CD46

Summary

CD46 (CD46 molecule, HGNC:6953) is a protein-coding gene on chromosome 1q32.2, encoding Membrane cofactor protein (P15529). Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue.

The protein encoded by this gene is a type I membrane protein and is a regulatory part of the complement system. The encoded protein has cofactor activity for inactivation of complement components C3b and C4b by serum factor I, which protects the host cell from damage by complement. In addition, the encoded protein can act as a receptor for the Edmonston strain of measles virus, human herpesvirus-6, and type IV pili of pathogenic Neisseria. Finally, the protein encoded by this gene may be involved in the fusion of the spermatozoa with the oocyte during fertilization. Mutations at this locus have been associated with susceptibility to hemolytic uremic syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 4179 — RefSeq curated summary.

At a glance

• Gene–disease (curated): atypical hemolytic-uremic syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 50
• Clinical variants (ClinVar): 579 total — 27 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 44
• MANE Select transcript: NM_172351

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6953
Approved symbol	CD46
Name	CD46 molecule
Location	1q32.2
Locus type	gene with protein product
Status	Approved
Aliases	TRA2.10, MGC26544, TLX
Ensembl gene	ENSG00000117335
Ensembl biotype	protein_coding
OMIM	120920
Entrez	4179

Gene structure

Transcript identifiers

Ensembl transcripts: 50 — 31 protein_coding, 15 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000322875, ENST00000322918, ENST00000354848, ENST00000357714, ENST00000358170, ENST00000360212, ENST00000367041, ENST00000367042, ENST00000367047, ENST00000462968, ENST00000464082, ENST00000469535, ENST00000471987, ENST00000480003, ENST00000488596, ENST00000490278, ENST00000493796, ENST00000496723, ENST00000636114, ENST00000695777, ENST00000695778, ENST00000695779, ENST00000695780, ENST00000695781, ENST00000695782, ENST00000695783, ENST00000695784, ENST00000695785, ENST00000695786, ENST00000695787, ENST00000695788, ENST00000695789, ENST00000695790, ENST00000887052, ENST00000887053, ENST00000887054, ENST00000887055, ENST00000887056, ENST00000887057, ENST00000887058, ENST00000887059, ENST00000915207, ENST00000970370, ENST00000970371, ENST00000970372, ENST00000970373, ENST00000970374, ENST00000970375, ENST00000970376, ENST00000970377

RefSeq mRNA: 12 — MANE Select: NM_172351 NM_002389, NM_153826, NM_172350, NM_172351, NM_172352, NM_172353, NM_172355, NM_172356, NM_172357, NM_172358, NM_172359, NM_172361

CCDS: CCDS1479, CCDS1480, CCDS1481, CCDS1482, CCDS1484, CCDS1485, CCDS31008, CCDS31009, CCDS86048

Canonical transcript exons

ENST00000367042 — 13 exons

Exon	Start	End
ENSE00000792032	207767779	207767823
ENSE00001167601	207767013	207767195
ENSE00001167611	207761249	207761446
ENSE00003504276	207757540	207757642
ENSE00003509765	207759639	207759724
ENSE00003520315	207785071	207785106
ENSE00003558309	207770321	207770362
ENSE00003582519	207783292	207783330
ENSE00003965001	207752054	207752309
ENSE00003965009	207757014	207757202
ENSE00003965011	207790253	207790345
ENSE00003965018	207785619	207785682
ENSE00003965028	207793519	207795504

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 157.7557 / max 2201.4763, expressed in 1826 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8260	156.1745	1826
8261	1.1257	416
8262	0.3967	187
201930	0.0588	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	99.52	gold quality
adrenal tissue	UBERON:0018303	99.39	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.19	gold quality
seminal vesicle	UBERON:0000998	99.16	gold quality
bronchial epithelial cell	CL:0002328	99.10	gold quality
jejunal mucosa	UBERON:0000399	99.09	gold quality
germinal epithelium of ovary	UBERON:0001304	99.04	gold quality
right adrenal gland cortex	UBERON:0035827	99.04	gold quality
parotid gland	UBERON:0001831	98.99	gold quality
left adrenal gland	UBERON:0001234	98.98	gold quality
adrenal cortex	UBERON:0001235	98.98	gold quality
placenta	UBERON:0001987	98.98	gold quality
left adrenal gland cortex	UBERON:0035825	98.98	gold quality
right uterine tube	UBERON:0001302	98.93	gold quality
esophagus squamous epithelium	UBERON:0006920	98.92	gold quality
right adrenal gland	UBERON:0001233	98.90	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.88	gold quality
adrenal gland	UBERON:0002369	98.84	gold quality
right lung	UBERON:0002167	98.82	gold quality
body of pancreas	UBERON:0001150	98.79	gold quality
caput epididymis	UBERON:0004358	98.79	gold quality
oral cavity	UBERON:0000167	98.78	gold quality
colonic mucosa	UBERON:0000317	98.76	gold quality
islet of Langerhans	UBERON:0000006	98.75	gold quality
visceral pleura	UBERON:0002401	98.73	gold quality
saliva-secreting gland	UBERON:0001044	98.72	gold quality
lower lobe of lung	UBERON:0008949	98.72	gold quality
minor salivary gland	UBERON:0001830	98.71	gold quality
metanephros	UBERON:0000081	98.65	gold quality
epithelium of nasopharynx	UBERON:0001951	98.60	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8530	yes	702.87
E-GEOD-135922	yes	42.85
E-HCAD-10	yes	13.36
E-GEOD-76312	no	856.04
E-MTAB-2983	no	297.38
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
DLL1	Repression
JAG1	Activation
JAG2	Activation
NOTCH1	Activation
NOTCH2	Activation

Upstream regulators (CollecTRI, top): CEBPB, NFKB, RELA, STAT3

miRNA regulators (miRDB)

101 targeting CD46, 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-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4262	100.00	73.26	3931
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-4760-3P	99.93	70.50	2385

Literature-anchored findings (GeneRIF, showing 40)

• CD46 costimulation induces morphological changes in T cells and activates the MAP Kinase Signaling System (PMID:11739493)
• peripheral blood monocytes treated for 5–8 days with GM-CSF (i.e. mature Mphi) acquired the capacity to assemble CD9, alpha3-beta1 integrin and the tyrosine phosphatase SHP-1 with their CD46 (PMID:11858824)
• The findings reported here strongly suggest that pilus binding to CD46 is not a simple static process. Rather, they support a model in which pilus interaction with CD46 promotes signaling cascades important for Neisseria infectivity. (PMID:11901164)
• Production and characterization of a pig line transgenic for human membrane cofactor protein. (PMID:11983016)
• required for HHV-6A induced fusion from without (PMID:12050388)
• For the classical pathway, MCP is the cofactor for C4b cleavage (and factor H for C3b cleavage); however, if the alternative pathway mediates C3b deposition, then MCP’s cofactor activity is sufficient to restrict complement activation. (PMID:12055245)
• CD46 plays a role in regulating T cell-induced inflammatory reaction and in fine-tuning the cellular immune response by bridging innate and acquired immunity. (PMID:12055630)
• CD46 isoforms function as receptors for human herpesvirus 6 and measles virus (PMID:12171934)
• Co-engagement of CD3 and the complement regulator CD46 in the presence of IL-2 induces a Tr1-specific cytokine phenotype in human CD4+ T cells (PMID:12540904)
• Human herpesvirus 6 variant A glycoprotein H-glycoprotein L-glycoprotein Q complex is a viral ligand for human CD46 (PMID:12663806)
• CD46 has a role as a receptor for fusion and entry of human herpesvirus 6 into target cells (PMID:12724329)
• role in meningococcal disease; results suggest that CD46 facilitates pilus-dependent interactions at the epithelial mucosa (PMID:12869763)
• Adenovirus type 11 uses CD46 as a cellular receptor. (PMID:12915534)
• elucidation of two pathways for CD46 internalization, which are regulated by the valence of cross-linking of CD46 and which utilize either clathrin-coated pits or pseudopodial extension (PMID:12958316)
• Mutations predispose to development of familial hemolytic uremic syndrome. (PMID:14566051)
• Data show that CD46 affords protection from antibody-mediated rejection when mouse anti-pig serum was administered to scid mice bearing grafts from either CD46 transgenic or normal pigs. (PMID:14708531)
• CD46 is localized to the plasma membrane and may have a role in the development of breast cancer epithelial cells (PMID:14712499)
• Highly efficient CD46 function, controlling both classical and alternative pathway complement activation, which suggests it might be the complement regulator of choice to protect kidney xenografts from pig to papio. (PMID:14962279)
• In pigs transgenic for human MCP, the transgene is expressed at similar levels to that in human embryonic neural tissue but at an insufficient level to prevent activation of the complement cascade. (PMID:14962294)
• serves as an attachment receptor for adenovirus-37 (PMID:15047806)
• all of the major splice forms of CD46 are predominant and functional binding sites of species B Adenovirus 3 on CD46-expressing rodent and human cells but may not be the sole receptor of species B Ads on human cells (PMID:15078926)
• Review discussing role of CD46 mutations in predisposition to hemolytic uremic syndrome. (PMID:15121049)
• Significant difference in intensity of the staining of CD55 and CD46 among cells in various layers of normal esophageal mucosa and esophageal carcinoma cells, but not in the staining of CD59. (PMID:15151618)
• CD46 costimulation promotes a Th1-biased response in human CD4+ T lymphocytes. CD46 enhanced TCR/CD3-induced tyrosine phosphorylation of CD3zeta and ZAP-70. (PMID:15307176)
• functional activity of CD46 is not restricted to the tumor cell membranes but can be liberated in vesicles and by a metalloproteinase. (PMID:15307194)
• binding site with measles virus hemagglutinin: attachment sites for MV receptors SLAM and CD46 overlap on the globular head (PMID:15308701)
• Expression of CD46 was not downregulated by the infection of measles virus strain S191 both on mRNA level and cellular surface protein level. (PMID:15336534)
• High levels of CD46 is associated with breast cancer (PMID:15378282)
• Does not provide additional bbenefit in preventing graft rejection in transgenic pig-baboon heart transplantation. (PMID:15385816)
• there are naturally occurring susceptibility factors in CFH and MCP for the development of atypical haemolytic-uraemic syndrome (PMID:15784724)
• In transgenic pigs, has no effect on endogenous retrovirus. (PMID:15808690)
• co-purification of sCD46 and HHV-6 DNA from multiple sclerosis sera indicates that HHV-6 is tightly connected to its receptor, CD46, in the serum of multiple sclerosis patients (PMID:15845255)
• data support the notion that pilus-mediated gonococcal infection of epithelial cells can occur in a CD46-independent manner, thus questioning the function of CD46 as an essential pilus receptor for pathogenic neisseriae (PMID:15845515)
• native conformation of the CCP2 domain is crucial for adenovirus serotype 35 binding and substitution of amino acids at positions 130 to 135 or 152 to 156 completely abolishes the receptor function of CD46 (PMID:15919905)
• CD46 has a role in tailoring innate immune recognition of apoptotic and necrotic cells (PMID:16087667)
• The combination of homozygosity for both IL1B-511*1 and CD46H*2 alleles is a high risk factor for recurrent pregnancy loss. (PMID:16253969)
• CD46 is a major cellular receptor on A549 cells for all species B adenoviruses except types 3 and 7. (PMID:16254377)
• Mutations in the complement regulators factor H, membrane cofactor protein (MCP), and factor I are associated with atypical hemolytic uremic syndrome. (PMID:16386793)
• the N481Y substitution in the measles virus haemagglutinin allowed it to utilize CD46 as an alternative receptor, but its ability to use CD46 was rather low in CD46+ SLAM- cell lines (PMID:16690929)
• ADAM10-mediated release of CD46 from apoptotic vesicles may represent a form of strategy to allow restricted complement activation to deal with modified self (PMID:16735514)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd46	ENSMUSG00000016493
rattus_norvegicus	Cd46l1	ENSRNOG00000026207

Paralogs (39): CFH (ENSG00000000971), SELE (ENSG00000007908), C8B (ENSG00000021852), C6 (ENSG00000039537), SEZ6 (ENSG00000063015), CFHR2 (ENSG00000080910), APOH (ENSG00000091583), SEZ6L (ENSG00000100095), SUSD6 (ENSG00000100647), SRPX (ENSG00000101955), SRPX2 (ENSG00000102359), C7 (ENSG00000112936), C9 (ENSG00000113600), PAPPA2 (ENSG00000116183), CFHR3 (ENSG00000116785), CR2 (ENSG00000117322), 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

Membrane cofactor protein — P15529 (reviewed: P15529)

Alternative names: TLX, Trophoblast leukocyte common antigen

All UniProt accessions (8): A0A8Q3WKR0, A0A8Q3WKR4, A0A8Q3WKS6, A0A8Q3WKW1, A0A8Q3WLA6, A0A8Q3WLU6, P15529, R4GN18

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue. May be involved in the fusion of the spermatozoa with the oocyte during fertilization. Also acts as a costimulatory factor for T-cells which induces the differentiation of CD4+ into T-regulatory 1 cells. T-regulatory 1 cells suppress immune responses by secreting interleukin-10, and therefore are thought to prevent autoimmunity. (Microbial infection) A number of viral and bacterial pathogens seem to bind MCP in order to exploit its immune regulation property and directly induce an immunosuppressive phenotype in T-cells. (Microbial infection) Acts as a receptor for Adenovirus subgroup B2 and Ad3. (Microbial infection) Acts as a receptor for cultured Measles virus. (Microbial infection) Acts as a receptor for Herpesvirus 6/HHV-6. (Microbial infection) May act as a receptor for pathogenic bacteria Neisseria and Streptococcus pyogenes.

Subunit / interactions. Interacts with C3b. Interacts with C4b. Interacts with moesin/MSN. (Microbial infection) Interacts (via N-terminus) with measles virus H protein; this interaction allows attachment and viral entry of vaccine and laboratory-adapted strains. (Microbial infection) Interacts with human herpesvirus 6 GH protein. (Microbial infection) Interacts with human adenovirus B/D fiber protein. (Microbial infection) Binds to Streptococcus pyogenes M protein and to type IV pili from Neisseria.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Acrosome inner membrane.

Tissue specificity. Expressed by all cells except erythrocytes.

Post-translational modifications. N-glycosylated on Asn-83; Asn-114 and Asn-273 in most tissues, but probably less N-glycosylated in testis. N-glycosylation on Asn-114 and Asn-273 is required for cytoprotective function. N-glycosylation on Asn-114 is required for Measles virus binding. N-glycosylation on Asn-273 is required for Neisseria binding. N-glycosylation is not required for human adenovirus binding. Extensively O-glycosylated in the Ser/Thr-rich domain. O-glycosylation is required for Neisseria binding but not for Measles virus or human adenovirus binding. In epithelial cells, isoforms B/D/F/H/J/L/3 are phosphorylated by YES1 in response to infection by Neisseria gonorrhoeae; which promotes infectivity. In T-cells, these isoforms may be phosphorylated by LCK.

Disease relevance. Hemolytic uremic syndrome, atypical, 2 (AHUS2) [MIM:612922] 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. Patients with CD46 mutations seem to have an overall better prognosis compared to patients carrying CFH mutations.

Domain organisation. Sushi domains 1 and 2 are required for interaction with human adenovirus B PIV/FIBER protein and with Measles virus H protein. Sushi domains 2 and 3 are required for Herpesvirus 6 binding. Sushi domain 3 is required for Neisseria binding. Sushi domains 3 and 4 are required for interaction with Streptococcus pyogenes M protein and are the most important for interaction with C3b and C4b.

Isoforms (16)

UniProt ID	Names	Canonical?
P15529-1	A, no del, ABC1	yes
P15529-2	B, del 13, ABC2
P15529-11	C, del 7, BC1
P15529-3	D, del 7-13, BC2
P15529-12	E, del 7-8, C1
P15529-4	F, del 7-8-13, C2
P15529-13	G, del 9
P15529-5	H, del 9-13
P15529-14	I, del 7-9
P15529-6	J, del 7-9-13
P15529-15	K, del 7-8-9
P15529-7	L, del 7-8-9-13
P15529-8	M, del 7-12a-13
P15529-9	N, del 7-8-12-13
P15529-10	2
P15529-16	3

RefSeq proteins (12): NP_002380, NP_722548, NP_758860, NP_758861, NP_758862, NP_758863, NP_758865, NP_758866, NP_758867, NP_758868, NP_758869, NP_758871 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR017341	CD46	Family
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR051277	SEZ6_CSMD_C4BPB_Regulators	Family

Pfam: PF00084

UniProt features (107 total): strand 27, glycosylation site 21, sequence variant 13, splice variant 11, disulfide bond 8, modified residue 7, domain 4, sequence conflict 4, mutagenesis site 3, topological domain 2, helix 2, signal peptide 1, chain 1, compositionally biased region 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
5FO8	X-RAY DIFFRACTION	2.4
3O8E	X-RAY DIFFRACTION	2.84
2O39	X-RAY DIFFRACTION	2.85
1CKL	X-RAY DIFFRACTION	3.1
3INB	X-RAY DIFFRACTION	3.1
8QK3	ELECTRON MICROSCOPY	3.2
3L89	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15529-F1	82.38	0.66

Functional residue map

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

Post-translational modifications (7): 384, 369, 354, 370, 355, 340, 321

Disulfide bonds (8): 35–80, 64–94, 99–141, 127–157, 162–210, 191–223, 228–270, 256–283

Glycosylation sites (21): 83, 114, 163, 273, 290, 291, 292, 298, 300, 302, 303, 304, 305, 306, 307, 309, 312, 313, 315, 320 …

Mutagenesis-validated functional residues (3):

Position	Phenotype
83	no effect on cytoprotective function. no effect on neisseria binding. no effect on measles virus binding.
114	strongly decreases cytoprotective function. decreases neisseria binding. abolishes measles virus binding.
273	strongly decreases cytoprotective function. abolishes neisseria binding. no effect on measles virus binding.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-977606	Regulation of Complement cascade
R-HSA-166658	Complement cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 324 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_SINGLE_FERTILIZATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, LEE_NEURAL_CREST_STEM_CELL_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOCC_SECRETORY_GRANULE, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOCC_CELL_SURFACE, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION

GO Biological Process (18): adaptive immune response (GO:0002250), T cell mediated immunity (GO:0002456), complement activation, classical pathway (GO:0006958), single fertilization (GO:0007338), regulation of Notch signaling pathway (GO:0008593), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), positive regulation of interleukin-10 production (GO:0032733), obsolete sequestering of extracellular ligand from receptor (GO:0035581), positive regulation of T cell proliferation (GO:0042102), positive regulation of memory T cell differentiation (GO:0043382), innate immune response (GO:0045087), positive regulation of regulatory T cell differentiation (GO:0045591), negative regulation of complement activation, classical pathway (GO:0045959), positive regulation of transforming growth factor beta production (GO:0071636), immune system process (GO:0002376), symbiont entry into host cell (GO:0046718), regulation of immune response (GO:0050776)

GO Molecular Function (4): virus receptor activity (GO:0001618), signaling receptor activity (GO:0038023), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (8): inner acrosomal membrane (GO:0002079), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), focal adhesion (GO:0005925), cell surface (GO:0009986), extracellular exosome (GO:0070062), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Complement cascade	1
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	3
gene expression	2
regulation of gene expression	2
positive regulation of cytokine production	2
positive regulation of T cell differentiation	2
cellular anatomical structure	2
lymphocyte mediated immunity	1
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
humoral immune response mediated by circulating immunoglobulin	1
complement activation	1
fertilization	1
Notch signaling pathway	1
regulation of signal transduction	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
interleukin-10 production	1
regulation of interleukin-10 production	1
T cell proliferation	1
regulation of T cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of T cell activation	1
positive regulation of immune effector process	1
memory T cell differentiation	1
regulation of memory T cell differentiation	1
positive regulation of immune response	1
defense response to symbiont	1
regulatory T cell differentiation	1
regulation of regulatory T cell differentiation	1
negative regulation of humoral immune response mediated by circulating immunoglobulin	1
complement activation, classical pathway	1
regulation of complement activation, classical pathway	1
negative regulation of complement activation	1
transforming growth factor beta production	1
regulation of transforming growth factor beta production	1
biological_process	1
viral life cycle	1
symbiont entry into host	1
regulation of immune system process	1
regulation of response to stimulus	1
symbiont entry into host cell	1

Protein interactions and networks

STRING

1587 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD46	C3	P01024	999
CD46	C4A	P01028	996
CD46	MYBPH	Q13203	993
CD46	SLAMF1	Q13291	966
CD46	CD59	P13987	965
CD46	MYOM2	P54296	948
CD46	CFI	P05156	923
CD46	GOPC	Q9HD26	890
CD46	CXADR	P78310	857
CD46	MSN	P26038	816
CD46	THBD	P07204	808
CD46	NECTIN4	Q96NY8	797
CD46	CD55	P08174	786
CD46	DSG2	Q14126	766
CD46	DGKE	P52429	764

IntAct

145 interactions, top by confidence:

A	B	Type	Score
JAG1	CD46	psi-mi:“MI:0407”(direct interaction)	0.730
CD46	JAG1	psi-mi:“MI:0407”(direct interaction)	0.730
JAG1	CD46	psi-mi:“MI:0403”(colocalization)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
C3	CD46	psi-mi:“MI:0407”(direct interaction)	0.620
CD81	C2orf72	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
	AP3D1	psi-mi:“MI:0914”(association)	0.460
H	CD46	psi-mi:“MI:0407”(direct interaction)	0.440
CD46	C3	psi-mi:“MI:0570”(protein cleavage)	0.440
CFI	C3	psi-mi:“MI:0570”(protein cleavage)	0.440
CD46	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
CD46	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
CD46	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
CD46	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
CD46	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
CD46	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
CD46	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
CD46	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
SCRIB	CD46	psi-mi:“MI:0407”(direct interaction)	0.440
CD46	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
PDZD7	CD46	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF11	CD46	psi-mi:“MI:0407”(direct interaction)	0.440
CD46	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (48): CD46 (Affinity Capture-MS), CD46 (Affinity Capture-MS), CD46 (Affinity Capture-MS), CD46 (Proximity Label-MS), CD46 (Affinity Capture-MS), CD46 (Two-hybrid), POU4F2 (Two-hybrid), MGAT5B (Two-hybrid), GPR37L1 (Two-hybrid), AGR3 (Two-hybrid), ANKRD46 (Two-hybrid), CD46 (Affinity Capture-Western), CD46 (Affinity Capture-Western), CD9 (Affinity Capture-Western), CD151 (Affinity Capture-Western)

ESM2 similar proteins: O02839, O08569, O19124, O62685, O62837, O88174, P02749, P04003, P05160, P08607, P14151, P15529, P16109, P17690, P19070, P20023, P26644, P27113, P30836, P42201, P49457, P70105, P79138, P98107, P98109, P98131, Q01102, Q03472, Q07968, Q28065, Q28768, Q2VPA4, Q5R4D0, Q60401, Q60736, Q61475, Q61476, Q63135, Q63514, Q64735

Diamond homologs: A0A182C2Z2, A0JNA2, B3EX01, E7FEC4, O08569, O19124, O57254, O62685, O62837, O88174, P08174, P0DTN2, P15529, P21115, P24083, P24084, P36980, P49457, P79138, P81475, Q01227, Q07968, Q28085, Q29RN8, Q4V9Z5, Q53EL9, Q5R4D0, Q5R8M2, Q5VX71, Q60736, Q63515, Q6AX42, Q6P1D5, Q6UXD5, Q7TSK2, Q7Z408, Q8BH32, Q9BYH1, Q9JF44, Q9W332

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
STAT3	“up-regulates quantity by expression”	CD46	“transcriptional regulation”
SRC	“up-regulates activity”	CD46	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	7	58.8×	2e-09
Unblocking of NMDA receptors, glutamate binding and activation	5	40.0×	1e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	40.0×	1e-05
Long-term potentiation	5	35.0×	2e-05
Assembly and cell surface presentation of NMDA receptors	9	33.6×	9e-10
Neurexins and neuroligins	10	29.0×	5e-10
Protein-protein interactions at synapses	6	23.4×	1e-05
RND3 GTPase cycle	5	19.1×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	65.2×	3e-15
protein localization to synapse	6	46.9×	4e-07
receptor clustering	7	44.6×	5e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	35.4×	2e-07
protein-containing complex assembly	9	10.5×	2e-05
cell-cell adhesion	9	9.3×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	27
Likely pathogenic	16
Uncertain significance	311
Likely benign	101
Benign	42

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1162901	NM_172351.3(CD46):c.412del (p.Ile138fs)	Pathogenic
1162902	NM_172351.3(CD46):c.464dup (p.Ile156fs)	Pathogenic
1163188	NM_172351.3(CD46):c.286+1G>C	Pathogenic
1371221	NM_172351.3(CD46):c.393_411del (p.Gly130_Tyr131insTer)	Pathogenic
1385626	NM_172351.3(CD46):c.857-148dup	Pathogenic
17044	NM_172351.3(CD46):c.800_801del (p.Thr267fs)	Pathogenic
17047	NM_172351.3(CD46):c.98-1G>C	Pathogenic
2075354	NM_172351.3(CD46):c.408del (p.Glu137fs)	Pathogenic
2577446	NM_172351.3(CD46):c.907del (p.Arg303fs)	Pathogenic
265981	NM_172351.3(CD46):c.776del (p.Gly259fs)	Pathogenic
2708593	NM_172351.3(CD46):c.948T>A (p.Tyr316Ter)	Pathogenic
3236244	NM_172351.3(CD46):c.126_127del (p.Glu42fs)	Pathogenic
3236246	NM_172351.3(CD46):c.735del (p.Lys245fs)	Pathogenic
3621483	NM_172351.3(CD46):c.456dup (p.Lys153Ter)	Pathogenic
369948	NM_172351.3(CD46):c.542_543del (p.Val180_Phe181insTer)	Pathogenic
3722028	NM_172351.3(CD46):c.272_276dup (p.Ala93fs)	Pathogenic
3895475	NM_172351.3(CD46):c.1082+2T>A	Pathogenic
4291174	NM_172351.3(CD46):c.747_751del (p.Lys249fs)	Pathogenic
4291191	NM_172351.3(CD46):c.770del (p.Asp257fs)	Pathogenic
4291200	NM_172351.3(CD46):c.350dup (p.Tyr117Ter)	Pathogenic
4291203	NM_172351.3(CD46):c.768C>A (p.Cys256Ter)	Pathogenic
4291209	NM_172351.3(CD46):c.476-2A>G	Pathogenic
4291210	NM_172351.3(CD46):c.857-2A>G	Pathogenic
4291212	NM_172351.3(CD46):c.982+2T>C	Pathogenic
4291258	NM_172351.3(CD46):c.202_203dup (p.Phe69fs)	Pathogenic
635500	NM_172351.3(CD46):c.404del (p.Gly135fs)	Pathogenic
829863	NM_172351.3(CD46):c.828G>A (p.Trp276Ter)	Pathogenic
1163186	NM_172351.3(CD46):c.153del (p.Lys51fs)	Likely pathogenic
1424447	NM_172351.3(CD46):c.857-174A>C	Likely pathogenic
1500521	NM_172351.3(CD46):c.389+1G>A	Likely pathogenic

SpliceAI

2053 predictions. Top by Δscore:

Variant	Effect	Δscore
1:207757006:A:AG	acceptor_gain	1.0000
1:207757007:T:G	acceptor_gain	1.0000
1:207757009:CCTA:C	acceptor_loss	1.0000
1:207757010:CTAG:C	acceptor_loss	1.0000
1:207757012:A:AC	acceptor_loss	1.0000
1:207757012:A:AG	acceptor_gain	1.0000
1:207757013:G:GT	acceptor_gain	1.0000
1:207757013:GAT:G	acceptor_gain	1.0000
1:207757013:GATGC:G	acceptor_gain	1.0000
1:207757198:TTATA:T	donor_gain	1.0000
1:207757199:TATA:T	donor_gain	1.0000
1:207757200:ATA:A	donor_gain	1.0000
1:207757201:TA:T	donor_gain	1.0000
1:207757202:AG:A	donor_loss	1.0000
1:207757203:GT:G	donor_loss	1.0000
1:207757203:GTAA:G	donor_gain	1.0000
1:207757204:T:A	donor_loss	1.0000
1:207757207:G:GG	donor_gain	1.0000
1:207757538:A:AG	acceptor_gain	1.0000
1:207757539:G:GG	acceptor_gain	1.0000
1:207757638:GAGGG:G	donor_gain	1.0000
1:207757640:GGG:G	donor_gain	1.0000
1:207757641:GG:G	donor_gain	1.0000
1:207757641:GGG:G	donor_gain	1.0000
1:207757642:GG:G	donor_gain	1.0000
1:207759637:A:AG	acceptor_gain	1.0000
1:207759638:G:GG	acceptor_gain	1.0000
1:207759638:GTT:G	acceptor_gain	1.0000
1:207759725:G:GG	donor_gain	1.0000
1:207761240:A:AG	acceptor_gain	1.0000

AlphaMissense

2449 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:207757174:G:C	W86C	1.000
1:207757174:G:T	W86C	1.000
1:207761421:G:C	W216C	1.000
1:207761421:G:T	W216C	1.000
1:207767167:G:C	W276C	1.000
1:207767167:G:T	W276C	1.000
1:207761344:T:A	C191S	0.999
1:207761345:G:A	C191Y	0.999
1:207761345:G:C	C191S	0.999
1:207761419:T:A	W216R	0.999
1:207761419:T:C	W216R	0.999
1:207761440:T:A	C223S	0.999
1:207761441:G:C	C223S	0.999
1:207767021:T:A	C228S	0.999
1:207767022:G:C	C228S	0.999
1:207767105:T:A	C256S	0.999
1:207767106:G:C	C256S	0.999
1:207767147:T:A	C270S	0.999
1:207767148:G:A	C270Y	0.999
1:207767148:G:C	C270S	0.999
1:207767165:T:A	W276R	0.999
1:207767165:T:C	W276R	0.999
1:207767186:T:A	C283S	0.999
1:207767187:G:C	C283S	0.999
1:207759699:G:C	W150C	0.998
1:207759699:G:T	W150C	0.998
1:207759718:T:A	C157S	0.998
1:207759719:G:C	C157S	0.998
1:207761257:T:A	C162S	0.998
1:207761258:G:C	C162S	0.998

dbSNP variants (sampled 300 via entrez): RS1000195196 (1:207770848 T>C), RS1000366003 (1:207789342 T>C), RS1000445683 (1:207784740 T>G), RS1000453575 (1:207784514 C>G), RS1000488532 (1:207756490 T>G), RS1000605266 (1:207791525 G>A), RS1000655803 (1:207778007 T>C), RS1000772099 (1:207752383 C>A,T), RS1000831596 (1:207759266 A>C), RS1000882184 (1:207758750 A>G), RS1000932953 (1:207768948 T>C), RS1001073144 (1:207781784 G>A,T), RS1001097524 (1:207782175 C>G), RS1001175481 (1:207790005 T>C), RS1001197951 (1:207782316 A>C,G)

Disease associations

OMIM: gene MIM:120920 | disease phenotypes: MIM:612922, MIM:612954

GenCC curated gene-disease

Disease	Classification	Inheritance
atypical hemolytic-uremic syndrome with MCP/CD46 anomaly	Definitive	Semidominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
atypical hemolytic-uremic syndrome	Definitive	SD

Mondo (6): atypical hemolytic-uremic syndrome with MCP/CD46 anomaly (MONDO:0013040), atypical hemolytic-uremic syndrome (MONDO:0016244), thrombotic microangiopathy (MONDO:0019737), kidney disorder (MONDO:0005240), myofibrillar myopathy 6 (MONDO:0013061), familial hemolytic anemia (MONDO:0003689)

Orphanet (4): Atypical hemolytic uremic syndrome (Orphanet:2134), Thrombotic microangiopathy (Orphanet:93573), BAG3-related myofibrillar myopathy (Orphanet:199340), OBSOLETE: Atypical hemolytic uremic syndrome with MCP/CD46 anomaly (Orphanet:93576)

HPO phenotypes

44 total (30 of 44 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0001058	Poor wound healing
HP:0001342	Cerebral hemorrhage
HP:0001873	Thrombocytopenia
HP:0001878	Hemolytic anemia
HP:0001903	Anemia
HP:0001919	Acute kidney injury
HP:0001937	Microangiopathic hemolytic anemia
HP:0002013	Vomiting
HP:0002018	Nausea
HP:0002027	Abdominal pain
HP:0002202	Pleural effusion
HP:0002315	Headache
HP:0002615	Hypotension
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003138	Increased blood urea nitrogen
HP:0003259	Elevated circulating creatinine concentration
HP:0003418	Back pain
HP:0003621	Juvenile onset
HP:0003641	Hemoglobinuria
HP:0004324	Increased body weight
HP:0005421	Decreased circulating complement C3 concentration
HP:0005521	Disseminated intravascular coagulation
HP:0005575	Hemolytic-uremic syndrome
HP:0007430	Generalized edema
HP:0008071	Maternal hypertension

GWAS associations

50 associations (top):

Study	Trait	p-value
GCST000381_2	Biomedical quantitative traits	3.000000e-09
GCST001762_651	Obesity-related traits	9.000000e-06
GCST001814_11	Age-related macular degeneration	5.000000e-06
GCST001814_23	Age-related macular degeneration	5.000000e-06
GCST001969_6	Heart rate	4.000000e-26
GCST002539_34	Schizophrenia	4.000000e-08
GCST002672_7	Febrile seizures	2.000000e-09
GCST002674_2	Febrile seizures (MMR vaccine-related)	1.000000e-10
GCST003818_63	Resting heart rate	5.000000e-31
GCST004269_2	Immune response to measles vaccine (measles-specific neutralising antibody titre)	3.000000e-09
GCST004269_4	Immune response to measles vaccine (measles-specific neutralising antibody titre)	5.000000e-09
GCST005789_4	Resting heart rate	3.000000e-10
GCST006416_5	Chronic central serous retinopathy	7.000000e-07
GCST006803_51	Schizophrenia	3.000000e-07
GCST007095_101	Systolic blood pressure	3.000000e-08
GCST007095_102	Systolic blood pressure	3.000000e-07
GCST007096_118	Pulse pressure	2.000000e-09
GCST007097_78	Pulse pressure	6.000000e-08
GCST007097_79	Pulse pressure	3.000000e-07
GCST007099_162	Systolic blood pressure	2.000000e-07
GCST007267_277	Systolic blood pressure	9.000000e-09
GCST007630_4	Drug experimentation measurement	2.000000e-06
GCST010002_375	Refractive error	2.000000e-54
GCST010723_1	Early age-related macular degeneration	5.000000e-08
GCST010796_1351	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_1352	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_1353	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-11
GCST010796_1480	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-10
GCST010796_1481	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-10
GCST010796_1482	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0006519	MMR-related febrile seizures
EFO:0004645	response to vaccine
EFO:0009363	chronic central serous retinopathy
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0007010	drug use measurement
EFO:0004327	electrocardiography

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D000745	Anemia, Hemolytic, Congenital	C15.378.050.141.150; C16.320.070
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
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
D057049	Thrombotic Microangiopathies	C15.378.140.855.925; C15.378.243.937.925
C567843	Myopathy, Myofibrillar, Bag3-Related (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
sodium arsenite	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
4-hydroxy-7-oxo-5-heptenoic acid lactone	increases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
deoxynivalenol	decreases expression	1
titanium dioxide	increases expression	1
trichostatin A	affects expression, decreases reaction	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
sulindac sulfide	decreases expression	1
cadmium acetate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
seocalcitol	increases expression	1
abiraterone	decreases response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
enzalutamide	increases expression	1
3’,4’-dimethoxy-alpha-naphthoflavone	decreases reaction, increases activity, increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Vorinostat	decreases expression	1
Allergens	decreases expression	1
Arsenic	decreases expression, increases abundance	1

Cellosaurus cell lines

17 cell lines: 15 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B4FI	MODE-K.CD46	Transformed cell line	Female
CVCL_D1VM	Abcam A-549 CD46 KO	Cancer cell line	Male
CVCL_D2A7	Abcam HCT 116 CD46 KO	Cancer cell line	Male
CVCL_D2N7	Abcam THP-1 CD46 KO	Cancer cell line	Male
CVCL_D7M5	Ubigene A-549 CD46 KO	Cancer cell line	Male
CVCL_E6PM	Genomeditech CHO-K1 H_CD46	Spontaneously immortalized cell line	Female
CVCL_SH73	HAP1 CD46 (-) 1	Cancer cell line	Male
CVCL_SH74	HAP1 CD46 (-) 2	Cancer cell line	Male
CVCL_SH75	HAP1 CD46 (-) 3	Cancer cell line	Male
CVCL_SH76	HAP1 CD46 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02574403	PHASE4	COMPLETED	Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With aHUS
NCT07308574	PHASE4	RECRUITING	Post-Marketing Clinical Study of Ravulizumab in Participants With Clinical aHUS
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	PHASE4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	PHASE4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	PHASE4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	PHASE4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	PHASE4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	PHASE4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	PHASE4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	PHASE4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	PHASE4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	PHASE4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	PHASE4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	PHASE4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	PHASE4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	PHASE4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
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