ADAMTS2

ADAM metallopeptidase with thrombospondin type 1 motif 2, the group of ADAM metallopeptidases with thrombospondin type 1 motif

Basic information

Region (hg38): 5:179110853-179345461

Links

ENSG00000087116 ∙ NCBI:9509 ∙ OMIM:604539 ∙ HGNC:218 ∙ Uniprot:O95450 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 9.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_014244.5	NP_055059.2	22	yes	-
ENST00000251582.12	ENSP00000251582.7	22	yes	-
NM_021599.4	NP_067610.1	11	-	-
ENST00000274609.5	ENSP00000274609.5	11	-	-

Phenotypes

GenCC

Source: genCC

• Ehlers-Danlos syndrome, dermatosparaxis type (Strong), mode of inheritance: AR
• Ehlers-Danlos syndrome, dermatosparaxis type (Definitive), mode of inheritance: AR
• Ehlers-Danlos syndrome, dermatosparaxis type (Strong), mode of inheritance: AR
• Ehlers-Danlos syndrome, dermatosparaxis type (Supportive), mode of inheritance: AR
• Ehlers-Danlos syndrome, dermatosparaxis type (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ehlers-Danlos syndrome, dermatosparaxis type	AR	Obstetric	Individuals may be prone to injuries (especially during delivery, as multiple congenital skull fractures and intracranial hemorrhage have been reported), and knowledge may allow delivery-based interventions to decrease related morbidity and mortality	Craniofacial; Dermatologic; Musculoskeletal; Obstetric	1303238; 8215497; 7735500; 10417273; 15373769; 15389701; 18973246

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADAMTS2 gene.

• Ehlers-Danlos_syndrome,_dermatosparaxis_type (1649 variants)
• not_provided (364 variants)
• not_specified (211 variants)
• Inborn_genetic_diseases (195 variants)
• Ehlers-Danlos_syndrome (71 variants)
• ADAMTS2-related_disorder (41 variants)
• See_cases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADAMTS2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_014244.5. 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			27	668	5	700
missense		3	558	37	3	601
nonsense	18	19	2			39
start loss		2				2
frameshift	28	44	4			76
splice donor/acceptor (+/-2bp)		17			2	19
Total	46	85	591	705	10

Highest pathogenic variant AF is 0.00007825902

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADAMTS2	protein_coding	protein_coding	ENST00000251582	22	234580

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125665	0	83	125748	0.000330

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.43	637	747	0.853	0.0000518	7846
Missense in Polyphen		212	326.2	0.64991		3393
Synonymous	-0.390	320	311	1.03	0.0000233	2391
Loss of Function	5.59	10	54.6	0.183	0.00000275	617

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000174	0.000174
Ashkenazi Jewish	0.00299	0.00298
East Asian	0.000278	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000238	0.000237
Middle Eastern	0.000278	0.000272
South Asian	0.000361	0.000359
Other	0.000493	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cleaves the propeptides of type I and II collagen prior to fibril assembly. Does not act on type III collagen. May also play a role in development that is independent of its role in collagen biosynthesis.
• Disease: DISEASE: Ehlers-Danlos syndrome, dermatosparaxis type (EDSDERMS) [MIM:225410]: A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSDERMS is an autosomal recessive form characterized by extreme skin fragility and easy bruising, large fontanels, blue sclerae, puffy eyelids, micrognathia, umbilical hernia, and short fingers. Joint hypermobility becomes more important with age. {ECO:0000269|PubMed:10417273}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Collagen biosynthesis and modifying enzymes;Post-translational protein modification;Metabolism of proteins;Collagen formation;Extracellular matrix organization;O-glycosylation of TSR domain-containing proteins;O-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.315

Intolerance Scores

• loftool: 0.135
• rvis_EVS: -1.8
• rvis_percentile_EVS: 2.22

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.213

Gene Damage Prediction

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

Gene ontology

• Biological process: spermatogenesis;protein processing;collagen fibril organization;lung development;collagen catabolic process;skin development
• Cellular component: extracellular region;collagen-containing extracellular matrix
• Molecular function: metalloendopeptidase activity;metallopeptidase activity;zinc ion binding