ADAMTS13

Summary

ADAMTS13 (ADAM metallopeptidase with thrombospondin type 1 motif 13, HGNC:1366) is a protein-coding gene on chromosome 9q34.2, encoding A disintegrin and metalloproteinase with thrombospondin motifs 13 (Q76LX8). Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation.

This gene encodes a member of a family of proteins containing several distinct regions, including a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. The enzyme encoded by this gene specifically cleaves von Willebrand Factor (vWF). Defects in this gene are associated with thrombotic thrombocytopenic purpura. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 11093 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital thrombotic thrombocytopenic purpura (Definitive, ClinGen)
• GWAS associations: 18
• Clinical variants (ClinVar): 1,207 total — 62 pathogenic, 53 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_139027

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1366
Approved symbol	ADAMTS13
Name	ADAM metallopeptidase with thrombospondin type 1 motif 13
Location	9q34.2
Locus type	gene with protein product
Status	Approved
Aliases	VWFCP, TTP, vWF-CP, FLJ42993, MGC118899, MGC118900, DKFZp434C2322
Ensembl gene	ENSG00000160323
Ensembl biotype	protein_coding
OMIM	604134
Entrez	11093

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000355699, ENST00000356589, ENST00000371910, ENST00000371911, ENST00000371916, ENST00000371929, ENST00000474918, ENST00000485925, ENST00000495234, ENST00000908290

RefSeq mRNA: 3 — MANE Select: NM_139027 NM_139025, NM_139026, NM_139027

CCDS: CCDS6970, CCDS6971, CCDS6972

Canonical transcript exons

ENST00000355699 — 29 exons

Exon	Start	End
ENSE00001135494	133429939	133430101
ENSE00001668874	133428634	133428771
ENSE00003466340	133442614	133442743
ENSE00003503578	133439366	133439446
ENSE00003507978	133425938	133426062
ENSE00003510596	133426199	133426345
ENSE00003515051	133443376	133443561
ENSE00003530088	133425529	133425612
ENSE00003537605	133436829	133436955
ENSE00003539970	133433378	133433529
ENSE00003543257	133432588	133432692
ENSE00003552932	133423101	133423167
ENSE00003556187	133455285	133455435
ENSE00003559969	133442399	133442534
ENSE00003561184	133457910	133458094
ENSE00003561950	133437749	133437897
ENSE00003579270	133424321	133424478
ENSE00003581683	133458974	133459386
ENSE00003581763	133444863	133445052
ENSE00003613557	133445699	133445819
ENSE00003627054	133454415	133454619
ENSE00003634854	133456543	133456719
ENSE00003650188	133449783	133449965
ENSE00003653630	133438246	133438366
ENSE00003659551	133440344	133440525
ENSE00003676185	133448599	133448728
ENSE00003684694	133456069	133456215
ENSE00003688033	133433641	133433704
ENSE00003904238	133422367	133422548

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 94.10.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2127 / max 48.4695, expressed in 84 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99274	0.0982	31
99276	0.0964	37
99275	0.0182	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	94.10	gold quality
liver	UBERON:0002107	90.06	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.31	gold quality
right uterine tube	UBERON:0001302	87.50	gold quality
cerebellar hemisphere	UBERON:0002245	87.18	gold quality
cerebellar cortex	UBERON:0002129	87.05	gold quality
cerebellum	UBERON:0002037	86.98	gold quality
right frontal lobe	UBERON:0002810	85.74	gold quality
right testis	UBERON:0004534	85.69	gold quality
left testis	UBERON:0004533	85.64	gold quality
testis	UBERON:0000473	84.52	gold quality
primary visual cortex	UBERON:0002436	84.14	gold quality
pituitary gland	UBERON:0000007	84.05	gold quality
apex of heart	UBERON:0002098	83.52	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.22	gold quality
putamen	UBERON:0001874	82.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.56	gold quality
adenohypophysis	UBERON:0002196	82.49	gold quality
Ammon’s horn	UBERON:0001954	82.40	gold quality
brain	UBERON:0000955	82.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.90	gold quality
anterior cingulate cortex	UBERON:0009835	81.80	gold quality
cerebral cortex	UBERON:0000956	81.73	gold quality
temporal lobe	UBERON:0001871	81.56	gold quality
amygdala	UBERON:0001876	81.53	gold quality
nucleus accumbens	UBERON:0001882	81.52	gold quality
caudate nucleus	UBERON:0001873	81.40	gold quality
frontal cortex	UBERON:0001870	81.35	gold quality
body of stomach	UBERON:0001161	80.49	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.09	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	502.60
E-ANND-3	no	0.86

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, ELK1, SP1, STAT3

miRNA regulators (miRDB)

12 targeting ADAMTS13, 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-3148	99.97	75.06	6478
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-1263	98.13	69.18	459
HSA-MIR-7850-5P	98.12	67.28	1111
HSA-MIR-596	97.48	63.13	469
HSA-MIR-4462	95.10	66.27	172

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• incodes a zinc proteinase involved in thrombotic thrombocytopenic purpura (PMID:11586344)
• mutation of gene causes thrombotic thrombocytopenic purpura (PMID:11586351)
• VWF-CPis composed of a single polypeptide with a molecular mass of approx. 190 kD,and cDNA cloning indicated it is uniquely produced in the liver. Its gene is on chromosome 9q34. (PMID:11843286)
• role of the vWF protease and vWF proteolysis in the pathogenesis of bone marrow transplant-associated thrombotic microangiopathy of the fulminant type (PMID:11920264)
• Complete defect in vWF-cleaving protease activity is associated with increased shear-induced platelet aggregation in thrombotic microangiopathy. (PMID:12038781)
• An acquired deficiency of vWF-CP due to an autoantibody is associated with responsiveness to plasma exchange therapy in TTP. Patients whose TTP is not caused by autoimmunity to vWF-CP may not respond to PE. (PMID:12084165)
• Deficiency of vWF-cp activity in patients with colon cancer was shown to be associated with the progression of the disease and metastasis. (PMID:12091044)
• A severely deficient activity is specific for thrombotic thrombocytopenic purpura. (PMID:12091372)
• ADAMTS13 is deficient in recurrent and familial thrombotic thrombocytopenic purpura and hemolytic uremic syndrome; its activity level cannot be used to distingush between TTP and HUS. (PMID:12130486)
• REVIEW: role of ADAMTS13 mutations and deficiencies in thrombotic microangiopathies (PMID:12172456)
• mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity (PMID:12181489)
• role of variation in modulating risk of thrombosis in cardiovascular disorders (PMID:12195022)
• a sensitive blood indicator for diagnosing thrombocytopenic thrombotic purpura (PMID:12223999)
• ADAMTS-13 rapidly cleaves newly secreted ultralarge VWF multimers on the vascular endothelial surface under flowing conditions (PMID:12393397)
• Cloning, expression, and functional characterization of the von Willebrand factor-cleaving protease (ADAMTS13). (PMID:12393399)
• Mutation analysis of the ADAMTS13 gene in the childhood TTP patients deficient in VWF-CP by direct sequencing of all 29 exons identified 8 different mutations. (PMID:12393505)
• vWF proteolysis by ADAMTS13 is critical in regulating vWF-platelet interaction and set the stage for improving the diagnosis and treatment of thrombotic thrombocytopenic purpura. (PMID:12395148)
• This article reviews the role of this cleavage in regulating vWF-platelet interaction and proposes a scheme for understanding how a deficiency of ADAMTS13 results in the development of microthrombi in patients with thrombotic thrombocytopenic purpura. (PMID:12615692)
• deficiency of ADAMTS13 is a molecular mechanism responsible for familial thrombotic thrombocytopenic purpura (PMID:12753286)
• high titers of IgM and IgG antibodies that bound to ADAMTS-13, but did not neutralize protease activity, in a patient with thrombotic thrombocytopenic purpura probably influenced the half-life of ADAMTS-13 or its binding to the endothelial cell surface. (PMID:12855569)
• truncation of the cysteine-rich/spacer domains caused a remarkable reduction in VWF-CP activity (PMID:12869506)
• REVIEW: mechanisms by which defects in ADAMTS13 cause TTP (PMID:12871390)
• REVIEW: defects in ADAMTS13 cause TTP and HUS (PMID:12871391)
• Acquired deficiency of this enzyme causes Schistocytic anaemia, severe thrombocytopenia, and renal dysfunction (PMID:12923577)
• The ADAMTS13 propeptide is not required for folding or secretion, and does not perform the common function of maintaining enzyme latency. (PMID:12975358)
• VWF73 is a specific substrate for ADAMTS-13 (PMID:14512308)
• Severe deficiency of the von Willebrand Factor (VWF)-cleaving proteinase, ADAMTS13, is associated with the development of thrombotic thrombocytopenic purpura (PMID:14512317)
• an amino acid polymorphism in VWF may influence susceptibility to ADAMTS13 proteolysis (PMID:14525793)
• Molecular models of the metalloprotease, fifth domain of thrombospondin 1 (Tsp1-5), and Tsp1-8 domains of ADAMTS13 suggest that the missense mutations could cause structural defects in the mutants. (PMID:14563640)
• No significant difference in ADAMTS-13 activity between the age- and sex-matched patients with benign and malignant brain tumors nor between the age matched patients with prostatic cancer. (PMID:14644076)
• REVIEW: role in thrombotic thrombocytopenic purpura (PMID:14727254)
• REVIEW: processing of von Willebrand factor by ADAMTS-13 on endothelial cells (PMID:14727255)
• REVIEW: recent advances in cell culture expression and functional characterization of human rADAMTS-13 (PMID:14727256)
• REVIEW: mutations in hereditary thrombotic thrombocytopenic purpura (PMID:14727257)
• the substitution of ADAMTS-13 by means of recombinant drug instead of plasma (PMID:14727259)
• REVIEW: ADAMTS-13 deficiency in childhood (PMID:14727263)
• thrombotic microangiopathy with severe ADAMTS13 deficiency is a distinct pathologic process. (PMID:14962303)
• ADAMTS13 auto-antibodies from 25 patients with severe ADAMTS13 deficiency (acquired thrombotic thrombocytopenia purpura) was evaluated in vitro (PMID:14976043)
• Role of ADAMTS13 mutations in the pathogenesis of congenital thrombotic thrombocytopenic purpura. (PMID:15009458)
• The metalloprotease ADAMTS-13 cleaves von Willebrand factor (VWF) at the Y842/M843 peptide bond located in the A2 domain. (PMID:15009467)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adamts13	ENSDARG00000076270
mus_musculus	Adamts13	ENSMUSG00000014852
rattus_norvegicus	Adamts13	ENSRNOG00000005780

Paralogs (25): ADAMTS6 (ENSG00000049192), ADAMTS2 (ENSG00000087116), PAPLN (ENSG00000100767), ADAMTS8 (ENSG00000134917), ADAMTS7 (ENSG00000136378), ADAMTS14 (ENSG00000138316), ADAMTS17 (ENSG00000140470), ADAMTS18 (ENSG00000140873), ADAMTS10 (ENSG00000142303), ADAMTSL4 (ENSG00000143382), ADAMTS16 (ENSG00000145536), ADAMTS19 (ENSG00000145808), ADAMTS12 (ENSG00000151388), ADAMTS1 (ENSG00000154734), ADAMTS5 (ENSG00000154736), ADAMTS3 (ENSG00000156140), ADAMTSL3 (ENSG00000156218), ADAMTS4 (ENSG00000158859), ADAMTS9 (ENSG00000163638), ADAMTS15 (ENSG00000166106), ADAMTS20 (ENSG00000173157), ADAMTSL1 (ENSG00000178031), ADAMTSL5 (ENSG00000185761), THSD4 (ENSG00000187720), ADAMTSL2 (ENSG00000197859)

Protein

Protein identifiers

A disintegrin and metalloproteinase with thrombospondin motifs 13 — Q76LX8 (reviewed: Q76LX8)

Alternative names: von Willebrand factor-cleaving protease

All UniProt accessions (5): Q76LX8, A0A0B4J229, A0A0C4DFV8, E7EV88, F6V803

UniProt curated annotations — full annotation on UniProt →

Function. Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation.

Subcellular location. Secreted.

Tissue specificity. Plasma. Expressed primarily in liver.

Post-translational modifications. Glycosylated. O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS13. May also be C-glycosylated on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and also N-glycosylated. These other glycosylations can also facilitate secretion. The precursor is processed by a furin endopeptidase which cleaves off the pro-domain.

Disease relevance. Thrombotic thrombocytopenic purpura, hereditary (TTP) [MIM:274150] An autosomal recessive hematologic disease characterized by hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and non-focal neurologic findings, decreased renal function and fever. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Zinc and calcium ions cooperatively modulate enzyme activity. The cleavage of the pro-domain is not required for protease activity. Dependence on calcium for proteolytic activity is mediated by the high affinity site.

Cofactor. Binds 1 zinc ion per subunit. Binds 4 Ca(2+) ions.

Domain organisation. The pro-domain is not required for folding or secretion and does not perform the common function of maintening enzyme latency. The globular cysteineless spacer domain adopts a jelly-roll topology, and is necessary to recognize and cleave vWF. The C-terminal TSP type-1 and CUB domains may modulate this interaction.

Polymorphism. Genetic variations in ADAMTS13 coding region influence plasmatic ADAMTS13 activity levels. Dependent on the sequence context, the same polymorphisms might be either positive or negative modifiers of gene expression, thereby altering the phenotype of ADAMTS13 deficiency.

Isoforms (4)

UniProt ID	Names	Canonical?
Q76LX8-1	1	yes
Q76LX8-2	2
Q76LX8-3	3
Q76LX8-4	4

RefSeq proteins (3): NP_620594, NP_620595, NP_620596* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000884	TSP1_rpt	Repeat
IPR001590	Peptidase_M12B	Domain
IPR006586	ADAM_Cys-rich	Domain
IPR010294	ADAMTS_spacer1	Domain
IPR013273	ADAMTS/ADAMTS-like	Family
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR041645	ADAMTS_CR_2	Domain
IPR045371	ADAMTS_CR_3	Domain
IPR050439	ADAMTS_ADAMTS-like	Family

Pfam: PF00090, PF01421, PF05986, PF17771, PF19030, PF19236

Enzyme classification (BRENDA):

• EC 3.4.24.87 — ADAMTS13 endopeptidase (BRENDA: 8 organisms, 140 substrates, 55 inhibitors, 28 Km, 22 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
VWF73 PEPTIDE	0.0017–0.022	8
VWF115	0.0009–0.59	4
FRET-VWF115 PEPTIDE	0.0013–0.0043	2
VON WILLEBRAND FACTOR 115	0.0006–0.0016	2
VWF115 D1614A MUTANT	0.37–0.47	2
DREQAPNLVYMVTGNPASDEIKRLPGDIQVVPIGVGPNANVQELERIG	0.0066	1
FRETS-VON WILLEBRAND FACTOR 73	0.0032	1
FRETSVWF73 PEPTIDE	0.0058	1
HRPH-A2-B	0.0003	1

UniProt features (219 total): sequence variant 61, strand 55, glycosylation site 18, helix 15, disulfide bond 15, mutagenesis site 14, domain 12, binding site 11, splice variant 5, turn 4, region of interest 3, signal peptide 1, propeptide 1, sequence conflict 1, short sequence motif 1, active site 1, chain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3GHM	X-RAY DIFFRACTION	2.6
3GHN	X-RAY DIFFRACTION	2.8
3VN4	X-RAY DIFFRACTION	2.8
6QIG	X-RAY DIFFRACTION	2.8
7B01	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q76LX8-F1	76.00	0.31

Antibody-complex structures (SAbDab): 1 — 6QIG

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): 225

Ligand- & substrate-binding residues (11): 83; 173; 182; 184; 187; 212; 224; 228; 234; 281; 284

Disulfide bonds (15): 155–208, 202–281, 242–265, 311–337, 322–347, 332–366, 360–371, 396–433, 400–438, 411–423, 450–487, 483–522, 508–527, 532–548, 545–555

Glycosylation sites (18): 142, 146, 387, 399, 552, 579, 614, 667, 698, 707, 757, 828, 907, 965, 1027, 1087, 1235, 1354

Mutagenesis-validated functional residues (14):

Position	Phenotype
71	abolishes pro-domain removal but no loss of proteolytic activity; when associated with d-73.
73	abolishes pro-domain removal but no loss of proteolytic activity; when associated with k-71.
83	no change in calcium dependence for proteolysis.
173	no change in calcium dependence for proteolysis.
184	dramatically reduced affinity for calcium.
187	dramatically reduced affinity for calcium.
212	dramatically reduced affinity for calcium.
399	no effect on cleavage of vwf and little change in secretion of adamts13. abolishes secretion of adamts13; when associate
698	no effect on cleavage of vwf and greatly reduced secretion of adamts13. abolishes secretion of adamts13; when associated
757	no effect on cleavage of vwf and little change in secretion of adamts13.
907	no effect on cleavage of vwf and greatly reduced secretion of adamts13. abolishes most of the secretion of adamts13; whe
965	no effect on cleavage of vwf and little change in secretion of adamts13. abolishes most of the secretion of adamts13; wh
1027	no effect on cleavage of vwf and little change in secretion of adamts13. abolishes most of the secretion of adamts13; wh
1087	no effect on cleavage of vwf and little change in secretion of adamts13. abolishes most of the secretion of adamts13; wh

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-5083635	Defective B3GALTL causes PpS
R-HSA-5173214	O-glycosylation of TSR domain-containing proteins
R-HSA-75892	Platelet Adhesion to exposed collagen
R-HSA-9769739	Regulation of clotting cascade
R-HSA-9845619	Enhanced cleavage of VWF variant by ADAMTS13
R-HSA-9845621	Defective VWF cleavage by ADAMTS13 variant
R-HSA-109582	Hemostasis
R-HSA-1643685	Disease
R-HSA-3781865	Diseases of glycosylation
R-HSA-3906995	Diseases associated with O-glycosylation of proteins
R-HSA-392499	Metabolism of proteins
R-HSA-5173105	O-linked glycosylation
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification
R-HSA-9671793	Diseases of hemostasis
R-HSA-9823587	Defects of platelet adhesion to exposed collagen

MSigDB gene sets: 151 (showing top): GCACCTT_MIR18A_MIR18B, TGGTGCT_MIR29A_MIR29B_MIR29C, RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, FREAC2_01, GOBP_RESPONSE_TO_AMINE, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_RESPONSE_TO_INTERLEUKIN_4, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_PLATELET_ACTIVATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOCC_CELL_SURFACE, GOBP_RESPONSE_TO_POTASSIUM_ION

GO Biological Process (21): proteolysis (GO:0006508), cell-matrix adhesion (GO:0007160), integrin-mediated signaling pathway (GO:0007229), blood coagulation (GO:0007596), glycoprotein metabolic process (GO:0009100), response to toxic substance (GO:0009636), response to amine (GO:0014075), protein processing (GO:0016485), protein catabolic process (GO:0030163), platelet activation (GO:0030168), extracellular matrix organization (GO:0030198), response to potassium ion (GO:0035864), peptide catabolic process (GO:0043171), cellular response to lipopolysaccharide (GO:0071222), cellular response to type II interferon (GO:0071346), cellular response to interleukin-4 (GO:0071353), cellular response to tumor necrosis factor (GO:0071356), hemostasis (GO:0007599), response to type II interferon (GO:0034341), response to tumor necrosis factor (GO:0034612), response to interleukin-4 (GO:0070670)

GO Molecular Function (10): metalloendopeptidase activity (GO:0004222), integrin binding (GO:0005178), calcium ion binding (GO:0005509), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), endopeptidase activity (GO:0004175), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), cell surface (GO:0009986), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Defects of platelet adhesion to exposed collagen	2
Disease	2
Diseases associated with O-glycosylation of proteins	1
O-linked glycosylation	1
Hemostasis	1
Coagulation pathway	1
Diseases of metabolism	1
Diseases of glycosylation	1
Post-translational protein modification	1
Metabolism of proteins	1
Diseases of hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	3
cellular response to cytokine stimulus	3
response to cytokine	2
peptidase activity	2
cellular anatomical structure	2
cell-substrate adhesion	1
cell surface receptor signaling pathway	1
hemostasis	1
wound healing	1
coagulation	1
carbohydrate derivative metabolic process	1
response to chemical	1
response to nitrogen compound	1
proteolysis	1
protein maturation	1
macromolecule catabolic process	1
cell activation	1
blood coagulation	1
extracellular structure organization	1
external encapsulating structure organization	1
response to metal ion	1
peptide metabolic process	1
catabolic process	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
response to type II interferon	1
response to interleukin-4	1
response to tumor necrosis factor	1
regulation of body fluid levels	1
innate immune response	1
endopeptidase activity	1
metallopeptidase activity	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
metal ion binding	1
transition metal ion binding	1
binding	1

Protein interactions and networks

STRING

1079 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADAMTS13	VWF	P04275	991
ADAMTS13	GP1BA	P07359	931
ADAMTS13	F8	P00451	920
ADAMTS13	CFH	P08603	853
ADAMTS13	CFHR1	Q03591	832
ADAMTS13	CFHR3	Q02985	824
ADAMTS13	HP	P00737	773
ADAMTS13	DGKE	P52429	768
ADAMTS13	C3	P01024	731
ADAMTS13	THBD	P07204	721
ADAMTS13	F3	P13726	720
ADAMTS13	CFI	P05156	719
ADAMTS13	CD46	P15529	712
ADAMTS13	F2	P00734	697
ADAMTS13	CFHR5	Q9BXR6	661

IntAct

22 interactions, top by confidence:

A	B	Type	Score
ADAMTS13	VWF	psi-mi:“MI:0570”(protein cleavage)	0.790
VWF	ADAMTS13	psi-mi:“MI:0570”(protein cleavage)	0.790
ADAMTS13	VWF	psi-mi:“MI:0407”(direct interaction)	0.790
VWF	ADAMTS13	psi-mi:“MI:0407”(direct interaction)	0.790
F8	ADAMTS13	psi-mi:“MI:0407”(direct interaction)	0.440
ADAMTS13	C2CD4B	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): KIAA0232 (Affinity Capture-MS), PASK (Affinity Capture-MS), SMTNL1 (Affinity Capture-MS), CELSR2 (Affinity Capture-MS), FREM2 (Affinity Capture-MS), ALDH18A1 (Affinity Capture-MS), C2CD4B (Affinity Capture-MS), B3GALTL (Affinity Capture-MS), TCF25 (Affinity Capture-MS), FAT3 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), DICER1 (Affinity Capture-MS), PDGFC (Affinity Capture-MS), HERC1 (Affinity Capture-MS), CELSR1 (Affinity Capture-MS)

ESM2 similar proteins: A1L0T3, A1L4H1, D3ZTE0, G3V801, O08762, O43866, O75636, O95428, O97507, P00748, P22457, P56730, P58215, P69525, P69526, P85521, P98140, Q02853, Q04756, Q04962, Q24K22, Q2VL90, Q2VLG4, Q2VLG6, Q2VLH6, Q499S5, Q4G0T1, Q5G265, Q5G268, Q5G269, Q5G270, Q5G271, Q5IJ48, Q6QNF4, Q70UZ7, Q769J6, Q76LX8, Q7Z410, Q80YA8, Q80YC5

Diamond homologs: A2VEC9, A6QNY1, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, O08721, O08722, O08747, O14514, O15072, O55225, O60241, O60242, O75173, O88783, O95185, O95450, P04275, P07358, P07996, P27918, P35441, P35442, P35448, P55314, P57110, P58397, P58459, P59384, P79331, P80012, P97857, P98088, P98092, P98160, P98164

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
HBB	“down-regulates activity”	ADAMTS13
HBA1	“down-regulates activity”	ADAMTS13
ADAMTS13	“down-regulates activity”	VWF	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

1207 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	62
Likely pathogenic	53
Uncertain significance	489
Likely benign	347
Benign	80

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1163033	NM_139027.6(ADAMTS13):c.1177C>T (p.Arg393Ter)	Pathogenic
1705385	NM_139027.6(ADAMTS13):c.3242G>A (p.Trp1081Ter)	Pathogenic
1705645	NM_139027.6(ADAMTS13):c.85G>T (p.Gly29Ter)	Pathogenic
1804165	NM_139027.6(ADAMTS13):c.1169G>A (p.Trp390Ter)	Pathogenic
1928771	NM_139027.6(ADAMTS13):c.1128_1132del (p.Glu376fs)	Pathogenic
2004982	NM_139027.6(ADAMTS13):c.2920_2938del (p.Ile974fs)	Pathogenic
2029124	NM_139027.6(ADAMTS13):c.870_876del (p.Gly291fs)	Pathogenic
2128690	NM_139027.6(ADAMTS13):c.1335del (p.Phe445fs)	Pathogenic
2136833	NM_139027.6(ADAMTS13):c.2728C>T (p.Arg910Ter)	Pathogenic
2136834	NM_139027.6(ADAMTS13):c.3198_3199del (p.Cys1067fs)	Pathogenic
2427273	NC_000009.11:g.(?136287564)(136291485_?)del	Pathogenic
2571344	NM_139027.6(ADAMTS13):c.3288dup (p.Asp1097Ter)	Pathogenic
2636095	NM_139027.6(ADAMTS13):c.1456_1457del (p.Met486fs)	Pathogenic
2691362	NM_139027.6(ADAMTS13):c.155del (p.Pro52fs)	Pathogenic
2704373	NM_139027.6(ADAMTS13):c.3573del (p.Leu1192fs)	Pathogenic
2735365	NM_139027.6(ADAMTS13):c.3448C>T (p.Arg1150Ter)	Pathogenic
2735366	NM_139027.6(ADAMTS13):c.3567G>A (p.Trp1189Ter)	Pathogenic
2804026	NM_139027.6(ADAMTS13):c.910dup (p.Tyr304fs)	Pathogenic
2810067	NM_139027.6(ADAMTS13):c.887dup (p.Pro297fs)	Pathogenic
3065326	NM_139027.6(ADAMTS13):c.3547G>A (p.Gly1183Arg)	Pathogenic
3245397	NC_000009.11:g.(?136287564)(136298844_?)del	Pathogenic
3245398	NC_000009.11:g.(?136313700)(136315106_?)del	Pathogenic
3251337	NM_139027.6(ADAMTS13):c.799_808del (p.Arg267fs)	Pathogenic
3362787	NM_139027.6(ADAMTS13):c.722del (p.Gly241fs)	Pathogenic
3362788	NM_139027.6(ADAMTS13):c.2865G>A (p.Trp955Ter)	Pathogenic
3609672	NM_139027.6(ADAMTS13):c.3514del (p.Arg1172fs)	Pathogenic
3616186	NM_139027.6(ADAMTS13):c.196_197insCTCCCCTGGCTTCC (p.Gln66fs)	Pathogenic
3620946	NM_139027.6(ADAMTS13):c.3921_3922del (p.His1308fs)	Pathogenic
3633272	NM_139027.6(ADAMTS13):c.2414_2418dup (p.Arg807fs)	Pathogenic
3720917	NM_139027.6(ADAMTS13):c.130C>T (p.Gln44Ter)	Pathogenic

SpliceAI

5263 predictions. Top by Δscore:

Variant	Effect	Δscore
9:133414663:A:AC	donor_gain	1.0000
9:133414664:C:CC	donor_gain	1.0000
9:133424319:A:AG	acceptor_gain	1.0000
9:133424320:G:GG	acceptor_gain	1.0000
9:133424476:ATC:A	donor_gain	1.0000
9:133424477:TC:T	donor_gain	1.0000
9:133424479:G:GG	donor_gain	1.0000
9:133426343:CAGGT:C	donor_loss	1.0000
9:133426345:GGT:G	donor_loss	1.0000
9:133426346:G:C	donor_loss	1.0000
9:133426347:T:A	donor_loss	1.0000
9:133440342:A:AG	acceptor_gain	1.0000
9:133440343:G:GG	acceptor_gain	1.0000
9:133440419:T:A	acceptor_gain	1.0000
9:133440508:G:GT	donor_gain	1.0000
9:133440522:CCAG:C	donor_loss	1.0000
9:133440523:CAGG:C	donor_loss	1.0000
9:133440525:GGTC:G	donor_loss	1.0000
9:133440526:GTCA:G	donor_loss	1.0000
9:133440535:A:T	donor_gain	1.0000
9:133454616:GGAG:G	donor_gain	1.0000
9:133454617:GAG:G	donor_gain	1.0000
9:133454617:GAGG:G	donor_gain	1.0000
9:133454618:AGGT:A	donor_loss	1.0000
9:133454619:GGTG:G	donor_loss	1.0000
9:133454620:G:GC	donor_loss	1.0000
9:133454620:G:GG	donor_gain	1.0000
9:133454621:T:G	donor_loss	1.0000
9:133414663:ACT:A	donor_gain	0.9900
9:133414664:CT:C	donor_gain	0.9900

AlphaMissense

8881 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:133428733:G:C	W262C	0.996
9:133428733:G:T	W262C	0.996
9:133433446:G:C	W387C	0.994
9:133433446:G:T	W387C	0.994
9:133454613:G:C	W1081C	0.994
9:133454613:G:T	W1081C	0.994
9:133454418:G:C	W1016C	0.993
9:133454418:G:T	W1016C	0.993
9:133430045:T:A	C311S	0.992
9:133430046:G:C	C311S	0.992
9:133433455:G:C	W390C	0.992
9:133433455:G:T	W390C	0.992
9:133436930:G:C	W470C	0.992
9:133436930:G:T	W470C	0.992
9:133449786:G:C	W955C	0.992
9:133449786:G:T	W955C	0.992
9:133426296:G:C	D213H	0.991
9:133442494:G:C	W688C	0.991
9:133442494:G:T	W688C	0.991
9:133425994:G:C	W157C	0.990
9:133425994:G:T	W157C	0.990
9:133432609:T:A	C337S	0.990
9:133432610:G:C	C337S	0.990
9:133425986:T:A	C155S	0.989
9:133425987:G:A	C155Y	0.989
9:133425987:G:C	C155S	0.989
9:133426333:A:T	E225V	0.989
9:133428731:T:A	W262R	0.989
9:133428731:T:C	W262R	0.989
9:133432678:T:A	C360S	0.989

dbSNP variants (sampled 300 via entrez): RS1000027729 (9:133450156 G>C), RS1000072422 (9:133414106 C>T), RS1000073885 (9:133438342 T>A,C), RS1000157935 (9:133451200 C>T), RS1000163674 (9:133421475 T>C), RS1000220449 (9:133450186 G>A,T), RS1000259246 (9:133429626 A>C,G,T), RS1000270539 (9:133452732 AT>A), RS1000343275 (9:133440697 C>T), RS1000390382 (9:133440917 G>A), RS1000395664 (9:133438077 T>C), RS1000395755 (9:133450971 G>A), RS1000524015 (9:133442297 A>C,G), RS1000555105 (9:133442599 C>T), RS1000586973 (9:133415624 C>T)

Disease associations

OMIM: gene MIM:604134 | disease phenotypes: MIM:274150

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital thrombotic thrombocytopenic purpura	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital thrombotic thrombocytopenic purpura	Definitive	AR

Mondo (4): congenital thrombotic thrombocytopenic purpura (MONDO:0010122), thrombotic thrombocytopenic purpura (MONDO:0018896), atypical hemolytic-uremic syndrome (MONDO:0016244), thrombocytopenia (MONDO:0002049)

Orphanet (3): Congenital thrombotic thrombocytopenic purpura (Orphanet:93583), Thrombotic thrombocytopenic purpura (Orphanet:54057), Atypical hemolytic uremic syndrome (Orphanet:2134)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000952	Jaundice
HP:0001289	Confusion
HP:0001297	Stroke
HP:0001337	Tremor
HP:0001658	Myocardial infarction
HP:0001873	Thrombocytopenia
HP:0001923	Reticulocytosis
HP:0001937	Microangiopathic hemolytic anemia
HP:0001945	Fever
HP:0001981	Schistocytosis
HP:0002098	Respiratory distress
HP:0002151	Increased circulating lactate concentration
HP:0002326	Transient ischemic attack
HP:0002907	Microscopic hematuria
HP:0003138	Increased blood urea nitrogen
HP:0003259	Elevated circulating creatinine concentration
HP:0005575	Hemolytic-uremic syndrome
HP:0006579	Prolonged neonatal jaundice
HP:0012211	Abnormal renal physiology

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000248_5	Liver enzyme levels	8.000000e-21
GCST001574_9	Activated partial thromboplastin time	9.000000e-100
GCST001793_1	Coagulation factor levels	4.000000e-34
GCST001793_4	Coagulation factor levels	1.000000e-128
GCST002553_4	Pancreatic cancer	2.000000e-16
GCST002881_1	ADAMTS13 activity	1.000000e-20
GCST002881_3	ADAMTS13 activity	1.000000e-63
GCST002930_12	Cobalt levels	5.000000e-06
GCST003854_49	Gut microbiota (functional units)	3.000000e-06
GCST004598_3	vWF levels in ischaemic stroke and hyperhomocysteinaemia	6.000000e-08
GCST005945_1	ADAMTS13 levels	1.000000e-57
GCST005945_3	ADAMTS13 levels	1.000000e-30
GCST005945_4	ADAMTS13 levels	9.000000e-09
GCST006491_13	Circulating fibroblast growth factor 23 levels	1.000000e-07
GCST010725_19	Malaria	9.000000e-11
GCST010725_31	Malaria	9.000000e-21
GCST010725_98	Malaria	1.000000e-19
GCST90002389_356	Lymphocyte percentage of white cells	9.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement
EFO:0006955	ADAMTS13 activity measurement
EFO:0007874	gut microbiome measurement
EFO:0008011	a disintegrin and metalloproteinase with thrombospondin motifs 13 measurement
EFO:0007993	lymphocyte percentage of leukocytes

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D065766	Atypical Hemolytic Uremic Syndrome	C12.050.351.968.419.936.463.500; C12.200.777.419.936.463.500; C12.950.419.936.463.500; C15.378.050.141.610.500; C15.378.140.855.925.500.500; C15.378.243.937.925.500.500
D011697	Purpura, Thrombotic Thrombocytopenic	C15.378.100.802.687.680; C15.378.140.855.925.750.680; C15.378.243.937.925.750.680; C15.378.925.850; C23.550.414.950.687.680; C23.888.885.687.687.680
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2346492 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — M12: Astacin/Adamalysin

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, increases mutagenesis	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
afuresertib	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	decreases methylation	1
bisphenol Z	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Methapyrilene	decreases methylation	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Toluene	decreases expression, increases methylation	1
Paclitaxel	affects cotreatment, decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2352582	Binding	Inhibition of ADAMTS-13 (unknown origin)	A series of thiazole derivatives bearing thiazolidin-4-one as non-competitive ADAMTS-5 (aggrecanase-2) inhibitors. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04767828	PHASE4	UNKNOWN	A Single Arm Study of Brain Metastasis in Patients With HER2-positive Breast Cancer
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
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT00411801	PHASE3	TERMINATED	Safety and Efficacy Study to Compare Uniplas With Cryosupernatant Plasma in Thrombotic Thrombocytopenic Purpura (TTP)
NCT00713193	PHASE3	COMPLETED	Study of Cyclosporine or Corticosteroids as an Adjunct to Plasma Exchange in Thrombotic Thrombocytopenic Purpura (TTP)
NCT00799773	PHASE3	TERMINATED	Evaluating the Effectiveness of Adding Rituximab to Standard Treatment for Thrombotic Thrombocytopenic Purpura (TTP)
NCT03237819	PHASE3	UNKNOWN	Magnesium Sulfate in Thrombotic Thrombocytopenic Purpura in Intensive Care
NCT03393975	PHASE3	COMPLETED	A Study of BAX 930 in Children, Teenagers, and Adults Born With Thrombotic Thrombocytopenic Purpura (TTP)
NCT04683003	PHASE3	ACTIVE_NOT_RECRUITING	A Study of TAK-755 in Participants With Congenital Thrombotic Thrombocytopenic Purpura
NCT05468320	PHASE3	COMPLETED	Caplacizumab and Immunosuppressive Therapy Without Firstline Therapeutic Plasma Exchange in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura
NCT02949128	PHASE3	COMPLETED	Study of ALXN1210 in Complement Inhibitor Treatment-Naïve Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT03131219	PHASE3	COMPLETED	Study of Ravulizumab in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT03205995	PHASE3	TERMINATED	Safety and Efficacy Study of OMS721 in Patients With Atypical Hemolytic Uremic Syndrome
NCT04861259	PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT04889430	PHASE3	COMPLETED	Efficacy and Safety of Iptacopan (LNP023) in Adult Patients With Atypical Hemolytic Uremic Syndrome Naive to Complement Inhibitor Therapy
NCT04958265	PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Pediatric Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT05795140	PHASE3	RECRUITING	Evaluate Long-term Safety, Tolerability and Efficacy of Iptacopan in Study Participants With aHUS
NCT05935215	PHASE3	RECRUITING	Efficacy and Safety of Switching From Anti-C5 Antibody Treatment to Iptacopan Treatment in Study Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma