ADAMTS3

ADAM metallopeptidase with thrombospondin type 1 motif 3, the group of ADAM metallopeptidases with thrombospondin type 1 motif

Basic information

Region (hg38): 4:72280969-72569221

Links

ENSG00000156140 ∙ NCBI:9508 ∙ OMIM:605011 ∙ HGNC:219 ∙ Uniprot:O15072 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hennekam lymphangiectasia-lymphedema syndrome 3 (Moderate), mode of inheritance: AR
• Hennekam syndrome (Supportive), mode of inheritance: AR
• hennekam lymphangiectasia-lymphedema syndrome 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hennekam lymphangiectasia-lymphedema syndrome 3	AR	Endocrine; Gastrointestinal	The condition can include manifestations such as protein-losing enteropathy, and awareness may allow prompt diagnosis and management (such as nutrition via feeding tube), Endocrine manifestations such as growth hormone deficiency have been observed, and awareness may allow prompt recognition and treatment	Craniofacial; Gastrointestinal	28985353

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADAMTS3 gene.

• Hennekam lymphangiectasia-lymphedema syndrome 3 (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADAMTS3 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				17	3	20
missense			71	6	8	85
nonsense	1					1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	2	3	6
non coding					2	2
Total	1	0	71	23	13

Highest pathogenic variant AF is 0.00000657

Variants in ADAMTS3

This is a list of pathogenic ClinVar variants found in the ADAMTS3 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-72283167-C-G		Inborn genetic diseases	Uncertain significance (Mar 27, 2023)
4-72283170-C-T		Inborn genetic diseases	Uncertain significance (Jun 17, 2024)
4-72283234-C-T		Inborn genetic diseases	Uncertain significance (Feb 28, 2023)
4-72283244-A-C		Inborn genetic diseases	Likely benign (May 10, 2024)
4-72283285-G-A		Inborn genetic diseases	Uncertain significance (Jul 09, 2021)
4-72283297-T-G		Inborn genetic diseases	Uncertain significance (Nov 29, 2023)
4-72283311-G-A		ADAMTS3-related disorder	Benign (Dec 31, 2019)
4-72283365-C-T		Inborn genetic diseases	Uncertain significance (Oct 22, 2021)
4-72283384-G-A		Inborn genetic diseases	Uncertain significance (Oct 20, 2023)
4-72283389-C-T		ADAMTS3-related disorder	Benign (Jul 01, 2024)
4-72283423-C-T		Inborn genetic diseases	Uncertain significance (Jun 01, 2023)
4-72283465-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 29, 2023)
4-72283495-T-C		Inborn genetic diseases	Uncertain significance (Nov 18, 2022)
4-72283534-A-G			Benign (Dec 31, 2019)
4-72283571-G-A		ADAMTS3-related disorder	Benign (Dec 31, 2019)
4-72283583-C-A			Likely benign (Jun 01, 2024)
4-72283623-T-C		Inborn genetic diseases	Uncertain significance (Apr 24, 2024)
4-72283641-G-A		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
4-72283650-C-T		Hennekam lymphangiectasia-lymphedema syndrome 3	Uncertain significance (Mar 29, 2024)
4-72283660-C-G		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
4-72283678-T-G		Inborn genetic diseases	Uncertain significance (Oct 02, 2023)
4-72288753-T-C		Inborn genetic diseases	Uncertain significance (Dec 21, 2023)
4-72288783-G-A		Inborn genetic diseases	Uncertain significance (Dec 16, 2023)
4-72288834-C-T		Inborn genetic diseases	Uncertain significance (Aug 02, 2023)
4-72288852-C-T		Inborn genetic diseases	Uncertain significance (Dec 14, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADAMTS3	protein_coding	protein_coding	ENST00000286657	22	287831

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.03e-10	1.00	125677	0	71	125748	0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.545	641	681	0.941	0.0000369	7960
Missense in Polyphen		161	200.5	0.80299		2274
Synonymous	0.384	228	236	0.968	0.0000128	2231
Loss of Function	4.13	28	63.5	0.441	0.00000343	742

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000641	0.000632
Ashkenazi Jewish	0.000199	0.0000992
East Asian	0.000493	0.000489
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000293	0.000290
Middle Eastern	0.000493	0.000489
South Asian	0.0000980	0.0000980
Other	0.000354	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cleaves the propeptides of type II collagen prior to fibril assembly. Does not act on types I and III collagens.
• 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: 0.117

Intolerance Scores

• loftool: 0.450
• rvis_EVS: -0.65
• rvis_percentile_EVS: 16.14

Haploinsufficiency Scores

• pHI: 0.223
• hipred: N
• hipred_score: 0.466
• ghis: 0.505

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.144

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adamts3
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; liver/biliary system phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; vision/eye phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); embryo phenotype

Gene ontology

• Biological process: vascular endothelial growth factor production;protein processing;collagen fibril organization;collagen catabolic process;collagen biosynthetic process;supramolecular fiber organization;positive regulation of vascular endothelial growth factor signaling pathway
• Cellular component: extracellular region;extracellular space;extracellular matrix;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: endopeptidase activity;metalloendopeptidase activity;protein binding;heparin binding;zinc ion binding