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.

not_specified (119 variants)
not_provided (6 variants)
Premature_ovarian_failure (1 variants)

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. These statistics are base on transcript: NM_000007038.5. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	2 clinvar	3
missense			120 clinvar		3 clinvar	123
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	120	1	5

Loading clinvar variants...

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