CFH

Summary

CFH (complement factor H, HGNC:4883) is a protein-coding gene on chromosome 1q31.3, encoding Complement factor H (P08603). Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation.

This gene is a member of the Regulator of Complement Activation (RCA) gene cluster and encodes a protein with twenty short consensus repeat (SCR) domains. This protein is secreted into the bloodstream and has an essential role in the regulation of complement activation, restricting this innate defense mechanism to microbial infections. Mutations in this gene have been associated with hemolytic-uremic syndrome (HUS) and chronic hypocomplementemic nephropathy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Source: NCBI Gene 3075 — RefSeq curated summary.

At a glance

• Gene–disease (curated): C3 glomerulonephritis (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 79
• Clinical variants (ClinVar): 1,599 total — 69 pathogenic, 47 likely-pathogenic
• Phenotypes (HPO): 89
• Druggable target: yes
• MANE Select transcript: NM_000186

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4883
Approved symbol	CFH
Name	complement factor H
Location	1q31.3
Locus type	gene with protein product
Status	Approved
Aliases	HUS, FHL1, ARMS1, ARMD4
Ensembl gene	ENSG00000000971
Ensembl biotype	protein_coding
OMIM	134370
Entrez	3075

Gene structure

Transcript identifiers

Ensembl transcripts: 62 — 43 protein_coding, 10 protein_coding_CDS_not_defined, 6 nonsense_mediated_decay, 3 retained_intron

ENST00000359637, ENST00000367429, ENST00000466229, ENST00000470918, ENST00000496761, ENST00000630130, ENST00000695968, ENST00000695969, ENST00000695970, ENST00000695971, ENST00000695972, ENST00000695973, ENST00000695974, ENST00000695975, ENST00000695976, ENST00000695977, ENST00000695978, ENST00000695979, ENST00000695980, ENST00000695981, ENST00000695983, ENST00000695984, ENST00000695986, ENST00000695987, ENST00000695990, ENST00000696018, ENST00000696019, ENST00000696020, ENST00000696021, ENST00000696022, ENST00000696023, ENST00000696024, ENST00000696025, ENST00000696026, ENST00000696027, ENST00000696028, ENST00000696029, ENST00000696030, ENST00000696031, ENST00000883397, ENST00000883398, ENST00000883399, ENST00000883400, ENST00000883401, ENST00000883402, ENST00000883403, ENST00000883404, ENST00000883405, ENST00000883406, ENST00000883407, ENST00000883408, ENST00000883409, ENST00000883410, ENST00000883411, ENST00000883412, ENST00000883413, ENST00000883414, ENST00000883415, ENST00000955307, ENST00000955308, ENST00000955310, ENST00000955311

RefSeq mRNA: 2 — MANE Select: NM_000186 NM_000186, NM_001014975

CCDS: CCDS1385, CCDS53452

Canonical transcript exons

ENST00000367429 — 22 exons

Exon	Start	End
ENSE00000469053	196741875	196742051
ENSE00000791016	196679623	196679793
ENSE00000791028	196740619	196740792
ENSE00001134426	196672978	196673163
ENSE00003520851	196689420	196689614
ENSE00003536337	196743452	196743628
ENSE00003540360	196685064	196685237
ENSE00003570710	196747111	196747504
ENSE00003602895	196745817	196745999
ENSE00003623048	196690063	196690239
ENSE00003631361	196737475	196737660
ENSE00003965659	196726470	196726652
ENSE00003965663	196677476	196677667
ENSE00003965667	196715593	196715769
ENSE00003965669	196726761	196726940
ENSE00003965686	196673857	196673962
ENSE00003965703	196728346	196728522
ENSE00003965709	196736824	196737006
ENSE00003965711	196713735	196713917
ENSE00003965712	196675989	196676065
ENSE00003965720	196725121	196725297
ENSE00003965817	196652043	196652175

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 99.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.7070 / max 1860.6969, expressed in 1116 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7503	25.2986	1115
7502	0.3596	194
201860	0.0488	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
urethra	UBERON:0000057	99.68	gold quality
calcaneal tendon	UBERON:0003701	99.47	gold quality
right coronary artery	UBERON:0001625	99.45	gold quality
right lobe of liver	UBERON:0001114	99.43	gold quality
saphenous vein	UBERON:0007318	99.25	gold quality
synovial joint	UBERON:0002217	99.07	gold quality
coronary artery	UBERON:0001621	99.03	gold quality
left coronary artery	UBERON:0001626	99.01	gold quality
parietal pleura	UBERON:0002400	98.98	gold quality
popliteal artery	UBERON:0002250	98.88	gold quality
tibial artery	UBERON:0007610	98.88	gold quality
gall bladder	UBERON:0002110	98.87	gold quality
right atrium auricular region	UBERON:0006631	98.86	gold quality
cardiac atrium	UBERON:0002081	98.61	gold quality
liver	UBERON:0002107	98.48	gold quality
aorta	UBERON:0000947	98.45	gold quality
right ovary	UBERON:0002118	98.44	gold quality
left ovary	UBERON:0002119	98.37	gold quality
tibial nerve	UBERON:0001323	98.36	gold quality
vena cava	UBERON:0004087	98.32	gold quality
palpebral conjunctiva	UBERON:0001812	98.18	gold quality
descending thoracic aorta	UBERON:0002345	98.13	gold quality
ascending aorta	UBERON:0001496	97.95	gold quality
pleura	UBERON:0000977	97.93	gold quality
thoracic aorta	UBERON:0001515	97.93	gold quality
minor salivary gland	UBERON:0001830	97.87	gold quality
layer of synovial tissue	UBERON:0007616	97.80	gold quality
right lobe of thyroid gland	UBERON:0001119	97.71	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.53	gold quality
pericardium	UBERON:0002407	97.47	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-CURD-126	yes	1344.00
E-CURD-119	yes	910.08
E-GEOD-131882	yes	891.53
E-MTAB-8142	yes	769.41
E-HCAD-1	yes	84.20
E-MTAB-8410	yes	61.00
E-HCAD-11	yes	42.79
E-CURD-46	yes	34.26
E-HCAD-4	yes	16.10
E-CURD-112	yes	13.34
E-GEOD-130148	yes	9.44
E-HCAD-35	yes	8.40
E-GEOD-84465	yes	7.22
E-MTAB-10553	yes	5.89
E-MTAB-7381	no	75.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, FOS, FOXA2, FOXO3, JUN, NFKB, SIRT1, STAT1

miRNA regulators (miRDB)

17 targeting CFH, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-148B-5P	97.29	66.30	992
HSA-MIR-6874-3P	97.29	66.34	975
HSA-MIR-3907	96.76	65.04	662

Literature-anchored findings (GeneRIF, showing 40)

• This paper (PMID 10781834) was the first to describe the detailed structure of the human CFH gene. (PMID:10781834)
• Three SIBLINGs (small integrin-binding ligand, N-linked glycoproteins) enhance factor H’s cofactor activity enabling MCP-like cellular evasion of complement-mediated attack. (PMID:11825898)
• molecular modelling of the C-terminal domains of factor H of human complement: a correlation between haemolytic uraemic syndrome and a predicted heparin binding site (PMID:11851332)
• acts as adrenomedullin binding protein - review (PMID:11921353)
• Recombinant factor H with deletions at the carboxyl-terminal end loses the ability to control the spontaneous activation of the alternative complement pathway on host-like surfaces, a functional defect that leads to acute renal failure in HUS. (PMID:12391176)
• structural and functional characterization of three different factor H proteins purified from the plasma of patients with atypical hemolytic uremic syndrome who carry the factor H mutations W1183L, V1197A, or R1210C (PMID:12424708)
• The site and putative residues on factor H (FH) essential for the interaction of the C-terminal end of FH with C3d, C3b, and heparin have been identified; the heparin- and C3d-binding sites are overlapping. (PMID:12471127)
• two specific binding sites for adrenomedullin were found in factor H (PMID:12630812)
• Screening for factor H gene (FH1) mutations contributes to the classification of atypical haemolytic uraemic syndrome (aHUS). (PMID:12960213)
• promoted entry of Fba(+) group A streptococci into epithelial cells in a dose-dependent manner but did not affect invasion by an isogenic fba mutant (PMID:14638802)
• CFH deficiency my favor acute allograft glomerulopathy. (PMID:14974950)
• Review. Factor H is an essential regulatory protein for complement homeostasis in plasma & for the protection of bystander host cells & tissues from damage by complement activation. Genetic & structural data delineate the functional domains responsible. (PMID:15163532)
• Complement factor H contributes to the control mechanism of in situ complement activation and prevents renal damage in idiopathic membranous nephropathy. (PMID:15331938)
• Human complement regulatory factor H binds to Streptococcal pyogenes M18 surface protein Emm18. (PMID:15557185)
• Binding to platelets is mediated by the C-terminal region of factor H and factor H mutated at the C-terminus exhibited reduces binding (PMID:15634279)
• Factor H is cleaved by a dermatan sulfate-mediated protease identified in blood. (PMID:15749837)
• A novel nucleotide substitution 3254T–>C causing a Ser1061Pro substitution in the short consensus repeat SCR18was found in a girl with hemolytic uremic sundrome. (PMID:15754282)
• a common coding variant, Y402H, that significantly increases the risk for age-related macular degeneration (AMD)with odds ratios between 2.45 and 5.57 was revealed; this common variant likely explains approximately 43% of AMD in older adults (PMID:15761120)
• tested single-nucleotide polymorphisms in CFH for association with age-related macular degeneration (AMD) in two case-control populations; possession of at least one histidine at amino acid position 402 increased the risk of AMD 2.7-fold (PMID:15761121)
• identified a tyrosine-histidine polymorphism in which the histidine variant almost always occurs in the context of the age-related macular degeneration risk haplotype (PMID:15761122)
• there are naturally occurring susceptibility factors in CFH and MCP for the development of atypical haemolytic-uraemic syndrome (PMID:15784724)
• Binding of CFH to endothelial cells is mediated by the carboxy-terminal glycosaminoglycan binding site. (PMID:16192651)
• no association of the complement factor H Y402H gene polymorphism with risk of incident thromboembolic events, nor with baseline levels of C-reactive protein (PMID:16229850)
• Three heparin-binding sites were identified in complement factor H1. (PMID:16263173)
• results suggest that the interaction with pneumococci PspC contributes to pneumococcal virulence. (PMID:16267773)
• Deficiency of and mutations and variations in the complement factor H (CFH) gene are associated with the development of membranoproliferative glomerulonephritis type II. (PMID:16299065)
• Keratinocytes are capable of synthesizing factor H and that this synthesis is regulated by IFN-gamma. (PMID:16310045)
• These results suggest the contribution of the Y402H polymorphism of the CFH gene to exudative AMD susceptibility also in the French population (PMID:16379025)
• Mutations in the complement regulators factor H, membrane cofactor protein (MCP), and factor I are associated with atypical hemolytic uremic syndrome. (PMID:16386793)
• The CFH Y402H variant is strongly associated with both GA(geographic atrophy) and CNV (choroidal neovascularization) in the U.K. population. (PMID:16431947)
• gene conversion is responsible for functionally significant CFH mutations in atypical hemolytic uremic syndrome (PMID:16470555)
• Two different factor H mutations associated with atypical hemolytic uremic syndrome were examined: in one, factor H accumulated in cells, and in the other, membrane binding was reduced. (PMID:16528247)
• three-dimensional solution structure of the C-terminal module pair of factor H (PMID:16533809)
• Four previously found haplotypes and one additional haplotype were found. Haplotype frequencies were significantly different from those in found Americans affected with macular degeneration. Two were risk factors and one was protective. (PMID:16541016)
• CFH gene determines susceptibility to myocardial infarction. HisHis homozygotes had a hazard ratio of 1.77 for myocardial infarction. (PMID:16630992)
• CFH does not appear to be a primary hereditary contributor to age-related macular degeneration {ARMD} in Japanese, and the absence of CFH contribution to ARMD in Japanese may correlate with the findings in ethnic differences of ARMD phenotypes. (PMID:16710702)
• No evidence was found to associate the complement factor H Y402H gene polymorphism with coronary artery disease and atherosclerosis. (PMID:16730735)
• When bound to Neisseria meningitidis, factor H retains its activity as cofactor of alternative complement pathway factor I and contributes to the ability of N. meningitidis to avoid complement-mediated killing in the presence of human serum. (PMID:16751403)
• Results describe age-related macular degeneration (AMD) genetic risk factors through identification of polymorphisms in ERCC6 and in complement factor H. (PMID:16754848)
• Factor H (fH) binds to an approximately 29-kDa outer membrane protein on Neisseria meningitidis identified as GNA1870; binding of down-regulator protein fH correlates with levels of neisserial GNA1870 expression. (PMID:16785547)

Cross-species orthologs

0 orthologs

Paralogs (39): 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), CFB (ENSG00000243649), CFHR1 (ENSG00000244414)

Protein

Protein identifiers

Complement factor H — P08603 (reviewed: P08603)

Alternative names: H factor 1

All UniProt accessions (26): A0A0D9SG88, A0A8Q3SI55, A0A8Q3SI73, A0A8Q3SI76, A0A8Q3SI78, A0A8Q3SI99, A0A8Q3SIB6, A0A8Q3SIC3, A0A8Q3SID7, A0A8Q3SID8, A0A8Q3SIE0, A0A8Q3SIE8, A0A8Q3SJ41, P08603, A0A8Q3WKW2, A0A8Q3WKW3, A0A8Q3WKW6, A0A8Q3WKW7, A0A8Q3WKX0, A0A8Q3WKX4, A0A8Q3WL05, A0A8Q3WLF7, A0A8Q3WLY2, A0A8Q3WM65, A0A8Q3WM71, Q5TFM2

UniProt curated annotations — full annotation on UniProt →

Function. Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. Acts as a soluble inhibitor of complement, where its binding to self markers such as glycan structures prevents complement activation and amplification on cell surfaces. Accelerates the decay of the complement alternative pathway (AP) C3 convertase C3bBb, thus preventing local formation of more C3b, the central player of the complement amplification loop. As a cofactor of the serine protease factor I, CFH also regulates proteolytic degradation of already-deposited C3b. In addition, mediates several cellular responses through interaction with specific receptors. For example, interacts with CR3/ITGAM receptor and thereby mediates the adhesion of human neutrophils to different pathogens. In turn, these pathogens are phagocytosed and destroyed. (Microbial infection) In the mosquito midgut, binds to the surface of parasite P.falciparum gametocytes and protects the parasite from alternative complement pathway-mediated elimination.

Subunit / interactions. Homodimer. Also forms homooligomers. Interacts with complement protein C3b; this interaction inhibits complement activation. Interacts with complement protein C3d. Interacts with CR3/ITGAM; this interaction mediates adhesion of neutrophils to pathogens leading to pathogen clearance. Interacts with complement factor I. (Microbial infection) Interacts with West nile virus non-structural protein 1 (NS1); this interaction leads to the degradation of C3. (Microbial infection) Interacts with C.albicans GPD2; the interaction is direct and leads to the degradation of C3 which enables the pathogen to evade the host innate immune system. (Microbial infection) Interacts with Neisseria meningitidis protein fHbp. (Microbial infection) Interacts with Borrelia burgdorferi outer surface protein E/OspE; this interaction recruits complement regulator factor H onto the bacterial surface to evade complement-mediated cell lysis. (Microbial infection) Interacts with Streptococcus pneumoniae protein virulence factor choline-binding protein A/CbpAN; this interaction enables Streptococcus pneumoniae to evade surveillance by human complement system. (Microbial infection) Interacts with Staphylococcus aureus surface protein serine-aspartate repeat protein E/SdrE; this interaction sequesters CFH on the surface of S.aureus for complement evasion. (Microbial infection) Interacts with Staphylococcus aureus protein Sbi; this interaction inhibits the complement activation of the alternative pathway. (Microbial infection) Interacts (via sushi 4-6 domains) with P.falciparum surface protein PF92; the interaction recruits CFH onto the merozoite surface preventing complement-mediated cell lysis. The interaction does not affect CFH activity. Interacts (via sushi 6-7 domains) with P.falciparum (strain NF54) GAP50; the interaction occurs in the vector mosquito midgut at the surface of the activated parasite gametocytes; the interaction protects the parasite from alternative complement pathway-mediated elimination. (Microbial infection) Interacts (via sushi 4-6 domains) with P.falciparum surface protein PF92; the interaction recruits FHL-1 isoform onto the merozoite surface preventing complement-mediated cell lysis. The interaction does not affect FHL-1 isoform activity. Interacts (via sushi 6-7 domains) with P.falciparum (strain NF54) GAP50; the interaction occurs in the vector mosquito midgut at the surface of the activated parasite gametocytes; the interaction protects the parasite from alternative complement pathway-mediated elimination.

Subcellular location. Secreted.

Tissue specificity. Expressed in the retinal pigment epithelium (at protein level). CFH is one of the most abundant complement components in blood where the liver is the major source of CFH protein in vivo. in addition, CFH is secreted by additional cell types including monocytes, fibroblasts, or endothelial cells.

Post-translational modifications. Sulfated on tyrosine residues. According to a report, Asn-217 is not glycosylated. Another study observed glycosylation at this position.

Disease relevance. Basal laminar drusen (BLD) [MIM:126700] Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch membrane. Basal laminar drusen refers to an early adult-onset drusen phenotype that shows a pattern of uniform small, slightly raised yellow subretinal nodules randomly scattered in the macula. In later stages, these drusen often become more numerous, with clustered groups of drusen scattered throughout the retina. In time these small basal laminar drusen may expand and ultimately lead to a serous pigment epithelial detachment of the macula that may result in vision loss. The gene represented in this entry is involved in disease pathogenesis. Complement factor H deficiency (CFHD) [MIM:609814] A disorder that can manifest as several different phenotypes, including asymptomatic, recurrent bacterial infections, and renal failure. Laboratory features usually include decreased serum levels of factor H, complement component C3, and a decrease in other terminal complement components, indicating activation of the alternative complement pathway. It is associated with a number of renal diseases with variable clinical presentation and progression, including membranoproliferative glomerulonephritis and atypical hemolytic uremic syndrome. The disease is caused by variants affecting the gene represented in this entry. Hemolytic uremic syndrome, atypical, 1 (AHUS1) [MIM:235400] 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. Other genes may play a role in modifying the phenotype. Macular degeneration, age-related, 4 (ARMD4) [MIM:610698] 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 is associated with variants affecting the gene represented in this entry.

Domain organisation. Sushi 1-3 domain represents the minimal unit capable of cofactor activity. The property to discriminate self surfaces from non-self surfaces depends on the C-terminal region made of Sushis 19-20.

Isoforms (2)

UniProt ID	Names	Canonical?
P08603-1	1	yes
P08603-2	2, FHL-1

RefSeq proteins (2): NP_000177, NP_001014975 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR051503	ComplSys_Reg/VirEntry_Med	Family

Pfam: PF00084

UniProt features (255 total): strand 105, sequence variant 59, disulfide bond 40, domain 20, glycosylation site 9, helix 6, mutagenesis site 5, sequence conflict 4, turn 3, splice variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

51 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
1HAQ	SOLUTION SCATTERING	0
3GAU	SOLUTION SCATTERING	0
3GAV	SOLUTION SCATTERING	0
3GAW	SOLUTION SCATTERING	0
4K12	X-RAY DIFFRACTION	1.08
3R62	X-RAY DIFFRACTION	1.52
3KZJ	X-RAY DIFFRACTION	1.65
2G7I	X-RAY DIFFRACTION	1.75
3SW0	X-RAY DIFFRACTION	1.8
6ATG	X-RAY DIFFRACTION	1.8
9MLU	X-RAY DIFFRACTION	1.82
9MMX	X-RAY DIFFRACTION	1.9
3KXV	X-RAY DIFFRACTION	2
3OXU	X-RAY DIFFRACTION	2.1
4ONT	X-RAY DIFFRACTION	2.15
6ZH1	X-RAY DIFFRACTION	2.2
4ZH1	X-RAY DIFFRACTION	2.24
9MMU	X-RAY DIFFRACTION	2.25
2XQW	X-RAY DIFFRACTION	2.31
4AYI	X-RAY DIFFRACTION	2.31
2UWN	X-RAY DIFFRACTION	2.35
2W80	X-RAY DIFFRACTION	2.35
2W81	X-RAY DIFFRACTION	2.35
3RJ3	X-RAY DIFFRACTION	2.35
4AYD	X-RAY DIFFRACTION	2.4
2V8E	X-RAY DIFFRACTION	2.5
7ZJM	X-RAY DIFFRACTION	2.59
7WKI	X-RAY DIFFRACTION	2.6
2WII	X-RAY DIFFRACTION	2.7
4AYE	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08603-F1	78.54	0.01

Antibody-complex structures (SAbDab): 1 — 7WKI

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (40): 21–66, 52–80, 85–129, 114–141, 146–192, 178–205, 210–251, 237–262, 267–309, 294–320, 325–374, 357–385, 389–431, 416–442, 448–494, 477–505, 509–553, 536–564, 569–611, 597–623 …

Glycosylation sites (9): 217, 529, 718, 802, 822, 882, 911, 1029, 1095

Mutagenesis-validated functional residues (5):

Position	Phenotype
337	about 10% loss of heparin-binding.
341	about 20% loss of heparin-binding.
1182	about 50% loss of c3b binding.
1186	about 20% loss of c3b binding.
1188	about 50% loss of c3b binding.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-977606	Regulation of Complement cascade

MSigDB gene sets: 1073 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, VERHAAK_AML_WITH_NPM1_MUTATED_DN, LI_CISPLATIN_RESISTANCE_DN, GOBP_MEMBRANE_DEPOLARIZATION, ZHAN_LATE_DIFFERENTIATION_GENES_UP, MORF_FLT1, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_DN, REACTOME_INNATE_IMMUNE_SYSTEM, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, TSENG_IRS1_TARGETS_UP, MORF_MSH3, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_INFLAMMATORY_RESPONSE, JAEGER_METASTASIS_DN, CHIARETTI_T_ALL_REFRACTORY_TO_THERAPY

GO Biological Process (10): proteolysis (GO:0006508), inflammatory response (GO:0006954), complement activation (GO:0006956), complement activation, alternative pathway (GO:0006957), central nervous system myelination (GO:0022010), regulation of complement activation (GO:0030449), regulation of complement activation, alternative pathway (GO:0030451), regulation of complement-dependent cytotoxicity (GO:1903659), immune system process (GO:0002376), innate immune response (GO:0045087)

GO Molecular Function (5): complement component C3b binding (GO:0001851), heparin binding (GO:0008201), identical protein binding (GO:0042802), heparan sulfate proteoglycan binding (GO:0043395), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), blood microparticle (GO:0072562), symbiont cell surface (GO:0106139), serine-type endopeptidase complex (GO:1905370)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Complement cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
complement activation	2
cellular anatomical structure	2
protein metabolic process	1
defense response	1
immune effector process	1
activation of immune response	1
humoral immune response	1
protein activation cascade	1
innate immune response	1
oligodendrocyte development	1
axon ensheathment in central nervous system	1
myelination	1
regulation of immune effector process	1
regulation of humoral immune response	1
complement activation, alternative pathway	1
regulation of complement activation	1
regulation of innate immune response	1
regulation of cell killing	1
complement-dependent cytotoxicity	1
biological_process	1
immune response	1
defense response to symbiont	1
opsonin binding	1
complement binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
protein binding	1
proteoglycan binding	1
binding	1
extracellular vesicle	1
extracellular region	1
other organism part	1
serine-type peptidase complex	1
endopeptidase complex	1

Protein interactions and networks

STRING

1508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFH	C3	P01024	999
CFH	CFI	P05156	981
CFH	CRP	P02741	970
CFH	C4A	P01028	962
CFH	ARMS2	P0C7Q2	953
CFH	C4A	P01028	947
CFH	APOE	P02649	940
CFH	ERVFRD-1	P60508	938
CFH	ERV3-1	Q14264	938
CFH	ERVW-1	Q9UQF0	937
CFH	VTN	P01141	929
CFH	CFP	P27918	873
CFH	C2	P06681	862
CFH	ADAMTS13	Q76LX8	853
CFH	PLEKHA1	Q9HB21	847

IntAct

192 interactions, top by confidence:

A	B	Type	Score
CFH	CRP	psi-mi:“MI:0407”(direct interaction)	0.980
CRP	CFH	psi-mi:“MI:0915”(physical association)	0.980
CRP	CFH	psi-mi:“MI:0407”(direct interaction)	0.980
CFH	CRP	psi-mi:“MI:0915”(physical association)	0.980

BioGRID (144): CFH (Affinity Capture-MS), CFH (Affinity Capture-MS), KLHL18 (Affinity Capture-MS), MUT (Affinity Capture-MS), CFH (Reconstituted Complex), PRA1 (Reconstituted Complex), CFH (Affinity Capture-MS), CFH (Far Western), CFH (Far Western), CFH (Far Western), CFH (Far Western), C3 (Reconstituted Complex), CFH (Reconstituted Complex), CFH (Reconstituted Complex), CFH (Affinity Capture-MS)

ESM2 similar proteins: O02839, O08569, O19124, O62685, O62837, O88174, P02749, P04003, P05160, P06909, P08174, P08603, P08607, P15529, P16109, P17690, P19070, P20023, P26644, P33703, P36980, P42201, P49457, P70105, P79138, P98109, Q01339, Q02985, Q03472, Q03591, Q07968, Q22328, Q28065, Q28768, Q2VPA4, Q5R4D0, Q60401, Q60736, Q61475, Q61476

Diamond homologs: O62837, P05160, P06909, P08174, P08603, P14650, P15529, P36980, P49457, P68638, P68639, P79138, Q02985, Q03472, Q03591, Q26422, Q28085, Q53EL9, Q5R4D0, Q60401, Q9BXR6, Q01016, Q09101, Q501P1, A0A1D5NSM8, A2AVA0, B3EWY9, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXF5, D3YXG0, D3ZTD8, E9Q6D8, G1FC92, G5ECS8, O08747, O19124, O62685

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
PTX3	“up-regulates activity”	CFH	binding
CFH	“down-regulates activity”	C3	binding
CFH	“down-regulates activity”	CFB	binding
CFH	“down-regulates activity”	CRP	binding
CFH	“up-regulates activity”	CFI	binding
CFHR1	“down-regulates activity”	CFH	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

1599 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	69
Likely pathogenic	47
Uncertain significance	858
Likely benign	318
Benign	62

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1163687	NM_000186.4(CFH):c.3610G>T (p.Gly1204Ter)	Pathogenic
1322067	NM_000186.4(CFH):c.1307G>A (p.Trp436Ter)	Pathogenic
1322068	NM_000186.4(CFH):c.729C>G (p.Tyr243Ter)	Pathogenic
1428739	NM_000186.4(CFH):c.471del (p.Ile157fs)	Pathogenic
1450348	NM_000186.4(CFH):c.1873G>T (p.Glu625Ter)	Pathogenic
1452931	NM_000186.4(CFH):c.1243del (p.Ala415fs)	Pathogenic
1457496	NM_000186.4(CFH):c.1953_1954del (p.His651fs)	Pathogenic
1459758	NM_000186.4(CFH):c.1797_1798delinsGT (p.Gly600Ter)	Pathogenic
16542	NM_000186.4(CFH):c.3643C>G (p.Arg1215Gly)	Pathogenic
16547	NM_000186.4(CFH):c.565G>T (p.Glu189Ter)	Pathogenic
16553	NM_000186.4(CFH):c.2697T>A (p.Tyr899Ter)	Pathogenic
16555	NM_000186.4(CFH):c.668AGA[1] (p.Lys224del)	Pathogenic
16559	NM_000186.4(CFH):c.3514G>T (p.Glu1172Ter)	Pathogenic
16560	NM_000186.4(CFH):c.1222C>T (p.Gln408Ter)	Pathogenic
2017582	NM_000186.4(CFH):c.1352C>G (p.Ser451Ter)	Pathogenic
21089	NC_000001.10:g.(196712876_196712928)_(196797494_196797546)del	Pathogenic
2441817	NM_000186.4(CFH):c.1820del (p.Asn607fs)	Pathogenic
2500782	NC_000001.11:g.196706898_196873196del	Pathogenic
2738506	NM_000186.4(CFH):c.1366G>T (p.Glu456Ter)	Pathogenic
2814347	NM_000186.4(CFH):c.1418_1419insAAGGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAAGAAAAAGC (p.Ala473_Lys474insArgAlaGlyArgGlyGlySerArgLeuTer)	Pathogenic
2847460	NM_000186.4(CFH):c.1390C>T (p.Gln464Ter)	Pathogenic
3234076	NM_000186.4(CFH):c.245-1G>C	Pathogenic
3236385	NM_000186.4(CFH):c.1609del (p.His537fs)	Pathogenic
3249396	NM_000186.4(CFH):c.2303del (p.Lys768fs)	Pathogenic
3249690	NM_000186.4(CFH):c.678_681del (p.Tyr227fs)	Pathogenic
3383230	NM_000186.4(CFH):c.2485dup (p.Tyr829fs)	Pathogenic
4085222	NM_000186.4(CFH):c.882T>A (p.Cys294Ter)	Pathogenic
429034	NM_000186.4(CFH):c.2397del (p.Glu800fs)	Pathogenic
4291295	NM_000186.4(CFH):c.550del (p.Ile184fs)	Pathogenic
4291305	NM_000186.4(CFH):c.593G>A (p.Trp198Ter)	Pathogenic

SpliceAI

4168 predictions. Top by Δscore:

Variant	Effect	Δscore
1:196673960:GGG:G	donor_gain	1.0000
1:196673961:GGG:G	donor_gain	1.0000
1:196685058:TTTCA:T	acceptor_loss	1.0000
1:196685059:TTCAG:T	acceptor_loss	1.0000
1:196685060:TCAGA:T	acceptor_loss	1.0000
1:196685061:CA:C	acceptor_loss	1.0000
1:196685062:A:AG	acceptor_gain	1.0000
1:196685062:AGAA:A	acceptor_loss	1.0000
1:196685063:G:GG	acceptor_gain	1.0000
1:196685063:GA:G	acceptor_gain	1.0000
1:196685063:GAA:G	acceptor_gain	1.0000
1:196685063:GAAA:G	acceptor_gain	1.0000
1:196685063:GAAAA:G	acceptor_gain	1.0000
1:196685233:TACCT:T	donor_gain	1.0000
1:196685234:ACCT:A	donor_gain	1.0000
1:196685234:ACCTG:A	donor_loss	1.0000
1:196685235:CCTGT:C	donor_loss	1.0000
1:196685236:CT:C	donor_gain	1.0000
1:196685236:CTGT:C	donor_loss	1.0000
1:196685238:G:GG	donor_gain	1.0000
1:196685238:GTAAG:G	donor_loss	1.0000
1:196685239:TAA:T	donor_loss	1.0000
1:196689418:A:G	acceptor_gain	1.0000
1:196713734:GAAAC:G	acceptor_gain	1.0000
1:196713913:CATTA:C	donor_gain	1.0000
1:196713914:ATTA:A	donor_gain	1.0000
1:196713915:TTA:T	donor_gain	1.0000
1:196713915:TTAGT:T	donor_loss	1.0000
1:196713916:TA:T	donor_gain	1.0000
1:196713917:AG:A	donor_loss	1.0000

AlphaMissense

8066 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:196676040:G:C	W134C	1.000
1:196676040:G:T	W134C	1.000
1:196673132:G:C	W71C	0.999
1:196673132:G:T	W71C	0.999
1:196676038:T:A	W134R	0.999
1:196676038:T:C	W134R	0.999
1:196742029:G:C	W1037C	0.999
1:196742029:G:T	W1037C	0.999
1:196676018:G:C	R127P	0.998
1:196676023:T:A	C129S	0.998
1:196676024:G:C	C129S	0.998
1:196676059:T:A	C141S	0.998
1:196676060:G:C	C141S	0.998
1:196685215:G:C	W314C	0.998
1:196685215:G:T	W314C	0.998
1:196740770:G:C	W978C	0.998
1:196740770:G:T	W978C	0.998
1:196743606:G:C	W1096C	0.998
1:196743606:G:T	W1096C	0.998
1:196673952:T:A	C114S	0.997
1:196673953:G:C	C114S	0.997
1:196679712:T:A	C237S	0.997
1:196679713:G:C	C237S	0.997
1:196679771:G:C	W256C	0.997
1:196679771:G:T	W256C	0.997
1:196685198:T:A	C309S	0.997
1:196685199:G:C	C309S	0.997
1:196685213:T:A	W314R	0.997
1:196685213:T:C	W314R	0.997
1:196689592:G:C	W379C	0.997

dbSNP variants (sampled 300 via entrez): RS1000006247 (1:196731402 C>A), RS1000015319 (1:196702289 A>C), RS1000028506 (1:196734661 G>C), RS1000046486 (1:196693393 G>A,T), RS1000058459 (1:196727639 A>G), RS1000064326 (1:196659140 T>C), RS1000094823 (1:196659361 G>A), RS1000098520 (1:196651491 A>C), RS1000133321 (1:196651272 G>C,T), RS1000146080 (1:196734260 T>C), RS1000191300 (1:196696112 C>T), RS1000215140 (1:196717771 C>T), RS1000231416 (1:196687321 GACTCTCTGTGGGT>G), RS1000241697 (1:196697345 G>A,C), RS1000278234 (1:196657150 T>G)

Disease associations

OMIM: gene MIM:134370 | disease phenotypes: MIM:126700, MIM:235400, MIM:609814, MIM:610698, MIM:612923, MIM:614809

GenCC curated gene-disease

Disease	Classification	Inheritance
C3 glomerulonephritis	Definitive	Autosomal recessive
basal laminar drusen	Strong	Autosomal dominant
hemolytic uremic syndrome, atypical, susceptibility to, 1	Strong	Autosomal dominant
complement factor H deficiency	Strong	Autosomal recessive
Doyne honeycomb retinal dystrophy	Supportive	Autosomal dominant
dense deposit disease	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
C3 glomerulonephritis	Definitive	AR
atypical hemolytic-uremic syndrome	Definitive	SD

Mondo (20): basal laminar drusen (MONDO:0007472), hemolytic uremic syndrome, atypical, susceptibility to, 1 (MONDO:0009335), complement factor H deficiency (MONDO:0012350), age related macular degeneration 4 (MONDO:0012540), atypical hemolytic-uremic syndrome (MONDO:0016244), thrombotic microangiopathy (MONDO:0019737), atypical hemolytic-uremic syndrome with I factor anomaly (MONDO:0013041), kidney disorder (MONDO:0005240), inherited retinal dystrophy (MONDO:0019118), focal segmental glomerulosclerosis (MONDO:0100313), breast ductal adenocarcinoma (MONDO:0005590), primary ovarian failure (MONDO:0005387), complement 3 glomerulopathy (MONDO:0018013), hereditary hemolytic uremic syndrome (MONDO:0957097), C3 glomerulonephritis (MONDO:0013892)

Orphanet (10): Atypical hemolytic uremic syndrome (Orphanet:2134), Familial drusen (Orphanet:75376), Shiga toxin-associated hemolytic uremic syndrome (Orphanet:90038), Thrombotic microangiopathy (Orphanet:93573), OBSOLETE: Inherited retinal disorder (Orphanet:71862), C3 glomerulopathy (Orphanet:329918), Genetic hemolytic uremic syndrome (Orphanet:576742), C3 glomerulonephritis (Orphanet:329931), OBSOLETE: Atypical hemolytic uremic syndrome with I factor anomaly (Orphanet:93580), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

89 total (30 of 89 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000529	Progressive visual loss
HP:0000572	Visual loss
HP:0000608	Macular degeneration
HP:0000613	Photophobia
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000979	Purpura
HP:0001058	Poor wound healing
HP:0001250	Seizure
HP:0001259	Coma
HP:0001269	Hemiparesis
HP:0001342	Cerebral hemorrhage
HP:0001873	Thrombocytopenia
HP:0001878	Hemolytic anemia
HP:0001919	Acute kidney injury
HP:0001923	Reticulocytosis
HP:0001937	Microangiopathic hemolytic anemia
HP:0001945	Fever
HP:0001981	Schistocytosis
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002018	Nausea
HP:0002027	Abdominal pain
HP:0002202	Pleural effusion
HP:0002315	Headache
HP:0002381	Aphasia
HP:0002615	Hypotension

GWAS associations

79 associations (top):

Study	Trait	p-value
GCST000001_1	Age-related macular degeneration	4.000000e-08
GCST000652_4	Age-related macular degeneration	6.000000e-16
GCST000652_6	Age-related macular degeneration	2.000000e-76
GCST000653_2	Age-related macular degeneration	4.000000e-117
GCST000653_6	Age-related macular degeneration	2.000000e-111
GCST000762_1	Meningococcal disease	5.000000e-13
GCST000806_1	Age-related macular degeneration	3.000000e-64
GCST001009_4	Nephropathy	3.000000e-10
GCST001100_8	Age-related macular degeneration	1.000000e-261
GCST001571_2	Age-related macular degeneration	2.000000e-47
GCST001578_5	Age-related macular degeneration (geographic atrophy)	5.000000e-67
GCST001579_1	Age-related macular degeneration (choroidal neovascularisation)	1.000000e-108
GCST001679_9	Complement C3 and C4 levels	7.000000e-11
GCST001814_3	Age-related macular degeneration	7.000000e-32
GCST001814_9	Age-related macular degeneration	2.000000e-31
GCST001884_12	Age-related macular degeneration	0.000000e+00
GCST001899_1	Age-related macular degeneration	1.000000e-16
GCST001979_1	Circulating myeloperoxidase levels (serum)	5.000000e-41
GCST001986_1	Age-related macular degeneration	1.000000e-31
GCST001987_2	Age-related macular degeneration (extreme sampling)	9.000000e-24
GCST002766_6	Exudative age-related macular degeneration	8.000000e-38
GCST003219_1	Advanced age-related macular degeneration	0.000000e+00
GCST003219_29	Advanced age-related macular degeneration	0.000000e+00
GCST003219_30	Advanced age-related macular degeneration	9.000000e-24
GCST003219_31	Advanced age-related macular degeneration	9.000000e-26
GCST003219_36	Advanced age-related macular degeneration	8.000000e-37
GCST003219_37	Advanced age-related macular degeneration	8.000000e-07
GCST003219_7	Advanced age-related macular degeneration	1.000000e-68
GCST003219_8	Advanced age-related macular degeneration	6.000000e-165
GCST003265_111	Post bronchodilator FEV1/FVC ratio in COPD	6.000000e-07

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:1001492	atrophic macular degeneration
EFO:0004983	complement C3 measurement
EFO:0005243	myeloperoxidase measurement
EFO:0004713	FEV/FVC ratio
EFO:0008336	disease progression measurement
EFO:0008543	c3d:C3 ratio
EFO:0009281	choroidal thickness measurement
EFO:0009363	chronic central serous retinopathy
EFO:0008097	complement factor H measurement
EFO:0010742	protein binding measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0600055	complement factor H-related protein 2 measurement
EFO:0600056	complement factor H-related protein 3 measurement
EFO:0600057	complement factor H-related protein 4A measurement
EFO:0008098	complement factor H-related protein 5 measurement
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (13)

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
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D015432	Glomerulonephritis, Membranoproliferative	C12.050.351.968.419.570.363.615; C12.200.777.419.570.363.615; C12.950.419.570.363.615; C20.425
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
D007676	Kidney Failure, Chronic	C12.050.351.968.419.780.750.500; C12.200.777.419.780.750.500; C12.950.419.780.750.500; C23.550.291.500.906.500
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D058499	Retinal Dystrophies	C11.768.585.658
D057049	Thrombotic Microangiopathies	C15.378.140.855.925; C15.378.243.937.925
C563034	Basal Laminar Drusen (supp.)
C562875	Complement Factor H Deficiency (supp.)
C565196	Macular Degeneration, Age-Related, 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4629 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

4 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1061170	Dosage	3	bevacizumab	Macular Degeneration
rs1061170	Efficacy	4	Photodynamic therapy	Macular Degeneration
rs1061170	Efficacy	4	bevacizumab;ranibizumab	Macular Degeneration
rs800292	Efficacy	3	bevacizumab

PharmGKB variants

8 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs800292	CFH	3	2.50	1	bevacizumab
rs1061170	CFH	3	1.75	3	bevacizumab;bevacizumab;ranibizumab;Photodynamic therapy
rs1329424	CFH		0.00	0
rs1329428	CFH		0.00	0
rs1410996	CFH		0.00	0
rs3753394	CFH		0.00	0
rs10737680	CFH		0.00	0
rs10801555	CFH		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	4
Air Pollutants	decreases expression, increases abundance	4
Cyclosporine	affects cotreatment, affects expression, decreases expression	4
Acetaminophen	decreases expression, increases expression	2
Progesterone	increases expression	2
Silicon Dioxide	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
sotorasib	affects cotreatment, increases expression	1
2,4,6-tribromophenol	increases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
arsenite	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	increases expression	1
zinc chromate	increases abundance, increases expression	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
S-1,2-dichlorovinyl-N-acetylcysteine	increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
abrine	decreases expression	1
quinocetone	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
jinfukang	increases expression, decreases expression, affects cotreatment	1
incobotulinumtoxinA	increases expression	1
trametinib	increases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Olanzapine	decreases phosphorylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL666763	Binding	In vitro activity against human Complement factor I	Discovery of 1-[3-(aminomethyl)phenyl]-N-3-fluoro-2’-(methylsulfonyl)-[1,1’-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide (DPC423), a highly potent, selective, and orally bioavailable inhibitor of blood coagulation factor Xa. — J Med Chem

Cellosaurus cell lines

19 cell lines: 17 induced pluripotent stem cell, 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A2YF	SCTCi011-A	Induced pluripotent stem cell	Female
CVCL_A2YG	SCTCi012-A	Induced pluripotent stem cell	Male
CVCL_A2YH	SCTCi013-A	Induced pluripotent stem cell	Male
CVCL_B2MC	Abcam A-549 CFH KO	Cancer cell line	Male
CVCL_B4IK	iChEC-1	Transformed cell line	Female
CVCL_IT85	UNEWi022-A	Induced pluripotent stem cell	Male
CVCL_IT86	UNEWi022-B	Induced pluripotent stem cell	Male
CVCL_IT87	UNEWi022-C	Induced pluripotent stem cell	Male
CVCL_IT91	UNEWi024-A	Induced pluripotent stem cell	Male
CVCL_IT92	UNEWi024-B	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

314 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