C2

Summary

C2 (complement C2, HGNC:1248) is a protein-coding gene on chromosome 6p21.33, encoding Complement C2 (P06681). Precursor of the catalytic component of the C3 and C5 convertase complexes, which are part of the complement pathway, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system.

Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been reported to associated with certain autoimmune diseases and SNPs in this gene have been associated with altered susceptibility to age-related macular degeneration. This gene localizes within the class III region of the MHC on the short arm of chromosome 6. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described in publications but their full-length sequence has not been determined.

Source: NCBI Gene 717 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complement component 2 deficiency (Strong, GenCC)
• GWAS associations: 68
• Clinical variants (ClinVar): 513 total — 17 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 3
• Druggable target: yes
• MANE Select transcript: NM_000063

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1248
Approved symbol	C2
Name	complement C2
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166278
Ensembl biotype	protein_coding
OMIM	613927
Entrez	717

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 17 protein_coding, 4 nonsense_mediated_decay, 4 retained_intron, 1 non_stop_decay, 1 protein_coding_CDS_not_defined

ENST00000299367, ENST00000383177, ENST00000411571, ENST00000413154, ENST00000418949, ENST00000442278, ENST00000447952, ENST00000452202, ENST00000452323, ENST00000468407, ENST00000469372, ENST00000482060, ENST00000484636, ENST00000485690, ENST00000486124, ENST00000494905, ENST00000497706, ENST00000695637, ENST00000695638, ENST00000695639, ENST00000695640, ENST00000695644, ENST00000695645, ENST00000695646, ENST00000862556, ENST00000862557, ENST00000862558

RefSeq mRNA: 6 — MANE Select: NM_000063 NM_000063, NM_001145903, NM_001178063, NM_001282457, NM_001282458, NM_001282459

CCDS: CCDS4728, CCDS54991, CCDS56416, CCDS75427, CCDS75428

Canonical transcript exons

ENST00000299367 — 18 exons

Exon	Start	End
ENSE00001863951	31927717	31927798
ENSE00003465506	31939231	31939320
ENSE00003510154	31933610	31933783
ENSE00003526031	31934166	31934299
ENSE00003542442	31935923	31936061
ENSE00003542622	31933867	31933965
ENSE00003555157	31945178	31945672
ENSE00003624113	31942959	31943099
ENSE00003625758	31943644	31943809
ENSE00003641559	31944980	31945029
ENSE00003646481	31943917	31943993
ENSE00003649345	31943416	31943527
ENSE00003674113	31943225	31943319
ENSE00003677538	31937319	31937459
ENSE00003681952	31944135	31944226
ENSE00003788330	31944727	31944853
ENSE00003964557	31927955	31928164
ENSE00003964559	31928732	31928917

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 99.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.7629 / max 761.6776, expressed in 1499 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67090	6.4129	589
67080	2.8402	1182
67084	0.6145	43
67087	0.4840	147
67088	0.2412	76
67085	0.0734	12
67083	0.0469	12
67086	0.0346	11
67082	0.0152	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
liver	UBERON:0002107	99.21	gold quality
right lobe of liver	UBERON:0001114	99.17	gold quality
placenta	UBERON:0001987	96.35	gold quality
spleen	UBERON:0002106	94.06	gold quality
upper lobe of left lung	UBERON:0008952	93.51	gold quality
gall bladder	UBERON:0002110	92.81	gold quality
vermiform appendix	UBERON:0001154	92.07	gold quality
omental fat pad	UBERON:0010414	92.01	gold quality
right lung	UBERON:0002167	91.96	gold quality
lymph node	UBERON:0000029	91.42	gold quality
lung	UBERON:0002048	90.50	gold quality
duodenum	UBERON:0002114	90.48	gold quality
colonic epithelium	UBERON:0000397	90.21	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.87	gold quality
small intestine	UBERON:0002108	89.72	gold quality
adipose tissue	UBERON:0001013	89.05	gold quality
smooth muscle tissue	UBERON:0001135	88.15	gold quality
rectum	UBERON:0001052	86.79	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.64	gold quality
right adrenal gland cortex	UBERON:0035827	86.64	gold quality
right coronary artery	UBERON:0001625	85.43	gold quality
right adrenal gland	UBERON:0001233	85.00	gold quality
left adrenal gland	UBERON:0001234	84.43	gold quality
urinary bladder	UBERON:0001255	84.40	gold quality
monocyte	CL:0000576	84.26	gold quality
left adrenal gland cortex	UBERON:0035825	83.65	gold quality
intestine	UBERON:0000160	83.64	gold quality
leukocyte	CL:0000738	83.62	gold quality
adrenal gland	UBERON:0002369	83.02	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.75	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	25.49
E-MTAB-6678	yes	10.58
E-HCAD-11	yes	7.40
E-MTAB-6142	no	8.40

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NKX2-5, TP53

miRNA regulators (miRDB)

29 targeting C2, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4500	99.99	72.72	2367
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-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-6831-5P	98.26	67.20	990
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-3927-3P	97.68	66.76	892
HSA-MIR-512-5P	97.47	66.48	591
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-582-3P	96.69	67.38	1019
HSA-MIR-6753-5P	94.70	64.08	470

Literature-anchored findings (GeneRIF, showing 38)

• C2 microheterogeneity and histocompatibility antigens Class I were studied in an Austrian population. (PMID:12823772)
• study of the formation of high affinity C5 convertase of the classical pathway of complement (PMID:12878586)
• Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2 (PMID:16670774)
• a weaker, independent protective effect exists for complement component 2 in age related macular degeneration. (PMID:17576744)
• C2/CFB significantly influences AMD susceptibility and although accounting for effects at this locus does not dramatically increase the overall accuracy of the genetic risk model, the improvement over the CFH-LOC387715 model is statistically significant (PMID:18493315)
• The SNPs rs3753394 and rs800292 of CFH and rs11200638 of HTRA1 are significantly associated with the risk of PCV (polypoidal choroidal vasculopathy) in Chinese patients. (PMID:18515590)
• These data confirm that the classical pathway is vital for complement-mediated phagocytosis of S. pneumoniae and demonstrate why subjects with a C2 deficiency have a marked increase in susceptibility to S. pneumoniae infections. (PMID:18541650)
• In this study, the association of the IVS10 and R32Q variants in the C2 and BF genes in AMD was replicated. Haplotype analysis indicated association of these variants with AMD in an Australian population. (PMID:18806293)
• Because of the high level of linkage disequilibrium within the extended CC2/CFB region, variation within SKIV2L may exert a functional effect in age-related macular degeneration. (PMID:18806297)
• Study provides insights into the genetic pathogenesis of AMD, and C2 has been shown as one of the five genes independently involved in progression from intermediate disease to advanced disease in which blindness is frequent. (PMID:19015224)
• Upon cleavage by C1s, C2a domains undergo conformational rotation while bound to C4b and the released C2b domains may remain folded together as seen in the intact protein. (PMID:19237749)
• Data show that SNPs, and haplotypes risk trends were consistent with those seen in other population studies for CFH, C3, C2, and CFB. (PMID:19259132)
• Our results do not support any major role of the 4 AMD-associated variants in the risk of developing PCV, but favor a predominant association with the RDBP-SKIV2L variants (PMID:19556007)
• The results of the present study provide an independent validation of the association of rs547154 (C2) and rs641153 (CFB) SNPs with reduced risk of AMD in an Indian cohort. (PMID:19696172)
• The polypoidal choroidal vasculopathy (PCV) phenotype in Caucasian patients is associated with the major alleles/genotypes in the age-related macular degeneration (AMD)-associated loci, suggesting that PCV and AMD are genetically similar. (PMID:20378180)
• These data suggest that patients with C2 deficiency are at increased risk of Streptococcus pyogenes infections. (PMID:20417301)
• This study showed that CFH was more likely to be age-related macular(AMD) susceptibility gene, and none of the other C2, CFB, and C3 genes were associated with AMD in a white population. (PMID:20523265)
• These overall results suggest a lack of strong association with the C2 and C7 gene polymorphisms to the susceptibility of systemic lupus erythematosus in the Malaysian population. (PMID:21881993)
• C2/CFB variants play a protective role in the risk of developing neovascular AMD and PCV in the Japanese. (PMID:22232432)
• In conclusion, the genetic effect of C2, CFB and C3 polymorphisms, which are known to be important for AMD in Caucasian, were not significant in the Korean population. (PMID:22273503)
• Results showed that missense mutations in transmembrane protein 2 p.Ser1254Asn, interferon alpha 2 p.Ala120Thr, its regulator NLR family member X1 p.Arg707Cys, and complement component 2 p.Glu318Asp were associated with chronic hepatitis B. (PMID:22610944)
• This meta-analysis provides evidence for an association between C2/CFB polymorphisms and age-related macular degeneration. (PMID:22869612)
• CFH (RS1061170), C2 (RS547154), OR CFB (RS438999) was not associated with early or late AMD. (PMID:23060141)
• Gene variants in CFH and C2/CFB contribute to age related macular degeneration in the Chinese population. (PMID:23233260)
• ARMS2 and C3 are major contributors to advanced age-related macular degeneration in Mexican patients, while the contributions of CFH, C2, and CFB are minor to those of other populations. (PMID:24453474)
• The rs547154, rs641153, and rs12614 SNPs were not associated with age-related macular degeneration development in Greek patients. (PMID:24519512)
• The C2 and CFB gene variants were shown to be associated with polypoidal CNV. Typical PCV was not associated with variants in these genes. (PMID:24965207)
• Inhibition of c3 convertase activity by hepatitis C virus as an additional lesion in the regulation of complement components. (PMID:24983375)
• our data indicate that C2 rs547154 polymorphism plays a protective role in the development of PCV. (PMID:25732348)
• The rs2844455 A allele of C2 is a risk factor for systemic lupus erythematosus development in a Chinese population, whereas the G allele might be a protective factor. (PMID:26176736)
• Solution Structures of Complement C2 and Its C4 Complexes Propose Pathway-specific Mechanisms for Control and Activation of the Complement Proconvertases. (PMID:27252379)
• Vag8 binding to human C1-inhibitor (C1-inh) interferes with the binding of C1-inh to C1s, C1r and MASP-2, resulting in the release of active proteases that subsequently cleave C2 and C4 away from the bacterial surface. (PMID:28742139)
• Logistic regression analyses showed that six C2 single nucleotide polymorphisms had significant associations with the risk of chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma among the Korean subjects. Stepwise analysis revealed that causal markers (rs9267665 and rs10947223) were identified among the C2 variants. (PMID:29283494)
• The pooled ORs for rs551397, rs2274700, rs4151667, rs641153, rs1047286, rs9332739, and rs547154 in the heterozygote model were 0.53, 0.53 , 0.54, 0.48, 1.42, 0.50, and 0.52, respectively. We confirmed the protective role of C2/CFB/CFH polymorphisms in the development of Age-Related Macular Degeneration (AMD), and showed single nucleotide polymorphism in C3 was a high-risk factor for AMD (PMID:30179527)
• Hereditary Deficiency of the Second Component of Complement: Early Diagnosis and 21-Year Follow-Up of a Family. (PMID:32164349)
• Complement protein levels and MBL2 polymorphisms are associated with dengue and disease severity. (PMID:32913345)
• Gain-of-Function Mutations R249C and S250C in Complement C2 Protein Increase C3 Deposition in the Presence of C-Reactive Protein. (PMID:34899688)
• Proteomic analysis of diabetes genetic risk scores identifies complement C2 and neuropilin-2 as predictors of type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. (PMID:36194249)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	C2	ENSMUSG00000024371
rattus_norvegicus	C2	ENSRNOG00000051235

Paralogs (39): CFH (ENSG00000000971), SELE (ENSG00000007908), C8B (ENSG00000021852), C6 (ENSG00000039537), SEZ6 (ENSG00000063015), CFHR2 (ENSG00000080910), APOH (ENSG00000091583), SEZ6L (ENSG00000100095), SUSD6 (ENSG00000100647), SRPX (ENSG00000101955), SRPX2 (ENSG00000102359), C7 (ENSG00000112936), C9 (ENSG00000113600), PAPPA2 (ENSG00000116183), CFHR3 (ENSG00000116785), CR2 (ENSG00000117322), CD46 (ENSG00000117335), CSMD2 (ENSG00000121904), C4BPA (ENSG00000123838), C4BPB (ENSG00000123843), CFHR4 (ENSG00000134365), CFHR5 (ENSG00000134389), F13B (ENSG00000143278), SUSD4 (ENSG00000143502), C8A (ENSG00000157131), SUSD3 (ENSG00000157303), CSMD3 (ENSG00000164796), SVEP1 (ENSG00000165124), SELP (ENSG00000174175), SEZ6L2 (ENSG00000174938), PRF1 (ENSG00000180644), PAPPA (ENSG00000182752), CSMD1 (ENSG00000183117), SELL (ENSG00000188404), CD55 (ENSG00000196352), CR1L (ENSG00000197721), CR1 (ENSG00000203710), CFB (ENSG00000243649), CFHR1 (ENSG00000244414)

Protein

Protein identifiers

Complement C2 — P06681 (reviewed: P06681)

Alternative names: C3/C5 convertase

All UniProt accessions (17): A0A8Q3WKM6, A0A8Q3WKM9, A0A8Q3WKN5, A0A8Q3WL70, P06681, A2ABG0, B4DQI1, C9JYQ5, E9PDZ0, F2Z306, F2Z3N2, F8WCJ9, H0Y3H6, H0Y868, Q5JP69, Q5ST52, Q8N6L6

UniProt curated annotations — full annotation on UniProt →

Function. Precursor of the catalytic component of the C3 and C5 convertase complexes, which are part of the complement pathway, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system. Component C2 is part of the classical, lectin and GZMK complement systems. Catalytic component of the complement C3 and C5 convertase complexes. Following complement activation, recruited to the surface of pathogens by complement C4b opsonin to form the C3 convertase, or C3b and C4b opsonins to form the C5 convertase. As part of the C3 convertase, cleaves and activate C3 into C3a anaphylatoxin and C3b opsonin, the next components of the complement pathways. As part of the C5 convertase, cleaves and activate C5 into C5a anaphylatoxin and C5b component of the membrane attack complex.

Subunit / interactions. Serine protease component of the C3 convertase, also named C4bC2b, composed of the serine protease complement C2b and complement C4b. Serine protease component of the C5 convertase, also named C4bC2bC3b, composed of the serine protease complement C2b, complement C3b, as well as complement C4b. (Microbial infection) Interacts with Schistosoma haematobium TOR (via N-terminal extracellular domain). This results in inhibition of the classical and lectin pathway of complement activation, probably due to interference with binding of C2a to C4b such that C3 convertase cannot be formed. This infers resistance to complement-mediated cell lysis, allowing parasite survival and infection.

Subcellular location. Secreted. Cell surface.

Post-translational modifications. Cleaved and activated by different proteases depending on the complement pathway to generate complement C2a and serine protease complement C2b chains. Cleaved and activated by C1S following activation by the classical complement system. Cleaved and activated by MASP2 following activation by the lectin complement system. Cleaved and activated by GZMK following activation by the GZMK complement system.

Disease relevance. Macular degeneration, age-related, 14 (ARMD14) [MIM:615489] A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Haplotype analyzes have identified a statistically significant common risk haplotype and two protective haplotypes. CFB variant His-9 and C2 variant Asp-318, as well as CFB variant Gln-32 and a variant in intron 10 of C2, confer a significantly reduced risk of AMD. Complement component 2 deficiency (C2D) [MIM:217000] A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus erythematosus. Skin and joint manifestations are common and renal disease is relatively rare. Patients with complement component 2 deficiency are also reported to have recurrent invasive infections. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The MIDAS-like motif in the VWFA domain binds divalent metal cations.

Miscellaneous. C2 is a major histocompatibility complex class-III protein.

Similarity. Belongs to the peptidase S1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P06681-1	1	yes
P06681-2	2
P06681-3	3

RefSeq proteins (6): NP_000054, NP_001139375, NP_001171534, NP_001269386, NP_001269387, NP_001269388 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR002035	VWF_A	Domain
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR011360	Compl_C2_B	Family
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR043504

Pfam: PF00084, PF00089, PF00092

UniProt features (128 total): strand 43, helix 24, disulfide bond 11, glycosylation site 8, binding site 6, sequence variant 6, domain 5, mutagenesis site 5, sequence conflict 5, chain 3, active site 3, turn 3, splice variant 3, signal peptide 1, site 1, short sequence motif 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
3ERB	X-RAY DIFFRACTION	1.8
8ACF	X-RAY DIFFRACTION	1.8
8ACI	X-RAY DIFFRACTION	1.85
2ODP	X-RAY DIFFRACTION	1.9
2I6Q	X-RAY DIFFRACTION	2.1
2ODQ	X-RAY DIFFRACTION	2.3
2I6S	X-RAY DIFFRACTION	2.7
9U60	ELECTRON MICROSCOPY	2.9
9U5Z	ELECTRON MICROSCOPY	3.1
9U61	ELECTRON MICROSCOPY	3.1
9QJ5	ELECTRON MICROSCOPY	3.5
9QK2	ELECTRON MICROSCOPY	3.5
9QJ4	ELECTRON MICROSCOPY	3.9
9QPY	ELECTRON MICROSCOPY	4.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06681-F1	88.61	0.66

Antibody-complex structures (SAbDab): 2 — 8ACF, 8ACI

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 (4): 507 (charge relay system); 561 (charge relay system); 679 (charge relay system); 243–244 (cleavage; by c1s, masp2 and gzmk)

Ligand- & substrate-binding residues (6): 262; 262; 264; 264; 337; 337

Disulfide bonds (11): 24–64, 51–84, 89–131, 117–144, 151–191, 177–204, 463–581, 492–508, 584–600, 638–665, 675–705

Glycosylation sites (8): 29, 112, 290, 333, 467, 471, 621, 651

Mutagenesis-validated functional residues (5):

Position	Phenotype
261	prolonged activity and half-life.
263	prolonged activity and half-life.
344	promotes partial resistance to degradation, slightly increasing half-life of the protein.
347	promotes resistance to degradation, increasing half-life of the protein.
348	promotes partial resistance to degradation, slightly increasing half-life of the protein.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-166663	Initial triggering of complement
R-HSA-174577	Activation of C3 and C5
R-HSA-977606	Regulation of Complement cascade

MSigDB gene sets: 259 (showing top): MODULE_172, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, MODULE_45, GOCC_CELL_SURFACE, GOBP_APOPTOTIC_CELL_CLEARANCE, GOBP_VESICLE_MEDIATED_TRANSPORT, GAURNIER_PSMD4_TARGETS, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_B_CELL_MEDIATED_IMMUNITY, YAN_ESCAPE_FROM_ANOIKIS, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, GOBP_REGULATION_OF_IMMUNE_RESPONSE, MODULE_75

GO Biological Process (11): proteolysis (GO:0006508), complement activation (GO:0006956), complement activation, classical pathway (GO:0006958), response to nutrient (GO:0007584), response to bacterium (GO:0009617), response to lipopolysaccharide (GO:0032496), response to thyroid hormone (GO:0097066), complement activation, GZMK pathway (GO:0160257), positive regulation of apoptotic cell clearance (GO:2000427), immune system process (GO:0002376), innate immune response (GO:0045087)

GO Molecular Function (6): serine-type endopeptidase activity (GO:0004252), metal ion binding (GO:0046872), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cell surface (GO:0009986), extracellular exosome (GO:0070062), symbiont cell surface (GO:0106139)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Complement cascade	3

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
complement activation	2
cellular anatomical structure	2
protein metabolic process	1
immune effector process	1
activation of immune response	1
humoral immune response	1
protein activation cascade	1
humoral immune response mediated by circulating immunoglobulin	1
response to nutrient levels	1
response to chemical	1
response to other organism	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
response to hormone	1
innate immune response	1
apoptotic cell clearance	1
positive regulation of phagocytosis	1
regulation of apoptotic cell clearance	1
biological_process	1
immune response	1
defense response to symbiont	1
endopeptidase activity	1
serine-type peptidase activity	1
cation binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
extracellular vesicle	1
other organism part	1

Protein interactions and networks

STRING

886 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C2	CFH	P08603	862
C2	ARMS2	P0C7Q2	765
C2	CFHR3	Q02985	758
C2	DXO	O77932	740
C2	CFHR1	Q03591	739
C2	C4A	P01028	732
C2	C3	P01024	729
C2	C4A	P01028	723
C2	CD55	P08174	702
C2	CFI	P05156	696
C2	HMCN1	Q96RW7	679
C2	SKIC2	Q15477	651
C2	WHR1	P49842	623
C2	FBLN5	Q9UBX5	616
C2	ABCA4	P78363	587
C2	PLEKHA1	Q9HB21	587

IntAct

37 interactions, top by confidence:

A	B	Type	Score
C1S	SERPING1	psi-mi:“MI:0570”(protein cleavage)	0.720
C2	CREB3	psi-mi:“MI:0915”(physical association)	0.560
C2	SEC11C	psi-mi:“MI:0915”(physical association)	0.560
C2	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
C2	STOM	psi-mi:“MI:0915”(physical association)	0.560
C2	SLC35C2	psi-mi:“MI:0915”(physical association)	0.560
C2	MUC1	psi-mi:“MI:0915”(physical association)	0.560
C2	FAM209A	psi-mi:“MI:0915”(physical association)	0.560
C2	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
C2	EBP	psi-mi:“MI:0915”(physical association)	0.560
C1S	C2	psi-mi:“MI:0570”(protein cleavage)	0.440
C2	CD55	psi-mi:“MI:0915”(physical association)	0.400
M		psi-mi:“MI:0914”(association)	0.350
C2	SEC11C	psi-mi:“MI:0915”(physical association)	0.000
C2	ERGIC3	psi-mi:“MI:0915”(physical association)	0.000
C2	STOM	psi-mi:“MI:0915”(physical association)	0.000
C2	SLC35C2	psi-mi:“MI:0915”(physical association)	0.000
C2	MUC1	psi-mi:“MI:0915”(physical association)	0.000
C2	SLC10A1	psi-mi:“MI:0915”(physical association)	0.000
C2	FAM209A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): CREB3 (Two-hybrid), CD55 (Affinity Capture-MS), C2 (Two-hybrid), C2 (Two-hybrid), C2 (Two-hybrid), C2 (Two-hybrid), C2 (Two-hybrid), C2 (Two-hybrid), SEC11C (Two-hybrid), MUC1 (Two-hybrid), C2 (Affinity Capture-RNA), C2 (Reconstituted Complex), C2 (Reconstituted Complex), CD55 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5NSM8, A2AVA0, B1AUH1, B3DK56, D3YXF5, E9Q6D8, G5E8Q8, O18016, O18023, O43278, O97827, P06681, P0C6B8, P13671, P21180, P28175, P35442, P35448, P61134, P61135, Q03350, Q05793, Q08E66, Q26422, Q29RU4, Q3SYW2, Q4LDE5, Q5E9P5, Q5G872, Q5MD89, Q5RDI1, Q6DIV5, Q6GP28, Q6NZL8, Q6UXH9, Q6YI48, Q7TQN3, Q811M5, Q863A0, Q8BU25

Diamond homologs: A0A1D5NSM8, A0JNA2, A2AVA0, A2AX52, D3YXF5, O02839, O19063, O35764, O43405, O70340, O76536, O89029, O95502, O96530, P02741, P02743, P06205, P06206, P06207, P06681, P07202, P07629, P08607, P09871, P0C6B8, P10643, P12246, P13944, P14151, P14847, P15697, P18337, P23680, P32018, P47970, P47971, P47972, P48199, P49254, P49262

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
MASP2	“up-regulates activity”	C2	cleavage
MASP1	“up-regulates activity”	C2	cleavage
C2	“form complex”	“C3 convertase complex”	binding
“Complement C1 complex”	“up-regulates activity”	C2	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	11
Uncertain significance	237
Likely benign	179
Benign	8

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
12128	NM_000063.6(C2):c.626C>T (p.Ser209Phe)	Pathogenic
1452098	NM_000063.6(C2):c.37del (p.Leu13fs)	Pathogenic
2054147	NM_000063.6(C2):c.275_276del (p.Pro92fs)	Pathogenic
2750154	NM_000063.6(C2):c.917del (p.Met306fs)	Pathogenic
2818188	NM_000063.6(C2):c.970G>T (p.Glu324Ter)	Pathogenic
2842298	NM_000063.6(C2):c.1654C>T (p.Gln552Ter)	Pathogenic
2870130	NM_000063.6(C2):c.795_796del (p.Ser266fs)	Pathogenic
2876427	NM_000063.6(C2):c.630T>A (p.Tyr210Ter)	Pathogenic
2965736	NM_000063.6(C2):c.768C>G (p.Tyr256Ter)	Pathogenic
3246079	NC_000006.11:g.(?31895530)(31905256_?)del	Pathogenic
3257316	NM_000063.6(C2):c.1215T>A (p.Tyr405Ter)	Pathogenic
3393189	NM_000063.6(C2):c.1902+1G>A	Pathogenic
3720679	NM_000063.6(C2):c.235_236del (p.Leu79fs)	Pathogenic
4712064	NM_000063.6(C2):c.1790del (p.Gly597fs)	Pathogenic
4781380	NM_000063.6(C2):c.626_627dup (p.Tyr210fs)	Pathogenic
4800554	NM_000063.6(C2):c.1366_1367del (p.Ser456fs)	Pathogenic
591016	NM_000063.6(C2):c.1102C>T (p.Arg368Ter)	Pathogenic
1910255	NM_000063.6(C2):c.715+1G>T	Likely pathogenic
1916286	NM_000063.6(C2):c.616+1G>A	Likely pathogenic
2125178	NM_000063.6(C2):c.1733+1G>A	Likely pathogenic
2179104	NM_000063.6(C2):c.616+2T>G	Likely pathogenic
2706458	NM_000063.6(C2):c.1361-1G>T	Likely pathogenic
2726593	NM_000063.6(C2):c.2030-1G>A	Likely pathogenic
3381002	NM_000063.6(C2):c.1829_1832del (p.Lys610fs)	Likely pathogenic
3692514	NM_000063.6(C2):c.1810+2T>G	Likely pathogenic
369516	NM_000063.6(C2):c.1360+1G>A	Likely pathogenic
4081217	NM_000063.6(C2):c.1683_1685delinsATA (p.Asp561_Ile562delinsGluTer)	Likely pathogenic
915386	NM_000063.6(C2):c.839_849del (p.Met280fs)	Likely pathogenic

SpliceAI

3454 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31933781:GCC:G	donor_gain	1.0000
6:31933784:G:GG	donor_gain	1.0000
6:31933861:CCACA:C	acceptor_loss	1.0000
6:31933862:CACA:C	acceptor_loss	1.0000
6:31933862:CACAG:C	acceptor_loss	1.0000
6:31933863:ACAG:A	acceptor_loss	1.0000
6:31933863:ACAGA:A	acceptor_loss	1.0000
6:31933864:CA:C	acceptor_loss	1.0000
6:31933865:A:AG	acceptor_gain	1.0000
6:31933865:A:G	acceptor_loss	1.0000
6:31933866:G:GA	acceptor_gain	1.0000
6:31933866:G:GG	acceptor_gain	1.0000
6:31933962:AAGG:A	donor_gain	1.0000
6:31933963:AGG:A	donor_gain	1.0000
6:31933964:GG:G	donor_gain	1.0000
6:31933964:GGG:G	donor_gain	1.0000
6:31933964:GGGTG:G	donor_loss	1.0000
6:31933965:GG:G	donor_gain	1.0000
6:31933965:GGT:G	donor_loss	1.0000
6:31933966:G:GG	donor_gain	1.0000
6:31933966:GTGA:G	donor_loss	1.0000
6:31933967:T:A	donor_loss	1.0000
6:31933967:T:G	donor_loss	1.0000
6:31934274:A:T	donor_gain	1.0000
6:31937306:T:TA	acceptor_gain	1.0000
6:31937307:G:A	acceptor_gain	1.0000
6:31937310:A:AG	acceptor_gain	1.0000
6:31937311:T:G	acceptor_gain	1.0000
6:31937312:A:AG	acceptor_gain	1.0000
6:31937314:TCCAG:T	acceptor_loss	1.0000

AlphaMissense

4972 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:31933758:G:C	W197C	0.999
6:31933758:G:T	W197C	0.999
6:31943302:T:A	W480R	0.998
6:31943302:T:C	W480R	0.998
6:31928886:G:C	W137C	0.997
6:31928886:G:T	W137C	0.997
6:31933756:T:A	W197R	0.997
6:31933756:T:C	W197R	0.997
6:31943304:G:C	W480C	0.997
6:31943304:G:T	W480C	0.997
6:31943924:T:C	C581R	0.997
6:31928118:G:C	W70C	0.996
6:31928118:G:T	W70C	0.996
6:31943924:T:A	C581S	0.996
6:31943925:G:C	C581S	0.996
6:31943926:C:G	C581W	0.996
6:31943933:T:C	C584R	0.996
6:31945190:A:C	S698R	0.996
6:31945192:C:A	S698R	0.996
6:31945192:C:G	S698R	0.996
6:31928866:T:A	C131S	0.995
6:31928867:G:C	C131S	0.995
6:31928884:T:A	W137R	0.995
6:31928884:T:C	W137R	0.995
6:31933738:T:A	C191S	0.995
6:31933739:G:C	C191S	0.995
6:31943465:T:A	V502D	0.995
6:31943482:T:A	C508S	0.995
6:31943483:G:C	C508S	0.995
6:31943484:C:G	C508W	0.995

dbSNP variants (sampled 300 via entrez): RS1000055943 (6:31906530 G>C), RS1000085928 (6:31908097 C>T), RS1000154409 (6:31916621 GGC>G), RS1000170944 (6:31938475 T>C), RS1000331243 (6:31924981 C>G), RS1000458044 (6:31908351 C>T), RS1000484025 (6:31931733 C>G,T), RS1000517218 (6:31922384 C>A), RS1000533023 (6:31907000 C>G,T), RS1000594486 (6:31913173 C>T), RS1000605161 (6:31938723 G>A), RS1000625618 (6:31913405 A>C,G), RS1000666722 (6:31929796 G>A), RS1000900895 (6:31899814 C>A), RS1001000490 (6:31940012 G>T)

Disease associations

OMIM: gene MIM:613927 | disease phenotypes: MIM:217000, MIM:615489, MIM:612924

GenCC curated gene-disease

Disease	Classification	Inheritance
complement component 2 deficiency	Strong	Autosomal recessive

Mondo (6): complement component 2 deficiency (MONDO:0009006), age related macular degeneration 14 (MONDO:0014207), atypical hemolytic-uremic syndrome with B factor anomaly (MONDO:0013042), atypical hemolytic-uremic syndrome (MONDO:0016244), focal segmental glomerulosclerosis (MONDO:0100313), macular degeneration (MONDO:0003004)

Orphanet (2): Atypical hemolytic uremic syndrome (Orphanet:2134), OBSOLETE: Atypical hemolytic uremic syndrome with B factor anomaly (Orphanet:93578)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000979	Purpura
HP:0002725	Systemic lupus erythematosus

GWAS associations

68 associations (top):

Study	Trait	p-value
GCST000652_5	Age-related macular degeneration	2.000000e-08
GCST000652_8	Age-related macular degeneration	3.000000e-21
GCST000653_7	Age-related macular degeneration	2.000000e-20
GCST000902_3	Hepatocellular carcinoma	2.000000e-06
GCST001100_11	Age-related macular degeneration	2.000000e-23
GCST001578_4	Age-related macular degeneration (geographic atrophy)	1.000000e-06
GCST001579_5	Age-related macular degeneration (choroidal neovascularisation)	2.000000e-08
GCST001884_13	Age-related macular degeneration	4.000000e-89
GCST001942_21	Prostate cancer	5.000000e-09
GCST001979_2	Circulating myeloperoxidase levels (serum)	1.000000e-08
GCST002463_14	Systemic lupus erythematosus	8.000000e-21
GCST003219_23	Advanced age-related macular degeneration	1.000000e-103
GCST003219_24	Advanced age-related macular degeneration	3.000000e-06
GCST003219_25	Advanced age-related macular degeneration	9.000000e-12
GCST003219_26	Advanced age-related macular degeneration	3.000000e-10
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_118	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_154	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_162	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_17	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_173	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_224	Autism spectrum disorder or schizophrenia	5.000000e-10
GCST004521_227	Autism spectrum disorder or schizophrenia	4.000000e-12

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:1001492	atrophic macular degeneration
EFO:0005243	myeloperoxidase measurement
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0008336	disease progression measurement
EFO:0006781	coffee consumption measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0009130	clostridium difficile infection
EFO:0004531	urate measurement
EFO:0009749	age at first sexual intercourse measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D065766	Atypical Hemolytic Uremic Syndrome	C12.050.351.968.419.936.463.500; C12.200.777.419.936.463.500; C12.950.419.936.463.500; C15.378.050.141.610.500; C15.378.140.855.925.500.500; C15.378.243.937.925.500.500
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D008268	Macular Degeneration	C11.768.585.439

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295701 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9332739	C2		0.00	0

ChEMBL bioactivities

3 potent at pChembl≥5 of 4 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.48	IC50	330	nM	CHEMBL4247125
6.30	IC50	500	nM	CHEMBL4247125
5.14	IC50	7300	nM	CHEMBL4247125

PubChem BioAssay actives

3 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-4-methylpentanamide	1393232: Competitive/reversible inhibition of human C2 using Ac-SHLGLAR-pNA as substrate	ic50	0.3300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, affects methylation, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
Smoke	decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	decreases methylation	1
chromium hexavalent ion	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Aripiprazole	increases expression, affects cotreatment	1
Fulvestrant	increases methylation	1
Acetaminophen	decreases expression	1
Glyphosate	increases expression	1
Air Pollutants, Occupational	increases expression	1
Allergens	affects cotreatment, increases expression	1
Vehicle Emissions	increases expression, affects cotreatment	1
Benzene	increases expression	1
Calcitriol	decreases expression	1
Estradiol	decreases expression, affects cotreatment	1
Methapyrilene	decreases methylation	1
Nickel	increases expression	1
Ozone	affects cotreatment, increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4229702	Binding	Competitive/reversible inhibition of human C2 using Ac-SHLGLAR-pNA as substrate	Chemical Approaches to Modulating Complement-Mediated Diseases. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02574403	PHASE4	COMPLETED	Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With aHUS
NCT07308574	PHASE4	RECRUITING	Post-Marketing Clinical Study of Ravulizumab in Participants With Clinical aHUS
NCT01129557	PHASE4	TERMINATED	Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
NCT02399462	PHASE4	WITHDRAWN	Acthar for Treatment of Post-transplant FSGS
NCT02585804	PHASE4	COMPLETED	Treating to Reduce Albuminuria and Normalize Hemodynamic Function in Focal ScLerosis With dApagliflozin Trial Effects
NCT02633046	PHASE4	COMPLETED	Acthar for Treatment-Resistant or Treatment-Intolerant Proteinuria
NCT07219121	PHASE4	RECRUITING	Sparsentan in Posttransplant Immunoglobulin A Nephropathy or Focal Segmental Glomerulosclerosis
NCT00312351	PHASE4	TERMINATED	A Clinical Trial to Explore the Safety and Efficacy of Three Different Doses of Pegaptanib Sodium in Patients With Wet Age-Related Macular Degeneration (AMD)
NCT00324116	PHASE4	COMPLETED	Evaluation Of Safety And Efficacy Of 0.3 Mg/Eye Macugen In Patients With Small Age-Related Macular Degeneration Lesions
NCT00327470	PHASE4	TERMINATED	An Open Label Trial to Investigate Macugen for the Preservation of Visual Function in Subjects With Neovascular AMD
NCT00533520	PHASE4	COMPLETED	Evaluation of Dosing Interval of Higher Doses of Ranibizumab
NCT00813891	PHASE4	UNKNOWN	Efficacy of Ranibizumab in Combination With Photodynamic Therapy for Wet Age-Related Macular Degeneration
NCT01006538	PHASE4	COMPLETED	Macular EpiRetinal Brachytherapy Versus Lucentis® Only Treatment (MERLOT)
NCT01213667	PHASE4	UNKNOWN	Genetics in Non-response to Anti-VEGF Treatment in Exudative AMD
NCT01831947	PHASE4	COMPLETED	Efficacy Study of Ranibizumab on Patients With Age-related Macular Degeneration.
NCT02581891	PHASE4	COMPLETED	Managing Neovascular (Known as Wet) Age-related Macular Degeneration Over 2 Years Using Different Treatment Schedules of 2 mg Intravitreal Aflibercept Injected in the Eye
NCT02689518	PHASE4	COMPLETED	EAGLE: Evaluating Genotypes Using Intravitreal Aflibercept Injection
NCT03804099	PHASE4	COMPLETED	Effect Aflibercept on Ocular Perfusion
NCT07367282	PHASE4	NOT_YET_RECRUITING	Evaluate the Efficacy of Faricimab in Patients With Neovascular Age-related Macular Degeneration
NCT02949128	PHASE3	COMPLETED	Study of ALXN1210 in Complement Inhibitor Treatment-Naïve Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT03131219	PHASE3	COMPLETED	Study of Ravulizumab in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT03205995	PHASE3	TERMINATED	Safety and Efficacy Study of OMS721 in Patients With Atypical Hemolytic Uremic Syndrome
NCT04861259	PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT04889430	PHASE3	COMPLETED	Efficacy and Safety of Iptacopan (LNP023) in Adult Patients With Atypical Hemolytic Uremic Syndrome Naive to Complement Inhibitor Therapy
NCT04958265	PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Pediatric Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT05795140	PHASE3	RECRUITING	Evaluate Long-term Safety, Tolerability and Efficacy of Iptacopan in Study Participants With aHUS
NCT05935215	PHASE3	RECRUITING	Efficacy and Safety of Switching From Anti-C5 Antibody Treatment to Iptacopan Treatment in Study Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT01164098	PHASE3	TERMINATED	Rituximab to Prevent Recurrence of Proteinuria
NCT02683889	PHASE3	COMPLETED	Use of Acthar in Patients With FSGS That Will be Undergoing Renal Transplantation
NCT03298698	PHASE3	UNKNOWN	Efficacy of Rituximab in Comparison to Continued Corticosteroid Treatment in Idiopathic Nephrotic Syndrome
NCT03493685	PHASE3	COMPLETED	Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS)
NCT05183646	PHASE3	RECRUITING	A Study of the Efficacy and Safety of DMX-200 in Patients With FSGS Who Are Receiving an ARB
NCT07220083	PHASE3	RECRUITING	A Study to Find Out if BI 764198 Helps Adults and Adolescents With a Kidney Condition Called Focal Segmental Glomerulosclerosis (FSGS)
NCT00000145	PHASE3	COMPLETED	Age-Related Eye Disease Study (AREDS)
NCT00000150	PHASE3	COMPLETED	Submacular Surgery Trials (SST)
NCT00000152	PHASE3	UNKNOWN	Randomized Trial of Beta-Carotene and Macular Degeneration
NCT00000158	PHASE3	UNKNOWN	Macular Photocoagulation Study (MPS)
NCT00000161	PHASE3	UNKNOWN	Randomized Trials of Vitamin Supplements and Eye Disease
NCT00000162	PHASE3	COMPLETED	Branch Vein Occlusion Study
NCT00000167	PHASE3	COMPLETED	Complications of Age-Related Macular Degeneration Prevention Trial