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 (top 2% of genes corpus-wide)
• Clinical variants (ClinVar): 684 total — 11 pathogenic, 8 likely-pathogenic (top 5% of genes corpus-wide)
• GTEx eGene: eQTL in 13 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 20
• Drug target: yes — 1 curated mechanism-of-action drug; 1 molecules with ChEMBL bioactivity
• Approved drugs (ChEMBL mechanism of action): 1 — Iptacopan
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.72 (unconstrained)
• 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: 83 — 46 protein_coding, 20 nonsense_mediated_decay, 14 retained_intron, 2 protein_coding_CDS_not_defined, 1 non_stop_decay

MANE Select: ENST00000425368

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 7, TSL 3: 1, TSL 4: 1, TSL 5: 4

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, ENST00000991685, ENST00000991689, ENST00000991690, ENST00000991693, ENST00000991696, ENST00000991698, ENST00000991700, ENST00000991701, ENST00000991702, ENST00000991703, ENST00000991705, ENST00000991708, ENST00000991709, ENST00000991712, ENST00000991713, ENST00000991715, ENST00000991718, ENST00000991723, ENST00001057474, ENST00001057476, ENST00001093269, ENST00001119744, ENST00001119745, ENST00001119746, ENST00001134790

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.

Highest expression (Bgee): lobe of liver, liver, gall bladder, vermiform appendix, duodenum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CFB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

16 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	4.7e-07	-0.17	6:31948623:A:G
Artery Aorta	sqtl	1.2e-05	-0.61	6:31947158:A:G
Adipose Subcutaneous	eqtl	1.5e-04	+0.65	6:32578854:T:C
Nerve Tibial	sqtl	7.6e-04	-0.37	6:31947158:A:G
Brain Nucleus accumbens basal ganglia	eqtl	1.0e-03	+0.21	6:31373131:G:A
Cells Cultured fibroblasts	eqtl	1.1e-03	-0.14	6:32140074:G:A
Lung	eqtl	1.4e-03	-0.21	6:31495393:G:C
Skin Sun Exposed Lower leg	eqtl	4.7e-03	-0.51	6:31618878:CGGGGTT:C
Muscle Skeletal	eqtl	9.5e-03	+0.20	6:32046679:C:T
Brain Cerebellum	eqtl	1.3e-02	-0.47	6:31918665:C:T
Artery Aorta	eqtl	1.4e-02	-0.27	6:32141388:G:A
Brain Anterior cingulate cortex BA24	eqtl	1.9e-02	+0.80	6:31665612:T:C
Skin Not Sun Exposed Suprapubic	eqtl	2.2e-02	+0.30	6:32638320:A:G
Brain Cerebellar Hemisphere	eqtl	3.0e-02	-0.30	6:31926578:C:T
Cells EBV-transformed lymphocytes	eqtl	4.3e-02	+0.85	6:32617406:T:C
Cells Cultured fibroblasts	sqtl	4.5e-02	-1.15	6:32748280:A:T

FANTOM5 promoters

showing 10 of 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

showing 100 of 134 tissues 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
left uterine tube	UBERON:0001303	92.46	gold quality
lung	UBERON:0002048	92.21	gold quality
thoracic mammary gland	UBERON:0005200	91.70	gold quality
right atrium auricular region	UBERON:0006631	91.61	gold quality
kidney	UBERON:0002113	91.50	gold quality
urinary bladder	UBERON:0001255	91.02	gold quality
rectum	UBERON:0001052	90.63	gold quality
intestine	UBERON:0000160	90.49	gold quality
colonic epithelium	UBERON:0000397	90.44	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.36	gold quality
cortex of kidney	UBERON:0001225	90.31	gold quality
tonsil	UBERON:0002372	90.22	gold quality
smooth muscle tissue	UBERON:0001135	90.11	gold quality
esophagus mucosa	UBERON:0002469	89.84	gold quality
adenohypophysis	UBERON:0002196	89.58	gold quality
fundus of stomach	UBERON:0001160	89.54	gold quality
transverse colon	UBERON:0001157	89.40	gold quality
spleen	UBERON:0002106	89.03	gold quality
esophagus	UBERON:0001043	89.02	gold quality
colon	UBERON:0001155	88.96	gold quality
tibial nerve	UBERON:0001323	88.96	gold quality
apex of heart	UBERON:0002098	88.31	gold quality
lower esophagus	UBERON:0013473	88.31	gold quality
tibial artery	UBERON:0007610	88.28	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.27	gold quality
popliteal artery	UBERON:0002250	88.25	gold quality
pituitary gland	UBERON:0000007	88.14	gold quality
left adrenal gland cortex	UBERON:0035825	88.08	gold quality
right adrenal gland	UBERON:0001233	88.03	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.02	gold quality
left adrenal gland	UBERON:0001234	87.98	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.54	gold quality
sural nerve	UBERON:0015488	87.52	gold quality
lower esophagus mucosa	UBERON:0035834	87.50	gold quality
right adrenal gland cortex	UBERON:0035827	87.09	gold quality
calcaneal tendon	UBERON:0003701	87.07	gold quality
adrenal gland	UBERON:0002369	87.02	gold quality
right lobe of thyroid gland	UBERON:0001119	86.97	gold quality
myometrium	UBERON:0001296	86.90	gold quality
lymph node	UBERON:0000029	86.49	gold quality
endocervix	UBERON:0000458	86.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.11	gold quality
mucosa of transverse colon	UBERON:0004991	86.07	gold quality
left lobe of thyroid gland	UBERON:0001120	85.92	gold quality
thyroid gland	UBERON:0002046	85.84	gold quality
right ovary	UBERON:0002118	85.64	gold quality
heart	UBERON:0000948	85.41	gold quality
placenta	UBERON:0001987	85.22	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.85	gold quality
body of uterus	UBERON:0009853	84.58	gold quality
ovary	UBERON:0000992	84.15	gold quality
multicellular organism	UBERON:0000468	84.07	gold quality
left ovary	UBERON:0002119	83.81	gold quality
uterine cervix	UBERON:0000002	83.53	gold quality
substantia nigra	UBERON:0002038	83.11	gold quality
skin of leg	UBERON:0001511	82.23	gold quality
zone of skin	UBERON:0000014	82.03	gold quality
vagina	UBERON:0000996	81.91	gold quality
skin of abdomen	UBERON:0001416	81.86	gold quality
putamen	UBERON:0001874	80.94	gold quality
amygdala	UBERON:0001876	80.63	gold quality
hypothalamus	UBERON:0001898	80.60	gold quality
Ammon’s horn	UBERON:0001954	80.48	gold quality
heart left ventricle	UBERON:0002084	80.45	gold quality
temporal lobe	UBERON:0001871	80.43	gold quality
right frontal lobe	UBERON:0002810	80.24	gold quality
ectocervix	UBERON:0012249	80.16	gold quality
caudate nucleus	UBERON:0001873	80.13	gold quality
nucleus accumbens	UBERON:0001882	79.26	gold quality
muscle tissue	UBERON:0002385	79.05	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

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 70 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	1086.0	not detected
Smooth muscle	tissue	44.4	not detected
Stomach 1	tissue	38.1	not detected
Superior colliculi	tissue	36.3
Appendix	tissue	31.2	not detected
Spinal cord	tissue	26.9
Small intestine	tissue	23.0	not detected
Substantia nigra	tissue	17.1
Urinary bladder	tissue	16.7	not detected
Duodenum	tissue	15.9	not detected
Pituitary gland	tissue	15.8
Medulla oblongata	tissue	14.9
Adipose tissue	tissue	13.3	not detected
Rectum	tissue	12.6	not detected
Prostate	tissue	12.3	not detected
Kidney	tissue	11.5	not detected
Epididymis	tissue	11.3	not detected
Breast	tissue	10.6	not detected
Hippocampal formation	tissue	9.9
Entorhinal cortex	tissue	9.5
Lung	tissue	9.2	not detected
Vagina	tissue	8.8	not detected
Thalamus	tissue	8.7
Fallopian tube	tissue	8.4	not detected
Midbrain	tissue	8.0
Pons	tissue	7.7
Colon	tissue	7.7	not detected
Tonsil	tissue	6.2	not detected
Cerebral cortex	tissue	5.9	not detected
Temporal cortex	tissue	5.9
Olfactory bulb	tissue	5.5
Hypothalamus	tissue	4.7
Cerebellum	tissue	4.7	not detected
Motor cortex	tissue	4.5
Ventral forebrain	tissue	4.1
Septum	tissue	4.0
Somatosensory cortex	tissue	3.9
Prefrontal cortex	tissue	3.8
Spleen	tissue	3.8	not detected
Retrosplenial and cingulate cortex	tissue	3.8
Corpus callosum	tissue	3.7
Insular cortex	tissue	3.7
Periaqueductal gray	tissue	3.6
Lymph node	tissue	3.5	not detected
Amygdala	tissue	3.5
Retrosplenial cortex	tissue	3.4
Esophagus	tissue	2.9	not detected
Salivary gland	tissue	2.8	not detected
Basal ganglia	tissue	2.8	not detected
Adrenal gland	tissue	2.8	not detected
Occipital cortex	tissue	2.8
Putamen	tissue	2.6
Placenta	tissue	2.6	not detected
Ovary	tissue	1.8	not detected
Pancreas	tissue	1.6	not detected
Endometrium 1	tissue	1.6	not detected
Thymus	tissue	1.5
Heart muscle	tissue	1.3	not detected
Thyroid gland	tissue	1.2	not detected
Skin 1	tissue	1.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 162; highest nTPM — Blood vessel (41.0), Dorsal spinal cord (26.9), Ventral spinal cord (19.9), Subiculum (9.9), Ventral hippocampus (4.6).

Regulation

Is transcription factor: no

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

Functional genomics

gnomAD constraint: pLI 1.47e-10, LOEUF 0.719, missense Z 2.75 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000425368 — one region, missense o/e 0.80.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:105975) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 13 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating phosphate level	1
reduced fertility	1
abnormal kidney morphology	1
increased susceptibility to bacterial infection	1
abnormal complement pathway	1
impaired complement alternative pathway	1
impaired complement classical pathway	1
increased hematocrit	1
increased erythrocyte cell number	1
decreased susceptibility to induced arthritis	1
increased hemoglobin content	1
increased fasting circulating glucose level	1
decreased susceptibility to Coronaviridae infection	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gorilla gorilla gorilla	Q864V9	99.6%	Diamond
Pongo pygmaeus	Q8SQ75	99.6%	Diamond
Pan troglodytes	Q8SQ74	99.5%	Diamond
Ateles geoffroyi	P50417	96.0%	Diamond
Papio hamadryas	Q5VAN1	96.0%	Diamond
Rattus norvegicus	P0C6B8	93.9%	Diamond
Bos taurus	P81187	85.9%	Diamond
Sus scrofa	Q03710	85.9%	Diamond
Gallus gallus	P81475	44.5%	Diamond
Caenorhabditis elegans	Q22328	39.8%	Diamond
Vaccinia virus WR	P68638	100.0%	Diamond
Vaccinia virus Copenhagen	P68639	100.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
C2-AS1	ncRNA	102060414
DXO	protein-coding	1797
SKIC2	protein-coding	6499
C2	protein-coding	717
NELFE	protein-coding	7936
WHR1	protein-coding	8859
MIR1236	ncRNA	100302242
EHMT2-AS1	ncRNA	107986588
EHMT2	protein-coding	10919
ZBTB12	protein-coding	221527
C4A	protein-coding	720
SLC44A4	protein-coding	80736

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 (165 total): strand 55, helix 33, sequence variant 17, disulfide bond 11, mutagenesis site 9, turn 7, sequence conflict 7, binding site 6, glycosylation site 5, domain 5, chain 3, active site 3, splice variant 2, signal peptide 1, site 1

Structure

Experimental structures (PDB)

28 structures by resolution:

PDB	Title	Method	Resolution (Å)
6QSW	Complement factor B protease domain in complex with the reversible inhibitor …	X-RAY DIFFRACTION	1.64
6RAV	Complement factor B protease domain in complex with the reversible inhibitor …	X-RAY DIFFRACTION	1.7
6T8W	Complement factor B in complex with …	X-RAY DIFFRACTION	1.7
6QSX	Complement factor B protease domain in complex with the reversible inhibitor …	X-RAY DIFFRACTION	1.77
1Q0P	A domain of Factor B	X-RAY DIFFRACTION	1.8
1RRK	Crystal Structure Analysis of the Bb segment of Factor B	X-RAY DIFFRACTION	2
1DLE	FACTOR B SERINE PROTEASE DOMAIN	X-RAY DIFFRACTION	2.1
3HRZ	Cobra Venom Factor (CVF) in complex with human factor B	X-RAY DIFFRACTION	2.2
6T8V	Complement factor B in complex with …	X-RAY DIFFRACTION	2.29
1RTK	Crystal Structure Analysis of the Bb segment of Factor B complexed with …	X-RAY DIFFRACTION	2.3
2OK5	Human Complement factor B	X-RAY DIFFRACTION	2.3
1RS0	Crystal Structure Analysis of the Bb segment of Factor B complexed with …	X-RAY DIFFRACTION	2.6
9U62	AP pathways C3 convertase C3bBbP and C3 complex	ELECTRON MICROSCOPY	2.7
6T8U	Complement factor B in complex with …	X-RAY DIFFRACTION	2.84
11MG	Cryo-EM Structure of Human C3 Pro-Convertase bound to the Compstatin Analog Cp60, TED …	ELECTRON MICROSCOPY	2.88
11MH	Cryo-EM Structure of Human C3 Pro-Convertase bound to the Compstatin Analog Cp60, TED …	ELECTRON MICROSCOPY	3
3HS0	Cobra Venom Factor (CVF) in complex with human factor B	X-RAY DIFFRACTION	3
7JTN	Human Complement Factor B Inhibited by a Slow Off-Rate Modified Aptamer of 29 Bases	X-RAY DIFFRACTION	3.1
8ENU	Structure of the C3bB proconvertase in complex with lufaxin	ELECTRON MICROSCOPY	3.22
2XWB	Crystal Structure of Complement C3b in complex with Factors B and D	X-RAY DIFFRACTION	3.49
7JTQ	Human Complement Factor B Inhibited by a Slow Off-Rate Modified Aptamer of 31 Bases	X-RAY DIFFRACTION	3.5
8EOK	Structure of the C3bB proconvertase in complex with lufaxin and factor Xa	ELECTRON MICROSCOPY	3.53
8UIN	Structure of the C3bBb-albicin complex	ELECTRON MICROSCOPY	3.86
2WIN	C3 convertase (C3bBb) stabilized by SCIN	X-RAY DIFFRACTION	3.9
7NOZ	Structure of the nanobody stablized properdin bound alternative pathway proconvertase …	X-RAY DIFFRACTION	3.9
2XWJ	Crystal Structure of Complement C3b in Complex with Factor B	X-RAY DIFFRACTION	4
6RUR	Structure of the SCIN stabilized C3bBb convertase bound to properdin	X-RAY DIFFRACTION	6
6RUV	Structure of the SCIN stabilized C3bBb convertase bound to Properdin and a the …	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 antibodies co-crystallized with this protein: 6RUV, 7NOZ

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Serine-type peptidases, Predicted secreted proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Primary immunodeficiency, Eye disease

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): endoplasmic reticulum; vesicles; cell junctions

Antibody reliability (HPA): IH supported · IF approved

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)

Position	Role
576	charge relay system
699	charge relay system
259–260	cleavage; by cfd
526	charge relay system

Ligand- & substrate-binding residues (6)

Position	Role
278	Mg(2+)
278	Mn(2+)
280	Mg(2+)
280	Mn(2+)
353	Mg(2+)
353	Mn(2+)

Disulfide bonds (11)

Type	Positions
Disulfide bond	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)

Type	Positions
N-linked (glcnac…) asparagine	122, 142, 285, 378
N-linked (glc) (glycation) lysine	291

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 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-174577	Activation of C3 and C5	curated
R-HSA-173736	Alternative complement activation	curated
R-HSA-977606	Regulation of Complement cascade	curated
R-HSA-166658	Complement cascade	—
R-HSA-168256	Immune System	—
R-HSA-166663	Initial triggering of complement	—
R-HSA-168249	Innate Immune System	—

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, alternative pathway (GO:0006957), response to bacterium (GO:0009617), immune system process (GO:0002376), complement activation (GO:0006956), 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 (6): extracellular region (GO:0005576), 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

4 top-level categories:

Category	Pathways
Complement cascade	3
Initial triggering of complement	1
Innate Immune System	1
Immune System	1

GO top-level categories

26 GO namespaces:

Category	Terms
cellular anatomical structure	3
protein metabolic process	1
complement activation	1
innate immune response	1
response to other organism	1
biological_process	1
immune effector process	1
activation of immune response	1
humoral immune response	1
protein activation cascade	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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 19 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
complement activation, alternative pathway	BP	direct assay
blood microparticle	CC	high-throughput assay
extracellular exosome	CC	high-throughput assay
symbiont cell surface	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,478 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFB	C3	P01024	932
CFB	CFI	P05156	927
CFB	CFHR1	Q03591	894
CFB	CFHR3	Q02985	884
CFB	C4A	P01028	877
CFB	C4A	P01028	799
CFB	CFP	P27918	792
CFB	ARMS2	P0C7Q2	790
CFB	DGKE	P52429	788
CFB	CFHR5	Q9BXR6	740
CFB	THBD	P07204	712
CFB	C1QA	P02745	675
CFB	C5AR1	P21730	655
CFB	CFHR4	Q92496	655
CFB	ADAMTS13	Q76LX8	652

IntAct

Human interaction partners of CFB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
CFHR4	physical association	0.610	3
C3	direct interaction	0.440	3
CFHR1	physical association	0.400	1
H1-1	physical association	0.400	1
LAMC3	physical association	0.370	1
RPA2	physical association	0.370	1
CST4	association	0.350	1
GRB14	association	0.350	1
HSPA5	association	0.350	1
NME2	association	0.350	1

BioGRID (56 interactions; top human partners by supporting records): GDPD1 (Affinity Capture-MS; 3 records), DDX19B (Affinity Capture-MS; 2 records), NPC2 (Affinity Capture-MS; 2 records), RSPRY1 (Affinity Capture-MS; 2 records), AGPAT1 (Affinity Capture-MS), ALB (Affinity Capture-MS), AMY1C (Affinity Capture-MS), C3 (Reconstituted Complex), CALR (Affinity Capture-MS), CCR1 (Affinity Capture-MS), CFP (Reconstituted Complex), COX3 (Cross-Linking-MS (XL-MS)), CST4 (Affinity Capture-MS), DNMT1 (Affinity Capture-MS), DSP (Cross-Linking-MS (XL-MS))

SIGNOR signaling

showing 4 of 5 signaling 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

Genetic variants

Variant evidence for CFB: 684 ClinVar records (19 pathogenic / likely pathogenic); 47 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	8
Uncertain significance	364
Likely benign	212
Benign	14

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 19 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
16080	NM_001710.6(CFB):c.967A>G (p.Lys323Glu)	Pathogenic	criteria provided, single submitter	2
4280397	NM_001710.6(CFB):c.836A>G (p.Asp279Gly)	Pathogenic	criteria provided, single submitter	1
4280398	NM_001710.6(CFB):c.967A>C (p.Lys323Gln)	Pathogenic	criteria provided, single submitter	1
4280404	NM_001710.6(CFB):c.1050G>C (p.Lys350Asn)	Pathogenic	criteria provided, single submitter	1
4280405	NM_001710.6(CFB):c.1050G>T (p.Lys350Asn)	Pathogenic	criteria provided, single submitter	1
4280406	NM_001710.6(CFB):c.1101C>G (p.Ser367Arg)	Pathogenic	criteria provided, single submitter	1
4280407	NM_001710.6(CFB):c.1101C>A (p.Ser367Arg)	Pathogenic	criteria provided, single submitter	1
4280408	NM_001710.6(CFB):c.1099A>C (p.Ser367Arg)	Pathogenic	criteria provided, single submitter	1
4280410	NM_001710.6(CFB):c.1112A>G (p.Asp371Gly)	Pathogenic	criteria provided, single submitter	1
16079	NM_001710.6(CFB):c.858C>G (p.Phe286Leu)	Likely pathogenic	criteria provided, single submitter	2
3066149	NM_001710.6(CFB):c.898-2A>C	Likely pathogenic	criteria provided, single submitter	1
3381003	NM_001710.6(CFB):c.888_891del (p.Ile297fs)	Likely pathogenic	criteria provided, single submitter	1
4280400	NM_001710.6(CFB):c.991A>G (p.Asn331Asp)	Likely pathogenic	criteria provided, single submitter	1
4280411	NM_001710.6(CFB):c.1298T>C (p.Leu433Ser)	Likely pathogenic	criteria provided, single submitter	1
4280412	NM_001710.6(CFB):c.1363G>A (p.Val455Ile)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CFB’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 1,567):

Position(s)	Effect	Δscore	Sites
6:31946286–31946287	donor_loss	1.0000	4
6:31947004	acceptor_gain	1.0000
6:31947483	donor_gain	1.0000
6:31947862	donor_gain	1.0000
6:31948971	donor_gain	1.0000
6:31949241–31949242	acceptor_loss	1.0000	6
6:31949332	donor_gain	1.0000
6:31949345–31949346	donor_loss	1.0000	5
6:31949418–31949419	acceptor_loss	1.0000	6
6:31949558–31949559	donor_loss	1.0000	5

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	favorable	1.37e-07
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	2.4e-05

Disease associations

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

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
atypical hemolytic-uremic syndrome with B factor anomaly	Strong	Autosomal dominant	4
complement factor b deficiency	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity

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

2 validity classifications:

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

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (6 panels, 5 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

6 panels:

Panel	Rating
Atypical haemolytic uraemic syndrome	green
COVID-19 research	green
Membranoproliferative glomerulonephritis including C3 glomerulopathy	green
Unexplained kidney failure in young people	green
Unexplained young onset end-stage renal disease	green
Primary immunodeficiency or monogenic inflammatory bowel disease	amber

Mondo (3): atypical hemolytic-uremic syndrome with B factor anomaly (MONDO:0013042), atypical hemolytic-uremic syndrome (MONDO:0016244), complement factor b deficiency (MONDO:0014255)

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

HPO phenotypes

20 phenotypes (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 Neisseria meningitidis infection
HP:0005416	Decreased circulating complement factor B concentration
HP:0005575	Hemolytic-uremic syndrome
HP:0011463	Childhood onset
HP:0100519	Anuria

GWAS associations

showing 30 of 47 associations:

Study	Trait	p-value
GCST003219_18	Advanced age-related macular degeneration	1e-103
GCST001884_13	Age-related macular degeneration	4e-89
GCST004133_55	Ulcerative colitis	5e-65
GCST002879_1	Chronic hepatitis B infection	1e-34
GCST004131_25	Inflammatory bowel disease	2e-31
GCST001100_9	Age-related macular degeneration	6e-31
GCST002876_5	Type 1 diabetes and autoimmune thyroid diseases	5e-25
GCST000652_8	Age-related macular degeneration	3e-21
GCST000653_7	Age-related macular degeneration	2e-20
GCST004521_71	Autism spectrum disorder or schizophrenia	6e-18
GCST001579_2	Age-related macular degeneration (choroidal neovascularisation)	1e-17
GCST004521_265	Autism spectrum disorder or schizophrenia	3e-17
GCST001571_5	Age-related macular degeneration	9e-17
GCST004521_214	Autism spectrum disorder or schizophrenia	2e-16
GCST004521_85	Autism spectrum disorder or schizophrenia	5e-16
GCST90020024_409	A body shape index	2e-15
GCST004521_268	Autism spectrum disorder or schizophrenia	3e-15
GCST004521_269	Autism spectrum disorder or schizophrenia	3e-15
GCST000806_3	Age-related macular degeneration	5e-15
GCST004521_87	Autism spectrum disorder or schizophrenia	5e-15
GCST004521_220	Autism spectrum disorder or schizophrenia	1e-14
GCST004521_124	Autism spectrum disorder or schizophrenia	4e-14
GCST002453_3	Ulcerative colitis	5e-14
GCST004521_89	Autism spectrum disorder or schizophrenia	5e-13
GCST005196_199	Coronary artery disease	6e-13
GCST004521_168	Autism spectrum disorder or schizophrenia	2e-12
GCST004521_128	Autism spectrum disorder or schizophrenia	4e-12
GCST003219_20	Advanced age-related macular degeneration	9e-12
GCST005790_38	Rosacea symptom severity	7e-11
GCST008163_81	Height	9e-11

EFO canonical traits (from GWAS)

6 canonical traits:

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

1 disease descriptors:

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5731 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the CFB protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
IPTACOPAN	Small molecule	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 417 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL4594448	IPTACOPAN	4	417

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S1: Chymotrypsin

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
iptacopan	Inhibition	7.92	pIC50
ciprocopan	Inhibition	7.71	pIC50
compound 51 [PMID: 19743866]	Inhibition	6.6	pIC50
lanoracopan	Inhibition	5.92	pIC50

Binding affinities (BindingDB)

354 measured of 457 human assays (699 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	decreases expression, increases methylation, affects expression	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	affects binding, increases expression	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	decreases expression, increases abundance	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT02574403	Phase 4	COMPLETED	Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With aHUS
NCT07308574	Phase 4	RECRUITING	Post-Marketing Clinical Study of Ravulizumab in Participants With Clinical aHUS
NCT00067990	Phase 4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	Phase 4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	Phase 4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	Phase 4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	Phase 4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	Phase 4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	Phase 4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	Phase 4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	Phase 4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	Phase 4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	Phase 4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	Phase 4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	Phase 4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	Phase 4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	Phase 4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	Phase 4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	Phase 4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	Phase 4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	Phase 4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	Phase 4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	Phase 4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	Phase 4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	Phase 4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	Phase 4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	Phase 4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	Phase 4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	Phase 4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients
NCT01437943	Phase 4	TERMINATED	Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
NCT01545479	Phase 4	COMPLETED	Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition
NCT01614431	Phase 4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01631149	Phase 4	COMPLETED	Effect of Deep BLock on Intraoperative Surgical Conditions
NCT01722513	Phase 4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01985360	Phase 4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02311010	Phase 4	UNKNOWN	Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism
NCT02413073	Phase 4	COMPLETED	Whole Body Vibration in Kidney Disease
NCT02444013	Phase 4	UNKNOWN	Folic Acid for Prevention of Contrast Induced Nephropathy
NCT02663713	Phase 4	COMPLETED	A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor to Clopidogrel in Patients With Prior Myocardial Infarction
NCT02707809	Phase 4	COMPLETED	Effects of Dexmedetomidine on Microcirculation of Kidney Transplant Recipient
NCT02761577	Phase 4	COMPLETED	A Prospective Study on Incidence and Prevention of Contrast-induced Nephropathy in Croatia
NCT03029351	Phase 4	TERMINATED	GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes
NCT03160729	Phase 4	TERMINATED	High vs Low Dose Dexamethasone on Complications in the Immediate Postoperative Phase After Nephrectomy
NCT03387826	Phase 4	COMPLETED	Low Dose Ticagrelor Versus Low Dose Prasugrel in Patients With Prior Myocardial Infarction
NCT03623568	Phase 4	WITHDRAWN	Direct Acting Antiviral Therapy in Donor HCV-positive to Recipient HCV-negative Kidney Transplant
NCT04080076	Phase 4	WITHDRAWN	Comparative and Efficacy Study of ACTHar Gel Alone or in Combination With Tacrolimus in Fibrillary Glomerulopathy
NCT04539418	Phase 4	COMPLETED	Vitamin K2 Supplementation and Vascular Calcification
NCT04653779	Phase 4	UNKNOWN	A Clinical Trial to Evaluate the Preference Regarding Convenience of Medication and Efficacy/Safety of SUGAMET®XR Tablet 5/1000mg
NCT04839536	Phase 4	UNKNOWN	Comparing Sevoflurane With Propofol Sedation in ESRF Patients
NCT05030974	Phase 4	COMPLETED	RECOVAC Repeated Vaccination Study
NCT05096195	Phase 4	ACTIVE_NOT_RECRUITING	PRevEnting FracturEs in REnal Disease - 1
NCT05700903	Phase 4	TERMINATED	Contributions to Hypertension With Androgen Deprivation Therapy
NCT06291077	Phase 4	RECRUITING	Comparison of the Effects of Belatacept and Anticalcineurins on Endothelial Function in Renal Transplant Patients -
NCT06625073	Phase 4	RECRUITING	Randomized Trial of SGLT2i in Heart Transplant Recipients
NCT06642623	Phase 4	RECRUITING	A Prospective Trial of Enavogliflozin to Evaluate Cardio-renal Outcome in Type 2 Diabetes Mellitus Patients
NCT07138521	Phase 4	NOT_YET_RECRUITING	Optimizing Linezolid Dosing in Patients With Advanced Renal Impairment: a Therapeutic Drug Monitoring-based Evaluation
NCT07182422	Phase 4	RECRUITING	AST-120 (Kremezin®) for the Renal Protection and Attenuation of Decline in Acute Kidney Disease
NCT07685886	Phase 4	NOT_YET_RECRUITING	MIRACLE-T2D Montelukast Intervention for Renal, Cardiovascular and Eye Health in Type 2 Diabetes
NCT07746219	Phase 4	NOT_YET_RECRUITING	The Clinical Research of Traditional Chinese Medicine Formula
NCT02949128	Phase 3	COMPLETED	Study of ALXN1210 in Complement Inhibitor Treatment-Naïve Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CFB across ~30M SureChEMBL compounds — explore on Sugi Predict.