ADAMTS12

ADAM metallopeptidase with thrombospondin type 1 motif 12, the group of ADAM metallopeptidases with thrombospondin type 1 motif

Basic information

Region (hg38): 5:33523534-33892019

Links

ENSG00000151388 ∙ NCBI:81792 ∙ OMIM:606184 ∙ HGNC:14605 ∙ Uniprot:P58397 ∙ 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 ADAMTS12 gene.

• Inborn genetic diseases (73 variants)
• not provided (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADAMTS12 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				3	3	6
missense			69	4	6	79
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	69	7	9

Variants in ADAMTS12

This is a list of pathogenic ClinVar variants found in the ADAMTS12 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-33527226-T-C		not specified	Uncertain significance (Dec 28, 2022)
5-33534886-G-C		not specified	Uncertain significance (Dec 02, 2022)
5-33534889-T-C			Benign (Jun 29, 2018)
5-33534911-C-T		not specified	Uncertain significance (Mar 01, 2024)
5-33546060-A-T		not specified	Uncertain significance (Mar 21, 2023)
5-33546096-T-G		not specified	Uncertain significance (Aug 10, 2021)
5-33549272-G-A		not specified	Uncertain significance (Jan 17, 2023)
5-33549278-T-C		not specified	Uncertain significance (Jan 17, 2024)
5-33549326-G-A		not specified	Uncertain significance (Feb 14, 2023)
5-33549330-G-C			Benign (Jul 16, 2018)
5-33549371-A-C		not specified	Uncertain significance (Jun 13, 2023)
5-33561086-G-C		not specified	Uncertain significance (Dec 07, 2023)
5-33561106-G-A		not specified	Uncertain significance (Oct 04, 2022)
5-33561137-C-G		not specified	Uncertain significance (Oct 26, 2021)
5-33561155-C-T		not specified	Uncertain significance (Jan 17, 2024)
5-33576092-G-T		not specified	Uncertain significance (Nov 06, 2023)
5-33576166-T-G		not specified	Uncertain significance (Jan 23, 2023)
5-33576203-T-C		not specified	Uncertain significance (Oct 05, 2023)
5-33576220-A-T		not specified	Uncertain significance (Jul 06, 2021)
5-33576293-C-T		not specified	Uncertain significance (Aug 01, 2022)
5-33576296-G-C		not specified	Uncertain significance (Sep 17, 2021)
5-33576317-C-T		not specified	Uncertain significance (Dec 15, 2023)
5-33576340-G-T		not specified	Uncertain significance (Jan 07, 2022)
5-33576371-C-T		not specified	Uncertain significance (Oct 27, 2022)
5-33576377-T-C		not specified	Uncertain significance (Nov 09, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADAMTS12	protein_coding	protein_coding	ENST00000504830	24	368658

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.48e-17	1.00	125542	0	206	125748	0.000819

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.980	819	902	0.908	0.0000493	10502
Missense in Polyphen		270	351.73	0.76762		4027
Synonymous	-0.0799	340	338	1.01	0.0000199	3044
Loss of Function	3.80	40	75.7	0.528	0.00000369	877

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00158	0.00158
Ashkenazi Jewish	0.00370	0.00368
East Asian	0.000437	0.000435
Finnish	0.000417	0.000416
European (Non-Finnish)	0.000678	0.000668
Middle Eastern	0.000437	0.000435
South Asian	0.000887	0.000850
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Metalloprotease that may play a role in the degradation of COMP. Cleaves also alpha-2 macroglobulin and aggregan. Has anti-tumorigenic properties. {ECO:0000269|PubMed:16611630, ECO:0000269|PubMed:17895370, ECO:0000269|PubMed:18485748}.
• Pathway: Post-translational protein modification;Metabolism of proteins;O-glycosylation of TSR domain-containing proteins;O-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.121

Intolerance Scores

• loftool: 0.867
• rvis_EVS: 0.87
• rvis_percentile_EVS: 88.75

Haploinsufficiency Scores

• pHI: 0.109
• hipred: N
• hipred_score: 0.492
• ghis: 0.500

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.160

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adamts12
• Phenotype: neoplasm; 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)

Gene ontology

• Biological process: cell-matrix adhesion;cell migration;proteoglycan catabolic process;negative regulation of chondrocyte differentiation;regulation of inflammatory response;proteolysis involved in cellular protein catabolic process;cellular response to interleukin-1;cellular response to tumor necrosis factor;cellular response to BMP stimulus;regulation of endothelial tube morphogenesis;negative regulation of hepatocyte growth factor receptor signaling pathway;negative regulation of cellular response to vascular endothelial growth factor stimulus;negative regulation of cellular response to hepatocyte growth factor stimulus
• Cellular component: collagen-containing extracellular matrix
• Molecular function: metalloendopeptidase activity;protein binding;metal ion binding