C5

Summary

C5 (complement C5, HGNC:1331) is a protein-coding gene on chromosome 9q33.2, encoding Complement C5 (P01031). Precursor of the C5a anaphylatoxin and complement C5b components of the complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system.

This gene encodes a component of the complement system, a part of the innate immune system that plays an important role in inflammation, host homeostasis, and host defense against pathogens. The encoded preproprotein is proteolytically processed to generate multiple protein products, including the C5 alpha chain, C5 beta chain, C5a anaphylatoxin and C5b. The C5 protein is comprised of the C5 alpha and beta chains, which are linked by a disulfide bridge. Cleavage of the alpha chain by a convertase enzyme results in the formation of the C5a anaphylatoxin, which possesses potent spasmogenic and chemotactic activity, and the C5b macromolecular cleavage product, a subunit of the membrane attack complex (MAC). Mutations in this gene cause complement component 5 deficiency, a disease characterized by recurrent bacterial infections. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 727 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complement component 5 deficiency (Strong, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 922 total — 37 pathogenic, 20 likely-pathogenic
• Phenotypes (HPO): 7
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001735

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1331
Approved symbol	C5
Name	complement C5
Location	9q33.2
Locus type	gene with protein product
Status	Approved
Aliases	CPAMD4, C5a, C5b
Ensembl gene	ENSG00000106804
Ensembl biotype	protein_coding
OMIM	120900
Entrez	727

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 5 protein_coding, 4 protein_coding_CDS_not_defined, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000223642, ENST00000460578, ENST00000466280, ENST00000480188, ENST00000489802, ENST00000696279, ENST00000696280, ENST00000696281, ENST00000696284, ENST00000696285, ENST00000697921, ENST00000697922, ENST00000697923, ENST00000867873, ENST00000867874

RefSeq mRNA: 2 — MANE Select: NM_001735 NM_001317163, NM_001735

CCDS: CCDS6826, CCDS94473

Canonical transcript exons

ENST00000223642 — 41 exons

Exon	Start	End
ENSE00000724289	120953730	120953868
ENSE00000724290	120957285	120957368
ENSE00000724295	120962671	120962776
ENSE00000724298	120962893	120962967
ENSE00000724299	120963636	120963738
ENSE00000724301	120969061	120969118
ENSE00000724304	120970170	120970251
ENSE00000724308	120971930	120971992
ENSE00000724311	120974779	120974931
ENSE00000724312	120976700	120976905
ENSE00000724315	120981844	120981939
ENSE00000724317	120982655	120982814
ENSE00000724320	120989046	120989121
ENSE00000724322	120989568	120989780
ENSE00000724325	120991191	120991280
ENSE00000724327	120996240	120996300
ENSE00000724329	120997547	120997774
ENSE00000724335	121006904	121006977
ENSE00000724339	121008408	121008498
ENSE00000724343	121013873	121014070
ENSE00000724347	121015199	121015261
ENSE00000724350	121016254	121016383
ENSE00000724353	121017362	121017511
ENSE00000724356	121017643	121017852
ENSE00000724358	121019976	121020179
ENSE00000724360	121021509	121021694
ENSE00000724364	121025454	121025580
ENSE00000724378	121034803	121034894
ENSE00000724383	121037881	121037951
ENSE00000724389	121043004	121043166
ENSE00000724393	121046191	121046383
ENSE00000806455	121023404	121023519
ENSE00000806456	121050182	121050275
ENSE00003480806	121027160	121027274
ENSE00003507217	120980083	120980254
ENSE00003520664	120960248	120960337
ENSE00003562136	121005919	121006058
ENSE00003586038	120961482	120961565
ENSE00003586902	121032113	121032195
ENSE00003647666	121030397	121030487
ENSE00003972393	120952335	120952868

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 98.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.8028 / max 1066.5413, expressed in 1073 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102333	2.9903	90
102334	1.8125	1042

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.60	gold quality
liver	UBERON:0002107	98.52	gold quality
oocyte	CL:0000023	91.12	gold quality
body of pancreas	UBERON:0001150	89.26	gold quality
secondary oocyte	CL:0000655	87.88	gold quality
calcaneal tendon	UBERON:0003701	86.02	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.46	gold quality
tibial nerve	UBERON:0001323	82.88	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.60	gold quality
pancreas	UBERON:0001264	82.37	gold quality
descending thoracic aorta	UBERON:0002345	82.08	gold quality
ventricular zone	UBERON:0003053	81.59	gold quality
left coronary artery	UBERON:0001626	80.28	gold quality
popliteal artery	UBERON:0002250	80.06	gold quality
tibial artery	UBERON:0007610	80.05	gold quality
body of stomach	UBERON:0001161	79.81	gold quality
lower lobe of lung	UBERON:0008949	79.31	silver quality
aorta	UBERON:0000947	79.26	gold quality
coronary artery	UBERON:0001621	79.18	gold quality
jejunal mucosa	UBERON:0000399	79.14	gold quality
right coronary artery	UBERON:0001625	79.09	gold quality
stomach	UBERON:0000945	78.51	gold quality
thoracic aorta	UBERON:0001515	78.42	gold quality
right lung	UBERON:0002167	78.24	gold quality
ascending aorta	UBERON:0001496	78.13	gold quality
lung	UBERON:0002048	77.13	gold quality
fundus of stomach	UBERON:0001160	77.08	gold quality
left ovary	UBERON:0002119	76.30	gold quality
right ovary	UBERON:0002118	75.97	gold quality
upper lobe of lung	UBERON:0008948	75.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.50

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, JUN

miRNA regulators (miRDB)

38 targeting C5, 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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-4464	98.95	67.73	820
HSA-MIR-4748	98.95	67.53	810
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-4290	98.51	65.17	907

Literature-anchored findings (GeneRIF, showing 40)

• function in regulating the inhibitory/activating FcgammaRII/III receptor pair to connect complement and FcgammaR effector pathways in immune inflammation (PMID:12488432)
• Specific inhibition of the C5a moiety of C5 before cleavage prohibited CR3 up-regulation, phagocytosis, and oxidative burst but had no effect on C5b-9 (TCC) formation, lysis, and bacterial killing. (PMID:12881318)
• Absence of C5 resulted in fiber loss and extensive scarring, whereas presence of C5-favored axonal survival and more efficient remyelination. (PMID:12937147)
• HMG-CoA inhibition with cerivastatin reduced vascular smooth muscle cells proliferation and C5b-9-induced ERK1/2 activation (PMID:14556080)
• Expressed in a bacterial system, a recombinant C5 segment of C345C module has substantial beta-sheet structure and internal disulfide bonds, and binds to complement components C6 and C7 with dissociation constants of 10 and 3 nM, respectively. (PMID:14662858)
• A model is suggested for an irreversible membrane attack complex assembly in which the complement 7 factor I modules, but not those in complement 6, are bound to the C345C (netrin receptor) domain of complement 5 within the fully assembled complex. (PMID:15383587)
• first report of a whole molecular characterization of C5 deficiency found homozygosity for a double mutation in the exon 40 of the C5 gene, leading to a premature stop codon (PMID:15488949)
• analysis of binding mode for C5a to the C5aR (PMID:15550394)
• C5a is a key mediator of meconium-induced neutrophil activation (PMID:15585680)
• analysis of multifunctional C345C domain of C5 of complement (PMID:15598652)
• The interaction between the C345C domain at the C terminus of the C5 alpha-chain and the factor I domain of C7 plays an essential role in complement membrane attack complex formation and complement lytic activity. (PMID:15879120)
• C5b-9 regulation of the cell cycle activation in aortic endothelial cells through Akt pathway is dependent on inactivation of FOXO1 (PMID:16670089)
• C3a is acutely elevated after human ischemic stroke, C5a shows delayed elevations 7 to 14 days after cerebral ischemia, and sC5b-9 is acutely depressed after stroke. (Complement 3a, c5a, and C5b-9) (PMID:16823297)
• C5a and its receptor have roles in PAI-1 production (PMID:16879222)
• analysis of the structural constraint for C5a docking with the complement factor 5a (C5a) receptor N terminus (PMID:17023413)
• data indicate that C5L2 can function as a positive modulator for both C5a- and C3a-anaphylatoxin-induced responses (PMID:17322907)
• C5 gene variants and Gc-globulin levels co-define the proinflammatory and profibrogenic effects of C5 in patients at-risk for progression of liver fibrosis (PMID:17428459)
• Impairment of the mechanisms involved in the regulation of activation of complement system factors C5b-9 may be important in the pathogenesis of endometriosis and endometriosis-associated infertility. (PMID:17482181)
• in stenotic aortic valves, complement is activated leading to generation of the anaphylatoxin C5a (PMID:17498719)
• in peripheral blood mononuclear cells, C5a activates the p38 cascade, and this pathway plays a major role in the C5a enhancement of LPS-induced IL-6 and TNF-alpha production (PMID:17505301)
• the amount of C5b-9-AF488 bound to K562 cells after complement activation was highly heterogeneous and inversely correlated with the CD59 level of expression (PMID:17644516)
• A polymorphism in the TRAF1/C5 region produces an increased genetic risk in susceptibility to and severity of rheumatoid arthritis. (PMID:17880261)
• C3a and C5a can bring about eosinophil extravasation and increase in vascular permeability that facilitates eosinophil accumulation at sites of allergic inflammation. (PMID:18039528)
• Glomerular TGF-beta1 may induce tubular expression of C5b-9. Increased tubular C5b-9 expression may result in interstitial fibrosis through increased TGF-beta1 production. (PMID:18300128)
• PLCbeta3 may provide a selective target for inhibiting Ca(2+) responses to mediators of inflammation, including C5a, UDP, PAF, and LPA (PMID:18411281)
• TRAF1-C5 locus genetic variant SNP rs3761847 is associated with juvenile idiopathic arthritis (PMID:18576341)
• There is no evidence that these C5 single nucleotide polymorphisms are genetic risk factors for the development of advanced fibrosis in chronic HCV infection or other chronic liver diseases. (PMID:18644651)
• release of C5a from human C5 by a serine protease (ASP) of Aeromonas sobria that induced neutrophil migration (PMID:18714034)
• Anaphylatoxin C5a may be involved in the pathogenesis of COPD. (PMID:18953960)
• The risk of death in rheumatoid arthritis is increased in TRAF1/C5 rs3761847 GG homozygotes (PMID:19116907)
• Cell cycle induction by C5b-9 in aortic endothelial cells is RGC-32 dependent and this is in part through regulation of Akt and growth factor release. (PMID:19162005)
• Glomerular deposition of C5b-9 may participate in the development of glomerulosclerosis in primary immunoglobulin A nephropathy. (PMID:19230171)
• In mesenchymal stem cells both C3a and C5a cause prolonged and robust extracellular signal-regulated kinase (ERK)1/2 and proto-oncogene protein c-akt (Akt) kinase phosphorylation. (PMID:19265162)
• C5a recapitulates impaired peripheral blood neutrophil phagocytosis and significantly down-regulates neutrophil CD88 (complement component 5a receptor) expression in vitro (PMID:19324972)
• The absence of component C5 in the serum of 3 siblings from a Brazilian family with history of consanguinity, was observed. (PMID:19375167)
• The characterization of these new mutations is interesting in order to elucidate structure-function relationships in the C5 gene and it also helps to understand the molecular basis of this uncommon deficiency. (PMID:19414197)
• Robust generation of both C3a and C5a by either the alternative pathway or classical pathway alone were observed with both mouse and human sera, after adherent IgG-induced complement activation. (PMID:19843088)
• Complement C5b-9 induce a JNK/Bid-dependent and JNK-independent necrotic cell death. (PMID:19864026)
• The tagging SNP rs17611 of the C5 gene and smoking may be associated with periodontitis among the Hong Kong Chinese population. (PMID:19909405)
• Results showed no influence of rs10818488 and rs2900180 TRAF1/C5 gene polymorphisms in susceptibility to and clinical expression of giant cell arteritis. (PMID:19918040)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	c5	ENSDARG00000021004
mus_musculus	Hc	ENSMUSG00000026874
mus_musculus	AI182371	ENSMUSG00000035875
rattus_norvegicus	C5	ENSRNOG00000018899
rattus_norvegicus	C5l1	ENSRNOG00000022033
drosophila_melanogaster	Tep4	FBGN0041180
drosophila_melanogaster	Tep3	FBGN0041181
drosophila_melanogaster	Tep2	FBGN0041182
drosophila_melanogaster	Tep1	FBGN0041183
caenorhabditis_elegans	tep-1	WBGENE00013969

Paralogs (8): C3 (ENSG00000125730), PZP (ENSG00000126838), CD109 (ENSG00000156535), CPAMD8 (ENSG00000160111), A2ML1 (ENSG00000166535), A2M (ENSG00000175899), C4B (ENSG00000224389), C4A (ENSG00000244731)

Protein

Protein identifiers

Complement C5 — P01031 (reviewed: P01031)

Alternative names: C3 and PZP-like alpha-2-macroglobulin domain-containing protein 4

All UniProt accessions (5): P01031, A0A8Q3SID6, A0A8Q3SIH6, A0A8V8TMU5, A0A8V8TN26

UniProt curated annotations — full annotation on UniProt →

Function. Precursor of the C5a anaphylatoxin and complement C5b components of the complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system. Activated downstream of classical, alternative, lectin and GZMK complement pathways. Component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane rupture and cell lysis. Complement C5b is generated following cleavage by C5 convertase and initiates formation of the MAC complex: C5b binds sequentially C6, C7, C8 and multiple copies of the pore-forming subunit C9. During MAC complex assembly, the C5b6 subcomplex, composed of complement C5b and C6, associates with the outer leaflet of target cell membrane, reducing the energy for membrane bending. Mediator of local inflammatory process released following cleavage by C5 convertase. Acts by binding to its receptor (C5AR1 or C5AR2), activating G protein-coupled receptor signaling and inducing a variety of responses including intracellular calcium release, contraction of smooth muscle, increased vascular permeability, and histamine release from mast cells and basophilic leukocytes. C5a is also a potent chemokine which stimulates the locomotion of polymorphonuclear leukocytes and directs their migration toward sites of inflammation.

Subunit / interactions. In absence of complement activation, the C5 precursor is first processed by the removal of 4 basic residues, forming two chains, beta and alpha, linked by a disulfide bond. Complement C5b is composed of complement C5b and complement C5 beta chains that are associated via disulfide bonds. Component of the membrane attack complex (MAC), composed of complement C5b, C6, C7, C8A, C8B, C8G and multiple copies of the pore-forming subunit C9. Interacts with the tick complement inhibitors OmCI, RaCI1 and CirpT1. Interacts with cobra venom factor (CVF). (Microbial infection) Interacts with Staphylococcus aureus protein SSL5.

Subcellular location. Secreted Secreted. Target cell membrane Secreted.

Post-translational modifications. C5 precursor is first processed by the removal of 4 basic residues, forming two chains, beta and alpha, linked by a disulfide bond. During activation of the complement systems, the alpha chain is cleaved into C5a and C5b by the C5 convertase: C5b stays linked to the beta chain, while C5a is released in the plasma. The alpha chain is cleaved by the serine protease complement C2b component of the C5 convertase to generate C5a and C5b following activation by the classical, lectin and GZMK complement systems. The alpha chain is cleaved by CFB component of the C5 convertase to generate C5a and C5b following activation by the alternative complement system.

Disease relevance. Complement component 5 deficiency (C5D) [MIM:609536] A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. The disease is caused by variants affecting the gene represented in this entry. An association study of C5 haplotypes and genotypes in individuals with chronic hepatitis C virus infection shows that individuals homozygous for the C5_1 haplotype have a significantly higher stage of liver fibrosis than individuals carrying at least 1 other allele.

Activity regulation. Membrane attack complex (MAC) assembly is inhibited by CD59, thereby protecting self-cells from damage during complement activation. MAC assembly is also inhibited by clusterin (CLU) chaperones that inhibit polymerization of C9.

Polymorphism. C5 variants are responsible for poor response to eculizumab [MIM:615749]. Eculizumab is a monoclonal antibody highly effective in reducing intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria. It specifically binds to the terminal complement protein C5, inhibits its cleavage into C5a and C5b, and prevents the formations of the cytolytic complement pore.

RefSeq proteins (2): NP_001304092, NP_001726* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000020	Anaphylatoxin/fibulin	Domain
IPR001134	Netrin_domain	Domain
IPR001599	Macroglobln_a2	Domain
IPR001840	Anaphylatoxn_comp_syst_dom	Domain
IPR002890	MG2	Domain
IPR008930	Terpenoid_cyclase/PrenylTrfase	Homologous_superfamily
IPR008993	TIMP-like_OB-fold	Homologous_superfamily
IPR009048	A-macroglobulin_rcpt-bd	Domain
IPR011625	A2M_N_BRD	Domain
IPR011626	Alpha-macroglobulin_TED	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR018081	Anaphylatoxin_comp_syst	Homologous_superfamily
IPR018933	Netrin_module_non-TIMP	Domain
IPR036595	A-macroglobulin_rcpt-bd_sf	Homologous_superfamily
IPR040839	MG4	Domain
IPR041425	C3/4/5_MG1	Domain
IPR041555	MG3	Domain
IPR048843	C5_CUB	Domain
IPR050473	A2M/Complement_sys	Family

Pfam: PF00207, PF01759, PF01821, PF01835, PF07677, PF07678, PF07703, PF17789, PF17790, PF17791, PF21309

Enzyme classification (BRENDA):

• EC 3.4.21.43 — classical-complement-pathway C3/C5 convertase (BRENDA: 4 organisms, 27 substrates, 36 inhibitors, 6 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
COMPLEMENT COMPONENT C5	—	4

UniProt features (219 total): strand 120, helix 33, sequence variant 20, turn 17, disulfide bond 14, chain 4, glycosylation site 4, domain 2, region of interest 2, signal peptide 1, site 1, propeptide 1

Structure

Experimental structures (PDB)

42 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9Y6C	X-RAY DIFFRACTION	2
5B71	X-RAY DIFFRACTION	2.11
4UU9	X-RAY DIFFRACTION	2.12
7AD7	X-RAY DIFFRACTION	2.3
5B4P	X-RAY DIFFRACTION	2.4
4P39	X-RAY DIFFRACTION	2.4
7OP0	X-RAY DIFFRACTION	2.57
3HQA	X-RAY DIFFRACTION	2.59
5HCC	X-RAY DIFFRACTION	2.59
6RPT	X-RAY DIFFRACTION	2.7
7AD6	X-RAY DIFFRACTION	2.75
7Y64	ELECTRON MICROSCOPY	2.9
5HCD	X-RAY DIFFRACTION	2.98
8B0F	ELECTRON MICROSCOPY	3
8HK5	ELECTRON MICROSCOPY	3
3CU7	X-RAY DIFFRACTION	3.1
9KX6	ELECTRON MICROSCOPY	3.11
5HCE	X-RAY DIFFRACTION	3.12
8IA2	ELECTRON MICROSCOPY	3.21
7NYD	ELECTRON MICROSCOPY	3.27
3HQB	X-RAY DIFFRACTION	3.3
8B0G	ELECTRON MICROSCOPY	3.3
8B0H	ELECTRON MICROSCOPY	3.3
8JZZ	ELECTRON MICROSCOPY	3.31
8AYH	ELECTRON MICROSCOPY	3.35
4A5W	X-RAY DIFFRACTION	3.5
6RQJ	ELECTRON MICROSCOPY	3.5
7NYC	ELECTRON MICROSCOPY	3.54
3KLS	X-RAY DIFFRACTION	3.6
8CML	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01031-F1	81.67	0.25

Antibody-complex structures (SAbDab): 10 — 4UU9, 5B71, 5I5K, 7Y64, 8CML, 8COE, 8HQC, 8IA2, 8JZZ, 9KX6

Functional residue map

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

Catalytic / active sites (1): 751–752 (cleavage; by c5 convertase)

Disulfide bonds (14): 567–810, 634–669, 698–724, 699–731, 711–732, 856–883, 866–1527, 1101–1159, 1375–1505, 1405–1474, 1520–1525, 1532–1606, 1553–1676, 1654–1657

Glycosylation sites (4): 741, 911, 1115, 1630

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-166665	Terminal pathway of complement
R-HSA-174577	Activation of C3 and C5
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-418594	G alpha (i) signalling events
R-HSA-977606	Regulation of Complement cascade

MSigDB gene sets: 254 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, HNF3ALPHA_Q6, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, HNF1_Q6, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_REGULATION_OF_MONONUCLEAR_CELL_MIGRATION, GOBP_B_CELL_MEDIATED_IMMUNITY, GOBP_TAXIS

GO Biological Process (18): chemotaxis (GO:0006935), inflammatory response (GO:0006954), complement activation, alternative pathway (GO:0006957), complement activation, classical pathway (GO:0006958), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of vascular endothelial growth factor production (GO:0010575), negative regulation of macrophage chemotaxis (GO:0010760), killing of cells of another organism (GO:0031640), positive regulation of chemokine production (GO:0032722), complement activation, GZMK pathway (GO:0160257), immune system process (GO:0002376), regulation of immune system process (GO:0002682), complement activation (GO:0006956), cell migration (GO:0016477), innate immune response (GO:0045087), regulation of chemotaxis (GO:0050920), cell chemotaxis (GO:0060326)

GO Molecular Function (5): endopeptidase inhibitor activity (GO:0004866), signaling receptor binding (GO:0005102), chemokine activity (GO:0008009), G protein-coupled receptor binding (GO:0001664), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), membrane attack complex (GO:0005579), obsolete extracellular space (GO:0005615), other organism cell membrane (GO:0044218), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Complement cascade	3
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
complement activation	3
innate immune response	2
signal transduction	2
positive regulation of cytokine production	2
chemotaxis	2
cellular anatomical structure	2
response to chemical	1
taxis	1
defense response	1
humoral immune response mediated by circulating immunoglobulin	1
G protein-coupled receptor activity	1
vascular endothelial growth factor production	1
regulation of vascular endothelial growth factor production	1
negative regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
negative regulation of macrophage migration	1
cell killing	1
disruption of cell in another organism	1
chemokine production	1
regulation of chemokine production	1
biological_process	1
immune system process	1
regulation of biological process	1
immune effector process	1
activation of immune response	1
humoral immune response	1
protein activation cascade	1
cell motility	1
immune response	1
defense response to symbiont	1
regulation of response to external stimulus	1
regulation of locomotion	1
cell migration	1
cellular response to chemical stimulus	1
endopeptidase activity	1
peptidase inhibitor activity	1
endopeptidase regulator activity	1
protein binding	1
cytokine activity	1

Protein interactions and networks

STRING

1230 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C5	C5AR1	P21730	998
C5	C5AR2	Q9P296	968
C5	C8A	P07357	909
C5	CFH	P08603	811
C5	C3AR1	Q16581	758
C5	C9	P02748	752
C5	VTN	P01141	740
C5	TRAF1	Q13077	694
C5	C7	P10643	687
C5	C8B	P07358	671
C5	C3	P01024	635
C5	CPB2	Q96IY4	569
C5	HP	P00737	563
C5	CFB	P00751	554
C5	PLG	P00747	553

IntAct

64 interactions, top by confidence:

A	B	Type	Score
CFHR1	C5	psi-mi:“MI:0407”(direct interaction)	0.610
C5	CFHR1	psi-mi:“MI:0915”(physical association)	0.610
C5	CFHR1	psi-mi:“MI:0407”(direct interaction)	0.610
CREB3L1	C5	psi-mi:“MI:0915”(physical association)	0.560
C5	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
C5	EBP	psi-mi:“MI:0915”(physical association)	0.560
C5	AQP6	psi-mi:“MI:0915”(physical association)	0.560
C5	SSMEM1	psi-mi:“MI:0915”(physical association)	0.560
C5	ANKS6	psi-mi:“MI:0915”(physical association)	0.560
C5	KIR3DL3	psi-mi:“MI:0915”(physical association)	0.560
C5	KEL	psi-mi:“MI:0915”(physical association)	0.560
PGRMC2	C5	psi-mi:“MI:0915”(physical association)	0.560
	C5	psi-mi:“MI:0915”(physical association)	0.560
NEMP1	C5	psi-mi:“MI:0915”(physical association)	0.560
C5	POU6F2	psi-mi:“MI:0915”(physical association)	0.560
C5	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
C5	MMGT1	psi-mi:“MI:0915”(physical association)	0.560
C5	C9	psi-mi:“MI:0915”(physical association)	0.550

BioGRID (43): CREB3L1 (Two-hybrid), C5 (Two-hybrid), C5 (Affinity Capture-MS), C5 (Synthetic Lethality), C5 (Two-hybrid), C5 (Two-hybrid), C5 (Two-hybrid), EBP (Two-hybrid), PGRMC2 (Two-hybrid), SSMEM1 (Two-hybrid), ANKS6 (Two-hybrid), CPLX4 (Two-hybrid), TMEM194A (Two-hybrid), MMGT1 (Two-hybrid), KEL (Two-hybrid)

ESM2 similar proteins: A0AAQ4VMX2, A0M8R7, A1X150, I2C090, O02668, P01029, P01030, P01031, P06238, P06684, P08581, P08649, P08650, P0C0L4, P0C0L5, P14046, P16056, P19069, P19823, P28665, P28666, P79263, P97523, P98093, P98094, Q00685, Q03626, Q07DY1, Q07DZ1, Q07E48, Q09YN5, Q108U6, Q14624, Q2IBA6, Q2IBC0, Q2IBD8, Q2IBF2, Q2IBG7, Q2QL89, Q2QLA9

Diamond homologs: P01031, P01032, P06684, P08650, P12082, A0RZC6, P12387, Q01833, Q0ZZJ6, Q2UVX4, Q91132, Q6ZMU1, J3S836, P01027

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
C5	up-regulates	C5AR2	binding
C5	“up-regulates activity”	C5AR1	binding
“C5 convertase complex (C3bBbC3b)”	“up-regulates activity”	C5	cleavage
C5	“form complex”	“Membrane attack complex”	binding
“C5 convertase complex”	“up-regulates activity”	C5	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	37
Likely pathogenic	20
Uncertain significance	380
Likely benign	392
Benign	26

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1350897	NM_001735.3(C5):c.3441del (p.Phe1147fs)	Pathogenic
1382437	NM_001735.3(C5):c.555del (p.Pro186fs)	Pathogenic
1452358	NM_001735.3(C5):c.1180_1183del (p.Thr394fs)	Pathogenic
1459009	NM_001735.3(C5):c.68dup (p.Tyr23Ter)	Pathogenic
1460355	NC_000009.11:g.(?123783767)(123785817_?)del	Pathogenic
17050	NM_001735.3(C5):c.55C>T (p.Gln19Ter)	Pathogenic
17051	NM_001735.3(C5):c.4426C>T (p.Arg1476Ter)	Pathogenic
17052	NM_001735.3(C5):c.4872_4873delinsG (p.Leu1625fs)	Pathogenic
17053	NM_001735.3(C5):c.1115A>G (p.Lys372Arg)	Pathogenic
1976954	NM_001735.3(C5):c.1786del (p.Met596fs)	Pathogenic
2002442	NM_001735.3(C5):c.1525del (p.Ile509fs)	Pathogenic
2041097	NM_001735.3(C5):c.3364del (p.Ser1122fs)	Pathogenic
2414298	NM_001735.3(C5):c.2782C>T (p.Arg928Ter)	Pathogenic
2785872	NM_001735.3(C5):c.52G>T (p.Gly18Ter)	Pathogenic
2789468	NM_001735.3(C5):c.4237del (p.Glu1413fs)	Pathogenic
2828257	NM_001735.3(C5):c.181_182insGATATGAGATGAAGGTCTGAACTAAGTAGCAGTGGGGATGGAGAGCTGGGGAAAGATGTGAGACATTCCTGAGGGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAAGTTATCCTG (p.Asp61delinsGlyTyrGluMetLysValTer)	Pathogenic
2847186	NM_001735.3(C5):c.2894T>G (p.Leu965Ter)	Pathogenic
2974114	NM_001735.3(C5):c.3482del (p.Leu1161fs)	Pathogenic
2983119	NM_001735.3(C5):c.1680G>A (p.Trp560Ter)	Pathogenic
2987179	NM_001735.3(C5):c.526G>T (p.Glu176Ter)	Pathogenic
2990559	NM_001735.3(C5):c.3059_3060del (p.Tyr1020fs)	Pathogenic
3245305	NC_000009.11:g.(?123768177)(123770796_?)del	Pathogenic
3245307	NC_000009.11:g.(?123742341)(123745112_?)del	Pathogenic
3616531	NM_001735.3(C5):c.2503C>T (p.Arg835Ter)	Pathogenic
3673804	NM_001735.3(C5):c.3412C>T (p.Arg1138Ter)	Pathogenic
3677715	NM_001735.3(C5):c.2140C>T (p.Arg714Ter)	Pathogenic
3724723	NM_001735.3(C5):c.3177C>A (p.Tyr1059Ter)	Pathogenic
3728570	NM_001735.3(C5):c.4510_4511del (p.Gln1504fs)	Pathogenic
4532110	NM_001735.3(C5):c.3610C>T (p.Gln1204Ter)	Pathogenic
4709688	NM_001735.3(C5):c.892C>T (p.Gln298Ter)	Pathogenic

SpliceAI

5975 predictions. Top by Δscore:

Variant	Effect	Δscore
9:120957365:TAAG:T	acceptor_gain	1.0000
9:120957369:C:CC	acceptor_gain	1.0000
9:120960343:T:TC	acceptor_gain	1.0000
9:120960345:T:TC	acceptor_gain	1.0000
9:120960347:G:GC	acceptor_gain	1.0000
9:120962886:AGCTT:A	donor_loss	1.0000
9:120962887:GCTTA:G	donor_loss	1.0000
9:120962888:CTTAC:C	donor_loss	1.0000
9:120962889:TTACC:T	donor_loss	1.0000
9:120962890:TA:T	donor_loss	1.0000
9:120962891:A:AC	donor_gain	1.0000
9:120962891:A:AG	donor_loss	1.0000
9:120962892:C:CC	donor_gain	1.0000
9:120962964:CAAG:C	acceptor_gain	1.0000
9:120962965:AAG:A	acceptor_gain	1.0000
9:120962965:AAGC:A	acceptor_loss	1.0000
9:120962966:AG:A	acceptor_gain	1.0000
9:120962968:C:CC	acceptor_gain	1.0000
9:120962968:C:T	acceptor_loss	1.0000
9:120963632:ATACG:A	donor_loss	1.0000
9:120963634:A:AC	donor_gain	1.0000
9:120963634:AC:A	donor_loss	1.0000
9:120963635:C:CA	donor_gain	1.0000
9:120963635:CG:C	donor_gain	1.0000
9:120963635:CGG:C	donor_gain	1.0000
9:120963635:CGGCT:C	donor_gain	1.0000
9:120963649:T:TA	donor_gain	1.0000
9:120963652:T:TA	donor_gain	1.0000
9:120963734:TGTAG:T	acceptor_gain	1.0000
9:120963735:GTAG:G	acceptor_gain	1.0000

AlphaMissense

11009 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:121032185:A:G	W199R	0.995
9:121032185:A:T	W199R	0.995
9:121006935:C:A	W797C	0.994
9:121006935:C:G	W797C	0.994
9:121006937:A:G	W797R	0.994
9:121006937:A:T	W797R	0.994
9:121017743:C:G	R539P	0.994
9:120960282:T:A	R1548S	0.993
9:120960282:T:G	R1548S	0.993
9:121016298:A:G	L651P	0.993
9:120974919:C:G	A1293P	0.992
9:120974931:C:G	D1289H	0.992
9:120976747:A:G	W1273R	0.992
9:120976747:A:T	W1273R	0.992
9:121013946:G:C	F728L	0.992
9:121013946:G:T	F728L	0.992
9:121013948:A:G	F728L	0.992
9:120969070:G:T	A1404E	0.991
9:120976882:A:G	W1228R	0.991
9:120976882:A:T	W1228R	0.991
9:121013989:C:G	R714P	0.991
9:121017687:A:G	S558P	0.991
9:121008431:C:A	W775C	0.990
9:121008431:C:G	W775C	0.990
9:120976743:A:G	L1274P	0.989
9:120976712:A:C	F1284L	0.988
9:120976712:A:T	F1284L	0.988
9:120976714:A:G	F1284L	0.988
9:120980160:G:T	A1194D	0.988
9:121017734:A:T	V542D	0.988

dbSNP variants (sampled 300 via entrez): RS1000105111 (9:120989035 C>T), RS1000136501 (9:120989255 G>A,T), RS1000141278 (9:121012972 G>A), RS1000163108 (9:121062602 C>T), RS1000180854 (9:120968579 C>T), RS1000183136 (9:121035836 A>G), RS1000184987 (9:121015686 G>A), RS1000224425 (9:121039829 C>T), RS1000269864 (9:120982408 C>A), RS1000273226 (9:120983529 T>A), RS1000330948 (9:121069195 A>G), RS1000340369 (9:120974609 T>G), RS1000389290 (9:121005471 G>A), RS1000392379 (9:121075121 G>A), RS1000418404 (9:121060663 TC>T)

Disease associations

OMIM: gene MIM:120900 | disease phenotypes: MIM:609536, MIM:607330

GenCC curated gene-disease

Disease	Classification	Inheritance
complement component 5 deficiency	Strong	Autosomal recessive

Mondo (3): complement component 5 deficiency (MONDO:0012295), prostate cancer (MONDO:0008315), lathosterolosis (MONDO:0011816)

Orphanet (2): Familial prostate cancer (Orphanet:1331), Lathosterolosis (Orphanet:46059)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002041	Intractable diarrhea
HP:0005381	Recurrent meningococcal disease
HP:0005430	Recurrent Neisserial infections
HP:0007569	Generalized seborrheic dermatitis
HP:0025434	Reduced circulating CH50 activity
HP:0033060	Decreased circulating complement C5 concentration

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000420_1	Rheumatoid arthritis	4.000000e-08
GCST002318_159	Rheumatoid arthritis	5.000000e-11
GCST002318_160	Rheumatoid arthritis	4.000000e-09
GCST004067_36	Hip circumference adjusted for BMI	6.000000e-09
GCST005194_153	Coronary artery disease	6.000000e-07
GCST006585_1074	Blood protein levels	2.000000e-13
GCST007096_53	Pulse pressure	6.000000e-09
GCST007843_17	Rheumatoid arthritis	6.000000e-09
GCST010002_279	Refractive error	2.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0005763	pulse pressure measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C537880	Lathosterolosis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2364163 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 242,512 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1071	OXAPROZIN	4	51,044
CHEMBL1316	CARPROFEN	4	32,707
CHEMBL15770	SULINDAC	4	80,712
CHEMBL81	RALOXIFENE	4	78,049

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs56040400	Efficacy	3	eculizumab

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs56040400	C5	3	0.25	1	eculizumab

ChEMBL bioactivities

11 potent at pChembl≥5 of 11 total, top 11 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.68	IC50	210	nM	CHEMBL2203296
6.36	IC50	440	nM	CHEMBL2204196
6.24	Kd	580	nM	CARPROFEN
6.24	Kd	570	nM	SULINDAC
6.21	IC50	620	nM	CHEMBL4756677
6.19	Kd	640	nM	OXAPROZIN
6.16	Kd	700	nM	CHEMBL5594178
6.15	Kd	710	nM	RALOXIFENE
6.09	Kd	820	nM	CHEMBL5594087
6.06	Kd	880	nM	CHEMBL5594178
6.03	Kd	940	nM	CHEMBL5594087

PubChem BioAssay actives

11 with measured affinity, of 60 total; 9 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
1-(3-hexoxy-4-methoxyphenyl)-3-[(1S)-1-phenylethyl]urea	1674155: Inhibition of C5 complement protein in 2% human serum incubated for 15 mins	ic50	0.2100	uM
1-[4-methoxy-3-(4-methylpentoxy)phenyl]-3-[(1S)-1-phenylethyl]urea	1674155: Inhibition of C5 complement protein in 2% human serum incubated for 15 mins	ic50	0.4400	uM
Sulindac	1601161: Binding affinity to human C5a assessed as dissociation constant after 1 hr by circular dichroism analysis	kd	0.5700	uM
Carprofen	1601161: Binding affinity to human C5a assessed as dissociation constant after 1 hr by circular dichroism analysis	kd	0.5800	uM
5-methoxy-4-(4-methylpentoxy)-2-[[(1S)-1-phenylethyl]carbamoylamino]benzoic acid	1674155: Inhibition of C5 complement protein in 2% human serum incubated for 15 mins	ic50	0.6200	uM
Oxaprozin	1601161: Binding affinity to human C5a assessed as dissociation constant after 1 hr by circular dichroism analysis	kd	0.6400	uM
(4R)-4-[[(2S)-2-[[(2S)-1-[(2R)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2R)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-amino-4-oxobutanoyl]amino]-4-carboxybutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-methylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-carboxypropanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-4-carboxybutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-6-aminohexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-carboxypropanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-5-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	2113408: Binding affinity to C5a (unknown origin) assessed as dissociation constant incubated for 1 hr by CD analysis	kd	0.7000	uM
Raloxifene	1601161: Binding affinity to human C5a assessed as dissociation constant after 1 hr by circular dichroism analysis	kd	0.7100	uM
(4S)-4-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-amino-4-oxobutanoyl]amino]-4-carboxybutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-methylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-carboxypropanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-4-carboxybutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-6-aminohexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-carboxypropanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-5-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	2113409: Binding affinity to C5a (unknown origin) assessed as dissociation constant by fluorescence quenching analysis	kd	0.8200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression, increases expression	4
Cyclosporine	affects expression, decreases expression, increases expression	4
titanium dioxide	increases secretion, increases expression	3
rEV576 protein, tick	affects binding, decreases activity, increases stability	3
Resveratrol	increases activity, increases localization, increases expression, decreases activity, decreases response to substance (+5 more)	3
Silicon Dioxide	decreases expression	3
Tetrachlorodibenzodioxin	decreases expression, increases expression	3
Asbestos, Crocidolite	decreases reaction, increases cleavage, decreases expression, increases expression, affects cotreatment	3
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases activity, increases phosphorylation	2
entinostat	decreases expression, affects cotreatment	2
Arsenic Trioxide	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression, increases expression	2
Calcium	increases abundance, increases activity, increases localization, decreases reaction	2
Copper	affects binding, decreases expression	2
Dexamethasone	affects cotreatment, decreases reaction, increases secretion, increases expression	2
Valproic Acid	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
1-Butanol	decreases reaction, increases activity, increases phosphorylation	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
4-hydroxy-7-oxo-5-heptenoic acid lactone	increases expression	1
dicrotophos	decreases expression	1
parthenolide	increases activity, decreases reaction	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
cobra venom factor	increases expression	1
sodium arsenite	decreases expression	1

ChEMBL screening assays

25 unique, capped per target: 25 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4400157	Binding	Binding affinity to recombinant human C5a assessed as conformational change at 1 to 100 uM incubated for 1 hr at 4degC by circular dichroism analysis	A rational search for discovering potential neutraligands of human complement fragment 5a (hC5a). — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SG31	HAP1 C5 (-) 1	Cancer cell line	Male
CVCL_SG32	HAP1 C5 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer