ADAMTS13

ADAM metallopeptidase with thrombospondin type 1 motif 13, the group of ADAM metallopeptidases with thrombospondin type 1 motif

Basic information

Region (hg38): 9:133414358-133459402

Previous symbols: [ "C9orf8" ]

Links

ENSG00000160323 ∙ NCBI:11093 ∙ OMIM:604134 ∙ HGNC:1366 ∙ Uniprot:Q76LX8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital thrombotic thrombocytopenic purpura (Strong), mode of inheritance: AR
• congenital thrombotic thrombocytopenic purpura (Strong), mode of inheritance: AR
• congenital thrombotic thrombocytopenic purpura (Supportive), mode of inheritance: AR
• congenital thrombotic thrombocytopenic purpura (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thrombotic thrombocytopenic purpura, hereditary (Schulman-Upshaw syndrome)	AR	Hematologic; Obstetric	Medical management (eg, with administration of plasma; trials of recombinant ADAMTS13 have also had promising results) can be beneficial; Specific treatment in pregnancy may be indicated	Hematologic; Neurologic; Renal	14443744; 651994; 7290149; 11530798; 11586351; 12181489; 12576319; 12637323; 19055667; 38692292

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADAMTS13 gene.

• not provided (26 variants)
• Upshaw-Schulman syndrome (9 variants)
• Thrombotic thrombocytopenic purpura (2 variants)
• ADAMTS13-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADAMTS13 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			9	120	12	141
missense	9	13	213	29	6	270
nonsense	9	4				13
start loss						0
frameshift	14	2	3			19
inframe indel			2			2
splice donor/acceptor (+/-2bp)		11	1	1		13
splice region			18	22	1	41
non coding			7	74	62	143
Total	32	30	235	224	80

Highest pathogenic variant AF is 0.000112

Variants in ADAMTS13

This is a list of pathogenic ClinVar variants found in the ADAMTS13 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-133414666-C-T		not specified	Uncertain significance (Jan 31, 2023)
9-133414714-C-T		not specified	Likely benign (May 30, 2023)
9-133414773-T-C		not specified	Likely benign (Oct 05, 2023)
9-133414800-C-T		not specified	Uncertain significance (Dec 21, 2022)
9-133414878-G-A		not specified	Uncertain significance (Oct 05, 2021)
9-133414885-C-T		not specified	Uncertain significance (Mar 01, 2024)
9-133414964-G-C		not specified	Uncertain significance (Apr 08, 2024)
9-133414972-G-A		not specified	Uncertain significance (Dec 14, 2023)
9-133414980-T-C		not specified	Uncertain significance (Jan 26, 2023)
9-133417632-C-A		not specified	Uncertain significance (Jul 21, 2021)
9-133417638-G-C		not specified	Uncertain significance (Jun 11, 2021)
9-133417681-G-A		not specified	Likely benign (Mar 20, 2024)
9-133417708-C-A		not specified	Uncertain significance (May 31, 2023)
9-133417752-G-C		not specified	Uncertain significance (Jan 26, 2022)
9-133417796-C-T		not specified	Uncertain significance (Jun 17, 2024)
9-133421761-G-A			Benign (Jun 18, 2021)
9-133422087-T-C		Upshaw-Schulman syndrome	Benign/Likely benign (Jun 18, 2021)
9-133422164-G-A		Upshaw-Schulman syndrome	Uncertain significance (Jun 14, 2016)
9-133422276-C-T		Upshaw-Schulman syndrome	Likely benign (Apr 27, 2017)
9-133422289-C-T		Upshaw-Schulman syndrome	Uncertain significance (Jan 13, 2018)
9-133422392-C-G		Upshaw-Schulman syndrome	Uncertain significance (Jan 13, 2018)
9-133422418-C-T		Upshaw-Schulman syndrome	Uncertain significance (Jan 12, 2018)
9-133422453-C-T			Uncertain significance (Oct 05, 2022)
9-133422458-C-T		Upshaw-Schulman syndrome	Conflicting classifications of pathogenicity (May 18, 2022)
9-133422459-C-T			Uncertain significance (Aug 19, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADAMTS13	protein_coding	protein_coding	ENST00000371929	29	45031

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.14e-15	1.00	125676	0	72	125748	0.000286

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.56	734	863	0.850	0.0000582	9105
Missense in Polyphen		176	235.34	0.74786		2683
Synonymous	0.864	337	358	0.942	0.0000241	2976
Loss of Function	3.70	35	67.9	0.515	0.00000333	740

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000796	0.000779
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.000560	0.000544
Finnish	0.0000930	0.0000924
European (Non-Finnish)	0.000233	0.000229
Middle Eastern	0.000560	0.000544
South Asian	0.000305	0.000294
Other	0.000528	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation. {ECO:0000269|PubMed:19880749}.
• Disease: DISEASE: Thrombotic thrombocytopenic purpura congenital (TTP) [MIM:274150]: A hematologic disease characterized by hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and non-focal neurologic findings, decreased renal function and fever. recessive. {ECO:0000269|PubMed:11586351, ECO:0000269|PubMed:12181489, ECO:0000269|PubMed:12393505, ECO:0000269|PubMed:12614216, ECO:0000269|PubMed:12753286, ECO:0000269|PubMed:14512317, ECO:0000269|PubMed:14563640, ECO:0000269|PubMed:15009458, ECO:0000269|PubMed:15126318, ECO:0000269|PubMed:15327386, ECO:0000269|PubMed:16160007, ECO:0000269|PubMed:16449289, ECO:0000269|PubMed:16453338, ECO:0000269|PubMed:16796708, ECO:0000269|PubMed:16807643, ECO:0000269|PubMed:17003922, ECO:0000269|PubMed:18443791, ECO:0000269|PubMed:19055667, ECO:0000269|PubMed:19116307, ECO:0000269|PubMed:22075512}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Post-translational protein modification;Metabolism of proteins;O-glycosylation of TSR domain-containing proteins;O-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.129

Intolerance Scores

• loftool: 0.523
• rvis_EVS: 0.62
• rvis_percentile_EVS: 83.42

Haploinsufficiency Scores

• pHI: 0.0682
• hipred: N
• hipred_score: 0.332
• ghis: 0.542

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.150

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Adamts13
• Phenotype: homeostasis/metabolism phenotype; vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; hematopoietic system phenotype; pigmentation phenotype; immune system phenotype

Gene ontology

• Biological process: proteolysis;cell-matrix adhesion;integrin-mediated signaling pathway;glycoprotein metabolic process;response to toxic substance;response to amine;protein processing;platelet activation;response to potassium ion;peptide catabolic process;cellular response to lipopolysaccharide;cellular response to interferon-gamma;cellular response to interleukin-4;cellular response to tumor necrosis factor
• Cellular component: extracellular space;endoplasmic reticulum lumen;cell surface;extracellular matrix
• Molecular function: metalloendopeptidase activity;integrin binding;calcium ion binding;protein binding;metallopeptidase activity;zinc ion binding