ADAMTS4

ADAM metallopeptidase with thrombospondin type 1 motif 4, the group of ADAM metallopeptidases with thrombospondin type 1 motif

Basic information

Region (hg38): 1:161184301-161199054

Links

ENSG00000158859 ∙ NCBI:9507 ∙ OMIM:603876 ∙ HGNC:220 ∙ Uniprot:O75173 ∙ 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 ADAMTS4 gene.

• Inborn genetic diseases (36 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADAMTS4 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						0
missense			35	1		36
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	35	1	1

Variants in ADAMTS4

This is a list of pathogenic ClinVar variants found in the ADAMTS4 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-161191082-T-C			Benign (Aug 05, 2018)
1-161191151-G-C		not specified	Uncertain significance (Aug 28, 2023)
1-161191160-C-A		not specified	Uncertain significance (Aug 17, 2022)
1-161191161-G-A		not specified	Uncertain significance (Feb 14, 2023)
1-161191164-G-A		not specified	Uncertain significance (Oct 05, 2022)
1-161191199-A-G		not specified	Uncertain significance (Nov 13, 2023)
1-161191212-G-A		not specified	Uncertain significance (Mar 27, 2023)
1-161191248-C-T		not specified	Uncertain significance (Dec 18, 2023)
1-161191296-G-C		not specified	Uncertain significance (Mar 01, 2023)
1-161191374-G-A		not specified	Uncertain significance (Jul 25, 2023)
1-161191380-T-C		not specified	Uncertain significance (Dec 09, 2023)
1-161191484-C-T		not specified	Uncertain significance (Dec 20, 2023)
1-161191485-G-A		not specified	Uncertain significance (Mar 29, 2023)
1-161191496-T-C		not specified	Uncertain significance (Feb 28, 2023)
1-161191501-C-A		not specified	Uncertain significance (Feb 28, 2024)
1-161192159-T-C		not specified	Likely benign (Jan 16, 2024)
1-161192161-C-T		not specified	Uncertain significance (Apr 12, 2022)
1-161193214-C-T		not specified	Uncertain significance (Dec 28, 2023)
1-161193293-T-G		not specified	Uncertain significance (Jan 29, 2024)
1-161193298-C-T		not specified	Uncertain significance (Sep 01, 2021)
1-161193374-C-T		not specified	Uncertain significance (Jul 25, 2023)
1-161193666-T-C		not specified	Uncertain significance (Jan 10, 2023)
1-161193687-C-T		not specified	Uncertain significance (Mar 01, 2024)
1-161193691-G-A		not specified	Uncertain significance (May 16, 2023)
1-161193759-C-T		not specified	Uncertain significance (Jan 24, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADAMTS4	protein_coding	protein_coding	ENST00000367996	9	14749

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000195	0.999	125679	0	69	125748	0.000274

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.15	454	529	0.859	0.0000328	5321
Missense in Polyphen		170	219.24	0.77542		2269
Synonymous	0.587	209	220	0.950	0.0000133	1829
Loss of Function	2.85	15	32.5	0.461	0.00000173	337

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.000656	0.000653
Finnish	0.000631	0.000601
European (Non-Finnish)	0.000268	0.000264
Middle Eastern	0.000656	0.000653
South Asian	0.000294	0.000294
Other	0.000492	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. Could also be a critical factor in the exacerbation of neurodegeneration in Alzheimer disease. Cleaves aggrecan at the '392-Glu-|-Ala-393' site.
• 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: 0.193

Intolerance Scores

• loftool: 0.447
• rvis_EVS: 0.09
• rvis_percentile_EVS: 60.71

Haploinsufficiency Scores

• pHI: 0.0847
• hipred: Y
• hipred_score: 0.655
• ghis: 0.398

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.172

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adamts4
• Phenotype: renal/urinary system 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); 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; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: skeletal system development;proteolysis;extracellular matrix disassembly
• Cellular component: extracellular region;extracellular space;nuclear speck;collagen-containing extracellular matrix
• Molecular function: protease binding;metalloendopeptidase activity;protein binding;peptidase activity;metallopeptidase activity;metal ion binding