ADAMTS5

ADAM metallopeptidase with thrombospondin type 1 motif 5, the group of ADAM metallopeptidases with thrombospondin type 1 motif

Basic information

Region (hg38): 21:26917922-26967088

Links

ENSG00000154736 ∙ NCBI:11096 ∙ OMIM:605007 ∙ HGNC:221 ∙ Uniprot:Q9UNA0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADAMTS5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADAMTS5 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				1	2	3
missense			54		4	58
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	54	1	6

Variants in ADAMTS5

This is a list of pathogenic ClinVar variants found in the ADAMTS5 region.

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

Position	Type	Phenotype	Significance	ClinVar
21-26924092-C-A		not specified	Uncertain significance (Sep 26, 2023)
21-26924126-C-T		not specified	Uncertain significance (Sep 14, 2023)
21-26924127-G-A		not specified	Uncertain significance (Dec 27, 2022)
21-26924129-T-G		not specified	Uncertain significance (Jun 03, 2024)
21-26924240-T-A		not specified	Uncertain significance (Mar 14, 2023)
21-26924303-C-A		not specified	Uncertain significance (Dec 05, 2022)
21-26924375-G-T		not specified	Uncertain significance (Sep 13, 2023)
21-26924418-C-T		not specified	Uncertain significance (Nov 12, 2021)
21-26924456-G-A		not specified	Uncertain significance (Aug 26, 2022)
21-26924466-T-G		not specified	Uncertain significance (Dec 17, 2023)
21-26924547-C-T		not specified	Uncertain significance (Dec 02, 2022)
21-26924564-C-T		not specified	Uncertain significance (Dec 19, 2023)
21-26929907-A-G		not specified	Uncertain significance (Jan 04, 2024)
21-26929921-G-C		not specified	Uncertain significance (Jan 09, 2024)
21-26929935-C-T		Premature ovarian failure	Uncertain significance (Mar 02, 2020)
21-26930030-C-T		not specified	Uncertain significance (Dec 20, 2023)
21-26930035-C-T			Benign (Feb 09, 2018)
21-26930036-A-G			Benign (Feb 23, 2021)
21-26932140-C-T		not specified	Uncertain significance (Dec 12, 2023)
21-26932149-G-A		not specified	Uncertain significance (Dec 06, 2021)
21-26932168-G-A		not specified	Uncertain significance (Dec 06, 2021)
21-26932893-C-T			Benign (Jul 15, 2020)
21-26932926-C-A		not specified	Uncertain significance (Mar 29, 2022)
21-26933010-G-T		not specified	Uncertain significance (Apr 24, 2024)
21-26934524-T-C		not specified	Uncertain significance (Feb 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADAMTS5	protein_coding	protein_coding	ENST00000284987	8	48602

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.03e-7	0.999	125707	0	41	125748	0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.768	488	538	0.907	0.0000292	5947
Missense in Polyphen		173	234.62	0.73738		2589
Synonymous	-1.56	258	228	1.13	0.0000130	1926
Loss of Function	2.93	16	34.6	0.463	0.00000164	418

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000454	0.000454
Ashkenazi Jewish	0.00	0.00
East Asian	0.000278	0.000272
Finnish	0.000126	0.0000924
European (Non-Finnish)	0.000135	0.000132
Middle Eastern	0.000278	0.000272
South Asian	0.000261	0.000261
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Metalloproteinase that plays an important role in connective tissue organization, development, inflammation, arthritis, and cell migration. ADAMTS5 is an extracellular matrix (ECM) degrading enzyme that show proteolytic activity toward the hyalectan group of chondroitin sulfate proteoglycans (CSPGs) including aggrecan, versican, brevican and neurocan (PubMed:16133547, PubMed:18992360). Cleavage within the hyalectans occurs at Glu-Xaa recognition motifs. Plays a role in embryonic development, including limb and cardiac morphogenesis, and skeletal muscle development through its versican remodeling properties. Participates in development of brown adipose tissue and browning of white adipose tissue. Plays an important role for T-lymphocyte migration from draining lymph nodes following viral infection. {ECO:0000250|UniProtKB:Q9R001, ECO:0000269|PubMed:16133547, ECO:0000269|PubMed:18992360}.
• Pathway: Vitamin D Receptor Pathway;Endochondral Ossification;Post-translational protein modification;Metabolism of proteins;Extracellular matrix organization;Degradation of the extracellular matrix;O-glycosylation of TSR domain-containing proteins;O-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.252

Intolerance Scores

• loftool: 0.324
• rvis_EVS: 0.25
• rvis_percentile_EVS: 69.62

Haploinsufficiency Scores

• pHI: 0.373
• hipred: Y
• hipred_score: 0.716
• ghis: 0.449

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.292

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adamts5
• Phenotype: cellular 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); skeleton phenotype; immune system phenotype; limbs/digits/tail phenotype; normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: proteolysis;extracellular matrix disassembly;defense response to bacterium;tooth eruption;negative regulation of cold-induced thermogenesis
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum lumen;extracellular matrix;collagen-containing extracellular matrix
• Molecular function: metalloendopeptidase activity;integrin binding;protein binding;heparin binding;metallopeptidase activity;zinc ion binding;extracellular matrix binding