ADAMTS13

Chr 9AR

ADAM metallopeptidase with thrombospondin type 1 motif 13

Also known as: ADAM-TS13, ADAMTS-13, C9orf8, VWFCP, vWF-CP

NCBI Gene: 11093 ENSG00000160323 UniProt: Q76LX8

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. [provided by RefSeq, Jul 2013]

Primary Disease Associations & Inheritance

Thrombotic thrombocytopenic purpura, hereditaryMIM #274150

Active trials

Pathogenic / LP

382

ClinVar variants

Pubs (1 yr)

1.6

Missense Z

0.68

LOEUF

Clinical Summary— ADAMTS13

🧬

Gene-Disease Validity (ClinGen)

congenital thrombotic thrombocytopenic purpura · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

34 Pathogenic / Likely Pathogenic· 244 VUS of 382 total submissions

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Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

📖

GeneReview available — ADAMTS13

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.68LOEUF

pLI 0.000

Z-score 3.70

OE 0.52 (0.39–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.56Z-score

OE missense 0.85 (0.80–0.90)

734 obs / 863.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.52 (0.39–0.68)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.80–0.90)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94

0≤1.21.6

LoF obs/exp: 35 / 67.9Missense obs/exp: 734 / 863.1Syn Z: 0.86

0.6744th %ile

GOF

0.7126th %ile

LOF

0.2678th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

382 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17

Likely Pathogenic17

VUS244

Likely Benign81

Benign6

Conflicting17

Pathogenic

Likely Pathogenic

244

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	8	1	8	0	17
Likely Pathogenic	7	5	5	0	17
VUS	3	214	15	12	244
Likely Benign	0	4	32	45	81
Benign	0	1	4	1	6
Conflicting	—				17
Total	18	225	64	58	382

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ADAMTS13 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — ADAMTS13

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Septic Shock

Therapeutic Plasma Exchange in Septic Shock: A Pilot Study

RECRUITING

NCT05093075Phase PHASE2University of ManitobaStarted 2023-06-01

Therapeutic Plasma Exchange

MASLDLiver Cirrhosis, AlcoholicCirrhosis of Liver

Acquisition of Cardiac Function Parameters in MRI and Echocardiography in Patients with Ethyltoxic Liver Cirrhosis and Transjugular Intrahepatic Portosystemic Shunt (TIPSS) Placement

RECRUITING

NCT06814990Phase NAStephanie GrägerStarted 2024-04-19

Cardiac MRIBlood samplesEchocardiography

Acute Respiratory Distress Syndrome

Association Between the Level of EV-TF and the Occurence of Pulmonary Embolism in Patients With ARDS

RECRUITING

NCT05855317Assistance Publique Hopitaux De MarseilleStarted 2023-10-31

Blood sample

Acute Liver Failure

ALSS - DPMAS and Therapeutic Plasma Exchange (TPE), Its Effect on Primary Coagulation, Inflammation and the Function of Vital Organs in ALF or ACLF

RECRUITING

NCT07329036Phase NAInstitute for Clinical and Experimental MedicineStarted 2024-04-01

The artificial liver support system (ALSS) - DPMAS/TPE

Liver CirrhosisPortal Hypertension

Exploration of Systemic and Portal Hemostasis in Patients Undergoing Transjugular Intrahepatic Portosystemic Shunt Placement

RECRUITING

NCT07439939Assistance Publique - Hôpitaux de ParisStarted 2026-04-02

Septic Shock

Efficacy of Add-on Plasma Exchange As an Adjunctive Strategy Against Septic Shock

RECRUITING

NCT05726825Phase NAHannover Medical SchoolStarted 2025-02-19

Therapeutic Plasma Exchange (TPE)

Immune-mediated Thrombotic Thrombocytopenic Purpura

A Pilot Study of Efgartigimod for Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)

RECRUITING

NCT06831058Phase PHASE2University of MinnesotaStarted 2025-05-01

efgartigimod

Venous Thromboembolism (VTE)NSCLC (Advanced Non-small Cell Lung Cancer)

Effects of Genomic Profiles on Thromboembolic Risk in Patients With Locally Advanced or Metastatic Non-small-cell Lung Cancer

RECRUITING

NCT07288632University Of PerugiaStarted 2024-02-09

Thrombotic Thrombocytopenic Purpura (TTP)

A Study to Learn More About the Treatment of People With Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Who Received Recombinant ADAMTS13 (rADAMTS13) as Part of the Early Access Program

NOT YET RECRUITING

NCT07429942TakedaStarted 2026-03-13

No Intervention

Thrombotic Thrombocytopenic Purpura

Aspirin for Prophylaxis of TTP

NOT YET RECRUITING

NCT05568147Phase PHASE2, PHASE3The First Affiliated Hospital of Soochow UniversityStarted 2022-10-01

Aspirin tabletPlacebo

Venous Thromboembolism

Variations in the Hemostatic System Induced by a Standardized Walking Test

RECRUITING

NCT06418633Phase NACentre Hospitalier Universitaire de NīmesStarted 2025-02-11