster Subunit Vaccine in Lupus