GeneBe

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Thrombotic thrombocytopenic purpura, hereditary (Schulman-Upshaw syndrome)ARHematologic; ObstetricMedical management (eg, with administration of plasma; trials of recombinant ADAMTS13 have also had promising results) can be beneficial; Specific treatment in pregnancy may be indicatedHematologic; Neurologic; Renal14443744; 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 (633 variants)
  • Upshaw-Schulman_syndrome (401 variants)
  • Inborn_genetic_diseases (143 variants)
  • not_specified (74 variants)
  • ADAMTS13-related_disorder (49 variants)
  • Thrombotic_thrombocytopenic_purpura (9 variants)
  • Atypical_hemolytic-uremic_syndrome (3 variants)
  • Thrombus (3 variants)
  • See_cases (3 variants)
  • Thrombocytopenia (2 variants)
  • Abnormal_bleeding (2 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. These statistics are base on transcript: NM_000139027.6. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
24
clinvar
162
clinvar
7
clinvar
 193
missense
12
clinvar
30
clinvar
395
clinvar
44
clinvar
3
clinvar
 484
nonsense
14
clinvar
8
clinvar
1
clinvar
 23
start loss
0
frameshift
24
clinvar
9
clinvar
4
clinvar
 37
splice donor/acceptor (+/-2bp)
2
clinvar
15
clinvar
1
clinvar
1
clinvar
 19
Total 52 62 425 207 10

Highest pathogenic variant AF is 0.0010946

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ADAMTS13protein_codingprotein_codingENST00000371929 2945031
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
5.14e-151.001256760721257480.000286
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.567348630.8500.00005829105
Missense in Polyphen176235.340.747862683
Synonymous0.8643373580.9420.00002412976
Loss of Function3.703567.90.5150.00000333740

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0007960.000779
Ashkenazi Jewish0.0001000.0000992
East Asian0.0005600.000544
Finnish0.00009300.0000924
European (Non-Finnish)0.0002330.000229
Middle Eastern0.0005600.000544
South Asian0.0003050.000294
Other0.0005280.000489

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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