CFB

Summary

CFB (complement factor B, HGNC:1037) is a protein-coding gene on chromosome 6p21.33, encoding Complement factor B (P00751). Precursor of the catalytic component of the C3 and C5 convertase complexes of the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system.

This gene encodes complement factor B, a component of the alternative pathway of complement activation. Factor B circulates in the blood as a single chain polypeptide. Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the catalytic subunit Bb. The active subunit Bb is a serine protease which associates with C3b to form the alternative pathway C3 convertase. Bb is involved in the proliferation of preactivated B lymphocytes, while Ba inhibits their proliferation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. This cluster includes several genes involved in regulation of the immune reaction. Polymorphisms in this gene are associated with a reduced risk of age-related macular degeneration. The polyadenylation site of this gene is 421 bp from the 5’ end of the gene for complement component 2.

Source: NCBI Gene 629 — RefSeq curated summary.

At a glance

• Gene–disease (curated): atypical hemolytic-uremic syndrome with B factor anomaly (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 47
• Clinical variants (ClinVar): 651 total — 8 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 20
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001710

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1037
Approved symbol	CFB
Name	complement factor B
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	H2-Bf
Ensembl gene	ENSG00000243649
Ensembl biotype	protein_coding
OMIM	138470
Entrez	629

Gene structure

Transcript identifiers

Ensembl transcripts: 58 — 40 protein_coding, 14 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 non_stop_decay

ENST00000425368, ENST00000452035, ENST00000460718, ENST00000461483, ENST00000465750, ENST00000467150, ENST00000467360, ENST00000472581, ENST00000475617, ENST00000482312, ENST00000482886, ENST00000483004, ENST00000497841, ENST00000498317, ENST00000698628, ENST00000698629, ENST00000698630, ENST00000698631, ENST00000698632, ENST00000698633, ENST00000698636, ENST00000885706, ENST00000885707, ENST00000885708, ENST00000885709, ENST00000885710, ENST00000885711, ENST00000885712, ENST00000885713, ENST00000885714, ENST00000885715, ENST00000885716, ENST00000885717, ENST00000885718, ENST00000885719, ENST00000885720, ENST00000885721, ENST00000885722, ENST00000885723, ENST00000885724, ENST00000885725, ENST00000885726, ENST00000885727, ENST00000885728, ENST00000885729, ENST00000885730, ENST00000885731, ENST00000885732, ENST00000885733, ENST00000885734, ENST00000885735, ENST00000885736, ENST00000885737, ENST00000885738, ENST00000885739, ENST00000961765, ENST00000961766, ENST00000961767

RefSeq mRNA: 1 — MANE Select: NM_001710 NM_001710

CCDS: CCDS4729

Canonical transcript exons

ENST00000375455 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.88.

FANTOM5 (CAGE): breadth broad, TPM avg 20.6092 / max 4095.1270, expressed in 866 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67093	15.6370	650
67094	2.6367	369
67092	1.0164	411
67095	0.5075	118
67091	0.2107	114
203951	0.1449	69
67097	0.0941	24
203950	0.0842	27
67099	0.0755	26
203952	0.0752	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.88	gold quality
liver	UBERON:0002107	99.83	gold quality
gall bladder	UBERON:0002110	98.66	gold quality
vermiform appendix	UBERON:0001154	97.75	gold quality
duodenum	UBERON:0002114	97.52	gold quality
islet of Langerhans	UBERON:0000006	96.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.70	gold quality
omental fat pad	UBERON:0010414	96.66	gold quality
descending thoracic aorta	UBERON:0002345	95.83	gold quality
mucosa of stomach	UBERON:0001199	95.65	gold quality
right coronary artery	UBERON:0001625	95.30	gold quality
metanephros cortex	UBERON:0010533	95.20	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.17	gold quality
small intestine	UBERON:0002108	94.82	gold quality
adult mammalian kidney	UBERON:0000082	94.35	gold quality
upper lobe of left lung	UBERON:0008952	94.17	gold quality
pancreas	UBERON:0001264	93.99	gold quality
thoracic aorta	UBERON:0001515	93.89	gold quality
ascending aorta	UBERON:0001496	93.81	gold quality
left coronary artery	UBERON:0001626	93.79	gold quality
fallopian tube	UBERON:0003889	93.63	gold quality
minor salivary gland	UBERON:0001830	93.59	gold quality
body of stomach	UBERON:0001161	93.41	gold quality
saliva-secreting gland	UBERON:0001044	93.40	gold quality
body of pancreas	UBERON:0001150	93.15	gold quality
adipose tissue	UBERON:0001013	93.09	gold quality
right uterine tube	UBERON:0001302	92.85	gold quality
prostate gland	UBERON:0002367	92.79	gold quality
right lung	UBERON:0002167	92.55	gold quality
stomach	UBERON:0000945	92.47	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	2259.07
E-MTAB-10662	yes	1668.51
E-CURD-114	yes	20.09
E-CURD-46	yes	13.63
E-HCAD-1	yes	13.26
E-GEOD-83139	yes	12.40
E-ENAD-27	yes	6.40
E-HCAD-31	no	3.54
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB5, HNF4A, IRF6, NFKB, STAT1, STAT2, STAT3

Literature-anchored findings (GeneRIF, showing 40)

• Allelic distribution of complement components BF, C4A, C4B, and C3 in Psoriasis vulgaris. (PMID:11803045)
• No factor B gene (BF) mutations were found in 20 patients with haemolytic uraemic syndrome. (PMID:16061287)
• properdin has a role in the assembly of the alternative pathway C3 convertases of complement (PMID:16301317)
• The crystal structure of human factor B, is presented, at 2.3-A resolution, which reveals how the five-domain proenzyme is kept securely inactive. (PMID:17310251)
• Information contained within the first 24 amino acid residues of human factor B precursor is sufficient for importing the 199-residue factor B polypeptide into the mitochondria. (PMID:17359931)
• DAF active site residues accelerate the decay of C3 convertases (PMID:17395591)
• complement factor B was significantly associated with protection from AMD in the family-based data set (P = 0.025). (PMID:17576744)
• a novel role of properdin in AP complement initiation and have implications for understanding the selective predisposition of properdin-deficient patients to meningococcal infection. (PMID:17916747)
• biochemical analysis of the enzymatic properties and inhibition of human complement factor B (PMID:17921140)
• Human oviduct possesses C3 convertase activity converting C3 to C3b, and Crry of the preimplantation embryos may be involved in the production of embryotrophic iC3b on the surface of the embryos. (PMID:18039777)
• The formation of the fluid-phase alternative pathway convertases C3(H(2)O)Bb and C3bBb and their regulation by factor H and factor I at specific time points was studied. (PMID:18096230)
• 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)
• 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)
• A significant relationship was found between an elevated Bb in early pregnancy and spontaneous preterm birth less than 34 weeks gestation. (PMID:18928972)
• We report the BF alleles located on the multiple human leukocyte antigen (HLA)-DR3 haplotypes that are unique in the Indian population and are associated with autoimmunity. (PMID:19000152)
• Significantly more transcripts encoding alternative pathway components factor B, C3 and properdin, and C3a receptor and C5a receptor were detected in grade 3 versus grade 0 or 1 biopsies of human cardiac allografts. (PMID:19005416)
• age-related macular degeneration-protective effect of fB(32Q) is consequent on decreased potential to form convertase and amplify complement activation (PMID:19255449)
• 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)
• Amyloid-beta up-regulates complement factor B in retinal pigment epithelial cells through cytokines released from recruited macrophages/microglia: Another mechanism of complement activation in age-related macular degeneration. (PMID:19277984)
• hBf gene expression is induced in monocytes from septic shock patients, and the induction of hBf by IFN-gamma, TNF-alpha, and LPS is through GAS and NF-kappaB cis-binding sites on the hBf promoter (PMID:19279234)
• 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)
• Presented is the crystal structure at 2.2-A resolution, small-angle X-ray scattering and electron microscopy data of the pro-convertase formed by human factor B and cobra venom factor, a potent homologue of C3b that generates more stable convertases. (PMID:19574954)
• A role for fragment Bb in the host immune response against intra-amniotic infection/inflammation. (PMID:19603351)
• 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)
• Circulating concentrations in patients with glucose intolerance may reflect increased vascular cell-induced activation of the alternativve pathway of complement in adipose tissue. (PMID:19833879)
• Case Report: 8-year-old girl diagnosed with atypical hemolytic uremic syndrome (aHUS) with a complement factor B (CFB) gene mutation. (PMID:20108004)
• sinus mucosa expression is increased in chronic rhinosinusitis patients (PMID:20109314)
• report an autoantibody that binds to complement factor B in a dense deposit disease patient who was negative for C3 nephritic factor. (PMID:20193965)
• 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)
• 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)
• Reduced expression of alpha-2 macroglobulin and complement factor B was detected in sera of patients with nasopharyngeal carcinoma. (PMID:20575108)
• Studies indicate that mutations or polymorphisms in complement genes C3 and factor B are genetic risk factors contributing hemolytic uremic syndrome. (PMID:20837143)
• These studies show that the acquisition of fH to the S. aureus surface inhibits complement-mediated opsonization via disruption of the alternative pathway convertase. (PMID:21163532)
• crystal structure of C3bB at 4 A and complex with factor D at 3.5 A; data show how factor B binding to C3b forms open “activation” state of C3bB; Factor D binds open conformation of factor B through a site distant from the catalytic center (PMID:21205667)
• the association with the known genetic susceptibility loci CFH, HTRA1, and AMRS2 were confirmed, and a risk-conferring polymorphism in one new locus, LRP5, was identified. (PMID:21282580)
• CFB 32W (rs12614; T) protects against age-related macular degeneration compared to the common CFB 32R. The protective effect is less strong than CFB 32Q. Knowledge of both rs641153 and rs12614 is required to predict the amino acid at residue 32. (PMID:21541267)
• Complement factor B polymorphism 32W protects against age-related macular degeneration. (PMID:21541267)
• the concept of a functional complotype (combination of C3(R102G), factor B (fB(R32Q), and factor H (fH(V62I) polymorphisms) in defining complement activity in an individual, influencing susceptibility to alternative pathway-driven disease. (PMID:21555552)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bfb	ENSDARG00000005616
danio_rerio	cfb	ENSDARG00000055278
danio_rerio	cfbl	ENSDARG00000090730
mus_musculus	Cfb	ENSMUSG00000090231

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), C2 (ENSG00000166278), SELP (ENSG00000174175), SEZ6L2 (ENSG00000174938), PRF1 (ENSG00000180644), PAPPA (ENSG00000182752), CSMD1 (ENSG00000183117), SELL (ENSG00000188404), CD55 (ENSG00000196352), CR1L (ENSG00000197721), CR1 (ENSG00000203710), CFHR1 (ENSG00000244414)

Protein

Protein identifiers

Complement factor B — P00751 (reviewed: P00751)

Alternative names: C3/C5 convertase, Glycine-rich beta glycoprotein, PBF2, Properdin factor B

All UniProt accessions (6): A0A1U9X7H8, A0A8V8TMI9, A0A8V8TNU0, P00751, F8WBL9, H7C5H1

UniProt curated annotations — full annotation on UniProt →

Function. Precursor of the catalytic component of the C3 and C5 convertase complexes of the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system. The alternative complement pathway acts as an amplification loop that enhances other complement pathways (classical, lectin and GZMK) by promoting formation of additional C3 and C5 convertases. CFB is cleaved and activated by CFD to generate Ba and Bb chains; Bb chain constituting the catalytic component of the C3 and C5 convertases. Serine protease component of the complement C3 and C5 convertase complexes of the alternative complement pathway. Following cleavage and activation by factor D (CFD), forms the C3 convertase together with complement C3b. As part of the C3 convertase, cleaves and activates C3 into C3a anaphylatoxin and C3b opsonin, the next components of the complement pathways. When an additional complement C3b molecule binds to the C3 convertase, forms the C5 convertase, which cleaves and activates C5 into C5a anaphylatoxin and C5b component of the membrane attack complex. Involved in proliferation and differentiation of preactivated B-lymphocytes, rapid spreading of peripheral blood monocytes, stimulation of lymphocyte blastogenesis and lysis of erythrocytes.

Subunit / interactions. Monomer. Interacts with complement C3b; this interaction is dependent on the presence of Mg(2+). Catalytic component of the C3 convertase of the alternative complement pathway, also named C3bBb, composed of complement factor B Bb and complement C3b. Catalytic component of the C5 convertase of the alternative complement pathway, also named C3bBb3b, composed of complement factor B Bb and additional molecules of complement C3b. Interacts to CFP; this interaction contributes to the stabilization of the active C3-convertase enzyme complex.

Subcellular location. Secreted Cell surface.

Post-translational modifications. Cleaved by CFD following activation of the alternative complement system, generating Ba and Bb chains. Cleavage and activation takes place when CFB is already associated with complement C3b.

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. Hemolytic uremic syndrome, atypical, 4 (AHUS4) [MIM:612924] An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Disease susceptibility is associated with variants affecting the gene represented in this entry. Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype. Complement factor B deficiency (CFBD) [MIM:615561] An immunologic disorder characterized by increased susceptibility to bacterial infections, particularly Neisseria infections, due to a defect in the alternative complement pathway. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The unliganded VWA domain has an inactive ’locked’ conformation whereby the scissile Arg-259|Lys-260 bond is protected from proteolytic activation.

Polymorphism. Two major variants, F and S, and 2 minor variants, as well as at least 14 very rare variants, have been identified.

Similarity. Belongs to the peptidase S1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P00751-1	1	yes
P00751-2	2

RefSeq proteins (1): NP_001701* (*=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
IPR028341	Complement_B	Family
IPR033116	TRYPSIN_SER	Active_site
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR036465	vWFA_dom_sf	Homologous_superfamily

Pfam: PF00084, PF00089, PF00092

Enzyme classification (BRENDA):

• EC 3.4.21.47 — alternative-complement-pathway C3/C5 convertase (BRENDA: 5 organisms, 28 substrates, 43 inhibitors, 19 Km, 19 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
COMPLEMENT COMPONENT C3	0.0059–0.0264	9
COMPLEMENT COMPONENT C5	—	8
T-BUTYLOXYCARBONYL-GLY-L-LEU-L-ALA-L-ARG-THIOBEN	2.75–5.63	2

UniProt features (158 total): strand 54, helix 28, sequence variant 17, disulfide bond 11, mutagenesis site 9, sequence conflict 7, binding site 6, turn 6, glycosylation site 5, domain 5, chain 3, active site 3, splice variant 2, signal peptide 1, site 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
6QSW	X-RAY DIFFRACTION	1.64
6RAV	X-RAY DIFFRACTION	1.7
6T8W	X-RAY DIFFRACTION	1.7
6QSX	X-RAY DIFFRACTION	1.77
1Q0P	X-RAY DIFFRACTION	1.8
1RRK	X-RAY DIFFRACTION	2
1DLE	X-RAY DIFFRACTION	2.1
3HRZ	X-RAY DIFFRACTION	2.2
6T8V	X-RAY DIFFRACTION	2.29
1RTK	X-RAY DIFFRACTION	2.3
2OK5	X-RAY DIFFRACTION	2.3
1RS0	X-RAY DIFFRACTION	2.6
9U62	ELECTRON MICROSCOPY	2.7
6T8U	X-RAY DIFFRACTION	2.84
3HS0	X-RAY DIFFRACTION	3
7JTN	X-RAY DIFFRACTION	3.1
8ENU	ELECTRON MICROSCOPY	3.22
2XWB	X-RAY DIFFRACTION	3.49
7JTQ	X-RAY DIFFRACTION	3.5
8EOK	ELECTRON MICROSCOPY	3.53
8UIN	ELECTRON MICROSCOPY	3.86
2WIN	X-RAY DIFFRACTION	3.9
7NOZ	X-RAY DIFFRACTION	3.9
2XWJ	X-RAY DIFFRACTION	4
6RUR	X-RAY DIFFRACTION	6
6RUV	X-RAY DIFFRACTION	6.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00751-F1	86.54	0.65

Antibody-complex structures (SAbDab): 2 — 6RUV, 7NOZ

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): 576 (charge relay system); 699 (charge relay system); 259–260 (cleavage; by cfd); 526 (charge relay system)

Ligand- & substrate-binding residues (6): 278; 278; 280; 280; 353; 353

Disulfide bonds (11): 37–76, 62–98, 103–145, 131–158, 165–205, 191–218, 478–596, 511–527, 599–615, 656–682, 695–725

Glycosylation sites (5): 122, 142, 285, 291, 378

Mutagenesis-validated functional residues (9):

Position	Phenotype
348–350	decreases binding to the pro-c3-convertase complex. does not affect complement c3 beta chain binding.
471	reduced formation of c3 convertase.
644	decreased cleavage and activation by cfd.
689	decreased cleavage and activation by cfd.
690	decreased cleavage and activation by cfd.
733	decreased cleavage and activation by cfd.
734	decreased cleavage and activation by cfd.
740	abolished ability to cleave c3, without affecting cleavage by cfd and interaction with complement c3b.
741	abolished ability to cleave c3, without affecting cleavage by cfd and interaction with complement c3b.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-173736	Alternative complement activation
R-HSA-174577	Activation of C3 and C5
R-HSA-977606	Regulation of Complement cascade

MSigDB gene sets: 378 (showing top): MODULE_172, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, MCLACHLAN_DENTAL_CARIES_UP, GOBP_B_CELL_ACTIVATION, PEREZ_TP63_TARGETS, GNF2_HPN, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOCC_CELL_SURFACE, GOBP_VESICLE_MEDIATED_TRANSPORT, LHX3_01, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, SMID_BREAST_CANCER_RELAPSE_IN_LIVER_DN

GO Biological Process (6): proteolysis (GO:0006508), complement activation (GO:0006956), complement activation, alternative pathway (GO:0006957), response to bacterium (GO:0009617), immune system process (GO:0002376), innate immune response (GO:0045087)

GO Molecular Function (6): complement binding (GO:0001848), serine-type endopeptidase activity (GO:0004252), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), cell surface (GO:0009986), extracellular exosome (GO:0070062), blood microparticle (GO:0072562), symbiont cell surface (GO:0106139)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Complement cascade	2
Initial triggering of complement	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein metabolic process	1
immune effector process	1
activation of immune response	1
humoral immune response	1
protein activation cascade	1
complement activation	1
innate immune response	1
response to other organism	1
biological_process	1
immune response	1
defense response to symbiont	1
protein binding	1
endopeptidase activity	1
serine-type peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
membrane	1
cell periphery	1
extracellular vesicle	1
extracellular region	1
other organism part	1

Protein interactions and networks

STRING

1906 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFB	C3	P01024	999
CFB	CFI	P05156	931
CFB	C4A	P01028	916
CFB	CFHR1	Q03591	901
CFB	CFHR3	Q02985	892
CFB	CFP	P27918	891
CFB	C4A	P01028	859
CFB	SERPING1	P05155	834
CFB	ARMS2	P0C7Q2	817
CFB	CFHR5	Q9BXR6	812
CFB	CFD	P00746	811
CFB	DGKE	P52429	797
CFB	C1QA	P02745	786
CFB	SERPINA1	P01009	682
CFB	CLU	P10909	675

IntAct

39 interactions, top by confidence:

A	B	Type	Score
CFHR4	CFB	psi-mi:“MI:0915”(physical association)	0.610
CFB	CFHR4	psi-mi:“MI:0407”(direct interaction)	0.610
CFB		psi-mi:“MI:0915”(physical association)	0.570
CFB	CFHR4	psi-mi:“MI:0407”(direct interaction)	0.540
NPC2	NME2P1	psi-mi:“MI:0914”(association)	0.530
CFB	C3	psi-mi:“MI:0407”(direct interaction)	0.440
CFB	H1-1	psi-mi:“MI:0915”(physical association)	0.400
CFHR1	CFB	psi-mi:“MI:0915”(physical association)	0.400
CFHR4	CFD	psi-mi:“MI:0915”(physical association)	0.400
	LECT2	psi-mi:“MI:0915”(physical association)	0.400
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
RPA2	CFB	psi-mi:“MI:0915”(physical association)	0.370
LAMC3	CFB	psi-mi:“MI:0915”(physical association)	0.370
Nedd1		psi-mi:“MI:0914”(association)	0.350
ALB	SH3BP5	psi-mi:“MI:0914”(association)	0.350
DDX19B	IGLL5	psi-mi:“MI:0914”(association)	0.350
CFB	NME2	psi-mi:“MI:0914”(association)	0.350
NPC2	NME2	psi-mi:“MI:0914”(association)	0.350
GDPD1	CP	psi-mi:“MI:0914”(association)	0.350
HTRA4	PSMD12	psi-mi:“MI:0914”(association)	0.350
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
GRB14	CFB	psi-mi:“MI:0914”(association)	0.350
CFB	CST4	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350

BioGRID (52): CFB (Two-hybrid), CFB (Affinity Capture-MS), CFB (Affinity Capture-MS), CFB (Synthetic Growth Defect), CFB (Affinity Capture-MS), CFB (Affinity Capture-MS), CFB (Affinity Capture-MS), NME2 (Affinity Capture-MS), CFB (Affinity Capture-MS), OAF (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), HIST1H1A (Proximity Label-MS), CFB (Reconstituted Complex), CFB (Affinity Capture-MS), CFB (Affinity Capture-MS)

ESM2 similar proteins: A2A863, A2AX52, A6H584, A6NMZ7, A8TX70, E1BMV3, O00339, O02668, O08746, O42422, P00751, P04186, P05099, P06681, P12111, P13944, P15989, P19823, P21180, P21941, P26007, P26008, P51942, P54759, P81187, Q03710, Q0V8S9, Q0VCM5, Q15375, Q21540, Q29052, Q3SYW2, Q60847, Q61702, Q61739, Q61772, Q64632, Q6DCQ6, Q6Q473, Q801S8

Diamond homologs: A0A1D5NSM8, A2AVA0, D3YXF5, O02839, O19124, O35764, O43405, O62685, O62837, O70340, O76536, O95502, O96530, P00751, P04003, P04186, P06205, P06206, P06207, P06681, P07629, P08174, P08607, P0C6B8, P13944, P14151, P14650, P15529, P17690, P18337, P26022, P32018, P33703, P35419, P42201, P47970, P47971, P47972, P48199, P48759

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CFH	“down-regulates activity”	CFB	binding
CREB5	“up-regulates quantity by expression”	CFB	“transcriptional regulation”
CFB	“form complex”	“C3 convertase complex (C3bBb)”	binding
CFD	“up-regulates activity”	CFB	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	6
Uncertain significance	350
Likely benign	200
Benign	17

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
16080	NM_001710.6(CFB):c.967A>G (p.Lys323Glu)	Pathogenic
3906267	CFB, 1-BP DUP, NT1938	Pathogenic
3906268	CFB, GLY396ARG	Pathogenic
4280404	NM_001710.6(CFB):c.1050G>C (p.Lys350Asn)	Pathogenic
4280405	NM_001710.6(CFB):c.1050G>T (p.Lys350Asn)	Pathogenic
4280406	NM_001710.6(CFB):c.1101C>G (p.Ser367Arg)	Pathogenic
4280407	NM_001710.6(CFB):c.1101C>A (p.Ser367Arg)	Pathogenic
4280408	NM_001710.6(CFB):c.1099A>C (p.Ser367Arg)	Pathogenic
16079	NM_001710.6(CFB):c.858C>G (p.Phe286Leu)	Likely pathogenic
3066149	NM_001710.6(CFB):c.898-2A>C	Likely pathogenic
3381003	NM_001710.6(CFB):c.888_891del (p.Ile297fs)	Likely pathogenic
4280397	NM_001710.6(CFB):c.836A>G (p.Asp279Gly)	Likely pathogenic
4280398	NM_001710.6(CFB):c.967A>C (p.Lys323Gln)	Likely pathogenic
4280410	NM_001710.6(CFB):c.1112A>G (p.Asp371Gly)	Likely pathogenic

SpliceAI

3155 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31946590:G:GT	donor_gain	1.0000
6:31946591:A:T	donor_gain	1.0000
6:31946614:GGCAA:G	donor_gain	1.0000
6:31947003:A:AG	acceptor_gain	1.0000
6:31947004:A:G	acceptor_gain	1.0000
6:31947005:A:AG	acceptor_gain	1.0000
6:31947006:G:GG	acceptor_gain	1.0000
6:31947006:GCA:G	acceptor_gain	1.0000
6:31947008:A:AG	acceptor_gain	1.0000
6:31947346:A:AG	acceptor_gain	1.0000
6:31947346:AGC:A	acceptor_gain	1.0000
6:31947346:AGCG:A	acceptor_gain	1.0000
6:31947346:AGCGG:A	acceptor_gain	1.0000
6:31947347:G:GA	acceptor_gain	1.0000
6:31947347:GC:G	acceptor_gain	1.0000
6:31947347:GCG:G	acceptor_gain	1.0000
6:31947347:GCGG:G	acceptor_gain	1.0000
6:31947347:GCGGG:G	acceptor_gain	1.0000
6:31947482:G:GT	donor_gain	1.0000
6:31947483:A:T	donor_gain	1.0000
6:31947740:A:AG	acceptor_gain	1.0000
6:31947741:G:GG	acceptor_gain	1.0000
6:31947828:G:GT	donor_gain	1.0000
6:31947861:G:GT	donor_gain	1.0000
6:31947862:G:T	donor_gain	1.0000
6:31948136:G:GT	donor_gain	1.0000
6:31948828:A:AG	acceptor_gain	1.0000
6:31948829:G:GG	acceptor_gain	1.0000
6:31948970:G:GT	donor_gain	1.0000
6:31948971:G:T	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000399741 (6:31946480 C>T), RS1000946917 (6:31952413 G>A,C,T), RS1001592051 (6:31948640 G>A,T), RS1001863663 (6:31947582 C>T), RS1002548768 (6:31944298 G>C), RS1003537805 (6:31945719 GA>G), RS1003782445 (6:31950207 G>A), RS1004455871 (6:31949186 C>T), RS1004867752 (6:31948904 G>A), RS1005250819 (6:31946927 A>G), RS1005845088 (6:31951659 A>C,G), RS1006547538 (6:31946850 A>G), RS1006779373 (6:31945964 C>T), RS1007547475 (6:31945104 G>A), RS1008437665 (6:31944613 T>G)

Disease associations

OMIM: gene MIM:138470 | disease phenotypes: MIM:612924, MIM:615561, MIM:615489, MIM:217000

GenCC curated gene-disease

Disease	Classification	Inheritance
atypical hemolytic-uremic syndrome with B factor anomaly	Strong	Autosomal dominant
complement factor b deficiency	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
C3 glomerulonephritis	Limited	AD
atypical hemolytic-uremic syndrome with B factor anomaly	Moderate	AD

Mondo (10): atypical hemolytic-uremic syndrome with B factor anomaly (MONDO:0013042), complement factor b deficiency (MONDO:0014255), atypical hemolytic-uremic syndrome (MONDO:0016244), kidney disorder (MONDO:0005240), age related macular degeneration 14 (MONDO:0014207), focal segmental glomerulosclerosis (MONDO:0100313), complement component 2 deficiency (MONDO:0009006), neutropenia (MONDO:0001475), lymphopenia (MONDO:0003783), 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

20 total (22 of 20 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0001287	Meningitis
HP:0001873	Thrombocytopenia
HP:0001903	Anemia
HP:0001919	Acute kidney injury
HP:0001937	Microangiopathic hemolytic anemia
HP:0002090	Pneumonia
HP:0002586	Peritonitis
HP:0002718	Recurrent bacterial infections
HP:0003138	Increased blood urea nitrogen
HP:0003259	Elevated circulating creatinine concentration
HP:0005381	Recurrent meningococcal disease
HP:0005416	Decreased circulating complement factor B concentration
HP:0005575	Hemolytic-uremic syndrome
HP:0011463	Childhood onset
HP:0100519	Anuria
HP:0001875	Decreased total neutrophil count
HP:0001888	Decreased total lymphocyte count

GWAS associations

47 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
GCST000806_3	Age-related macular degeneration	5.000000e-15
GCST001100_9	Age-related macular degeneration	6.000000e-31
GCST001571_5	Age-related macular degeneration	9.000000e-17
GCST001578_3	Age-related macular degeneration (geographic atrophy)	2.000000e-09
GCST001579_2	Age-related macular degeneration (choroidal neovascularisation)	1.000000e-17
GCST001779_12	Hematology traits	2.000000e-08
GCST001884_13	Age-related macular degeneration	4.000000e-89
GCST001942_21	Prostate cancer	5.000000e-09
GCST001986_2	Age-related macular degeneration	2.000000e-10
GCST001987_3	Age-related macular degeneration (extreme sampling)	3.000000e-07
GCST002453_3	Ulcerative colitis	5.000000e-14
GCST002876_5	Type 1 diabetes and autoimmune thyroid diseases	5.000000e-25
GCST002879_1	Chronic hepatitis B infection	1.000000e-34
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

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:1001492	atrophic macular degeneration
EFO:0008336	disease progression measurement
EFO:0009180	rosacea severity measurement
EFO:0004531	urate measurement
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (6)

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
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
D008231	Lymphopenia	C15.378.243.750.605; C15.378.553.546.605; C20.673.627
D008268	Macular Degeneration	C11.768.585.439
D009503	Neutropenia	C15.378.243.750.184.564; C15.378.553.546.184.564

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5731 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 397 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL4594448	IPTACOPAN	4	397

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs641153	CFB		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S1: Chymotrypsin

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
iptacopan	Inhibition	7.92	pIC50
compound 51 [PMID: 19743866]	Inhibition	6.6	pIC50

Binding affinities (BindingDB)

357 measured of 456 human assays (549 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[4-ethyl-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzoic acid	IC50	0.01 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[6-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-6-azaspiro[2.5]octan-7-yl]benzoic acid	IC50	0.01 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[(2S,4R)-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-4-methylpiperidin-2-yl]benzoic acid	IC50	0.01 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-4,4-dimethylpiperidin-2-yl]benzoic acid	IC50	0.01 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[1-[(5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl]-4-methoxypiperidin-2-yl]benzoic acid	IC50	0.01 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[1-[(5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl]-4-ethoxypiperidin-2-yl]benzoic acid	IC50	0.01 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[(2S)-1-[(5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzoic acid	IC50	0.02 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[(2S,4S)-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-4-propoxypiperidin-2-yl]benzoic acid	IC50	0.02 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[(2S,4S)-4-methoxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzoic acid	IC50	0.02 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
5-[4-ethoxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]pyridine-2-carboxylic acid	IC50	0.02 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[1-[(5,7-dimethyl-1H-indol-4-yl)methyl]-4-methoxypiperidin-2-yl]benzoic acid	IC50	0.02 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[1-[(5,7-dimethyl-1H-indol-4-yl)methyl]-4-ethoxypiperidin-2-yl]benzoic acid	IC50	0.02 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[[4-ethoxy-2-[4-(2H-tetrazol-5-yl)phenyl]piperidin-1-yl]methyl]-5-methoxy-7-methyl-1H-indole	IC50	0.02 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[(2S,4S)-4-ethoxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]-N-methylsulfonylbenzamide	IC50	0.02 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[(2S)-1-[(5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]-2-fluorobenzoic acid	IC50	0.03 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[(2S)-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzoic acid	IC50	0.03 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
5-[1-[(5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl]-4-methoxypiperidin-2-yl]pyridine-2-carboxylic acid	IC50	0.03 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
5,7-dimethyl-4-[[2-[4-(2H-tetrazol-5-yl)phenyl]piperidin-1-yl]methyl]-1H-indole	IC50	0.04 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
5-[(2S)-1-[(5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]pyridine-2-carboxylic acid	IC50	0.04 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
5-methoxy-7-methyl-4-[[(2S)-2-[4-(1H-pyrazol-5-yl)phenyl]piperidin-1-yl]methyl]-1H-indole	IC50	0.04 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]naphthalene-1-carboxylic acid	IC50	0.05 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[1-[(5,7-dimethyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzoic acid	IC50	0.05 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]-3-methylbenzoic acid	IC50	0.06 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
N-[4-[1-[(5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]phenyl]sulfonylacetamide	IC50	0.06 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
3-fluoro-4-[(2S)-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzoic acid	IC50	0.07 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[(2S)-1-[(5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]-3-methoxybenzoic acid	IC50	0.09 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
6-[(2S)-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]pyridine-3-carboxylic acid	IC50	0.1 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]azepan-2-yl]benzoic acid	IC50	0.1 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[1-[(5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl]pyrrolidin-2-yl]benzoic acid	IC50	0.12 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[(2S,4S)-4-methoxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]-N-methylbenzamide	IC50	0.13 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[1-[(5-chloro-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzoic acid	IC50	0.14 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
2-methoxy-4-[1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzoic acid	IC50	0.16 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
N-ethyl-4-[(2S,4R)-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-4-methylpiperidin-2-yl]benzamide	IC50	0.17 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[1-[(5,7-dimethyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzenesulfonamide	IC50	0.18 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[1-[(5,7-dimethyl-1H-indol-4-yl)methyl]-4-hydroxypiperidin-2-yl]benzamide	IC50	0.23 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
ethyl 4-[(2S,4S)-4-ethoxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzoate	IC50	0.24 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
N-(2-hydroxyethyl)-4-[(2S,4S)-4-methoxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzamide	IC50	0.28 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[(2R,4S)-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-4-methylpiperidin-2-yl]benzoic acid	IC50	0.29 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
N-(2-methoxyethyl)-4-[(2S,4S)-4-methoxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzamide	IC50	0.3 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
[4-[4-methoxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]phenyl]methanol	IC50	0.34 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[(2S,4S)-4-hydroxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzoic acid	IC50	0.45 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[(6S)-2-fluoro-7-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-2-methyl-7-azaspiro[3.5]nonan-6-yl]benzoic acid	IC50	0.5 nM	US-20250115572: SPIROCYCLIC PIPERIDINYL DERIVATIVES AS COMPLEMENT FACTOR B INHIBITORS AND USES THEREOF
(S)-4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid	IC50	0.5 nM	US-20250115572: SPIROCYCLIC PIPERIDINYL DERIVATIVES AS COMPLEMENT FACTOR B INHIBITORS AND USES THEREOF
4-[[(6S)-2,2-difluoro-6-[4-(2H-tetrazol-5-yl)phenyl]-7-azaspiro[3.5]nonan-7-yl]methyl]-5-methoxy-7-methyl-1H-indole	IC50	0.6 nM	US-20250115572: SPIROCYCLIC PIPERIDINYL DERIVATIVES AS COMPLEMENT FACTOR B INHIBITORS AND USES THEREOF
4-[1-[(5,7-dimethyl-1H-indol-4-yl)methyl]-4-methoxypiperidin-2-yl]benzamide	IC50	0.64 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[(2R,4R)-4-methoxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzoic acid	IC50	0.65 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[1-[(5,7-dimethyl-1H-indol-4-yl)methyl]piperidin-2-yl]-N-methylbenzenesulfonamide	IC50	0.66 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[1-[(5,7-dimethyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzamide	IC50	0.71 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[(4-methoxy-2-phenylpiperidin-1-yl)methyl]-5,7-dimethyl-1H-indole	IC50	0.72 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
4-[1-[(5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl]-4-methoxypiperidin-2-yl]benzoic acid	IC50	0.74 nM	US-9682968: Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof

ChEMBL bioactivities

219 potent at pChembl≥5 of 251 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL5981804
11.00	IC50	0.01	nM	CHEMBL6024618
11.00	IC50	0.01	nM	CHEMBL6043471
11.00	IC50	0.01	nM	CHEMBL5932429
11.00	IC50	0.01	nM	IPTACOPAN
11.00	IC50	0.01	nM	CHEMBL5778053
11.00	IC50	0.01	nM	CHEMBL5804420
10.70	IC50	0.02	nM	CHEMBL5759287
10.70	IC50	0.02	nM	CHEMBL6009765
10.70	IC50	0.02	nM	CHEMBL6024618
10.70	IC50	0.02	nM	CHEMBL4632794
10.70	IC50	0.02	nM	CHEMBL5786380
10.70	IC50	0.02	nM	CHEMBL5877871
10.70	IC50	0.02	nM	CHEMBL5867904
10.70	IC50	0.02	nM	CHEMBL5742644
10.70	IC50	0.02	nM	CHEMBL5885876
10.52	IC50	0.03	nM	CHEMBL6014350
10.52	IC50	0.03	nM	CHEMBL5746213
10.52	IC50	0.03	nM	CHEMBL6000572
10.40	IC50	0.04	nM	CHEMBL5746835
10.40	IC50	0.04	nM	CHEMBL5839570
10.40	IC50	0.04	nM	CHEMBL6026552
10.30	IC50	0.05	nM	CHEMBL6011435
10.30	IC50	0.05	nM	CHEMBL4644994
10.22	IC50	0.06	nM	CHEMBL6031306
10.22	IC50	0.06	nM	CHEMBL5818564
10.15	IC50	0.07	nM	CHEMBL6003272
10.05	IC50	0.09	nM	CHEMBL5903309
10.00	IC50	0.1	nM	CHEMBL5909868
10.00	IC50	0.1	nM	CHEMBL5994439
9.92	IC50	0.12	nM	CHEMBL5909766
9.89	IC50	0.13	nM	CHEMBL6064397
9.85	IC50	0.14	nM	CHEMBL6010962
9.80	IC50	0.16	nM	CHEMBL5831878
9.77	IC50	0.17	nM	CHEMBL5833948
9.74	IC50	0.18	nM	CHEMBL6014967
9.64	IC50	0.23	nM	CHEMBL5864470
9.62	IC50	0.24	nM	CHEMBL5968743
9.55	IC50	0.28	nM	CHEMBL5862159
9.54	IC50	0.29	nM	CHEMBL5847273
9.52	IC50	0.3	nM	CHEMBL5869243
9.47	IC50	0.34	nM	CHEMBL5823358
9.35	IC50	0.45	nM	CHEMBL6016984
9.19	IC50	0.64	nM	CHEMBL5839517
9.19	IC50	0.65	nM	CHEMBL5929526
9.18	IC50	0.66	nM	CHEMBL5890193
9.15	IC50	0.71	nM	CHEMBL4647418
9.14	IC50	0.72	nM	CHEMBL4633437
9.13	IC50	0.74	nM	CHEMBL5778053
9.08	IC50	0.84	nM	CHEMBL6060716

PubChem BioAssay actives

48 with measured affinity, of 140 total; 34 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
4-[(1R)-3-[4-(4-amino-8-fluoro-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-1-(ethylamino)-3-oxopropyl]benzonitrile	1393244: Inhibition of recombinant human factor B expressed in drosophila cells assessed as decrease in C3a formation using CVF-Bb complex and human complement C3 substrate in presence of human factor D after 1 hr by ELISA	ic50	0.0010	uM
4-[(2S,4S)-1-[(5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl]-4-ethoxypiperidin-2-yl]benzoic acid	1654379: Inhibition of human serine protease factor B by TR-FRET based competition binding assay	ic50	0.0060	uM
Iptacopan	1654374: Binding affinity to human serine protease factor B by SPR assay	kd	0.0079	uM
4-[(2S,4S)-4-methoxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzoic acid	1654379: Inhibition of human serine protease factor B by TR-FRET based competition binding assay	ic50	0.0180	uM
4-[(2S,4S)-1-[(5,7-dimethyl-1H-indol-4-yl)methyl]-4-ethoxypiperidin-2-yl]benzoic acid	1654379: Inhibition of human serine protease factor B by TR-FRET based competition binding assay	ic50	0.0180	uM
4-[(2S,4S)-1-[(5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl]-4-methoxypiperidin-2-yl]benzoic acid	1654379: Inhibition of human serine protease factor B by TR-FRET based competition binding assay	ic50	0.0180	uM
2-[2,2,2-trifluoro-1-(2-methoxy-4,6-dimethylphenyl)-1-(methylamino)ethyl]-3H-benzimidazole-5-carbonitrile	1393243: Displacement of Cy5 from recombinant human biotin-labeled factor B expressed in drosophila cells after 2 hrs by TR-FRET assay	ic50	0.0230	uM
4-[(2S,4S)-1-[(5,7-dimethyl-1H-indol-4-yl)methyl]-4-methoxypiperidin-2-yl]benzoic acid	1654379: Inhibition of human serine protease factor B by TR-FRET based competition binding assay	ic50	0.0240	uM
2-[2-(5-methoxy-7-methyl-1H-indol-4-yl)propan-2-yl]-1H-imidazo[4,5-b]pyridine-6-carbonitrile	1393243: Displacement of Cy5 from recombinant human biotin-labeled factor B expressed in drosophila cells after 2 hrs by TR-FRET assay	ic50	0.0300	uM
4-[1-[(5,7-dimethyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzoic acid	1654379: Inhibition of human serine protease factor B by TR-FRET based competition binding assay	ic50	0.0330	uM
(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-N-[(2S)-1-[[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-formamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-4,4-dimethylpentanamide	1393242: Inhibition of human factor B-induced cleavage of C3 after 3 hrs by coomassie brilliant blue staining-based gel electrophoresis	ic50	0.2500	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	475776: Inhibition of human complement factor B treated for 5 mins before addition of substrate Ac-SHLGLAR-pNA at pH 9.5 by chromogenic assay	ic50	0.2500	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	475776: Inhibition of human complement factor B treated for 5 mins before addition of substrate Ac-SHLGLAR-pNA at pH 9.5 by chromogenic assay	ic50	0.6000	uM
4-[1-[(5,7-dimethyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzamide	1654379: Inhibition of human serine protease factor B by TR-FRET based competition binding assay	ic50	0.7100	uM
4-[(4-methoxy-2-phenylpiperidin-1-yl)methyl]-5,7-dimethyl-1H-indole	1654379: Inhibition of human serine protease factor B by TR-FRET based competition binding assay	ic50	0.7200	uM
5,7-dimethyl-4-[[2-(4-methylsulfonylphenyl)piperidin-1-yl]methyl]-1H-indole	1654379: Inhibition of human serine protease factor B by TR-FRET based competition binding assay	ic50	1.3000	uM
[1-[(5,7-dimethyl-1H-indol-4-yl)methyl]-2-phenylpiperidin-4-yl]methanol	1654379: Inhibition of human serine protease factor B by TR-FRET based competition binding assay	ic50	2.5000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	475776: Inhibition of human complement factor B treated for 5 mins before addition of substrate Ac-SHLGLAR-pNA at pH 9.5 by chromogenic assay	ic50	3.0000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	475776: Inhibition of human complement factor B treated for 5 mins before addition of substrate Ac-SHLGLAR-pNA at pH 9.5 by chromogenic assay	ic50	3.0000	uM
[(2S,4S)-1-[(5,7-dimethyl-1H-indol-4-yl)methyl]-4-methoxypiperidin-2-yl]methanol	1654373: Inhibition of human serine protease factor B catalytic domain (D470 to L764 residues) assessed as inhibition of cleavage cobra venom factor (CVF):Bb complex pre-incubated for 1 hr before addition of C3 by ELISA	ic50	3.3500	uM
2-[(4R,7S,10S,13S,19S,22S,25S,28S,31S,34R)-4-[[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]carbamoyl]-34-[[(2S,3S)-2-amino-3-methylpentanoyl]amino]-25-(3-amino-3-oxopropyl)-7-[3-(diaminomethylideneamino)propyl]-10,13-bis(1H-imidazol-5-ylmethyl)-19-(1H-indol-3-ylmethyl)-6,9,12,15,18,21,24,27,30,33-decaoxo-28,31-di(propan-2-yl)-1,2-dithia-5,8,11,14,17,20,23,26,29,32-decazacyclopentatriacont-22-yl]acetic acid	321220: Inhibition of C3 convertase	ic50	3.4000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	475776: Inhibition of human complement factor B treated for 5 mins before addition of substrate Ac-SHLGLAR-pNA at pH 9.5 by chromogenic assay	ic50	4.0000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	475776: Inhibition of human complement factor B treated for 5 mins before addition of substrate Ac-SHLGLAR-pNA at pH 9.5 by chromogenic assay	ic50	5.0000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-cyclohexylbutanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	475776: Inhibition of human complement factor B treated for 5 mins before addition of substrate Ac-SHLGLAR-pNA at pH 9.5 by chromogenic assay	ic50	5.0000	uM
5,7-dimethyl-4-[[(2S)-2-phenylpiperidin-1-yl]methyl]-1H-indole	1654373: Inhibition of human serine protease factor B catalytic domain (D470 to L764 residues) assessed as inhibition of cleavage cobra venom factor (CVF):Bb complex pre-incubated for 1 hr before addition of C3 by ELISA	ic50	5.9000	uM
[1-[(5,7-dimethyl-1H-indol-4-yl)methyl]piperidin-2-yl]methanol	1654373: Inhibition of human serine protease factor B catalytic domain (D470 to L764 residues) assessed as inhibition of cleavage cobra venom factor (CVF):Bb complex pre-incubated for 1 hr before addition of C3 by ELISA	ic50	6.0000	uM
4-(4,5-dihydro-1H-imidazol-2-ylmethyl)-5,7-dimethyl-1H-indole	1654373: Inhibition of human serine protease factor B catalytic domain (D470 to L764 residues) assessed as inhibition of cleavage cobra venom factor (CVF):Bb complex pre-incubated for 1 hr before addition of C3 by ELISA	ic50	6.3000	uM
N-(2-bromo-4-methylnaphthalen-1-yl)-4,5-dihydro-1H-imidazol-2-amine	1654373: Inhibition of human serine protease factor B catalytic domain (D470 to L764 residues) assessed as inhibition of cleavage cobra venom factor (CVF):Bb complex pre-incubated for 1 hr before addition of C3 by ELISA	ic50	6.6000	uM
N-(4,5-dihydro-1H-imidazol-2-yl)-5,7-dimethyl-1H-indol-4-amine	1654373: Inhibition of human serine protease factor B catalytic domain (D470 to L764 residues) assessed as inhibition of cleavage cobra venom factor (CVF):Bb complex pre-incubated for 1 hr before addition of C3 by ELISA	ic50	6.6000	uM
2-[(5,7-dimethyl-1H-indol-4-yl)methyl]-1H-benzimidazole	1654373: Inhibition of human serine protease factor B catalytic domain (D470 to L764 residues) assessed as inhibition of cleavage cobra venom factor (CVF):Bb complex pre-incubated for 1 hr before addition of C3 by ELISA	ic50	6.7000	uM
1-[(5,7-dimethyl-1H-indol-4-yl)methyl]-N-methyl-2-phenylpiperidin-4-amine	1654379: Inhibition of human serine protease factor B by TR-FRET based competition binding assay	ic50	6.8000	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-5-(diaminomethylideneamino)pentanoic acid	475776: Inhibition of human complement factor B treated for 5 mins before addition of substrate Ac-SHLGLAR-pNA at pH 9.5 by chromogenic assay	ic50	7.0000	uM
5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-7-methyl-1H-indol-4-amine	1654373: Inhibition of human serine protease factor B catalytic domain (D470 to L764 residues) assessed as inhibition of cleavage cobra venom factor (CVF):Bb complex pre-incubated for 1 hr before addition of C3 by ELISA	ic50	8.0000	uM
N-(2-chloro-4-methylnaphthalen-1-yl)-4,5-dihydro-1H-imidazol-2-amine	1654373: Inhibition of human serine protease factor B catalytic domain (D470 to L764 residues) assessed as inhibition of cleavage cobra venom factor (CVF):Bb complex pre-incubated for 1 hr before addition of C3 by ELISA	ic50	8.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases expression, increases methylation	4
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Aflatoxin B1	affects expression, decreases expression	3
Acetaminophen	decreases expression	2
Air Pollutants	increases abundance, increases expression	2
Copper	affects binding, increases expression	2
Mercury	affects expression, decreases expression	2
Nickel	affects binding, increases expression	2
Quercetin	affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Valproic Acid	decreases expression, increases expression	2
Zinc	increases expression, affects binding	2
Cyclosporine	decreases expression	2
Particulate Matter	increases abundance, increases expression	2
4-hydroxy-7-oxo-5-heptenoic acid lactone	increases expression	1
parthenolide	decreases expression	1
2,4,6-tribromophenol	increases expression	1
methyleugenol	decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
sodium arsenate	increases abundance, decreases expression	1
terbufos	increases methylation	1
cobaltous chloride	decreases secretion	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2,3-dimethoxy-1,4-naphthoquinone	decreases expression	1

ChEMBL screening assays

33 unique, capped per target: 33 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1112743	Binding	Inhibition of human complement factor B at pH 9.5 by chromogenic assay	Structure-activity relationships for substrate-based inhibitors of human complement factor B. — J Med Chem

Cellosaurus cell lines

6 cell lines: 6 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A3HJ	HPS2036	Induced pluripotent stem cell	Female
CVCL_A3HK	HPS2037	Induced pluripotent stem cell	Female
CVCL_A3HL	HPS2038	Induced pluripotent stem cell	Female
CVCL_A3HM	HPS2039	Induced pluripotent stem cell	Female
CVCL_A3HN	HPS2040	Induced pluripotent stem cell	Female
CVCL_A3HP	HPS2041	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

300 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
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	PHASE4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	PHASE4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	PHASE4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	PHASE4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	PHASE4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	PHASE4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	PHASE4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	PHASE4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	PHASE4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	PHASE4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	PHASE4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	PHASE4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	PHASE4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	PHASE4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	PHASE4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	PHASE4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	PHASE4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	PHASE4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	PHASE4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients
NCT01437943	PHASE4	TERMINATED	Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
NCT01545479	PHASE4	COMPLETED	Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition
NCT01614431	PHASE4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01631149	PHASE4	COMPLETED	Effect of Deep BLock on Intraoperative Surgical Conditions
NCT01722513	PHASE4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01985360	PHASE4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02311010	PHASE4	UNKNOWN	Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism
NCT02413073	PHASE4	COMPLETED	Whole Body Vibration in Kidney Disease
NCT02444013	PHASE4	UNKNOWN	Folic Acid for Prevention of Contrast Induced Nephropathy
NCT02663713	PHASE4	COMPLETED	A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor to Clopidogrel in Patients With Prior Myocardial Infarction
NCT02707809	PHASE4	COMPLETED	Effects of Dexmedetomidine on Microcirculation of Kidney Transplant Recipient