CD59

Summary

CD59 (CD59 molecule (CD59 blood group), HGNC:1689) is a protein-coding gene on chromosome 11p13, encoding CD59 glycoprotein (P13987). Potent inhibitor of the complement membrane attack complex (MAC) action, which protects human cells from damage during complement activation.

This gene encodes a cell surface glycoprotein that regulates complement-mediated cell lysis, and it is involved in lymphocyte signal transduction. This protein is a potent inhibitor of the complement membrane attack complex, whereby it binds complement C8 and/or C9 during the assembly of this complex, thereby inhibiting the incorporation of multiple copies of C9 into the complex, which is necessary for osmolytic pore formation. This protein also plays a role in signal transduction pathways in the activation of T cells. Mutations in this gene cause CD59 deficiency, a disease resulting in hemolytic anemia and thrombosis, and which causes cerebral infarction. Multiple alternatively spliced transcript variants, which encode the same protein, have been identified for this gene.

Source: NCBI Gene 966 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary CD59 deficiency (Strong, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 121 total — 4 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 12
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000611

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1689
Approved symbol	CD59
Name	CD59 molecule (CD59 blood group)
Location	11p13
Locus type	gene with protein product
Status	Approved
Aliases	16.3A5, EJ16, EJ30, EL32, G344, p18-20
Ensembl gene	ENSG00000085063
Ensembl biotype	protein_coding
OMIM	107271
Entrez	966

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 31 protein_coding, 1 retained_intron

ENST00000351554, ENST00000395850, ENST00000415002, ENST00000426650, ENST00000437761, ENST00000445143, ENST00000527577, ENST00000528700, ENST00000528987, ENST00000533403, ENST00000642928, ENST00000643183, ENST00000651485, ENST00000651785, ENST00000652086, ENST00000652678, ENST00000706436, ENST00000873801, ENST00000873802, ENST00000873803, ENST00000873804, ENST00000873805, ENST00000873806, ENST00000873807, ENST00000873808, ENST00000938901, ENST00000969476, ENST00000969477, ENST00000969478, ENST00000969479, ENST00000969480, ENST00000969481

RefSeq mRNA: 8 — MANE Select: NM_000611 NM_000611, NM_001127223, NM_001127225, NM_001127226, NM_001127227, NM_203329, NM_203330, NM_203331

CCDS: CCDS7886

Canonical transcript exons

ENST00000642928 — 4 exons

Exon	Start	End
ENSE00000824399	33722379	33722463
ENSE00003903673	33736382	33736423
ENSE00003995841	33703010	33710343
ENSE00003995842	33717370	33717471

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 261.2579 / max 2711.9429, expressed in 1820 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119217	250.2485	1820
119205	3.6043	1100
119219	2.2775	1367
119212	1.3798	764
119213	1.3587	750
119218	1.2803	923
119214	0.4609	216
119215	0.4479	195
119216	0.1752	44
206244	0.0248	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.78	gold quality
bronchial epithelial cell	CL:0002328	99.69	gold quality
right lung	UBERON:0002167	99.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.63	gold quality
gall bladder	UBERON:0002110	99.60	gold quality
epithelium of bronchus	UBERON:0002031	99.58	gold quality
upper lobe of left lung	UBERON:0008952	99.58	gold quality
minor salivary gland	UBERON:0001830	99.57	gold quality
bronchus	UBERON:0002185	99.54	gold quality
upper lobe of lung	UBERON:0008948	99.53	gold quality
saliva-secreting gland	UBERON:0001044	99.48	gold quality
smooth muscle tissue	UBERON:0001135	99.47	gold quality
tibial nerve	UBERON:0001323	99.47	gold quality
dorsal root ganglion	UBERON:0000044	99.43	gold quality
right lobe of thyroid gland	UBERON:0001119	99.42	gold quality
right coronary artery	UBERON:0001625	99.41	gold quality
left coronary artery	UBERON:0001626	99.41	gold quality
descending thoracic aorta	UBERON:0002345	99.41	gold quality
heart right ventricle	UBERON:0002080	99.40	gold quality
metanephros cortex	UBERON:0010533	99.40	gold quality
peritoneum	UBERON:0002358	99.38	gold quality
omental fat pad	UBERON:0010414	99.38	gold quality
islet of Langerhans	UBERON:0000006	99.37	gold quality
coronary artery	UBERON:0001621	99.37	gold quality
left lobe of thyroid gland	UBERON:0001120	99.36	gold quality
thoracic aorta	UBERON:0001515	99.36	gold quality
ascending aorta	UBERON:0001496	99.35	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.34	gold quality
thyroid gland	UBERON:0002046	99.32	gold quality
lower esophagus	UBERON:0013473	99.32	gold quality

Single-cell (SCXA)

Detected in 30 experiment(s), a significant marker in 27.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	4331.53
E-MTAB-8495	yes	3286.03
E-GEOD-75688	yes	1994.94
E-MTAB-8322	yes	1679.32
E-HCAD-1	yes	1380.39
E-GEOD-130473	yes	1287.23
E-MTAB-10553	yes	1255.43
E-HCAD-4	yes	145.55
E-MTAB-10287	yes	87.78
E-GEOD-134144	yes	51.06
E-HCAD-11	yes	49.34
E-MTAB-6701	yes	48.27
E-MTAB-9467	yes	47.56
E-CURD-46	yes	42.28
E-GEOD-135922	yes	41.37

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, NFKB, REST, TP53

miRNA regulators (miRDB)

164 targeting CD59, 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-3924	100.00	72.09	2394
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-574-5P	100.00	66.01	989
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The complement inhibitor CD59 and the lymphocyte function-associated antigen-3 (LFA-3, CD58) genes possess functional binding sites for the p53 tumor suppressor protein. (PMID:12553064)
• Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59. (PMID:12645951)
• CD59 is an adaptor for ecto-calreticulin in neutrophils (PMID:12646570)
• Although CD55 and CD59 deficiency in primary or secondary AIHA, it appears that this defect plays a facilitator rather than a triggering role for the hemolytic process. (PMID:12880676)
• CD59 is physically associated with NKp46 and NKp30 and activate human nk cell-mediated cytotoxicity. (PMID:14635045)
• Complement regulatory proteins such as MCP and CD59 are expressed in the human and wild-type embryonic brain. (PMID:14962294)
• Presence of CD59 on Purkinje cells at various levels in eight of 14 cases with no cerebellar pathology suggests that Purkinje cells not expressing CD59 could be especially prone to complement-mediated damage. (PMID:15147772)
• 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)
• During respiratory syncytial virus assembly in Hep2 cells, the cellular distribution of the complement regulatory protein, CD59 changes and high levels of this cellular protein are incorporated into mature virus filaments. (PMID:15351205)
• Prostasomes from cancer cells had higher expression of CD59 than those of normal cells. (PMID:15389819)
• Glycation inactivation of hCD59 leads to increased membrane attack complex deposition may contribute to the extensive vascular pathology that complicates human diabetes. (PMID:15448097)
• Streptococcus intermedius intermedilysin specifically binds to huCD59 via residues that are the binding site for the C8alpha and C9 complement proteins (PMID:15543155)
• Both mutant CD59 had the anti-complement activity, which was weakened after glycosylation. (PMID:15766396)
• CD55-CD59- deficient granulocytes and red blood cells predicts responsse to immunosuppressive agents in aplastic anemia. (PMID:16179371)
• demonstrated by site-directed mutagenesis that mutated CD59 was more susceptible to glycation-inactivation for hyperglycemia (PMID:16274631)
• CD59 on target cells enhances the cytotoxicity of natural killer cells, an effect dependent on the glycosylphosphatidylinositol anchor in CD59. (PMID:16493049)
• The expression of CD59 is up-regulated after atorvastatin treatment independently of blood lipids. (PMID:16563273)
• analysis of the CD59-C9 binding interaction (PMID:16844690)
• Upregulation of CD59 and decay-accelerating factor by atorvastatin in hypoxia prevented deposition of C3, C9 and cell lysis that follows exposure of reoxygenated vascular endothelial cells to serum. (PMID:16859540)
• CD55/59 deficiency in Campath-treated patients with paroxysmal nocturnal hemoglobinuria msay indicate that deficiency could predispose to a complication of this immunosuppressive therapy. (PMID:16908271)
• HHV-7 infection causes elevation of the CRPs CD46 and CD59, which may be a possible mechanism for HHV-7 to evade humoral immunity via complement. (PMID:17412968)
• When compared with previous models of CD59 determined using NMR, some interesting differences are noted, including the position of helix alpha1, which contributes to the binding surface for C8 and C9. (PMID:17505110)
• These results suggest that IRE1alpha-mediated mRNA cleavage functions even in mammals as a common system to regulate gene expression. (PMID:17585877)
• Essential for the protection of neurons in the NT2-N teratocarcinoma cell line against complement attack. (PMID:17635812)
• 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)
• Electron-density map of recombinant CD59 crystals shows an as yet unidentified small molecule in the predicted C8/C9-binding site. (PMID:17671359)
• Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by absence of CD59 from the surface of affected granulocytes. (PMID:18158579)
• up-regulation of CD59 via ERK5/KLF2 activation leads to endothelial resistance to complement-mediated injury and protects from atherogenesis in regions of laminar shear stress (PMID:18362151)
• erythrocytes are deficient in CD55 and/or CD59 in HIV patients (PMID:18443552)
• Results indicate that W40 of human CD59 is important to its activity, and prohibition of this site may be a potential way to increase complement activity and to treat tumors (PMID:18445344)
• Adenovirus-mediated delivery of hCD59 to retinal pigment epithelium, or cornea culturee protects these cells from membrane attach comlpex-mediated ddamage. (PMID:18487376)
• Expression levels of CD47, CD35, CD55, and CD59 on red blood cells and signal-regulatory protein-alpha,beta on monocytes from patients with warm autoimmune hemolytic anemia. (PMID:18954403)
• In prostate cancer cells in culture, delta-catenin was co-localized with caveolin-1 and CD59, suggesting its potential excretion into extracellular milieu through exosome/prostasome associated pathways. (PMID:19116988)
• Complement regulator CD59 protects against atherosclerosis by restricting the formation of complement membrane attack complex. (PMID:19131645)
• CD59 is trafficked to the cytoplasmic inclusion by a Golgi apparatus-independent pathway during a Chlamydia cell infection. [CD59] (PMID:19168743)
• A peptide modeled on the CD59-binding site inhibits intermedilysin-mediated haemolysis suggesting that such peptides might be useful in treating infections caused by intermedilysin-producing bacteria. (PMID:19200600)
• Variants within protectin (CD59) genes linked to an inherited haplotype in a family with coeliac disease (PMID:19254252)
• Total plasma cholesterol levels in female CD59(-/-)ApoE(-/-) mice were found to be elevated compared with CD59(+/+)ApoE(-/-) mice. (PMID:19297024)
• CD59 expression is increased on activated CD4-positive T cells; blocking CD59 on CD4-positive T cells increases the immune response to tumor antigens in individuals with cancer. (PMID:19380765)
• Neutralization of complement regulatory proteins CD55 and CD59 augments therapeutic effect of herceptin against lung carcinoma cells. (PMID:19424617)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd59a	ENSMUSG00000032679
mus_musculus	Cd59b	ENSMUSG00000068686
rattus_norvegicus	Cd59b	ENSRNOG00000042821

Paralogs (3): SLURP1 (ENSG00000126233), LYPD1 (ENSG00000150551), LYPD2 (ENSG00000197353)

Protein

Protein identifiers

CD59 glycoprotein — P13987 (reviewed: P13987)

Alternative names: 1F5 antigen, 20 kDa homologous restriction factor, MAC-inhibitory protein, MEM43 antigen, Membrane attack complex inhibition factor, Membrane inhibitor of reactive lysis, Protectin

All UniProt accessions (8): P13987, A0A2U3TZL5, A0A494C059, A0A494C0W4, A0A499FJN7, A0A9L9PXZ4, E9PI80, Q6FHM9

UniProt curated annotations — full annotation on UniProt →

Function. Potent inhibitor of the complement membrane attack complex (MAC) action, which protects human cells from damage during complement activation. Acts by binding to the beta-haipins of C8 (C8A and C8B) components of the assembling MAC, forming an intermolecular beta-sheet that prevents incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore. The soluble form from urine retains its specific complement binding activity, but exhibits greatly reduced ability to inhibit complement membrane attack complex (MAC) assembly on cell membranes.

Subunit / interactions. Interacts with T-cell surface antigen CD2.

Subcellular location. Cell membrane. Secreted.

Post-translational modifications. N- and O-glycosylated. The N-glycosylation mainly consists of a family of biantennary complex-type structures with and without lactosamine extensions and outer arm fucose residues. Also significant amounts of triantennary complexes (22%). Variable sialylation also present in the Asn-43 oligosaccharide. The predominant O-glycans are mono-sialylated forms of the disaccharide, Gal-beta-1,3GalNAc, and their sites of attachment are probably on Thr-76 and Thr-77. The GPI-anchor of soluble urinary CD59 has no inositol-associated phospholipid, but is composed of seven different GPI-anchor variants of one or more monosaccharide units. Major variants contain sialic acid, mannose and glucosamine. Sialic acid linked to an N-acetylhexosamine-galactose arm is present in two variants. Glycated. Glycation is found in diabetic subjects, but only at minimal levels in nondiabetic subjects. Glycated CD59 lacks MAC-inhibitory function and confers to vascular complications of diabetes.

Disease relevance. Hemolytic anemia, CD59-mediated, with or without polyneuropathy (HACD59) [MIM:612300] An autosomal recessive disorder characterized by infantile onset of chronic hemolysis and a relapsing-remitting polyneuropathy, often exacerbated by infection, and manifested as hypotonia, limb muscle weakness, and hyporeflexia. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
P13987-1	1	yes
P13987-2	2

RefSeq proteins (8): NP_000602, NP_001120695, NP_001120697, NP_001120698, NP_001120699, NP_976074, NP_976075, NP_976076 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016054	LY6_UPA_recep-like	Domain
IPR018363	CD59_antigen_CS	Conserved_site
IPR045860	Snake_toxin-like_sf	Homologous_superfamily
IPR056949	CD59	Family

Pfam: PF25152

UniProt features (44 total): mutagenesis site 18, strand 7, disulfide bond 5, glycosylation site 4, helix 3, signal peptide 1, chain 1, splice variant 1, sequence variant 1, propeptide 1, domain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
2J8B	X-RAY DIFFRACTION	1.15
2UWR	X-RAY DIFFRACTION	1.34
2UX2	X-RAY DIFFRACTION	1.8
2OFS	X-RAY DIFFRACTION	2.12
5IMY	X-RAY DIFFRACTION	2.4
8CN6	X-RAY DIFFRACTION	2.43
5IMT	X-RAY DIFFRACTION	2.7
8B0F	ELECTRON MICROSCOPY	3
8B0G	ELECTRON MICROSCOPY	3.3
8B0H	ELECTRON MICROSCOPY	3.3
4BIK	X-RAY DIFFRACTION	3.49
6ZD0	ELECTRON MICROSCOPY	4.6
1CDQ	SOLUTION NMR
1CDR	SOLUTION NMR
1CDS	SOLUTION NMR
1ERG	SOLUTION NMR
1ERH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13987-F1	80.15	0.54

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 (1): 102

Disulfide bonds (5): 31–38, 44–64, 70–88, 89–94, 28–51

Glycosylation sites (4): 43, 66, 76, 77

Mutagenesis-validated functional residues (18):

Position	Phenotype
29	no loss of function.
33	no loss of function.
37	no loss of function.
48	some loss of function. some lysis.
49	loss of function. lysis.
58	no loss of function.
63	no loss of function.
65	complete loss of function. lysis.
66	no loss of function.
66	loss of glycation mediated inactivation.
67	no loss of function.
69	loss of glycation mediated inactivation.
72	almost complete loss of function. lysis.
78	loss of function. lysis.
79	no loss of function.
81	almost complete loss of function. lysis.
82	no loss of function.
87	no loss of function.

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-5694530	Cargo concentration in the ER
R-HSA-6798695	Neutrophil degranulation
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-977606	Regulation of Complement cascade
R-HSA-166658	Complement cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-948021	Transport to the Golgi and subsequent modification

MSigDB gene sets: 336 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, MACLACHLAN_BRCA1_TARGETS_DN, KAAB_FAILED_HEART_ATRIUM_DN, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOCC_CELL_SURFACE, REACTOME_MEMBRANE_TRAFFICKING, GOBP_WOUND_HEALING, CAIRO_HEPATOBLASTOMA_CLASSES_DN, MARTINEZ_RB1_TARGETS_UP, GOBP_REGULATION_OF_IMMUNE_RESPONSE, MODULE_75, GOBP_COMPLEMENT_ACTIVATION, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN

GO Biological Process (8): negative regulation of activation of membrane attack complex (GO:0001971), cell surface receptor signaling pathway (GO:0007166), blood coagulation (GO:0007596), regulation of complement activation (GO:0030449), negative regulation of complement activation (GO:0045916), regulation of complement-dependent cytotoxicity (GO:1903659), negative regulation of complement-dependent cytotoxicity (GO:1903660), complement activation (GO:0006956)

GO Molecular Function (3): complement binding (GO:0001848), protein sequestering activity (GO:0140311), protein binding (GO:0005515)

GO Cellular Component (17): Golgi membrane (GO:0000139), obsolete extracellular space (GO:0005615), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), focal adhesion (GO:0005925), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), ER to Golgi transport vesicle membrane (GO:0012507), membrane (GO:0016020), transport vesicle (GO:0030133), vesicle (GO:0031982), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), specific granule membrane (GO:0035579), extracellular exosome (GO:0070062), tertiary granule membrane (GO:0070821), extracellular region (GO:0005576), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	3
Innate Immune System	2
Complement cascade	1
Immune System	1
Membrane Trafficking	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Post-translational protein modification	1
Metabolism of proteins	1
Asparagine N-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
complement activation	2
complement-dependent cytotoxicity	2
protein binding	2
bounding membrane of organelle	2
membrane	2
secretory granule membrane	2
activation of membrane attack complex	1
regulation of activation of membrane attack complex	1
negative regulation of complement activation	1
signal transduction	1
hemostasis	1
wound healing	1
coagulation	1
regulation of immune effector process	1
regulation of humoral immune response	1
negative regulation of immune effector process	1
negative regulation of humoral immune response	1
regulation of complement activation	1
regulation of cell killing	1
negative regulation of cell killing	1
regulation of complement-dependent cytotoxicity	1
immune effector process	1
activation of immune response	1
humoral immune response	1
protein activation cascade	1
molecular sequestering activity	1
binding	1
Golgi apparatus	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cell periphery	1
cell-substrate junction	1
plasma membrane	1
cell surface	1
side of membrane	1
COPII-coated ER to Golgi transport vesicle	1
transport vesicle membrane	1
coated vesicle membrane	1

Protein interactions and networks

STRING

1932 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD59	CD55	P08174	981
CD59	PIGA	P37287	972
CD59	CD46	P15529	965
CD59	CD2	P06729	952
CD59	C3	P01024	838
CD59	CR1	P17927	824
CD59	CFH	P08603	823
CD59	VTN	P01141	810
CD59	ADGRE5	P48960	775
CD59	SERPING1	P05155	770
CD59	ADGRE2	Q9UHX3	756
CD59	CAV1	Q03135	751
CD59	CLU	P10909	728
CD59	CD44	P16070	726
CD59	LYNX1	P0DP58	713

IntAct

109 interactions, top by confidence:

A	B	Type	Score
GRB2	EGFR	psi-mi:“MI:0914”(association)	0.980
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CD59	HTT	psi-mi:“MI:0915”(physical association)	0.670
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
CD59	TMED10	psi-mi:“MI:0915”(physical association)	0.580
TMED2	CD59	psi-mi:“MI:0915”(physical association)	0.580
TMED10	CD59	psi-mi:“MI:0915”(physical association)	0.580
CD59	TMED10	psi-mi:“MI:0403”(colocalization)	0.580
CD59	FAM209A	psi-mi:“MI:0915”(physical association)	0.560
CD59		psi-mi:“MI:0915”(physical association)	0.560
CD59	C	psi-mi:“MI:0915”(physical association)	0.540
C	CD59	psi-mi:“MI:0915”(physical association)	0.540
CD59	C	psi-mi:“MI:0403”(colocalization)	0.540
GALK2	POTEF	psi-mi:“MI:0914”(association)	0.530
IGFBP1	SUSD5	psi-mi:“MI:0914”(association)	0.530

BioGRID (126): CD59 (Affinity Capture-MS), CD59 (Affinity Capture-MS), CD59 (Affinity Capture-MS), CD59 (Affinity Capture-MS), CD59 (Affinity Capture-MS), CD59 (Affinity Capture-MS), CD59 (Affinity Capture-MS), CD59 (Affinity Capture-MS), CD59 (Affinity Capture-MS), CD59 (Affinity Capture-MS), CD59 (Affinity Capture-MS), CD59 (Affinity Capture-MS), CD59 (Affinity Capture-MS), CD59 (Affinity Capture-MS), CD59 (Affinity Capture-MS)

ESM2 similar proteins: A0JNB3, A0JNL5, A6NC86, H3BJG9, H3BQJ8, O55186, O94772, O95867, P05533, P0CW02, P0CW03, P0DTL4, P13987, P35456, P35459, P35460, P35461, P46657, P47777, P49616, P57096, P58019, Q03405, Q05588, Q14210, Q148C3, Q28216, Q28785, Q32PB3, Q4R5M8, Q5R510, Q63317, Q64253, Q6UWN5, Q6UX82, Q80ZQ0, Q8K1T6, Q8SQ46, Q8TDM5, Q924B5

Diamond homologs: O55186, O62680, O77541, P13987, P27274, P46657, P47777, P51447, P58019, Q00996, Q28216, Q28785, Q5R510, Q8SQ46, P35459, P55000

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	7
Uncertain significance	34
Likely benign	60
Benign	2

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
100766	NM_000611.6(CD59):c.146del (p.Asp49fs)	Pathogenic
18052	NM_000611.6(CD59):c.123del (p.Val42fs)	Pathogenic
4848546	NM_000611.6(CD59):c.146A>T (p.Asp49Val)	Pathogenic
64690	NM_000611.6(CD59):c.266G>A (p.Cys89Tyr)	Pathogenic
1685256	NM_000611.6(CD59):c.83G>A (p.Cys28Tyr)	Likely pathogenic
3027278	NM_000611.6(CD59):c.183_184dup (p.Asn62fs)	Likely pathogenic
3599565	NM_000611.6(CD59):c.301del (p.Glu101fs)	Likely pathogenic
3599566	NM_000611.6(CD59):c.190del (p.Cys64fs)	Likely pathogenic
3599567	NM_000611.6(CD59):c.143_144del (p.Asp47_Phe48insTer)	Likely pathogenic
3599568	NM_000611.6(CD59):c.2T>C (p.Met1Thr)	Likely pathogenic
3778882	NM_000611.6(CD59):c.282del (p.Leu93_Cys94insTer)	Likely pathogenic

SpliceAI

669 predictions. Top by Δscore:

Variant	Effect	Δscore
11:33710342:CC:C	acceptor_gain	1.0000
11:33710343:CCTG:C	acceptor_gain	1.0000
11:33717363:CTCTT:C	donor_loss	1.0000
11:33717364:TCTTA:T	donor_loss	1.0000
11:33717365:CTTAC:C	donor_loss	1.0000
11:33717366:TTA:T	donor_loss	1.0000
11:33717367:TA:T	donor_loss	1.0000
11:33717368:A:AC	donor_gain	1.0000
11:33717368:ACCA:A	donor_loss	1.0000
11:33717369:C:A	donor_loss	1.0000
11:33717369:C:CC	donor_gain	1.0000
11:33717369:CCAG:C	donor_gain	1.0000
11:33722374:CTCA:C	donor_loss	1.0000
11:33722375:TCA:T	donor_loss	1.0000
11:33722376:CACCT:C	donor_loss	1.0000
11:33722377:A:AC	donor_gain	1.0000
11:33722377:A:T	donor_loss	1.0000
11:33722378:C:CC	donor_gain	1.0000
11:33722460:GAACC:G	acceptor_loss	1.0000
11:33722461:AACCT:A	acceptor_loss	1.0000
11:33722463:CCT:C	acceptor_loss	1.0000
11:33722464:C:CC	acceptor_gain	1.0000
11:33722464:CTGG:C	acceptor_loss	1.0000
11:33722465:T:A	acceptor_loss	1.0000
11:33736380:ACCT:A	donor_loss	1.0000
11:33710343:CCTGT:C	acceptor_loss	0.9900
11:33710344:C:CC	acceptor_gain	0.9900
11:33710344:CTGTG:C	acceptor_loss	0.9900
11:33710345:T:A	acceptor_loss	0.9900
11:33716887:CCA:C	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000051887 (11:33713198 A>G,T), RS1000093285 (11:33716613 C>T), RS1000166933 (11:33716840 T>C), RS1000212737 (11:33735604 A>G), RS1000318094 (11:33735244 A>C), RS1000340633 (11:33703574 G>A), RS1000438215 (11:33722630 A>G), RS1000498558 (11:33718473 ACT>A), RS1000653155 (11:33733511 T>C), RS1000793588 (11:33705069 T>C), RS1000917536 (11:33703873 G>A,C,T), RS1001003957 (11:33711911 G>A), RS1001063198 (11:33735747 T>C), RS1001214648 (11:33728298 G>T), RS1001232986 (11:33735293 C>T)

Disease associations

OMIM: gene MIM:107271 | disease phenotypes: MIM:612300

GenCC curated gene-disease

Disease	Classification	Inheritance
primary CD59 deficiency	Strong	Autosomal recessive

Mondo (1): primary CD59 deficiency (MONDO:0012858)

Orphanet (1): Primary CD59 deficiency (Orphanet:169464)

HPO phenotypes

12 total (12 of 12 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001252	Hypotonia
HP:0001271	Polyneuropathy
HP:0001284	Areflexia
HP:0001290	Generalized hypotonia
HP:0001878	Hemolytic anemia
HP:0002922	Increased CSF protein concentration
HP:0003202	Skeletal muscle atrophy
HP:0003470	Paralysis
HP:0003593	Infantile onset
HP:0003690	Limb muscle weakness
HP:0004818	Paroxysmal nocturnal hemoglobinuria

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST006585_240	Blood protein levels	1.000000e-14
GCST007565_99	Morning person	1.000000e-27
GCST007576_296	Chronotype	1.000000e-27
GCST010136_39	Fruit consumption	1.000000e-10
GCST010989_96	Body size at age 10	6.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0008111	diet measurement
EFO:0009819	comparative body size at age 10, self-reported

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567355	CD59 Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724795 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.51	IC50	310	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178890: Inhibition of CD59 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.3100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation, increases mutagenesis	4
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	3
Cisplatin	decreases expression, affects cotreatment	3
Tobacco Smoke Pollution	affects expression, increases expression, decreases expression	3
Valproic Acid	decreases expression, increases expression	3
Cyclosporine	decreases expression	3
sodium arsenite	decreases expression, increases mutagenesis	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Dimethyl Sulfoxide	decreases reaction, increases mutagenesis	2
Doxorubicin	affects expression, decreases expression	2
Hydrogen Peroxide	decreases reaction, increases mutagenesis	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Asbestos, Crocidolite	increases mutagenesis, decreases reaction	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
4-hydroxy-7-oxo-5-heptenoic acid lactone	increases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
lead acetate	increases mutagenesis	1
beta-lapachone	increases expression	1
tetrachloroethane	increases mutagenesis	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
ICG 001	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697620	Binding	Inhibition of CD59 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7WK	Abcam Raji CD59 KO	Cancer cell line	Male
CVCL_B9X5	Abcam THP-1 CD59 KO	Cancer cell line	Male
CVCL_C6Z2	Abcam PC-3 CD59 KO	Cancer cell line	Male
CVCL_SH88	HAP1 CD59 (-) 1	Cancer cell line	Male
CVCL_SH89	HAP1 CD59 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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